DolceraWiki - User contributions [en]

Pictorial view of analysis

2007-09-13T16:33:47Z

67.180.82.65:

Pictorial view of analysis

2007-09-13T16:33:08Z

67.180.82.65:

Main Page

2007-09-12T08:02:42Z

67.180.82.65:

__NOTOC__
== Technology ==
==== Landscape Reports ====
* [[Hybrid Electric Vehicle Battery System]]
* [[Supply Chain RFID Applications]]
* [[Insurance sector]]
* [[Quality of Service on CDMA platforms]]
* [[OLED - Organic Light Emitting Diode]]

==== Dashboard ====
* [http://client.dolcera.com/dash_auto/dashboard.html Automotive dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/rfid_model.swf RFID dashboard]

==== Innovation Explorer ====
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics Innovation Explorer]
* [[Web video]]

==== IPMaps ====
* [http://www.dolcera.com/ipmapdemo/satellite_antenna/ipmap.html Satellite Antenna IPMap]
* [http://www.dolcera.com/ipmapdemo/rfid/ipmap.html RFID IPMap]
* [http://www.dolcera.com/ipmapdemo/multimodal_apps/ipmap.html Multimodal Applications IPMap]

===Market research===
* [[4G wireless technology developments]]

== Life sciences and Chemistry ==
==== Landscape reports ====
* [[Alopecia - Hair Loss]]
* [[Diabetes products and services]]
* [[Inflammation and cardiovascular drugs]]
* [[Non-wovens]]

==== Dashboard ====
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]

==== IPMap ====
* [http://dolcera.com/client/d8r3/hairloss_map.htm Alopecia/Hair loss IPMap]

==== [[Disease database]] ====

== Finance ==
* [[Innovative personal finance products]]

== Dolcera Offerings summary ==
* [[Dolcera Offerings|Dolcera offerings summary]]

== Dolcera Training ==
* [[Training Manual]]

== Chinese Page ==
* [[Home Page]]
* [[Service Page]]
* [[About]]

Main Page

2007-09-12T08:01:54Z

67.180.82.65: /* Landscape Reports */

__NOTOC__
== Technology ==
==== Landscape Reports ====
* [[Hybrid Electric Vehicle Battery System]]
* [[Supply Chain RFID Applications]]
* [[Insurance sector]]
* [[Quality of Service on CDMA platforms]]
* [[OLED - Organic Light Emitting Diode]]

==== Innovation Explorer ====
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics Innovation Explorer]
* [[Web video]]

==== IPMaps ====
* [http://www.dolcera.com/ipmapdemo/satellite_antenna/ipmap.html Satellite Antenna IPMap]
* [http://www.dolcera.com/ipmapdemo/rfid/ipmap.html RFID IPMap]
* [http://www.dolcera.com/ipmapdemo/multimodal_apps/ipmap.html Multimodal Applications IPMap]

===Market research===
* [[4G wireless technology developments]]

== Life sciences and Chemistry ==
==== Landscape reports ====
* [[Alopecia - Hair Loss]]
* [[Diabetes products and services]]
* [[Inflammation and cardiovascular drugs]]
* [[Non-wovens]]

==== Dashboard ====
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]

==== IPMap ====
* [http://dolcera.com/client/d8r3/hairloss_map.htm Alopecia/Hair loss IPMap]

==== [[Disease database]] ====

== Finance ==
* [[Innovative personal finance products]]

== Dolcera Offerings summary ==
* [[Dolcera Offerings|Dolcera offerings summary]]

== Dolcera Training ==
* [[Training Manual]]

== Chinese Page ==
* [[Home Page]]
* [[Service Page]]
* [[About]]

Disease database

2007-09-12T07:14:29Z

67.180.82.65:

The Dolcera disease database is a subscription service with monthly updates for a number of diseases, listed below. Each report consists of the following sections:
# Incidence and prevalence data
# Market overview
# Product pipeline
# Intellectual property updates
# Clinical Trials
# Major conferences and conference updates

== Disease and drug classes ==
* '''Endocrine & Metabolism'''
** [[Oral Diabetes Drugs]]
** [[Osteoporosis]]

* '''GI and Liver Disease'''
** Irritable bowel disease
** Hepatitis C
** Ulcerative Colitis
** Crohn’s Disease

* '''Cardiovascular Disease'''
** Arrythmia and Rhythm disturbances
** Hypertension

* '''Eye Disorder'''
** Age-related macular degeneration (AMD)

* '''Oncology'''
** Renal cell carcinoma
** Lung cancer
** Prostate cancer
** Breast cancer

* '''Neurology'''
** ADHD
** Multiple sclerosis
** Depression
** Parkinson’s Disease
** Alzheimer’s Disease
** Dementia

* '''Infectious Disease'''
** HIV infection
** Methicillin Resistant Staphylococcus Aureus infections
** Vancomycin resistant S. aureus infection
** Vancomycin resistant Enterococcus infection

Disease database

2007-09-12T06:50:06Z

67.180.82.65:

The Dolcera disease database is a subscription service with monthly updates for a number of diseases, listed below. Each report consists of the following sections:
# Incidence and prevalence data
# Market overview
# Product pipeline
# Intellectual property updates
# Clinical Trials
# Major conferences and conference updates

The following disease and drug classes will be covered:
* Endocrine & Metabolism
** [[Oral Diabetes Drugs]]
** [[Osteoporosis]]

* GI and Liver Disease
** Irritable bowel disease
** Hepatitis C
** Ulcerative Colitis
** Crohn’s Disease

* Cardiovascular Disease
** Arrythmia and Rhythm disturbances
** Hypertension

* Eye Disorder
** Age-related macular degeneration (AMD)

* Oncology
** Renal cell carcinoma
** Lung cancer
** Prostate cancer
** Breast cancer

* Neurology
** ADHD
** Multiple sclerosis
** Depression
** Parkinson’s Disease
** Alzheimer’s Disease
** Dementia

* Infectious Disease
** HIV infection
** Methicillin Resistant Staphylococcus Aureus infections
** Vancomycin resistant S. aureus infection
** Vancomycin resistant Enterococcus infection

Main Page

2007-09-12T03:38:12Z

67.180.82.65: /* IPMap */

Main Page

2007-09-06T05:25:38Z

67.180.82.65:

__NOTOC__
== Technology ==
==== Landscape Reports ====
* [[Hybrid Electric Vehicle Battery System]]
* [[Supply Chain RFID Applications]]
* [[Insurance sector]]
* [[Quality of Service on CDMA platforms]]
* [[OLED - Organic Light Emitting Diode]]

==== Dashboard ====
* [http://client.dolcera.com/dash_auto/dashboard.html Automotive dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/rfid_model.swf RFID dashboard]

==== Innovation Explorer ====
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics Innovation Explorer]
* [[Web video]]

==== IPMaps ====
* [http://www.dolcera.com/ipmapdemo/satellite_antenna/ipmap.html Satellite Antenna IPMap]
* [http://www.dolcera.com/ipmapdemo/rfid/ipmap.html RFID IPMap]
* [http://www.dolcera.com/ipmapdemo/multimodal_apps/ipmap.html Multimodal Applications IPMap]

===Market research===
* [[4G wireless technology developments]]

== Life sciences and Chemistry ==
==== Landscape reports ====
* [[Alopecia - Hair Loss]]
* [[Diabetes products and services]]
* [[Inflammation and cardiovascular drugs]]
* [[Non-wovens]]

==== Dashboard ====
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]

==== IPMap ====
* [http://dolcera.com/client/d8r3/hairloss_map.htm Alopecia/Hair loss IPMap]

== Finance ==
* [[Innovative personal finance products]]

== Dolcera Offerings summary ==
* [[Dolcera Offerings|Dolcera offerings summary]]

== Dolcera Training ==
* [[Training Manual]]

== Chinese Page ==
* [[Home Page]]
* [[Service Page]]
* [[About]]

Main Page

2007-08-17T05:42:02Z

67.180.82.65: /* Landscape Reports */

__NOTOC__
== Technology ==
==== Landscape Reports ====
* [[Hybrid Electric Vehicle Battery System]]
* [[Supply Chain RFID Applications]]
* [[Insurance sector]]
* [[Quality of Service on CDMA platforms]]
* [[OLED - Organic Light Emitting Diode]]

==== Dashboard ====
* [http://client.dolcera.com/dash_auto/dashboard.html Automotive dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/rfid_model.swf RFID dashboard]

==== Innovation Explorer ====
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics Innovation Explorer]

==== IPMaps ====
* [http://www.dolcera.com/ipmapdemo/satellite_antenna/ipmap.html Satellite Antenna IPMap]
* [http://www.dolcera.com/ipmapdemo/rfid/ipmap.html RFID IPMap]
* [http://www.dolcera.com/ipmapdemo/multimodal_apps/ipmap.html Multimodal Applications IPMap]

===Subscription service===
[[4G Subscription]]

== Life sciences and Chemistry ==
==== Landscape reports ====
* [[Alopecia - Hair Loss]]
* [[Diabetes products and services]]
* [[Inflammation and cardiovascular drugs]]
* [[Non-wovens]]

==== Dashboard ====
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]

==== IPMap ====
* [http://dolcera.com/client/d8r3/hairloss_map.htm Alopecia/Hair loss IPMap]

== Finance ==
* [[Innovative personal finance products]]

== Dolcera Offerings summary ==
* [[Dolcera Offerings|Dolcera offerings summary]]

== Dolcera Training ==
* [[Training Manual]]

== Chinese Page ==
* [[Home Page]]
* [[Service Page]]
* [[About]]

Alopecia - Hair Loss

2007-08-17T03:52:42Z

67.180.82.65: /* Treatment approaches */

{{TOCrightEx}}
== Rationale ==
* "Medication for men plagued by hair loss has become a topic of interest in Japan since a drug company began marketing it at the end of last year." March 5th, 2006 – [http://stophair.setupmyblog.com/?p=55 source]

* "An increasing number of companies are apparently turning the Chinese fear of a bald spot into big bucks with some doing so well they are branching out into other countries." February 16, 2006 – [http://stophair.setupmyblog.com/]

* "There is something in the air, or should we say in the hair, these days. Scientific research into hair loss remedies has never been more active or more exciting." June 7, 2006 - [http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/06-07-2005/0003821470&EDATE=]

== Introduction ==

=== Hair basics ===
* Hair is a complex and delicate part of the body.
* Keeping it healthy and beautiful is a challenge.
* Hair grows everywhere on the body with the exception of lips, eyelids, palms of the hands and soles of the feet.
* Hair is basically a form of skin.
* Hair is made up of a protein called keratin.
* Each shaft of hair is made of two or three inter-twined layers of keratin which grow from a follicle beneath the skin.
* Hair Structure - [http://www.pg.com/science/haircare/hair_twh_12.htm]
* Hair Cycle - [http://www.follicle.com/hair-structure-life-cycle.html]

[[Image:Hairbasics.jpg|center|400px|Structure of Hair root and Hair bulb]]

=== What causes hair loss? ===
* Decrease in growth of hair
* Increase in shedding of hair
* Breakage of hair
* Conversion of thick terminal hairs to thin vellus hairs
[[Image:Facts.jpg|thumb|right|250px|Survey results from Japan]]
Both men and women lose hair for similar reasons. Hair loss in men is often more dramatic, and follows a specific pattern of loss, one of which has been termed “Male Pattern Baldness" or "Androgenetic Alopecia".

=== Types of alopecia===

* Alopecia Areata (AA): Hair loss occurring in patches anywhere on the body.
* Alopecia Totalis (AT): Total loss of the hair on the scalp.
* Alopecia Universalis (AU): Total loss of all hair on the body.
* Alopecia Barbae: Loss of facial hair (for a man) especially in the beard area.
* Alopecia Mucinosa: A type of alopecia which results in scaley patches.
* Androgenetic Alopecia (AGA): Also known as male pattern baldness. It is a thinning of the hair to an almost transparent state, in both men or women. It is thought to be a hereditary form of hair loss.
* Traction Alopecia: Traction alopecia is usually due to excessive pulling or tension on hair shafts as a result of certain hair styles. It is seen more often in women, particularly those of East Indian and Afro-Caribbean origin. Hair loss depends on the way the hair is being pulled. Prolonged traction alopecia can stop new hair follicles from developing and leads to permanent hair loss.
* Anagen Effluvium: This hair loss is generally caused by chemicals such as those used to treat cancer. Initially it causes patchy hair loss, which often then leads to total hair loss. The good news is that when you stop using these chemicals the hair normally grows back (usually about 6 months later). Other drugs also can cause hair loss. Many medicines used to treat even common diseases can cause hair loss.
* Scarring Alopecia: A form of alopecia which leaves scarring on the area of hair loss.
* Telogen Effluvium: A form of hair loss where more than normal numbers of hair fall out. There is a general 'thinning' of the hair. Unlike some other hair and scalp conditions, it is temporary and the hair growth usually recovers. ([http://www.alopeciaonline.org.uk/about/types.asp Source])

=== Androgenetic alopecia ===
* Gradual onset
* Transition from large, thick, pigmented terminal hairs to thinner, shorter, indeterminate hairs and finally to short, wispy, non-pigmented vellus hairs in the involved areas
* Characterized by a receding hairline and/or hair loss on the top of the head

'''Main causes'''
* Genetic predisposition
* Hormonal effect of androgen
* Reduction of blood circulation around hair follicle
* Deactivation of hair matrix cells

'''Some facts from Japan'''

* Market size: ¥ 30 Billion
* Number of products: more than 100

(JICST-EPlus - Japanese Science & Technology)

== IP activity over the years ==
The graph indicates:
* Number of patents filed every 5 years (except for first 7 years).
* First solution proposed in 1973
* Filing trend indicates steep rise in activity recently.
[[Image:Year1.jpg|thumb|center|400px|IP Activity over years]]

== Major players ==
[[Image:players.jpg|thumb|left|400px|Assignees with more than 20 patents ]]
[[Image:players1.jpg|thumb|center|400px|Assignees with fewer than 20 patents ]] 

* '''Active assignees'''
Assignees currently active with more than 5 patents to their credit during 2000-2005.
* Warner with 9 patents,
* Bristol with 6 and
* Abbott with 5.

[[Image:Active.jpg|thumb|center|500px|Active Assignees]]

== Treatment Approaches==
Composition of treatment for causes are identified and categorized as follows:

* Anti-androgens (Finasteride) [http://www.emedicine.com/DERM/topic21.htm source]
* Vasodilators (Minoxidil) [http://www.emedicine.com/DERM/topic21.htm source]
* Double action (Anti-androgen + Vasodilator)
* Hair matrix cells activator

{|border="1" cellpadding="2", style="#008080" align="center"
|- style="font-weight:bold" valign="top"
! Cause !! Treatment approach !! Pathways affected

|- valign="top"
| Hormonal effect of androgen || Anti-androgens || Testosterone pathway

|- valign="top"
| Reduction of blood circulation around hair follicle || Vasodilators (eg. Minoxidil) || NO/cGMP Pathway

|- valign="top"
| Deactivation of hair matrix cells || Hair matrix cells activator
|
* Wnt pathway
* STAT pathway
* TGF beta/BMP Pathway
* FGF Pathway
* MAPK Pathway
* NOTCH Pathway
* Hedgehog Pathway
|}

=== Anti-androgens ===
* Anti-androgens are used in hormone therapy.
* Anti-androgens are designed to affect the hormones made in the adrenal glands. They don't stop the hormones from being made, but they stop them from having an effect leading to hair loss.

'''What causes hair loss?'''
* Testosterone is reduced to its active metabolite, Dihydrotestosterone (DHT) by the enzyme 5 alpha reductase.
* DHT attaches to androgen receptor sites at the hair follicle.
* DHT causes gradual miniaturization of the follicle, which eventually results in hair loss.

'''How do anti-androgens treat hair loss?'''
* Anti-androgens compete with DHT to bind to the androgen receptor.
* Upon binding of anti-androgen in place of DHT, follicle miniaturization is lowered and hair loss prevented.

==== Functions of Anti-androgen ====
[http://www.revivogen.com/revivogen/work.html Anti-androgen]

[[Image:Andogen1.jpg|thumb|center|500px|Functions of Anti-androgen]]

==== IP Map for anti-androgen ====

{| border="1" cellpadding="0", style="#008080"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="100" bgcolor=DodgerBlue|'''Nature'''
!width="450" bgcolor=DodgerBlue|'''Composition'''
!width="400" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
BLOTECH (2004)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Palmetto berry extract (fatty acids & sterols), Pumpkin seed extract (Vitamins-B, alpha-linolenic acid, amino acids and phytosterols), Quercetin (Flavonoids) and Beta-sitosterol (Rice bran, wheat germ, corn oils and soybeans)
|bgcolor=LightCyan|Fatty acids – Inhibit testosterone
Sterols - Mechanism of action unknown.

Quercetin results in cell growth cycle.

Beta-sitosterol reduce inflammation on scalp
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
WARNER LAMBERT(2004)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 4-cycloalkoxy benzonitrile derivatives and salts
|bgcolor=LightCyan|Acts as androgen receptor modulator and blocks formation of DHT.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
WARNER LAMBERT(2004)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 6-sulfonamido-quinolin-2-one and 6-sulfonamido-2-oxo-chromene derivatives.
|bgcolor=LightCyan|The compounds inhibit, or decrease, activation of androgen receptor by androgens.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
APHIOS Corp (2003)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Supercritical fluid isolate of Saw Palmetto and Sperol (Serenoa repens berry) and their analogs or derivatives.
|bgcolor=LightCyan|Modulates androgenic activity by inhibiting 5.alpha.-reductase activity.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
Fundacion Pablo Cassara (2003)
|bgcolor=LightCyan|Nucleotide
|bgcolor=LightCyan|Pharmacologically active oligonucleotides (encompass both DNA and S-DNA bond)
|bgcolor=LightCyan|Oligonucleotides inhibit androgen receptor (AR) expression at very low concentrations in skin and hair follicle
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
PFIZER INC (2001)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|Thyromimetic compounds (structurally similar to thyronine) with finasteride, or cyproterone acetate
|bgcolor=LightCyan|Activates thyroid hormone receptors in hair follicle which in turn promote elasticisation of follicle walls and hair follicle
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
N/A (1995)
|bgcolor=LightCyan|Peptides/nucleic acid
|bgcolor=LightCyan|Bradykinin antagonist (peptide of plasma origin from kininogen precursor-kallikrein)
|bgcolor=LightCyan|Inhibits synthesis of bradykinin receptors or compounds by binding to B2 receptor
|- style="height:20px"
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
KAO Corp (1987)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Walnut extract (leaves/pericarps) with an organic solvent
|bgcolor=LightCyan|Blocks formation of DHT
|}

=== Minoxidil (Vasodilators) ===
* Minoxidil is a "potassium channel opener" that leads to vasodilation.
* The drug is available in two forms. Oral minoxidil is used to treat high blood pressure and the topical solution form is used to treat hair loss and baldness.

'''What causes hair loss?'''
* A thick network of tiny veins and arteries line the outer wall of the follicle. Blood pumps through the bulb and hair via this network.
* DHT accumulates in the hair follicles and roots, constricting the blood supply of oxygen and nutrients to the hair roots; which is also seen to possibly contribute towards hair loss.

'''How does Minoxidil treat hair loss?'''
* Minoxidil is applied to the scalp topically, where it dilates blood vessels in the scalp and sustains the hair follicles for longer period of time.
* Minoxidil is thought to have a direct mitogenic effect on epidermal cells, as has been observed both in vitro and in vivo. Though the mechanism of its action for causing cell proliferation is not very clear, minoxidil is thought to prevent intracellular calcium entry. Calcium normally enhances epidermal growth factors to inhibit hair growth, and Minoxidil by getting converted to minoxidil sulfate acts as a potassium channel agonist and enhances potassium ion permeability to prevent calcium ions from entering into cells. ([http://www.hairtransplantadvice.com/medical-hair-restoration.php Source])
* Minoxidil sulfate (MS) appears to be the active metabolite responsible for hair growth stimulation.

==== Functions of Vasodilators ====

[[Image:minoxidil1.jpg|thumb|center|500px|Functions of Monoxidil [http://www.nurseminerva.co.uk/diagrams.htm#Diagram%201 source]]]

==== IP Map for Vasodilators ====

{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75" bgcolor=DodgerBlue|'''Nature'''
!width="600" bgcolor=DodgerBlue|'''Composition'''
!width="300" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
WARNER LAMBERT(2002)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|Benzopyran compounds
|bgcolor=LightCyan|Rapidly metabolizes, and causes reduced cardiovascular effects as compared to other known potassium channel openers
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
LG HOUSEHOLD & HEALTH CARE(2001)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Sophora flavescens extract (alkaloids & flavonoids, luteolin-7-glucose and cytosine) Hinokitiol (Taiwan hinoki oil, Aomori, Western Red Cedar oil) and Nicotinamide (Vitamin B complex)
|bgcolor=LightCyan|Promotes function of cell activity and dilates blood vessels
|}

=== Double action (Anti-androgen + Vasodilator) ===
* Combination of Vasodilator + Anti-androgen (double action) composition for effective treatment of Male-Pattern Baldness.

'''What is the problem with using only Anti-androgen therapy?'''
* Anti-androgen is not effective in addressing the issue of vasocontriction around hair follicles due to sebum oil build up.
* Anti-androgen only prevents binding of DHT to androgen receptors. However, the effects of improper oxygen and nutrient supply to the brain due to vasocontriction still remains and gradually causes hair loss.

'''What is the problem with using only Vasodilator (or Minoxidil only) therapy?'''
* Vasodilator or Minoxidil-based products are generally not effective in stopping hair loss as vasodilators (or Minoxidil) do not block the harmful effects of DHT in the scalp and hair follicles.
* Vasodilators or Minoxidil simply dilate blood vessels in the scalp. However, the harmful DHT still gets produced in the body, enters the scalp and hair follicles causing hair loss.

'''How is the combination of Anti-androgens and Vasodilator (or Minoxidil) effective?'''
* Anti-androgens target the problem of DHT binding to androgen receptors and prevents follicle miniaturization.
* Vasodilators like Minoxidil cause vasodilation and therefore improve supply of oxygen and nutrients to the hair follicle and roots.
* Combination therapy therefore proves to be much more effective than individual therapy.

==== Functions of (Anti-androgen + Vasodilators) ====
[http://www.revivogen.com/revivogen/work.html Anti-androgen ]and [http://www.xandrox.net/articles/article01.htm Minoxidil]
[[Image:Doubleaction1.jpg|thumb|center|500px|Functions of (Anti-androgen + Vasodilators)]]

==== IP Map for (Anti-androgen + Vasodilators) ====
{| border="1" cellpadding="3"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75" bgcolor=DodgerBlue|'''Nature'''
!width="500" bgcolor=DodgerBlue|'''Composition'''
!width="500" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
N/A(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Testosterone blocker or vascular toner (Flutamide, cyproterone acetate, spironolactone, progesterone, or analogs or derivatives) and minoxidil mixed along with non-retinoid penetration enhancer and sunscreen
|bgcolor=LightCyan|Inhibits 5.alpha.-reductase activity (block DHT) and increase blood flow on the scalp
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
L'OREAL(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Prostaglandin (polyunsaturated fatty acids) EP-2, EP-3 EP-4 receptor agonist with Minoxidil, 2,4-diaminopyrimidine 3-oxide, and Aminexil, cyclic AMP
|bgcolor=LightCyan|Minoxidil (designed to mimic nitric oxide's effects) grows hair via prostaglandin-H synthase stimulation. EP-3 and EP-4 are expressed in anagen hair follicles which induce a reduction in the level of cAMP
|- style="height:100px"
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
COLOMER GROUP(1999)
|bgcolor=LightCyan|Natural extract
|bgcolor=LightCyan|Hop extract (oil contains terpenes and humulene), Rosemary extract (hydroalcohol), Swertia extract (glycol with a swertiamarin), Silanodiol salicylate (biologically active silicon compound)
|bgcolor=LightCyan|Inhibits activity of 5-alpha-reductase, protects follicular cell membranes by neutralizing action of oxidation reaction in tissues, stimulates hair follicles and blood circulation to the hair root, supplies oxygen and nutrients to base of follicle, retains humidity, avoids dehydration of scalp
|}

=== Hair matrix cell activator ===
Hair matrix cell activator is a substance that acts at the matrix cells in the hair follicle preventing their degradation.

'''What causes hair loss?'''
* Stem cells are interspersed within the basal layer of the outer root sheath and in an area called the bulge.
* Stem cells migrate to hair matrix where they start to divide and differentiate, under the influence of substances produced by cells of the dermal papilla.
* Perifollicular matrix cells undergo slow degradation which prevents follicle stimulation.
* Hair follicle activation is required for hair growth and thus inhibition of follicle activation eventually leads to hair loss.

'''How does hair cell matrix activator treat hair loss?'''
* Hair cell matrix activator slows down and inhibits degradation of the perifollicular matrix.
* This leads to an increase in hair follicle matrix cells that differentiate from progenitor stem cells.
* Matrix activator allows activation of hair matrix cells and therefore follicle stimulation leading to hair growth.

==== Functions of Hair matrix cell activator ====
[http://www.ijdb.ehu.es/fullaccess/fulltext.04023/ft163.pdf Hair matrix cell activator]
[[Image:Hair matrix.jpg|thumb|center|500px|Functions of Hair matrix cell activator ]]

==== IP Map for Hair matrix cell activator ====
{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="100" bgcolor=DodgerBlue|'''Nature'''
!width="200" bgcolor=DodgerBlue|'''Composition'''
!width="600" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
SHISEIDO(1999)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|(2-substituted oxyphenyl) alkanamide derivative and its salt
|bgcolor=LightCyan|Mechanism of action has not been made clear, having excellent hair follicle activating action and regrowth promoting effect
|- style="height:50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
L'OREAL(1998)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Metalloprotease (MMP-9) inhibitor (thiol or a hydroxamate) other than chelating calcium ions
|bgcolor=LightCyan|Reducing the expression of MMPs (Metalloproteases) in the scalp - slows down or inhibits the degradation of the perifollicular matrix (extracellular matrix surrounding the hair follicle)
|}

== Technology mapping based on patents analyzed ==

=== IPMap: Composition nature matrix ===

{| border="1" cellpadding="11", style="#008080"
!width="120" bgcolor=DodgerBlue|'''Year'''
!width="200" bgcolor=DodgerBlue|'''Organic Compound'''
!width="200" bgcolor=DodgerBlue|'''Natural extracts'''
!width="200" bgcolor=DodgerBlue|'''Peptides'''
!width="200" bgcolor=DodgerBlue|'''Nucleotides'''
!width="200" bgcolor=DodgerBlue|'''Natural extract + Organic comp'''
|- style="height:10px"
|bgcolor=LightCyan|2005
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|UNILEVER (1)
|-
|bgcolor=LightCyan|2004
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|BLOTECH (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|KAO (1)
|-
|bgcolor=LightCyan|2003
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|APHIOS (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|FUNDACION (1)
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2002
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2001
|bgcolor=LightCyan |PFIZER (1)
|bgcolor=LightCyan|LG HEALTH-CARE (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2000
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|L’OREAL (1) / N/A (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1999
|bgcolor=LightCyan|SHISEDIO (1)
|bgcolor=LightCyan|COLOMER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1998
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|L’OREAL (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1995
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|N/A (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1987
|bgcolor=LightCyan|....
|bgcolor=LightCyan|KAO (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1982
|bgcolor=LightCyan|UNILEVER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|}

=== Focus of patents ===

{| border="1" cellpadding="17", style="#008080"
!width="800" bgcolor=DodgerBlue|'''Focus of patents'''
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="100" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|2-substituted oxyphenyl alkanamide derivative having excellent hair growth effect.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
|bgcolor=LightCyan|1
|-
|bgcolor=LightCyan|Thyromimetic compounds, and its role in treating hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
|bgcolor=LightCyan|2
|-
|bgcolor=LightCyan|Saw Palmetto berry extract, pumpkin seed extract, sitosterol and quercetin for the treatment and prevention of the biologically detrimental effects of DHT
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
|bgcolor=LightCyan|3
|-
|bgcolor=LightCyan|4-cycloalkoxy benzonitriles and its use as androgen receptor modulators
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
|bgcolor=LightCyan|4
|-
|bgcolor=LightCyan|Supercritical fluid isolate of Saw Palmetto, Sperol for inhibition of 5-.alpha.-reductase activity
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
|bgcolor=LightCyan|5
|-
|bgcolor=LightCyan|New class of quinolin-2-ones and chromen-2-ones andtheir use as androgen receptor antagonists
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|6
|-
|bgcolor=LightCyan|Antiandrogen oligonucleotides usable for the treatment of dermatological androgen-related disorders
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
|bgcolor=LightCyan|7
|-
|bgcolor=LightCyan|Bradykinin antagonists for stimulating or inducing hair growth and/or arresting hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
|bgcolor=LightCyan|8
|-
|bgcolor=LightCyan|Extract from walnut leaves and/or pericarps as 5 alpha -reductase inhibitor
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
|bgcolor=LightCyan|9
|-
|bgcolor=LightCyan|Stimulating hair growth using benzopyrans
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
|bgcolor=LightCyan|10
|-
|bgcolor=LightCyan|Sophora flavescens extract, Coicis semen extract, clove extract, etc for promoting hair growth, function of cell activity and dilating peripheral blood vessels.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
|bgcolor=LightCyan|11
|-
|bgcolor=LightCyan|Compositions to prevent or reduce hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
|bgcolor=LightCyan|12
|-
|bgcolor=LightCyan|Prostaglandin EP-3 receptor antagonists for reducing hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
|bgcolor=LightCyan|13
|-
|bgcolor=LightCyan|Synergic effect arising from the interaction of active ingredients, consisting of three plant extracts and a synthetic organosilicic compound for prevent hair loss and stimulate hair growth
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
|bgcolor=LightCyan|14
|-
|bgcolor=LightCyan|Metalloprotease inhibitors to induce and/or stimulate the growth
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
|bgcolor=LightCyan|15
|-
|bgcolor=LightCyan|Method of decreasing sebum production and pore size
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050277699%22.PGNR.&OS=DN/20050277699&RS=DN/20050277699 US20050277699 ]
|bgcolor=LightCyan|16
|-
|bgcolor=LightCyan|Method for reducing sebum on the hair and skin
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=4529587.PN.&OS=PN/4529587&RS=PN/4529587 US4529587]
|bgcolor=LightCyan|17
|}

=== Technology focus===
[[Image:Technologyfocus2.jpg|thumb|center|700px|Technology focus]]

=== Distribution of patents ===

==== By patent types ====
[[Image:Didtribution.jpg|thumb|center|700px|Distribution based on patent types ]]

==== By key ingredients ====
[[Image:key1.jpg|thumb|center|700px|Distribution of key ingredients]]

==== By target disease ====
[[Image:target.jpg|thumb|center|700px|Distribution based on target diseases]]

==== Key ingredients vs. Target disease ====
[[Image:key&target1.jpg|thumb|center|1000px|Key ingredients vs. Target disease]]

==== Target species ====
[[Image:Species.jpg|thumb|center|700px|Target species]]

==== Mode of administration ====
[[Image:Mode.jpg|thumb|center|700px|Mode of administration]]

==== Product type vs. Product form ====
[[Image:prod.jpg|thumb|center|700px|Product type vs. Product form]]

==== Patents by target diseases ====
{| border="1" cellpadding="16", style="#008080"
!width="800" bgcolor=DodgerBlue|'''Target disease/ disorder'''
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="150" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|Alopecia areata, alopecia pityrodes or alopecia seborrheica, or androgenic alopecia (i.e. male pattern baldness)
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
|bgcolor=LightCyan|1
|-
|bgcolor=LightCyan|Alopecia areata, male pattern baldness and female pattern baldness
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
|bgcolor=LightCyan|2
|-
|bgcolor=LightCyan|Androgenic alopecia (i.e. male pattern baldness), prostatic hyperplasia or both.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
|bgcolor=LightCyan|3
|-
|bgcolor=LightCyan|Inappropriate activation of the androgen receptor, acne, oily skin, alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
|bgcolor=LightCyan|4
|-
|bgcolor=LightCyan|Prostatic hyperplasia, prostatic cancer, hirsutism, acne, male pattern baldness, seborrhea, and other diseases related to androgen hyperactivity
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
|bgcolor=LightCyan|5
|-
|bgcolor=LightCyan|Alopecia, acne, oily skin, prostrate cancer, hirsutism, and benign prostate hyperplasia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|6
|-
|bgcolor=LightCyan|Androgen-associated hair loss and androgen-skin related disorders.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
|bgcolor=LightCyan|7
|-
|bgcolor=LightCyan|Androgenetic or androgenic alopecia or androgeno-genetic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
|bgcolor=LightCyan|8
|-
|bgcolor=LightCyan|Diseases caused by testosterone (male-pattern alopecia)
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
|bgcolor=LightCyan|9
|-
|bgcolor=LightCyan|Alopecia areata, female pattern hair loss, hair loss secondary to chemotherapy or radiation treatment, stress-related hair loss, self-induced hair loss, scarring alopecia, and alopecia in non-human mammal
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
|bgcolor=LightCyan|10
|-
|bgcolor=LightCyan|Male pattern alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
|bgcolor=LightCyan|11
|-
|bgcolor=LightCyan|Alopecia, androgenic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
|bgcolor=LightCyan|12
|-
|bgcolor=LightCyan|Hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
|bgcolor=LightCyan|13
|-
|bgcolor=LightCyan|Male pattern alopecia
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
|bgcolor=LightCyan|14
|-
|bgcolor=LightCyan|Androgenetic, androgenic or androgenogenetic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
|bgcolor=LightCyan|15
|-
|bgcolor=LightCyan|Curing other scalp related problems
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050244362%22.PGNR.&OS=DN/20050244362&RS=DN/20050244362 US20050244362]
|bgcolor=LightCyan|16
|}

==== Patents by application ====
[[Image:application.jpg|thumb|center|700px|Distribution of patents based on application]]

==== [[List of patents]] ====

== Pathways and linkages ==

=== Pathways associated with hair matrix cell activation===

'''Molecular mediators of hair follicle embryogenesis:''' Identification of the molecular pathways controlling differentiation and proliferation in mammalian hair follicles provides the crucial link to understanding the regulation of normal hair growth, the basis of hereditary hair loss diseases, and the origin of follicle-based tumors. Homeobox (hox), hedgehog (hh), patched (ptc), wingless (wg}/wnt, disheveled (dsh), engrailed (en), Notch 1 and armadillo/B-catenin genes are all critical for hair follicle.

* '''Wnt pathway:''' Maintains hair-inducing activity of the dermal papilla.
* '''Hedgehog pathway:''' Sonic hedgehog (SHH) signaling plays a critical role in hair follicle development. Sonic hedgehog gene. Sonic hedgehog, SHH for short, helps guide hair follicles from a resting stage into growth activity. SHH is particularly important in the embryonic formation of hair follicles.
* '''STAT pathway'''
* '''TGF beta/BMP Pathway:''' Bone morphogenetic protein (BMP) signaling have been implicated in the regulation of both proliferation and differentiation in the hair follicle. BMP2 is expressed in the embryonic ectoderm, but then localizes to the early hair follicle placode and underlying mesenchyme. BMP4 is expressed in the early dermal condensate. Research results show that BMPs are a key component of the signaling network controlling hair development and are required to induce the genetic program regulating hair shaft differentiation in the anagen hair follicle. Transforming growth factor beta (TGF-beta), inhibits mitogen - induced dermal papilla cell proliferation
* '''FGF Pathway:''' Fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) potentiate the growth of dermal papilla cells. It is proposed that these proteins increase the synthesis of stromelysin (an enzyme, matrix metalloproteinase) which acts on the papilla cells and accelerates their growth.
* '''MAPK Pathway:''' Mitogen-activated protein kinase (MAPK) activation, increases keratinocyte turnover.
* '''NOTCH Pathway''': Notch-1 is expressed in ectodermal-derived cells of the follicle, in the inner cells of the embryonic placode and the follicle bulb, and in the suprabasal cells of the mature outer root sheath. Delta-1, one of the three ligands is only expressed during embryonic follicle development and is exclusive to the mesenchymal cells of the pre-papilla located beneath the follicle placode, and appears to promote and accelerate placode formation, while suppressing placode formation in surrounding cells. Other ligands, Serrate 1 and Serrate 2, are expressed in matrix cells destined to form the inner root sheath and hair shaft.

=== Pathways associated with Anti Androgen===
[[Image:Slide1.GIF|thumb|center|700 px|Alopecia pathways]]

==== Players of WNT inhibition Pathway ====
[[Image:wnt.jpg|thumb|right|200 px|Wnt inhibition]]
{| border="1" cellpadding="15", style="#008080"
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="200" bgcolor=DodgerBlue|'''Key compound'''
!width="200" bgcolor=DodgerBlue|'''Players of inhibition'''
|- style="height:10px"
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|GSK3
|-
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6989385.PN.&OS=PN/6989385&RS=PN/6989385 US6989385]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|GSK3
|-
|bgcolor=lightyellow|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|CDK,GSK3
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6974819.PN.&OS=PN/6974819&RS=PN/6974819 US6974819]
|bgcolor=LightCyan|Pyrimidine derivative
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6743791.PN.&OS=PN/6743791&RS=PN/6743791 US6743791]
|bgcolor=LightCyan|Heterocyclic compounds
|bgcolor=LightCyan|AKT3, GSK-3, ERK2
|-
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050277773%22.PGNR.&OS=DN/20050277773&RS=DN/20050277773 US20050277773]
|bgcolor=LightCyan|Pyrrolo[3,2-d]pyrimidine derivatives
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040072836%22.PGNR.&OS=DN/20040072836&RS=DN/20040072836 US20040072836]
|bgcolor=LightCyan|Aza-oxindole derivatives
|bgcolor=LightCyan|GSK3, AKT, PKC
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP1477489&F=0 EP1477489]
|bgcolor=LightCyan|Pyrrolopyrimidine derivatives
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO0056710&F=0 WO0056710]
|bgcolor=LightCyan|3-(Anilinomethylene) oxindoles
|bgcolor=LightCyan|GSK3, AKT, PKC
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO03011287&F=0 WO2003011287]
|bgcolor=LightCyan|Pyrazolon derivatives
|bgcolor=LightCyan|GSK3, β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6924141.PN.&OS=PN/6924141&RS=PN/6924141 US6924141]
|bgcolor=LightCyan|Lithium chloride, Wnt3/4/ 7
|bgcolor=LightCyan|β-catenin, GSK3, Wnt
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6706685.PN.&OS=PN/6706685&RS=PN/6706685 US6706685]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6683048.PN.&OS=PN/6683048&RS=PN/6683048 US6683048]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|α-catenin, β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6677116.PN.&OS=PN/6677116&RS=PN/6677116 US6677116]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6303576.PN.&OS=PN/6303576&RS=PN/6303576 US6303576]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|β-catenin
|}

==== Role of Pyrazole compounds in Wnt Pathway====
'''Pyrazole'''
* '''Pyrazole''' (C3H4N2) refers both to the class of simple aromatic ring organic compounds of the heterocyclic series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions and to the unsubstituted parent compound. Being so composed and having pharmacological effects on humans, they are classified as alkaloids although they are not known to occur in nature.
* Pyrazoles are produced synthetically through the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation
[[Image:pyrazole1.jpg|thumb|center|500px|Pyrazole (C3H4N2)]]
* Pyrazoles are used for their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, tranquilizing, muscle relaxing, psychoanaleptic, anticonvulsant, monoamineoxidase inhibiting, antidiabetic and antibacterial activities.
* Structurally related compounds are pyrazoline and pyrazolidine.
[[Image:pyrazole2.jpg|thumb|center|500px|Structurally related compounds]]

==== GSK3 inhibition by pyrazole compounds ====
[[Image:bold3.jpg]]
{| border="1" cellpadding="2", style="#008080"
!width="350"|[http://patft1.uspto.gov/netacgi/nph-Parser?TERM1=6989385+&Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=0&f=S&l=50 US6989385]
[[Image:US6989385.jpg]]
!width="350"|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
[[Image:US6664247.jpg]]
!width="350"|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
[[Image:WO2005012256.jpg]]
|-
|bgcolor=lightcyan|R1=T-Ring D, wherein
T is a valence bond and
Ring D = 5-6 membered aryl or heteroaryl ring;

R2 = hydrogen or C1-4 aliphatic and
R2'= hydrogen;

R3 = -R, -OR, or -N(R4)2, wherein
R = hydrogen, C1-6 aliphatic, 5-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl, and
L is -O-, -S-, or -NH-; and
Ring D is substituted by up to three substituents selected from -halo, -CN, -NO2, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R<4>), -N(R4)COR, -N(R4)CO2R, -SO2N(R4)2, -N(R4)SO2R, -N(R6)COCH2N(R4)2, -N(R6)COCH2CH2N(R4)2, or -N(R6)COCH2CH2CH2N(R4)2, wherein R = hydrogen, C1-6 aliphatic, phenyl, 5-6 membered heteroaryl ring, or 5-6 membered heterocyclic ring

|bgcolor=lightcyan|X = R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, S02, C=O, NRg(C=O) or O(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;

R1 is hydrogen; carbocyclic or heterocyclic group having from 3 to 12 ring members; or C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from 0, S, NH, SO, S02;

R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and

R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

|bgcolor=lightcyan|X is a groupR1-A-NR4-or a 5-or 6-membered carbocyclic or heterocyclic ring;
A is a bond,SO2, C=O, NRg (C=O) or O(C=O) wherein Rg is hydrogen orC14 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;Y is a bond or an alkylene chain of 1,2 or 3 carbon atoms in length;R'is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e. g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono-ordi-Cl 4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected fromO, S, NH, SO, SO2 ;R2 is hydrogen; halogen;C14 alkoxy (e. g. methoxy); or aC14 hydrocarbyl group optionally substituted by halogen (e. g. fluorine), hydroxyl orC14 alkoxy (e. g. methoxy);R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; andR4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e. g. fluorine), hydroxyl or C1-4 alkoxy (e. g. methoxy).
|}

==== Inhibition by amine derivatives ====

'''Patent Number''': US6989385
'''Applicant''': ''Vertex Pharmaceuticals Incorporated''
'''Title''': Pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure''':

[[Image:pyrazol1.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6989385 patent]]

'''Patent Number''': US7008948
'''Applicant''': Vertex Pharmaceuticals Incorporated
'''Title''': Fused pyrimidyl pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure'''

[[Image:pyrazol2.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US7008948 patent]]

'''Patent Number''': US6977262
'''Assignee''': Mitsubishi Pharma Corporation
'''Title''': Dihydropyrazolopyridine compounds and pharmaceutical use thereof

'''Basic Structure''':

[[Image:pyrazol3.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6977262 patent]]

----
'''Patent Number''': US6664247
'''Assignee''': Vertex Pharmaceuticals Incorporated
'''Title''': Pyrazole compounds useful as protein kinase inhibitors'''

'''Basic Structure''':

[[Image:pyrazol4.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6664247 patent]]

----
'''Patent Number''': US2004224944
'''Assignee''': VERTEX PHARMACEUTICALS INC
'''Title''': Pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure''':

[[Image:pyrazol5.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US2004224944 patent]]

[[Other derivates for alopecia]]

==== GSK-3 Inhibition Mechanism - Phosphorylation====
* ''GSK-3 inhibition targets treatment of chemotherapy-induced alopecia'' [http://www.biomedcentral.com/1471-2199/5/15 source]
* In the canonical Wnt signaling cascade, adenomatous polyposis coli (APC), axin, and GSK3 constitute the so-called destruction complex, which controls the stability of beta-catenin. It is generally believed that four conserved Ser/Thr residues in the N terminus of beta-catenin are the pivotal targets for the constitutively active serine kinase GSK3. GSK3 covalently modifies beta-catenin by attaching phosphate groups (from ATP) to serine, and threonine residues. In so doing, the functional properties of the protein kinase’s substrate (beta-catenin) are modified.

* In the absence of Wnt signals, glycogen synthase kinase (GSK) is presumed to phosphorylate the N-terminal end of beta-catenin, thus promote degradation of beta-catenin and subsequent ubiquitination and proteasomal targeting.

* Exposure of cells to Wnts leads to inactivation of GSK-3 through an as yet unclear mechanism.The phosphoprotein Dishevelled is required, after receptor-ligand interaction, to transduce the signal that results in the inactivation of GSK-3. As a result, beta-catenin is dephosphorylated and escapes the ubiqduitylation-dependent destruction machinery.

* Unphosphorylated beta-catanin accumulates in the cytoplasm and translocates to the nucleus, where it can associate with the TCF/LEFs and become a transcriptional transactivator.

'''[[More details on GSK-3]]'''

'''Key points'''

* Beta-catenin phosphorylation at serine 45 (Ser45), threonine 41 (Thr41), Ser37, and Ser33 is critical for beta-catenin degradation. [http://jb.oxfordjournals.org/cgi/content/abstract/132/5/697 source]
* Regulation of beta-catenin phosphorylation is a central part of the canonical Wnt signaling pathway. [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=223838&ArtikelNr=66755&filename=66755.pdf source]
* Ser-X-X-X-Ser (X is any amino acid) motif is obligatory for beta-catenin phosphorylation by GSK3.[http://lib.bioinfo.pl/auth:He,X source]
* Beta-catenin phosphorylation/degradation and its regulation by Wnt can occur normally in the absence of Thr41 as long as the Ser-X-X-X-Ser motif/spacing is preserved. [httSp://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2006/45/i16/abs/bi0601149.html source]

'''GK3 Inhibition:'''

* GSK3 is regulated by phosphorylation.
* Phosphorylation of GSK3beta on Ser9 (Ser21 in GSK3alpha) by protein kinase B (PKB) causes its inactivation is the primary mechanism responsible for growth factor inhibition of this kinase. Activation of GSK3beta is dependent upon the phosphorylation of Tyr216 (Tyr279 in GSK3alpha). Upon activation, it has been shown to phosphorylate a number of different cellular proteins, including p53, c-Myc, c-Jun, heat shock factor-1 (HSF-1), beta-catenin and cyclin D1. [http://www.bioreagents.com/index.cfm/fuseaction/products.detail/CatNbr/OPA1-03082 source]
* GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3beta and GSK3alpha, respectively. [http://lib.bioinfo.pl/auth:Friedman,AB source]
* GSK3’s substrate specificity is unique in that phosphorylation of substrate only occurs if a phosphoserine or phosphotyrosine is present four residues C-terminal to the site of GSK phosphorylation. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11430833&dopt=Abstract source]
* A phosphorylation cascade starts from GSK3 itself and initiates it in beta-catenin. [http://www.genesdev.org/cgi/content/full/16/16/2073 source]
* Thus our goal is to stop the phosphorylation of the serine and threonine residue of GSK3.
* The figure below illustrates the phosphorylation mechanism of serine and threonine by ATP.

[[image:GSK3_phosphorylation.jpg|400 px|center|thumb|Phosphorylation mechanism [http://images.google.com/images?q=tbn:DGnhgZ7y7pSejM:bass.bio.uci.edu/~hudel/bs99a/lecture26/phosphoaa.gif source]]]

* We can't stop conversion of ADP to ATP that relaseas Phosphorous group causing Phosphorylation.
* We can only block the oxygen atom on serine and threonine as a result which will in turn stop Phosphorylation.
* The two probable ways of blocking the oxygen atom are (a) As oxygen is a Lewis acid with strong electron donating capacity, so usually a strong electron pair acceptor can easily bind to oxygen atom and preventing phosphorylation or (b) breaking of the -OH bond with the carbon atom.

'''Serine - pyrazole reaction'''

[[image:serine-pyrazol.jpg|600 px|center|thumb|Serine and Pyrazole reaction [http://www.genome.ad.jp/dbget-bin/www_bget?rn+R03134 source]]]

* The T-loop of GSK-3 is tyrosine phosphorylated at Y216 and Y279 in GSK-3b and GSK-3a, respectively, but not threonine phosphorylated. Y216/Y279 phosphorylation could play a role in forcing open the substrate (e.g, beta-catanin)-binding site.

* Thus, T-loop tyrosine might facilitate substrate phosphorylation but is not strictly required for kinase activity.

* Stimulation of cells with pyrazole compounds cause inactivation of GSK-3 through phosphorylation (S9 of GSK-3 beta and S21 of GSK-3 alpha), which inhibits GSK-3 activity. Thus leading to dephosphorylation of substrates (e.g., beta-catanin) resulting in their functional activation and consequent increased hair follicle morphogenisis.

* Phosphorylation of S9/S21 creates a primed pesudosubstrate that binds intramolecularly to the positively charged pocket of the GSK-3. This folding precludes phosphorylation of substrates (eg., beta-catanin) because the catalytic groove is occupied. The mechanism of inhibition is competitive.

* A consequence of this is that primed substrates, in high enough concentrations, out-compete the pesudosubstrate and thus become phosphorylated.

* Thus, small molecule inhibitors modeled to fit in the positively charged pocket of the GSK-3 kinease domain could potentially be very effective for selective inhibition of primed substrates.

'''Proposed mechanisms to regulate GSK-3''' [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12615961 source]

# inactivation of GSK-3 through serine phosphorylation
# activation of GSK-3 through tyrosine phosphorylation
# inactivation of GSK-3 through tyrosine dephosphorylation
# Covalant modifications of substrates through priming phosphorylation
# inhibition or facilation of GSK-3 mediated substrate phosphorylation thriugh interation of GSK-3 with binding or scaffolding proteins
# targeting of GSK-3 to different subcellular localizations
# differential usage of isoforms or splice variants to alter subcellular localization or substrate specificity
# integration of parellel signals conveyed by a signal stimulus.

'''Key Finding'''
* '''Pyrazole compounds with inhibition constant (Ki) of <0.1 mM''' are a good starting point for developing molecules that can inhibit serine/threonine protein kinase (such as GSK-3) and the proteins they help to regulate. [http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html?DOC=patentwatch%5Carchive%5C011204_patentwatch.html source]

=== Pathway associated with anti-androgen ===

* Dihydrotestosterone
** Formed by peripheral conversion of testosterone by 5-alpha reductase
** Binds to androgen receptor on susceptible hair follicles
* Hormone-receptor complex activates genes responsible for gradual transformation of large terminal follicles to miniaturized (progressive diminution of hair shaft diameter and length in response to systemic androgens) follicles

[[Image:5-alpha-reductase inhibition.jpeg|center|500 px]]

==== Structure-Activity Relationships(SARs) ====
[[Image:SAR_map.gif|center|600px]]

=== Pathway associated with Minoxidil (vasodilators) ===
Minoxidil is a well know drug used for the treatment of alopecia. A co-relation between Sesquiterpene lactone (Helenalin) produced from Arnica montana and Minoxidil is illustrated in the figure below. Arnica montana, a Vasodilator, acts on the NO/cGMP Pathway through T-cells, B-cells and epithelial cells & abrogates kappa B-driven gene expression.
[[image:vasodiator-rev.jpg|800 px|center]]

== Alopecia IPMap ==
[http://www.dolcera.com/client/d8r3/hairloss_map.htm Dolcera IPMap for Alopecia]

== Patent activity in China ==
===Treatment approaches===
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center"|'''Treatment approach'''
|align = "center"|'''Patent number'''
|align = "center"|'''Priority year'''
|align = "center"|'''Assignee/Inventor'''
|-
|rowspan = "7"|Vasodilators
|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN200510107497.8&leixin=fmzl&title=治疗瘀血阻滞型脱发的中草药汤剂及制备方法&ipc=A61K36/804(2006.01)I CN1772105]
|2005
|叶明伟
|-
|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=CN1772139&F=0 CN1772139]
|2005
|王亚杰
|-
|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN03139861.8&leixin=fmzl&title=一种可用于治疗脱发、白发的天然中草药提取组合物及应用&ipc=A61K35/78 CN1569080]
|2003
|谈汝标
|-
|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN02155404.8&leixin=fmzl&title=毛囊激活液&ipc=A61K35/78 CN1506103]
|2002
|赵章光
|-
|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN01127395.X&leixin=fmzl&title=一种止脱生发药物及其制备方法&ipc=A61K35/78 CN1403100]
|2001
|范希田
|-
|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN96116925.7&leixin=fmzl&title=免洗养发生发香波&ipc=C11D3/48 CN1165181]
|1996
|殷国健
|-
|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN88103853.9&leixin=fmzl&title=一种通络生发香波&ipc=A61K7/06 CN1031022]
|1988
|天津市轻工业化学研究所
|-
|Hair matrix activator
|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN02111941.4&leixin=fmzl&title=一种含中西药复方的育发剂&ipc=A61K7/06 CN1463693]
|2002
|朱静建
|-
|Anti-androgen <nowiki>+</nowiki> Vasodilator
|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN96109964.X&leixin=fmzl&title=一种治疗脂溢性脱发的高效低副作用外用药物&ipc=A61K35/78 CN1150043]
|1996
|梅晓春
|-
|}

=== Details of treatment approaches===

{|border="2" cellspacing="0" cellpadding="4" width="100%" align="left"
|align = "center"|'''Patent number'''
|align = "center"|'''Patent title'''
|align = "center"|'''Treatment approach'''
|align = "center"|'''Composition nature'''
|align = "center"|'''Composition'''
|align = "center"|'''Composition action'''
|-
|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN200510107497.8&leixin=fmzl&title=治疗瘀血阻滞型脱发的中草药汤剂及制备方法&ipc=A61K36/804(2006.01)I CN1772105] YE MINGWEI (CN) 叶明伟 (2005)
|align = "justify"|Chinese herbal medicine decoction for treating blood stasis obstruction type alopecia and its prepn 治疗瘀血阻滞型脱发的中草药汤剂及制备方法
|align = "justify"|Vasodilators
|align = "justify"|Herbal extract
|align = "justify"|Astragalus root, prepared rhizome of rehmannia, white peony root, angelica, peach kernel and sufflower
|align = "justify"|Promote blood circulation
|-
|align = "justify"|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=CN1772139&F=0 CN1772139 ]WANG YAJIE (CN) 王亚杰 2005
|align = "justify"|Alopecia areata treating medicine 一种治疗斑秃的药物
|align = "justify"|Vasodilators
|align = "justify"|Herbal extract
|align = "justify"|Pinellia tuber, fleeceflower root, arborvitae seed, chickení s gizzard membrane, prepared rhizome of rehmannia, Poris cocos, Codonopsis pilosula, etc
|align = "justify"|Promote blood circulation
|-
|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN03139861.8&leixin=fmzl&title=一种可用于治疗脱发、白发的天然中草药提取组合物及应用&ipc=A61K35/78 CN1569080] TAN RUBIAO (CN) 谈汝标 2003
|align = "justify"|Natural Chinese herb composition for treating alopecia and leucotrichia and its application 一种可用于治疗脱发、白发的天然中草药提取组合物及应用
|align = "justify"|Vasodilators
|align = "justify"|Herbal extract
|align = "justify"|Ginger, Cinnamomum cassia, myrrh, clove, mace nutmeg, Loranthus mulberry mistletoe, rhizoma dioscoreae, ligustrum japonicum, drynaria, fleece-flower root, and black sesame seeds
|align = "justify"|Enhances the hair growth and healthier hairs
|-
|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN02111941.4&leixin=fmzl&title=一种含中西药复方的育发剂&ipc=A61K7/06 CN1463693] 朱静建 2002
|Hair growing preparation containing compound of Chinese medicine and Western medicine 一种含中西药复方的育发剂
|align = "justify"|Hair matrix activator
|Mixture of Herbal extracts and western medicine
|align = "justify"|Persimmon leaf, oriental arbor-vitae leaf, ginseng leaf, yellow qi, fruit of the glossy privet, polygonum multiflorum, Kudzu root, dry ginger; Plus：Minoxidil, Vitamins and derivative, cystine, serine, leucine.
|align = "justify"|Better and faster hair growth
|-
|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN02155404.8&leixin=fmzl&title=毛囊激活液&ipc=A61K35/78 CN1506103] 赵章光2002
|align = "justify"|Hair follice activating liquid 毛囊激活液
|align = "justify"|Vasodilators
|align = "justify"|Herbal extract
|align = "justify"|Ginseng, twists the stock blue, the licorice, the Sophora flavescens and hot peppers
|align = "justify"|Activates the hair-follicle and enhances the hair growth.
|-
|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN01127395.X&leixin=fmzl&title=一种止脱生发药物及其制备方法&ipc=A61K35/78 CN1403100] 范希田 2001
|align = "justify"|Trichogen and its prepn 一种止脱生发药物及其制备方法
|align = "justify"|Vasodilators
|align = "justify"|Herbal extract
|align = "justify"|Ginseng, ganoderma lucidum, Chinese rhubarb, polygonum multiflorum, Chinese prickly ash, ginger, grass seed
|align = "justify"|Promote blood circulation and enhance hair growth
|-
|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN96116925.7&leixin=fmzl&title=免洗养发生发香波&ipc=C11D3/48 CN1165181] 殷国健 1996
|Washing free shampoo for nourishing and growing hair 免洗养发生发香波
|align = "justify"|Vasodilator
|Vitamin composition
|align = "justify"|Vitamin P (Bioflavonoids), Vitamin B15, Vitamin B2, nicotinic acid, bromo—geramineum
|align = "justify"|Stimulate hair growth
|-
|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN96109964.X&leixin=fmzl&title=一种治疗脂溢性脱发的高效低副作用外用药物&ipc=A61K35/78 CN1150043] 梅晓春 1996
|Efficient low-side effect external use medicine for curing seborrheic baldness 一种治疗脂溢性脱发的高效低副作用外用药物
|align = "justify"|Anti-androgen <nowiki>+</nowiki> Vasodilator
|Mixture of Herbal extracts and organic compounds
|align = "justify"|Polygonum multiflorum, Ligustrum lucidum, Morus alba, Rehmannia glutinosa, Eclipta prostrata, Saliva miltiorrhiza, Carthamus tinctorius, Cnidium monnieri, Sophora flavescens, Dictamnus dasycarpus, Kochia scoparia, and antioxidants
|align = "justify"|Inhibit the excess secretion of the sebaceous glands, increase the blood circulation on scalp and enhance the hair growth
|-
|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN88103853.9&leixin=fmzl&title=一种通络生发香波&ipc=A61K7/06 CN1031022] 天津市轻工业化学研究所 1988
|Channel-stimulating and hair-growing hair shampoo 一种通络生发香波
|align = "justify"|Vasodilators
|Herbal extract <nowiki>+</nowiki> detergent
|align = "justify"|Herbal extracts, Penetration media, Detergents.
|align = "justify"|Increases the blood circulation under the scalp, reduces the hair los
|-
|} 

== Conclusions ==
* Hair loss medication is a very active area of research and intellectual property development.
* One of the most promising areas of development is the area of Anti-androgens.
* The top companies are Merck, L’Oreal and Smithkline.

Alopecia - Hair Loss

2007-08-17T03:51:54Z

67.180.82.65: /* Alopecia IPMap */

Alopecia - Hair Loss

2007-08-17T03:51:15Z

67.180.82.65:

Alopecia - Hair Loss

2007-08-17T03:50:49Z

67.180.82.65:

{{TOCrightEx}}
== Rationale ==
* "Medication for men plagued by hair loss has become a topic of interest in Japan since a drug company began marketing it at the end of last year." March 5th, 2006 – [http://stophair.setupmyblog.com/?p=55 source]

* "An increasing number of companies are apparently turning the Chinese fear of a bald spot into big bucks with some doing so well they are branching out into other countries." February 16, 2006 – [http://stophair.setupmyblog.com/]

* "There is something in the air, or should we say in the hair, these days. Scientific research into hair loss remedies has never been more active or more exciting." June 7, 2006 - [http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/06-07-2005/0003821470&EDATE=]

== Alopecia IPMap ==
[http://www.dolcera.com/client/d8r3/hairloss_map.htm Dolcera IPMap for Alopecia]

== Introduction ==

=== Hair basics ===
* Hair is a complex and delicate part of the body.
* Keeping it healthy and beautiful is a challenge.
* Hair grows everywhere on the body with the exception of lips, eyelids, palms of the hands and soles of the feet.
* Hair is basically a form of skin.
* Hair is made up of a protein called keratin.
* Each shaft of hair is made of two or three inter-twined layers of keratin which grow from a follicle beneath the skin.
* Hair Structure - [http://www.pg.com/science/haircare/hair_twh_12.htm]
* Hair Cycle - [http://www.follicle.com/hair-structure-life-cycle.html]

[[Image:Hairbasics.jpg|center|400px|Structure of Hair root and Hair bulb]]

=== What causes hair loss? ===
* Decrease in growth of hair
* Increase in shedding of hair
* Breakage of hair
* Conversion of thick terminal hairs to thin vellus hairs
[[Image:Facts.jpg|thumb|right|250px|Survey results from Japan]]
Both men and women lose hair for similar reasons. Hair loss in men is often more dramatic, and follows a specific pattern of loss, one of which has been termed “Male Pattern Baldness" or "Androgenetic Alopecia".

=== Types of alopecia===

* Alopecia Areata (AA): Hair loss occurring in patches anywhere on the body.
* Alopecia Totalis (AT): Total loss of the hair on the scalp.
* Alopecia Universalis (AU): Total loss of all hair on the body.
* Alopecia Barbae: Loss of facial hair (for a man) especially in the beard area.
* Alopecia Mucinosa: A type of alopecia which results in scaley patches.
* Androgenetic Alopecia (AGA): Also known as male pattern baldness. It is a thinning of the hair to an almost transparent state, in both men or women. It is thought to be a hereditary form of hair loss.
* Traction Alopecia: Traction alopecia is usually due to excessive pulling or tension on hair shafts as a result of certain hair styles. It is seen more often in women, particularly those of East Indian and Afro-Caribbean origin. Hair loss depends on the way the hair is being pulled. Prolonged traction alopecia can stop new hair follicles from developing and leads to permanent hair loss.
* Anagen Effluvium: This hair loss is generally caused by chemicals such as those used to treat cancer. Initially it causes patchy hair loss, which often then leads to total hair loss. The good news is that when you stop using these chemicals the hair normally grows back (usually about 6 months later). Other drugs also can cause hair loss. Many medicines used to treat even common diseases can cause hair loss.
* Scarring Alopecia: A form of alopecia which leaves scarring on the area of hair loss.
* Telogen Effluvium: A form of hair loss where more than normal numbers of hair fall out. There is a general 'thinning' of the hair. Unlike some other hair and scalp conditions, it is temporary and the hair growth usually recovers. ([http://www.alopeciaonline.org.uk/about/types.asp Source])

=== Androgenetic alopecia ===
* Gradual onset
* Transition from large, thick, pigmented terminal hairs to thinner, shorter, indeterminate hairs and finally to short, wispy, non-pigmented vellus hairs in the involved areas
* Characterized by a receding hairline and/or hair loss on the top of the head

'''Main causes'''
* Genetic predisposition
* Hormonal effect of androgen
* Reduction of blood circulation around hair follicle
* Deactivation of hair matrix cells

'''Some facts from Japan'''

* Market size: ¥ 30 Billion
* Number of products: more than 100

(JICST-EPlus - Japanese Science & Technology)

== IP activity over the years ==
The graph indicates:
* Number of patents filed every 5 years (except for first 7 years).
* First solution proposed in 1973
* Filing trend indicates steep rise in activity recently.
[[Image:Year1.jpg|thumb|center|400px|IP Activity over years]]

== Major players ==
[[Image:players.jpg|thumb|left|400px|Assignees with more than 20 patents ]]
[[Image:players1.jpg|thumb|center|400px|Assignees with fewer than 20 patents ]] 

* '''Active assignees'''
Assignees currently active with more than 5 patents to their credit during 2000-2005.
* Warner with 9 patents,
* Bristol with 6 and
* Abbott with 5.

[[Image:Active.jpg|thumb|center|500px|Active Assignees]]

== Treatment Approaches==
Composition of treatment for causes are identified and categorized as follows:

* Anti-androgens (Finasteride) [http://www.emedicine.com/DERM/topic21.htm source]
* Vasodilators (Minoxidil) [http://www.emedicine.com/DERM/topic21.htm source]
* Double action (Anti-androgen + Vasodilator)
* Hair matrix cells activator

{|border="1" cellpadding="2", style="#008080" align="center"
|- style="font-weight:bold" valign="top"
! Cause !! Treatment approach !! Pathways affected

|- valign="top"
| Hormonal effect of androgen || Anti-androgens || Testosterone pathway

|- valign="top"
| Reduction of blood circulation around hair follicle || Vasodilators (eg. Minoxidil) || NO/cGMP Pathway

|- valign="top"
| Deactivation of hair matrix cells || Hair matrix cells activator
|
* Wnt pathway
* STAT pathway
* TGF beta/BMP Pathway
* FGF Pathway
* MAPK Pathway
* NOTCH Pathway
* Hedgehog Pathway
|}

=== Anti-androgens ===
* Anti-androgens are used in hormone therapy.
* Anti-androgens are designed to affect the hormones made in the adrenal glands. They don't stop the hormones from being made, but they stop them from having an effect leading to hair loss.

'''What causes hair loss?'''
* Testosterone is reduced to its active metabolite, Dihydrotestosterone (DHT) by the enzyme 5 alpha reductase.
* DHT attaches to androgen receptor sites at the hair follicle.
* DHT causes gradual miniaturization of the follicle, which eventually results in hair loss.

'''How do anti-androgens treat hair loss?'''
* Anti-androgens compete with DHT to bind to the androgen receptor.
* Upon binding of anti-androgen in place of DHT, follicle miniaturization is lowered and hair loss prevented.

==== Functions of Anti-androgen ====
[http://www.revivogen.com/revivogen/work.html Anti-androgen]

[[Image:Andogen1.jpg|thumb|center|500px|Functions of Anti-androgen]]

==== IP Map for anti-androgen ====

{| border="1" cellpadding="0", style="#008080"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="100" bgcolor=DodgerBlue|'''Nature'''
!width="450" bgcolor=DodgerBlue|'''Composition'''
!width="400" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
BLOTECH (2004)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Palmetto berry extract (fatty acids & sterols), Pumpkin seed extract (Vitamins-B, alpha-linolenic acid, amino acids and phytosterols), Quercetin (Flavonoids) and Beta-sitosterol (Rice bran, wheat germ, corn oils and soybeans)
|bgcolor=LightCyan|Fatty acids – Inhibit testosterone
Sterols - Mechanism of action unknown.

Quercetin results in cell growth cycle.

Beta-sitosterol reduce inflammation on scalp
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
WARNER LAMBERT(2004)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 4-cycloalkoxy benzonitrile derivatives and salts
|bgcolor=LightCyan|Acts as androgen receptor modulator and blocks formation of DHT.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
WARNER LAMBERT(2004)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 6-sulfonamido-quinolin-2-one and 6-sulfonamido-2-oxo-chromene derivatives.
|bgcolor=LightCyan|The compounds inhibit, or decrease, activation of androgen receptor by androgens.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
APHIOS Corp (2003)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Supercritical fluid isolate of Saw Palmetto and Sperol (Serenoa repens berry) and their analogs or derivatives.
|bgcolor=LightCyan|Modulates androgenic activity by inhibiting 5.alpha.-reductase activity.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
Fundacion Pablo Cassara (2003)
|bgcolor=LightCyan|Nucleotide
|bgcolor=LightCyan|Pharmacologically active oligonucleotides (encompass both DNA and S-DNA bond)
|bgcolor=LightCyan|Oligonucleotides inhibit androgen receptor (AR) expression at very low concentrations in skin and hair follicle
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
PFIZER INC (2001)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|Thyromimetic compounds (structurally similar to thyronine) with finasteride, or cyproterone acetate
|bgcolor=LightCyan|Activates thyroid hormone receptors in hair follicle which in turn promote elasticisation of follicle walls and hair follicle
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
N/A (1995)
|bgcolor=LightCyan|Peptides/nucleic acid
|bgcolor=LightCyan|Bradykinin antagonist (peptide of plasma origin from kininogen precursor-kallikrein)
|bgcolor=LightCyan|Inhibits synthesis of bradykinin receptors or compounds by binding to B2 receptor
|- style="height:20px"
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
KAO Corp (1987)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Walnut extract (leaves/pericarps) with an organic solvent
|bgcolor=LightCyan|Blocks formation of DHT
|}

=== Minoxidil (Vasodilators) ===
* Minoxidil is a "potassium channel opener" that leads to vasodilation.
* The drug is available in two forms. Oral minoxidil is used to treat high blood pressure and the topical solution form is used to treat hair loss and baldness.

'''What causes hair loss?'''
* A thick network of tiny veins and arteries line the outer wall of the follicle. Blood pumps through the bulb and hair via this network.
* DHT accumulates in the hair follicles and roots, constricting the blood supply of oxygen and nutrients to the hair roots; which is also seen to possibly contribute towards hair loss.

'''How does Minoxidil treat hair loss?'''
* Minoxidil is applied to the scalp topically, where it dilates blood vessels in the scalp and sustains the hair follicles for longer period of time.
* Minoxidil is thought to have a direct mitogenic effect on epidermal cells, as has been observed both in vitro and in vivo. Though the mechanism of its action for causing cell proliferation is not very clear, minoxidil is thought to prevent intracellular calcium entry. Calcium normally enhances epidermal growth factors to inhibit hair growth, and Minoxidil by getting converted to minoxidil sulfate acts as a potassium channel agonist and enhances potassium ion permeability to prevent calcium ions from entering into cells. ([http://www.hairtransplantadvice.com/medical-hair-restoration.php Source])
* Minoxidil sulfate (MS) appears to be the active metabolite responsible for hair growth stimulation.

==== Functions of Vasodilators ====

[[Image:minoxidil1.jpg|thumb|center|500px|Functions of Monoxidil [http://www.nurseminerva.co.uk/diagrams.htm#Diagram%201 source]]]

==== IP Map for Vasodilators ====

{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75" bgcolor=DodgerBlue|'''Nature'''
!width="600" bgcolor=DodgerBlue|'''Composition'''
!width="300" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
WARNER LAMBERT(2002)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|Benzopyran compounds
|bgcolor=LightCyan|Rapidly metabolizes, and causes reduced cardiovascular effects as compared to other known potassium channel openers
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
LG HOUSEHOLD & HEALTH CARE(2001)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Sophora flavescens extract (alkaloids & flavonoids, luteolin-7-glucose and cytosine) Hinokitiol (Taiwan hinoki oil, Aomori, Western Red Cedar oil) and Nicotinamide (Vitamin B complex)
|bgcolor=LightCyan|Promotes function of cell activity and dilates blood vessels
|}

=== Double action (Anti-androgen + Vasodilator) ===
* Combination of Vasodilator + Anti-androgen (double action) composition for effective treatment of Male-Pattern Baldness.

'''What is the problem with using only Anti-androgen therapy?'''
* Anti-androgen is not effective in addressing the issue of vasocontriction around hair follicles due to sebum oil build up.
* Anti-androgen only prevents binding of DHT to androgen receptors. However, the effects of improper oxygen and nutrient supply to the brain due to vasocontriction still remains and gradually causes hair loss.

'''What is the problem with using only Vasodilator (or Minoxidil only) therapy?'''
* Vasodilator or Minoxidil-based products are generally not effective in stopping hair loss as vasodilators (or Minoxidil) do not block the harmful effects of DHT in the scalp and hair follicles.
* Vasodilators or Minoxidil simply dilate blood vessels in the scalp. However, the harmful DHT still gets produced in the body, enters the scalp and hair follicles causing hair loss.

'''How is the combination of Anti-androgens and Vasodilator (or Minoxidil) effective?'''
* Anti-androgens target the problem of DHT binding to androgen receptors and prevents follicle miniaturization.
* Vasodilators like Minoxidil cause vasodilation and therefore improve supply of oxygen and nutrients to the hair follicle and roots.
* Combination therapy therefore proves to be much more effective than individual therapy.

==== Functions of (Anti-androgen + Vasodilators) ====
[http://www.revivogen.com/revivogen/work.html Anti-androgen ]and [http://www.xandrox.net/articles/article01.htm Minoxidil]
[[Image:Doubleaction1.jpg|thumb|center|500px|Functions of (Anti-androgen + Vasodilators)]]

==== IP Map for (Anti-androgen + Vasodilators) ====
{| border="1" cellpadding="3"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75" bgcolor=DodgerBlue|'''Nature'''
!width="500" bgcolor=DodgerBlue|'''Composition'''
!width="500" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
N/A(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Testosterone blocker or vascular toner (Flutamide, cyproterone acetate, spironolactone, progesterone, or analogs or derivatives) and minoxidil mixed along with non-retinoid penetration enhancer and sunscreen
|bgcolor=LightCyan|Inhibits 5.alpha.-reductase activity (block DHT) and increase blood flow on the scalp
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
L'OREAL(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Prostaglandin (polyunsaturated fatty acids) EP-2, EP-3 EP-4 receptor agonist with Minoxidil, 2,4-diaminopyrimidine 3-oxide, and Aminexil, cyclic AMP
|bgcolor=LightCyan|Minoxidil (designed to mimic nitric oxide's effects) grows hair via prostaglandin-H synthase stimulation. EP-3 and EP-4 are expressed in anagen hair follicles which induce a reduction in the level of cAMP
|- style="height:100px"
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
COLOMER GROUP(1999)
|bgcolor=LightCyan|Natural extract
|bgcolor=LightCyan|Hop extract (oil contains terpenes and humulene), Rosemary extract (hydroalcohol), Swertia extract (glycol with a swertiamarin), Silanodiol salicylate (biologically active silicon compound)
|bgcolor=LightCyan|Inhibits activity of 5-alpha-reductase, protects follicular cell membranes by neutralizing action of oxidation reaction in tissues, stimulates hair follicles and blood circulation to the hair root, supplies oxygen and nutrients to base of follicle, retains humidity, avoids dehydration of scalp
|}

=== Hair matrix cell activator ===
Hair matrix cell activator is a substance that acts at the matrix cells in the hair follicle preventing their degradation.

'''What causes hair loss?'''
* Stem cells are interspersed within the basal layer of the outer root sheath and in an area called the bulge.
* Stem cells migrate to hair matrix where they start to divide and differentiate, under the influence of substances produced by cells of the dermal papilla.
* Perifollicular matrix cells undergo slow degradation which prevents follicle stimulation.
* Hair follicle activation is required for hair growth and thus inhibition of follicle activation eventually leads to hair loss.

'''How does hair cell matrix activator treat hair loss?'''
* Hair cell matrix activator slows down and inhibits degradation of the perifollicular matrix.
* This leads to an increase in hair follicle matrix cells that differentiate from progenitor stem cells.
* Matrix activator allows activation of hair matrix cells and therefore follicle stimulation leading to hair growth.

==== Functions of Hair matrix cell activator ====
[http://www.ijdb.ehu.es/fullaccess/fulltext.04023/ft163.pdf Hair matrix cell activator]
[[Image:Hair matrix.jpg|thumb|center|500px|Functions of Hair matrix cell activator ]]

==== IP Map for Hair matrix cell activator ====
{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="100" bgcolor=DodgerBlue|'''Nature'''
!width="200" bgcolor=DodgerBlue|'''Composition'''
!width="600" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
SHISEIDO(1999)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|(2-substituted oxyphenyl) alkanamide derivative and its salt
|bgcolor=LightCyan|Mechanism of action has not been made clear, having excellent hair follicle activating action and regrowth promoting effect
|- style="height:50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
L'OREAL(1998)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Metalloprotease (MMP-9) inhibitor (thiol or a hydroxamate) other than chelating calcium ions
|bgcolor=LightCyan|Reducing the expression of MMPs (Metalloproteases) in the scalp - slows down or inhibits the degradation of the perifollicular matrix (extracellular matrix surrounding the hair follicle)
|}

== Technology mapping based on patents analyzed ==

=== IPMap: Composition nature matrix ===

{| border="1" cellpadding="11", style="#008080"
!width="120" bgcolor=DodgerBlue|'''Year'''
!width="200" bgcolor=DodgerBlue|'''Organic Compound'''
!width="200" bgcolor=DodgerBlue|'''Natural extracts'''
!width="200" bgcolor=DodgerBlue|'''Peptides'''
!width="200" bgcolor=DodgerBlue|'''Nucleotides'''
!width="200" bgcolor=DodgerBlue|'''Natural extract + Organic comp'''
|- style="height:10px"
|bgcolor=LightCyan|2005
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|UNILEVER (1)
|-
|bgcolor=LightCyan|2004
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|BLOTECH (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|KAO (1)
|-
|bgcolor=LightCyan|2003
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|APHIOS (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|FUNDACION (1)
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2002
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2001
|bgcolor=LightCyan |PFIZER (1)
|bgcolor=LightCyan|LG HEALTH-CARE (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2000
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|L’OREAL (1) / N/A (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1999
|bgcolor=LightCyan|SHISEDIO (1)
|bgcolor=LightCyan|COLOMER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1998
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|L’OREAL (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1995
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|N/A (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1987
|bgcolor=LightCyan|....
|bgcolor=LightCyan|KAO (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1982
|bgcolor=LightCyan|UNILEVER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|}

=== Focus of patents ===

{| border="1" cellpadding="17", style="#008080"
!width="800" bgcolor=DodgerBlue|'''Focus of patents'''
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="100" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|2-substituted oxyphenyl alkanamide derivative having excellent hair growth effect.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
|bgcolor=LightCyan|1
|-
|bgcolor=LightCyan|Thyromimetic compounds, and its role in treating hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
|bgcolor=LightCyan|2
|-
|bgcolor=LightCyan|Saw Palmetto berry extract, pumpkin seed extract, sitosterol and quercetin for the treatment and prevention of the biologically detrimental effects of DHT
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
|bgcolor=LightCyan|3
|-
|bgcolor=LightCyan|4-cycloalkoxy benzonitriles and its use as androgen receptor modulators
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
|bgcolor=LightCyan|4
|-
|bgcolor=LightCyan|Supercritical fluid isolate of Saw Palmetto, Sperol for inhibition of 5-.alpha.-reductase activity
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
|bgcolor=LightCyan|5
|-
|bgcolor=LightCyan|New class of quinolin-2-ones and chromen-2-ones andtheir use as androgen receptor antagonists
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|6
|-
|bgcolor=LightCyan|Antiandrogen oligonucleotides usable for the treatment of dermatological androgen-related disorders
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
|bgcolor=LightCyan|7
|-
|bgcolor=LightCyan|Bradykinin antagonists for stimulating or inducing hair growth and/or arresting hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
|bgcolor=LightCyan|8
|-
|bgcolor=LightCyan|Extract from walnut leaves and/or pericarps as 5 alpha -reductase inhibitor
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
|bgcolor=LightCyan|9
|-
|bgcolor=LightCyan|Stimulating hair growth using benzopyrans
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
|bgcolor=LightCyan|10
|-
|bgcolor=LightCyan|Sophora flavescens extract, Coicis semen extract, clove extract, etc for promoting hair growth, function of cell activity and dilating peripheral blood vessels.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
|bgcolor=LightCyan|11
|-
|bgcolor=LightCyan|Compositions to prevent or reduce hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
|bgcolor=LightCyan|12
|-
|bgcolor=LightCyan|Prostaglandin EP-3 receptor antagonists for reducing hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
|bgcolor=LightCyan|13
|-
|bgcolor=LightCyan|Synergic effect arising from the interaction of active ingredients, consisting of three plant extracts and a synthetic organosilicic compound for prevent hair loss and stimulate hair growth
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
|bgcolor=LightCyan|14
|-
|bgcolor=LightCyan|Metalloprotease inhibitors to induce and/or stimulate the growth
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
|bgcolor=LightCyan|15
|-
|bgcolor=LightCyan|Method of decreasing sebum production and pore size
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050277699%22.PGNR.&OS=DN/20050277699&RS=DN/20050277699 US20050277699 ]
|bgcolor=LightCyan|16
|-
|bgcolor=LightCyan|Method for reducing sebum on the hair and skin
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=4529587.PN.&OS=PN/4529587&RS=PN/4529587 US4529587]
|bgcolor=LightCyan|17
|}

=== Technology focus===
[[Image:Technologyfocus2.jpg|thumb|center|700px|Technology focus]]

=== Distribution of patents ===

==== By patent types ====
[[Image:Didtribution.jpg|thumb|center|700px|Distribution based on patent types ]]

==== By key ingredients ====
[[Image:key1.jpg|thumb|center|700px|Distribution of key ingredients]]

==== By target disease ====
[[Image:target.jpg|thumb|center|700px|Distribution based on target diseases]]

==== Key ingredients vs. Target disease ====
[[Image:key&target1.jpg|thumb|center|1000px|Key ingredients vs. Target disease]]

==== Target species ====
[[Image:Species.jpg|thumb|center|700px|Target species]]

==== Mode of administration ====
[[Image:Mode.jpg|thumb|center|700px|Mode of administration]]

==== Product type vs. Product form ====
[[Image:prod.jpg|thumb|center|700px|Product type vs. Product form]]

==== Patents by target diseases ====
{| border="1" cellpadding="16", style="#008080"
!width="800" bgcolor=DodgerBlue|'''Target disease/ disorder'''
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="150" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|Alopecia areata, alopecia pityrodes or alopecia seborrheica, or androgenic alopecia (i.e. male pattern baldness)
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
|bgcolor=LightCyan|1
|-
|bgcolor=LightCyan|Alopecia areata, male pattern baldness and female pattern baldness
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
|bgcolor=LightCyan|2
|-
|bgcolor=LightCyan|Androgenic alopecia (i.e. male pattern baldness), prostatic hyperplasia or both.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
|bgcolor=LightCyan|3
|-
|bgcolor=LightCyan|Inappropriate activation of the androgen receptor, acne, oily skin, alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
|bgcolor=LightCyan|4
|-
|bgcolor=LightCyan|Prostatic hyperplasia, prostatic cancer, hirsutism, acne, male pattern baldness, seborrhea, and other diseases related to androgen hyperactivity
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
|bgcolor=LightCyan|5
|-
|bgcolor=LightCyan|Alopecia, acne, oily skin, prostrate cancer, hirsutism, and benign prostate hyperplasia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|6
|-
|bgcolor=LightCyan|Androgen-associated hair loss and androgen-skin related disorders.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
|bgcolor=LightCyan|7
|-
|bgcolor=LightCyan|Androgenetic or androgenic alopecia or androgeno-genetic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
|bgcolor=LightCyan|8
|-
|bgcolor=LightCyan|Diseases caused by testosterone (male-pattern alopecia)
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
|bgcolor=LightCyan|9
|-
|bgcolor=LightCyan|Alopecia areata, female pattern hair loss, hair loss secondary to chemotherapy or radiation treatment, stress-related hair loss, self-induced hair loss, scarring alopecia, and alopecia in non-human mammal
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
|bgcolor=LightCyan|10
|-
|bgcolor=LightCyan|Male pattern alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
|bgcolor=LightCyan|11
|-
|bgcolor=LightCyan|Alopecia, androgenic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
|bgcolor=LightCyan|12
|-
|bgcolor=LightCyan|Hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
|bgcolor=LightCyan|13
|-
|bgcolor=LightCyan|Male pattern alopecia
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
|bgcolor=LightCyan|14
|-
|bgcolor=LightCyan|Androgenetic, androgenic or androgenogenetic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
|bgcolor=LightCyan|15
|-
|bgcolor=LightCyan|Curing other scalp related problems
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050244362%22.PGNR.&OS=DN/20050244362&RS=DN/20050244362 US20050244362]
|bgcolor=LightCyan|16
|}

==== Patents by application ====
[[Image:application.jpg|thumb|center|700px|Distribution of patents based on application]]

==== [[List of patents]] ====

== Pathways and linkages ==

=== Pathways associated with hair matrix cell activation===

'''Molecular mediators of hair follicle embryogenesis:''' Identification of the molecular pathways controlling differentiation and proliferation in mammalian hair follicles provides the crucial link to understanding the regulation of normal hair growth, the basis of hereditary hair loss diseases, and the origin of follicle-based tumors. Homeobox (hox), hedgehog (hh), patched (ptc), wingless (wg}/wnt, disheveled (dsh), engrailed (en), Notch 1 and armadillo/B-catenin genes are all critical for hair follicle.

* '''Wnt pathway:''' Maintains hair-inducing activity of the dermal papilla.
* '''Hedgehog pathway:''' Sonic hedgehog (SHH) signaling plays a critical role in hair follicle development. Sonic hedgehog gene. Sonic hedgehog, SHH for short, helps guide hair follicles from a resting stage into growth activity. SHH is particularly important in the embryonic formation of hair follicles.
* '''STAT pathway'''
* '''TGF beta/BMP Pathway:''' Bone morphogenetic protein (BMP) signaling have been implicated in the regulation of both proliferation and differentiation in the hair follicle. BMP2 is expressed in the embryonic ectoderm, but then localizes to the early hair follicle placode and underlying mesenchyme. BMP4 is expressed in the early dermal condensate. Research results show that BMPs are a key component of the signaling network controlling hair development and are required to induce the genetic program regulating hair shaft differentiation in the anagen hair follicle. Transforming growth factor beta (TGF-beta), inhibits mitogen - induced dermal papilla cell proliferation
* '''FGF Pathway:''' Fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) potentiate the growth of dermal papilla cells. It is proposed that these proteins increase the synthesis of stromelysin (an enzyme, matrix metalloproteinase) which acts on the papilla cells and accelerates their growth.
* '''MAPK Pathway:''' Mitogen-activated protein kinase (MAPK) activation, increases keratinocyte turnover.
* '''NOTCH Pathway''': Notch-1 is expressed in ectodermal-derived cells of the follicle, in the inner cells of the embryonic placode and the follicle bulb, and in the suprabasal cells of the mature outer root sheath. Delta-1, one of the three ligands is only expressed during embryonic follicle development and is exclusive to the mesenchymal cells of the pre-papilla located beneath the follicle placode, and appears to promote and accelerate placode formation, while suppressing placode formation in surrounding cells. Other ligands, Serrate 1 and Serrate 2, are expressed in matrix cells destined to form the inner root sheath and hair shaft.

=== Pathways associated with Anti Androgen===
[[Image:Slide1.GIF|thumb|center|700 px|Alopecia pathways]]

==== Players of WNT inhibition Pathway ====
[[Image:wnt.jpg|thumb|right|200 px|Wnt inhibition]]
{| border="1" cellpadding="15", style="#008080"
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="200" bgcolor=DodgerBlue|'''Key compound'''
!width="200" bgcolor=DodgerBlue|'''Players of inhibition'''
|- style="height:10px"
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|GSK3
|-
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6989385.PN.&OS=PN/6989385&RS=PN/6989385 US6989385]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|GSK3
|-
|bgcolor=lightyellow|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|CDK,GSK3
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6974819.PN.&OS=PN/6974819&RS=PN/6974819 US6974819]
|bgcolor=LightCyan|Pyrimidine derivative
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6743791.PN.&OS=PN/6743791&RS=PN/6743791 US6743791]
|bgcolor=LightCyan|Heterocyclic compounds
|bgcolor=LightCyan|AKT3, GSK-3, ERK2
|-
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050277773%22.PGNR.&OS=DN/20050277773&RS=DN/20050277773 US20050277773]
|bgcolor=LightCyan|Pyrrolo[3,2-d]pyrimidine derivatives
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040072836%22.PGNR.&OS=DN/20040072836&RS=DN/20040072836 US20040072836]
|bgcolor=LightCyan|Aza-oxindole derivatives
|bgcolor=LightCyan|GSK3, AKT, PKC
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP1477489&F=0 EP1477489]
|bgcolor=LightCyan|Pyrrolopyrimidine derivatives
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO0056710&F=0 WO0056710]
|bgcolor=LightCyan|3-(Anilinomethylene) oxindoles
|bgcolor=LightCyan|GSK3, AKT, PKC
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO03011287&F=0 WO2003011287]
|bgcolor=LightCyan|Pyrazolon derivatives
|bgcolor=LightCyan|GSK3, β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6924141.PN.&OS=PN/6924141&RS=PN/6924141 US6924141]
|bgcolor=LightCyan|Lithium chloride, Wnt3/4/ 7
|bgcolor=LightCyan|β-catenin, GSK3, Wnt
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6706685.PN.&OS=PN/6706685&RS=PN/6706685 US6706685]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6683048.PN.&OS=PN/6683048&RS=PN/6683048 US6683048]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|α-catenin, β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6677116.PN.&OS=PN/6677116&RS=PN/6677116 US6677116]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6303576.PN.&OS=PN/6303576&RS=PN/6303576 US6303576]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|β-catenin
|}

==== Role of Pyrazole compounds in Wnt Pathway====
'''Pyrazole'''
* '''Pyrazole''' (C3H4N2) refers both to the class of simple aromatic ring organic compounds of the heterocyclic series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions and to the unsubstituted parent compound. Being so composed and having pharmacological effects on humans, they are classified as alkaloids although they are not known to occur in nature.
* Pyrazoles are produced synthetically through the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation
[[Image:pyrazole1.jpg|thumb|center|500px|Pyrazole (C3H4N2)]]
* Pyrazoles are used for their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, tranquilizing, muscle relaxing, psychoanaleptic, anticonvulsant, monoamineoxidase inhibiting, antidiabetic and antibacterial activities.
* Structurally related compounds are pyrazoline and pyrazolidine.
[[Image:pyrazole2.jpg|thumb|center|500px|Structurally related compounds]]

==== GSK3 inhibition by pyrazole compounds ====
[[Image:bold3.jpg]]
{| border="1" cellpadding="2", style="#008080"
!width="350"|[http://patft1.uspto.gov/netacgi/nph-Parser?TERM1=6989385+&Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=0&f=S&l=50 US6989385]
[[Image:US6989385.jpg]]
!width="350"|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
[[Image:US6664247.jpg]]
!width="350"|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
[[Image:WO2005012256.jpg]]
|-
|bgcolor=lightcyan|R1=T-Ring D, wherein
T is a valence bond and
Ring D = 5-6 membered aryl or heteroaryl ring;

R2 = hydrogen or C1-4 aliphatic and
R2'= hydrogen;

R3 = -R, -OR, or -N(R4)2, wherein
R = hydrogen, C1-6 aliphatic, 5-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl, and
L is -O-, -S-, or -NH-; and
Ring D is substituted by up to three substituents selected from -halo, -CN, -NO2, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R<4>), -N(R4)COR, -N(R4)CO2R, -SO2N(R4)2, -N(R4)SO2R, -N(R6)COCH2N(R4)2, -N(R6)COCH2CH2N(R4)2, or -N(R6)COCH2CH2CH2N(R4)2, wherein R = hydrogen, C1-6 aliphatic, phenyl, 5-6 membered heteroaryl ring, or 5-6 membered heterocyclic ring

|bgcolor=lightcyan|X = R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, S02, C=O, NRg(C=O) or O(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;

R1 is hydrogen; carbocyclic or heterocyclic group having from 3 to 12 ring members; or C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from 0, S, NH, SO, S02;

R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and

R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

|bgcolor=lightcyan|X is a groupR1-A-NR4-or a 5-or 6-membered carbocyclic or heterocyclic ring;
A is a bond,SO2, C=O, NRg (C=O) or O(C=O) wherein Rg is hydrogen orC14 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;Y is a bond or an alkylene chain of 1,2 or 3 carbon atoms in length;R'is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e. g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono-ordi-Cl 4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected fromO, S, NH, SO, SO2 ;R2 is hydrogen; halogen;C14 alkoxy (e. g. methoxy); or aC14 hydrocarbyl group optionally substituted by halogen (e. g. fluorine), hydroxyl orC14 alkoxy (e. g. methoxy);R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; andR4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e. g. fluorine), hydroxyl or C1-4 alkoxy (e. g. methoxy).
|}

==== Inhibition by amine derivatives ====

'''Patent Number''': US6989385
'''Applicant''': ''Vertex Pharmaceuticals Incorporated''
'''Title''': Pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure''':

[[Image:pyrazol1.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6989385 patent]]

'''Patent Number''': US7008948
'''Applicant''': Vertex Pharmaceuticals Incorporated
'''Title''': Fused pyrimidyl pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure'''

[[Image:pyrazol2.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US7008948 patent]]

'''Patent Number''': US6977262
'''Assignee''': Mitsubishi Pharma Corporation
'''Title''': Dihydropyrazolopyridine compounds and pharmaceutical use thereof

'''Basic Structure''':

[[Image:pyrazol3.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6977262 patent]]

----
'''Patent Number''': US6664247
'''Assignee''': Vertex Pharmaceuticals Incorporated
'''Title''': Pyrazole compounds useful as protein kinase inhibitors'''

'''Basic Structure''':

[[Image:pyrazol4.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6664247 patent]]

----
'''Patent Number''': US2004224944
'''Assignee''': VERTEX PHARMACEUTICALS INC
'''Title''': Pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure''':

[[Image:pyrazol5.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US2004224944 patent]]

[[Other derivates for alopecia]]

==== GSK-3 Inhibition Mechanism - Phosphorylation====
* ''GSK-3 inhibition targets treatment of chemotherapy-induced alopecia'' [http://www.biomedcentral.com/1471-2199/5/15 source]
* In the canonical Wnt signaling cascade, adenomatous polyposis coli (APC), axin, and GSK3 constitute the so-called destruction complex, which controls the stability of beta-catenin. It is generally believed that four conserved Ser/Thr residues in the N terminus of beta-catenin are the pivotal targets for the constitutively active serine kinase GSK3. GSK3 covalently modifies beta-catenin by attaching phosphate groups (from ATP) to serine, and threonine residues. In so doing, the functional properties of the protein kinase’s substrate (beta-catenin) are modified.

* In the absence of Wnt signals, glycogen synthase kinase (GSK) is presumed to phosphorylate the N-terminal end of beta-catenin, thus promote degradation of beta-catenin and subsequent ubiquitination and proteasomal targeting.

* Exposure of cells to Wnts leads to inactivation of GSK-3 through an as yet unclear mechanism.The phosphoprotein Dishevelled is required, after receptor-ligand interaction, to transduce the signal that results in the inactivation of GSK-3. As a result, beta-catenin is dephosphorylated and escapes the ubiqduitylation-dependent destruction machinery.

* Unphosphorylated beta-catanin accumulates in the cytoplasm and translocates to the nucleus, where it can associate with the TCF/LEFs and become a transcriptional transactivator.

'''[[More details on GSK-3]]'''

'''Key points'''

* Beta-catenin phosphorylation at serine 45 (Ser45), threonine 41 (Thr41), Ser37, and Ser33 is critical for beta-catenin degradation. [http://jb.oxfordjournals.org/cgi/content/abstract/132/5/697 source]
* Regulation of beta-catenin phosphorylation is a central part of the canonical Wnt signaling pathway. [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=223838&ArtikelNr=66755&filename=66755.pdf source]
* Ser-X-X-X-Ser (X is any amino acid) motif is obligatory for beta-catenin phosphorylation by GSK3.[http://lib.bioinfo.pl/auth:He,X source]
* Beta-catenin phosphorylation/degradation and its regulation by Wnt can occur normally in the absence of Thr41 as long as the Ser-X-X-X-Ser motif/spacing is preserved. [httSp://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2006/45/i16/abs/bi0601149.html source]

'''GK3 Inhibition:'''

* GSK3 is regulated by phosphorylation.
* Phosphorylation of GSK3beta on Ser9 (Ser21 in GSK3alpha) by protein kinase B (PKB) causes its inactivation is the primary mechanism responsible for growth factor inhibition of this kinase. Activation of GSK3beta is dependent upon the phosphorylation of Tyr216 (Tyr279 in GSK3alpha). Upon activation, it has been shown to phosphorylate a number of different cellular proteins, including p53, c-Myc, c-Jun, heat shock factor-1 (HSF-1), beta-catenin and cyclin D1. [http://www.bioreagents.com/index.cfm/fuseaction/products.detail/CatNbr/OPA1-03082 source]
* GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3beta and GSK3alpha, respectively. [http://lib.bioinfo.pl/auth:Friedman,AB source]
* GSK3’s substrate specificity is unique in that phosphorylation of substrate only occurs if a phosphoserine or phosphotyrosine is present four residues C-terminal to the site of GSK phosphorylation. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11430833&dopt=Abstract source]
* A phosphorylation cascade starts from GSK3 itself and initiates it in beta-catenin. [http://www.genesdev.org/cgi/content/full/16/16/2073 source]
* Thus our goal is to stop the phosphorylation of the serine and threonine residue of GSK3.
* The figure below illustrates the phosphorylation mechanism of serine and threonine by ATP.

[[image:GSK3_phosphorylation.jpg|400 px|center|thumb|Phosphorylation mechanism [http://images.google.com/images?q=tbn:DGnhgZ7y7pSejM:bass.bio.uci.edu/~hudel/bs99a/lecture26/phosphoaa.gif source]]]

* We can't stop conversion of ADP to ATP that relaseas Phosphorous group causing Phosphorylation.
* We can only block the oxygen atom on serine and threonine as a result which will in turn stop Phosphorylation.
* The two probable ways of blocking the oxygen atom are (a) As oxygen is a Lewis acid with strong electron donating capacity, so usually a strong electron pair acceptor can easily bind to oxygen atom and preventing phosphorylation or (b) breaking of the -OH bond with the carbon atom.

'''Serine - pyrazole reaction'''

[[image:serine-pyrazol.jpg|600 px|center|thumb|Serine and Pyrazole reaction [http://www.genome.ad.jp/dbget-bin/www_bget?rn+R03134 source]]]

* The T-loop of GSK-3 is tyrosine phosphorylated at Y216 and Y279 in GSK-3b and GSK-3a, respectively, but not threonine phosphorylated. Y216/Y279 phosphorylation could play a role in forcing open the substrate (e.g, beta-catanin)-binding site.

* Thus, T-loop tyrosine might facilitate substrate phosphorylation but is not strictly required for kinase activity.

* Stimulation of cells with pyrazole compounds cause inactivation of GSK-3 through phosphorylation (S9 of GSK-3 beta and S21 of GSK-3 alpha), which inhibits GSK-3 activity. Thus leading to dephosphorylation of substrates (e.g., beta-catanin) resulting in their functional activation and consequent increased hair follicle morphogenisis.

* Phosphorylation of S9/S21 creates a primed pesudosubstrate that binds intramolecularly to the positively charged pocket of the GSK-3. This folding precludes phosphorylation of substrates (eg., beta-catanin) because the catalytic groove is occupied. The mechanism of inhibition is competitive.

* A consequence of this is that primed substrates, in high enough concentrations, out-compete the pesudosubstrate and thus become phosphorylated.

* Thus, small molecule inhibitors modeled to fit in the positively charged pocket of the GSK-3 kinease domain could potentially be very effective for selective inhibition of primed substrates.

'''Proposed mechanisms to regulate GSK-3''' [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12615961 source]

# inactivation of GSK-3 through serine phosphorylation
# activation of GSK-3 through tyrosine phosphorylation
# inactivation of GSK-3 through tyrosine dephosphorylation
# Covalant modifications of substrates through priming phosphorylation
# inhibition or facilation of GSK-3 mediated substrate phosphorylation thriugh interation of GSK-3 with binding or scaffolding proteins
# targeting of GSK-3 to different subcellular localizations
# differential usage of isoforms or splice variants to alter subcellular localization or substrate specificity
# integration of parellel signals conveyed by a signal stimulus.

'''Key Finding'''
* '''Pyrazole compounds with inhibition constant (Ki) of <0.1 mM''' are a good starting point for developing molecules that can inhibit serine/threonine protein kinase (such as GSK-3) and the proteins they help to regulate. [http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html?DOC=patentwatch%5Carchive%5C011204_patentwatch.html source]

=== Pathway associated with anti-androgen ===

* Dihydrotestosterone
** Formed by peripheral conversion of testosterone by 5-alpha reductase
** Binds to androgen receptor on susceptible hair follicles
* Hormone-receptor complex activates genes responsible for gradual transformation of large terminal follicles to miniaturized (progressive diminution of hair shaft diameter and length in response to systemic androgens) follicles

[[Image:5-alpha-reductase inhibition.jpeg|center|500 px]]

==== Structure-Activity Relationships(SARs) ====
[[Image:SAR_map.gif|center|600px]]

=== Pathway associated with Minoxidil (vasodilators) ===
Minoxidil is a well know drug used for the treatment of alopecia. A co-relation between Sesquiterpene lactone (Helenalin) produced from Arnica montana and Minoxidil is illustrated in the figure below. Arnica montana, a Vasodilator, acts on the NO/cGMP Pathway through T-cells, B-cells and epithelial cells & abrogates kappa B-driven gene expression.
[[image:vasodiator-rev.jpg|800 px|center]]

Alopecia - Hair Loss

2007-08-17T03:47:54Z

67.180.82.65:

Alopecia - Hair Loss

2007-08-17T03:47:27Z

67.180.82.65:

{{TOCrightEx}}
== Rationale ==
* "Medication for men plagued by hair loss has become a topic of interest in Japan since a drug company began marketing it at the end of last year." March 5th, 2006 – [http://stophair.setupmyblog.com/?p=55 source]

* "An increasing number of companies are apparently turning the Chinese fear of a bald spot into big bucks with some doing so well they are branching out into other countries." February 16, 2006 – [http://stophair.setupmyblog.com/]

* "There is something in the air, or should we say in the hair, these days. Scientific research into hair loss remedies has never been more active or more exciting." June 7, 2006 - [http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/06-07-2005/0003821470&EDATE=]

== Alopecia IPMap ==
[http://www.dolcera.com/client/d8r3/hairloss_map.htm Dolcera IPMap for Alopecia]

== Introduction ==

=== Hair basics ===
* Hair is a complex and delicate part of the body.
* Keeping it healthy and beautiful is a challenge.
* Hair grows everywhere on the body with the exception of lips, eyelids, palms of the hands and soles of the feet.
* Hair is basically a form of skin.
* Hair is made up of a protein called keratin.
* Each shaft of hair is made of two or three inter-twined layers of keratin which grow from a follicle beneath the skin.
* Hair Structure - [http://www.pg.com/science/haircare/hair_twh_12.htm]
* Hair Cycle - [http://www.follicle.com/hair-structure-life-cycle.html]

[[Image:Hairbasics.jpg|center|400px|Structure of Hair root and Hair bulb]]

=== What causes hair loss? ===
* Decrease in growth of hair
* Increase in shedding of hair
* Breakage of hair
* Conversion of thick terminal hairs to thin vellus hairs
[[Image:Facts.jpg|thumb|right|250px|Survey results from Japan]]
Both men and women lose hair for similar reasons. Hair loss in men is often more dramatic, and follows a specific pattern of loss, one of which has been termed “Male Pattern Baldness" or "Androgenetic Alopecia".

=== Types of alopecia===

* Alopecia Areata (AA): Hair loss occurring in patches anywhere on the body.
* Alopecia Totalis (AT): Total loss of the hair on the scalp.
* Alopecia Universalis (AU): Total loss of all hair on the body.
* Alopecia Barbae: Loss of facial hair (for a man) especially in the beard area.
* Alopecia Mucinosa: A type of alopecia which results in scaley patches.
* Androgenetic Alopecia (AGA): Also known as male pattern baldness. It is a thinning of the hair to an almost transparent state, in both men or women. It is thought to be a hereditary form of hair loss.
* Traction Alopecia: Traction alopecia is usually due to excessive pulling or tension on hair shafts as a result of certain hair styles. It is seen more often in women, particularly those of East Indian and Afro-Caribbean origin. Hair loss depends on the way the hair is being pulled. Prolonged traction alopecia can stop new hair follicles from developing and leads to permanent hair loss.
* Anagen Effluvium: This hair loss is generally caused by chemicals such as those used to treat cancer. Initially it causes patchy hair loss, which often then leads to total hair loss. The good news is that when you stop using these chemicals the hair normally grows back (usually about 6 months later). Other drugs also can cause hair loss. Many medicines used to treat even common diseases can cause hair loss.
* Scarring Alopecia: A form of alopecia which leaves scarring on the area of hair loss.
* Telogen Effluvium: A form of hair loss where more than normal numbers of hair fall out. There is a general 'thinning' of the hair. Unlike some other hair and scalp conditions, it is temporary and the hair growth usually recovers. ([http://www.alopeciaonline.org.uk/about/types.asp Source])

=== Androgenetic alopecia ===
* Gradual onset
* Transition from large, thick, pigmented terminal hairs to thinner, shorter, indeterminate hairs and finally to short, wispy, non-pigmented vellus hairs in the involved areas
* Characterized by a receding hairline and/or hair loss on the top of the head

'''Main causes'''
* Genetic predisposition
* Hormonal effect of androgen
* Reduction of blood circulation around hair follicle
* Deactivation of hair matrix cells

'''Some facts from Japan'''

* Market size: ¥ 30 Billion
* Number of products: more than 100

(JICST-EPlus - Japanese Science & Technology)

== IP activity over the years ==
The graph indicates:
* Number of patents filed every 5 years (except for first 7 years).
* First solution proposed in 1973
* Filing trend indicates steep rise in activity recently.
[[Image:Year1.jpg|thumb|center|400px|IP Activity over years]]

== Major players ==
[[Image:players.jpg|thumb|left|400px|Assignees with more than 20 patents ]]
[[Image:players1.jpg|thumb|center|400px|Assignees with fewer than 20 patents ]] 

* '''Active assignees'''
Assignees currently active with more than 5 patents to their credit during 2000-2005.
* Warner with 9 patents,
* Bristol with 6 and
* Abbott with 5.

[[Image:Active.jpg|thumb|center|500px|Active Assignees]]

== Treatment Approaches==
Composition of treatment for causes are identified and categorized as follows:

* Anti-androgens (Finasteride) [http://www.emedicine.com/DERM/topic21.htm source]
* Vasodilators (Minoxidil) [http://www.emedicine.com/DERM/topic21.htm source]
* Double action (Anti-androgen + Vasodilator)
* Hair matrix cells activator

{|border="1" cellpadding="2", style="#008080" align="center"
|- style="font-weight:bold" valign="top"
! Cause !! Treatment approach !! Pathways affected

|- valign="top"
| Hormonal effect of androgen || Anti-androgens || Testosterone pathway

|- valign="top"
| Reduction of blood circulation around hair follicle || Vasodilators (eg. Minoxidil) || NO/cGMP Pathway

|- valign="top"
| Deactivation of hair matrix cells || Hair matrix cells activator
|
* Wnt pathway
* STAT pathway
* TGF beta/BMP Pathway
* FGF Pathway
* MAPK Pathway
* NOTCH Pathway
* Hedgehog Pathway
|}

=== Anti-androgens ===
* Anti-androgens are used in hormone therapy.
* Anti-androgens are designed to affect the hormones made in the adrenal glands. They don't stop the hormones from being made, but they stop them from having an effect leading to hair loss.

'''What causes hair loss?'''
* Testosterone is reduced to its active metabolite, Dihydrotestosterone (DHT) by the enzyme 5 alpha reductase.
* DHT attaches to androgen receptor sites at the hair follicle.
* DHT causes gradual miniaturization of the follicle, which eventually results in hair loss.

'''How do anti-androgens treat hair loss?'''
* Anti-androgens compete with DHT to bind to the androgen receptor.
* Upon binding of anti-androgen in place of DHT, follicle miniaturization is lowered and hair loss prevented.

==== Functions of Anti-androgen ====
[http://www.revivogen.com/revivogen/work.html Anti-androgen]

[[Image:Andogen1.jpg|thumb|center|500px|Functions of Anti-androgen]]

==== IP Map for anti-androgen ====

{| border="1" cellpadding="0", style="#008080"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="100" bgcolor=DodgerBlue|'''Nature'''
!width="450" bgcolor=DodgerBlue|'''Composition'''
!width="400" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
BLOTECH (2004)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Palmetto berry extract (fatty acids & sterols), Pumpkin seed extract (Vitamins-B, alpha-linolenic acid, amino acids and phytosterols), Quercetin (Flavonoids) and Beta-sitosterol (Rice bran, wheat germ, corn oils and soybeans)
|bgcolor=LightCyan|Fatty acids – Inhibit testosterone
Sterols - Mechanism of action unknown.

Quercetin results in cell growth cycle.

Beta-sitosterol reduce inflammation on scalp
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
WARNER LAMBERT(2004)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 4-cycloalkoxy benzonitrile derivatives and salts
|bgcolor=LightCyan|Acts as androgen receptor modulator and blocks formation of DHT.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
WARNER LAMBERT(2004)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 6-sulfonamido-quinolin-2-one and 6-sulfonamido-2-oxo-chromene derivatives.
|bgcolor=LightCyan|The compounds inhibit, or decrease, activation of androgen receptor by androgens.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
APHIOS Corp (2003)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Supercritical fluid isolate of Saw Palmetto and Sperol (Serenoa repens berry) and their analogs or derivatives.
|bgcolor=LightCyan|Modulates androgenic activity by inhibiting 5.alpha.-reductase activity.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
Fundacion Pablo Cassara (2003)
|bgcolor=LightCyan|Nucleotide
|bgcolor=LightCyan|Pharmacologically active oligonucleotides (encompass both DNA and S-DNA bond)
|bgcolor=LightCyan|Oligonucleotides inhibit androgen receptor (AR) expression at very low concentrations in skin and hair follicle
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
PFIZER INC (2001)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|Thyromimetic compounds (structurally similar to thyronine) with finasteride, or cyproterone acetate
|bgcolor=LightCyan|Activates thyroid hormone receptors in hair follicle which in turn promote elasticisation of follicle walls and hair follicle
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
N/A (1995)
|bgcolor=LightCyan|Peptides/nucleic acid
|bgcolor=LightCyan|Bradykinin antagonist (peptide of plasma origin from kininogen precursor-kallikrein)
|bgcolor=LightCyan|Inhibits synthesis of bradykinin receptors or compounds by binding to B2 receptor
|- style="height:20px"
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
KAO Corp (1987)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Walnut extract (leaves/pericarps) with an organic solvent
|bgcolor=LightCyan|Blocks formation of DHT
|}

=== Minoxidil (Vasodilators) ===
* Minoxidil is a "potassium channel opener" that leads to vasodilation.
* The drug is available in two forms. Oral minoxidil is used to treat high blood pressure and the topical solution form is used to treat hair loss and baldness.

'''What causes hair loss?'''
* A thick network of tiny veins and arteries line the outer wall of the follicle. Blood pumps through the bulb and hair via this network.
* DHT accumulates in the hair follicles and roots, constricting the blood supply of oxygen and nutrients to the hair roots; which is also seen to possibly contribute towards hair loss.

'''How does Minoxidil treat hair loss?'''
* Minoxidil is applied to the scalp topically, where it dilates blood vessels in the scalp and sustains the hair follicles for longer period of time.
* Minoxidil is thought to have a direct mitogenic effect on epidermal cells, as has been observed both in vitro and in vivo. Though the mechanism of its action for causing cell proliferation is not very clear, minoxidil is thought to prevent intracellular calcium entry. Calcium normally enhances epidermal growth factors to inhibit hair growth, and Minoxidil by getting converted to minoxidil sulfate acts as a potassium channel agonist and enhances potassium ion permeability to prevent calcium ions from entering into cells. ([http://www.hairtransplantadvice.com/medical-hair-restoration.php Source])
* Minoxidil sulfate (MS) appears to be the active metabolite responsible for hair growth stimulation.

==== Functions of Vasodilators ====

[[Image:minoxidil1.jpg|thumb|center|500px|Functions of Monoxidil [http://www.nurseminerva.co.uk/diagrams.htm#Diagram%201 source]]]

==== IP Map for Vasodilators ====

{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75" bgcolor=DodgerBlue|'''Nature'''
!width="600" bgcolor=DodgerBlue|'''Composition'''
!width="300" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
WARNER LAMBERT(2002)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|Benzopyran compounds
|bgcolor=LightCyan|Rapidly metabolizes, and causes reduced cardiovascular effects as compared to other known potassium channel openers
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
LG HOUSEHOLD & HEALTH CARE(2001)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Sophora flavescens extract (alkaloids & flavonoids, luteolin-7-glucose and cytosine) Hinokitiol (Taiwan hinoki oil, Aomori, Western Red Cedar oil) and Nicotinamide (Vitamin B complex)
|bgcolor=LightCyan|Promotes function of cell activity and dilates blood vessels
|}

=== Double action (Anti-androgen + Vasodilator) ===
* Combination of Vasodilator + Anti-androgen (double action) composition for effective treatment of Male-Pattern Baldness.

'''What is the problem with using only Anti-androgen therapy?'''
* Anti-androgen is not effective in addressing the issue of vasocontriction around hair follicles due to sebum oil build up.
* Anti-androgen only prevents binding of DHT to androgen receptors. However, the effects of improper oxygen and nutrient supply to the brain due to vasocontriction still remains and gradually causes hair loss.

'''What is the problem with using only Vasodilator (or Minoxidil only) therapy?'''
* Vasodilator or Minoxidil-based products are generally not effective in stopping hair loss as vasodilators (or Minoxidil) do not block the harmful effects of DHT in the scalp and hair follicles.
* Vasodilators or Minoxidil simply dilate blood vessels in the scalp. However, the harmful DHT still gets produced in the body, enters the scalp and hair follicles causing hair loss.

'''How is the combination of Anti-androgens and Vasodilator (or Minoxidil) effective?'''
* Anti-androgens target the problem of DHT binding to androgen receptors and prevents follicle miniaturization.
* Vasodilators like Minoxidil cause vasodilation and therefore improve supply of oxygen and nutrients to the hair follicle and roots.
* Combination therapy therefore proves to be much more effective than individual therapy.

==== Functions of (Anti-androgen + Vasodilators) ====
[http://www.revivogen.com/revivogen/work.html Anti-androgen ]and [http://www.xandrox.net/articles/article01.htm Minoxidil]
[[Image:Doubleaction1.jpg|thumb|center|500px|Functions of (Anti-androgen + Vasodilators)]]

==== IP Map for (Anti-androgen + Vasodilators) ====
{| border="1" cellpadding="3"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75" bgcolor=DodgerBlue|'''Nature'''
!width="500" bgcolor=DodgerBlue|'''Composition'''
!width="500" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
N/A(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Testosterone blocker or vascular toner (Flutamide, cyproterone acetate, spironolactone, progesterone, or analogs or derivatives) and minoxidil mixed along with non-retinoid penetration enhancer and sunscreen
|bgcolor=LightCyan|Inhibits 5.alpha.-reductase activity (block DHT) and increase blood flow on the scalp
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
L'OREAL(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Prostaglandin (polyunsaturated fatty acids) EP-2, EP-3 EP-4 receptor agonist with Minoxidil, 2,4-diaminopyrimidine 3-oxide, and Aminexil, cyclic AMP
|bgcolor=LightCyan|Minoxidil (designed to mimic nitric oxide's effects) grows hair via prostaglandin-H synthase stimulation. EP-3 and EP-4 are expressed in anagen hair follicles which induce a reduction in the level of cAMP
|- style="height:100px"
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
COLOMER GROUP(1999)
|bgcolor=LightCyan|Natural extract
|bgcolor=LightCyan|Hop extract (oil contains terpenes and humulene), Rosemary extract (hydroalcohol), Swertia extract (glycol with a swertiamarin), Silanodiol salicylate (biologically active silicon compound)
|bgcolor=LightCyan|Inhibits activity of 5-alpha-reductase, protects follicular cell membranes by neutralizing action of oxidation reaction in tissues, stimulates hair follicles and blood circulation to the hair root, supplies oxygen and nutrients to base of follicle, retains humidity, avoids dehydration of scalp
|}

=== Hair matrix cell activator ===
Hair matrix cell activator is a substance that acts at the matrix cells in the hair follicle preventing their degradation.

'''What causes hair loss?'''
* Stem cells are interspersed within the basal layer of the outer root sheath and in an area called the bulge.
* Stem cells migrate to hair matrix where they start to divide and differentiate, under the influence of substances produced by cells of the dermal papilla.
* Perifollicular matrix cells undergo slow degradation which prevents follicle stimulation.
* Hair follicle activation is required for hair growth and thus inhibition of follicle activation eventually leads to hair loss.

'''How does hair cell matrix activator treat hair loss?'''
* Hair cell matrix activator slows down and inhibits degradation of the perifollicular matrix.
* This leads to an increase in hair follicle matrix cells that differentiate from progenitor stem cells.
* Matrix activator allows activation of hair matrix cells and therefore follicle stimulation leading to hair growth.

==== Functions of Hair matrix cell activator ====
[http://www.ijdb.ehu.es/fullaccess/fulltext.04023/ft163.pdf Hair matrix cell activator]
[[Image:Hair matrix.jpg|thumb|center|500px|Functions of Hair matrix cell activator ]]

==== IP Map for Hair matrix cell activator ====
{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="100" bgcolor=DodgerBlue|'''Nature'''
!width="200" bgcolor=DodgerBlue|'''Composition'''
!width="600" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
SHISEIDO(1999)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|(2-substituted oxyphenyl) alkanamide derivative and its salt
|bgcolor=LightCyan|Mechanism of action has not been made clear, having excellent hair follicle activating action and regrowth promoting effect
|- style="height:50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
L'OREAL(1998)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Metalloprotease (MMP-9) inhibitor (thiol or a hydroxamate) other than chelating calcium ions
|bgcolor=LightCyan|Reducing the expression of MMPs (Metalloproteases) in the scalp - slows down or inhibits the degradation of the perifollicular matrix (extracellular matrix surrounding the hair follicle)
|}

== Technology mapping based on patents analyzed ==

=== IPMap: Composition nature matrix ===

{| border="1" cellpadding="11", style="#008080"
!width="120" bgcolor=DodgerBlue|'''Year'''
!width="200" bgcolor=DodgerBlue|'''Organic Compound'''
!width="200" bgcolor=DodgerBlue|'''Natural extracts'''
!width="200" bgcolor=DodgerBlue|'''Peptides'''
!width="200" bgcolor=DodgerBlue|'''Nucleotides'''
!width="200" bgcolor=DodgerBlue|'''Natural extract + Organic comp'''
|- style="height:10px"
|bgcolor=LightCyan|2005
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|UNILEVER (1)
|-
|bgcolor=LightCyan|2004
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|BLOTECH (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|KAO (1)
|-
|bgcolor=LightCyan|2003
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|APHIOS (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|FUNDACION (1)
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2002
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2001
|bgcolor=LightCyan |PFIZER (1)
|bgcolor=LightCyan|LG HEALTH-CARE (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2000
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|L’OREAL (1) / N/A (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1999
|bgcolor=LightCyan|SHISEDIO (1)
|bgcolor=LightCyan|COLOMER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1998
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|L’OREAL (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1995
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|N/A (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1987
|bgcolor=LightCyan|....
|bgcolor=LightCyan|KAO (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1982
|bgcolor=LightCyan|UNILEVER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|}

=== Focus of patents ===

{| border="1" cellpadding="17", style="#008080"
!width="800" bgcolor=DodgerBlue|'''Focus of patents'''
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="100" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|2-substituted oxyphenyl alkanamide derivative having excellent hair growth effect.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
|bgcolor=LightCyan|1
|-
|bgcolor=LightCyan|Thyromimetic compounds, and its role in treating hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
|bgcolor=LightCyan|2
|-
|bgcolor=LightCyan|Saw Palmetto berry extract, pumpkin seed extract, sitosterol and quercetin for the treatment and prevention of the biologically detrimental effects of DHT
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
|bgcolor=LightCyan|3
|-
|bgcolor=LightCyan|4-cycloalkoxy benzonitriles and its use as androgen receptor modulators
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
|bgcolor=LightCyan|4
|-
|bgcolor=LightCyan|Supercritical fluid isolate of Saw Palmetto, Sperol for inhibition of 5-.alpha.-reductase activity
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
|bgcolor=LightCyan|5
|-
|bgcolor=LightCyan|New class of quinolin-2-ones and chromen-2-ones andtheir use as androgen receptor antagonists
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|6
|-
|bgcolor=LightCyan|Antiandrogen oligonucleotides usable for the treatment of dermatological androgen-related disorders
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
|bgcolor=LightCyan|7
|-
|bgcolor=LightCyan|Bradykinin antagonists for stimulating or inducing hair growth and/or arresting hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
|bgcolor=LightCyan|8
|-
|bgcolor=LightCyan|Extract from walnut leaves and/or pericarps as 5 alpha -reductase inhibitor
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
|bgcolor=LightCyan|9
|-
|bgcolor=LightCyan|Stimulating hair growth using benzopyrans
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
|bgcolor=LightCyan|10
|-
|bgcolor=LightCyan|Sophora flavescens extract, Coicis semen extract, clove extract, etc for promoting hair growth, function of cell activity and dilating peripheral blood vessels.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
|bgcolor=LightCyan|11
|-
|bgcolor=LightCyan|Compositions to prevent or reduce hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
|bgcolor=LightCyan|12
|-
|bgcolor=LightCyan|Prostaglandin EP-3 receptor antagonists for reducing hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
|bgcolor=LightCyan|13
|-
|bgcolor=LightCyan|Synergic effect arising from the interaction of active ingredients, consisting of three plant extracts and a synthetic organosilicic compound for prevent hair loss and stimulate hair growth
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
|bgcolor=LightCyan|14
|-
|bgcolor=LightCyan|Metalloprotease inhibitors to induce and/or stimulate the growth
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
|bgcolor=LightCyan|15
|-
|bgcolor=LightCyan|Method of decreasing sebum production and pore size
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050277699%22.PGNR.&OS=DN/20050277699&RS=DN/20050277699 US20050277699 ]
|bgcolor=LightCyan|16
|-
|bgcolor=LightCyan|Method for reducing sebum on the hair and skin
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=4529587.PN.&OS=PN/4529587&RS=PN/4529587 US4529587]
|bgcolor=LightCyan|17
|}

=== Technology focus===
[[Image:Technologyfocus2.jpg|thumb|center|700px|Technology focus]]

=== Distribution of patents ===

==== By patent types ====
[[Image:Didtribution.jpg|thumb|center|700px|Distribution based on patent types ]]

==== By key ingredients ====
[[Image:key1.jpg|thumb|center|700px|Distribution of key ingredients]]

==== By target disease ====
[[Image:target.jpg|thumb|center|700px|Distribution based on target diseases]]

==== Key ingredients vs. Target disease ====
[[Image:key&target1.jpg|thumb|center|1000px|Key ingredients vs. Target disease]]

==== Target species ====
[[Image:Species.jpg|thumb|center|700px|Target species]]

==== Mode of administration ====
[[Image:Mode.jpg|thumb|center|700px|Mode of administration]]

==== Product type vs. Product form ====
[[Image:prod.jpg|thumb|center|700px|Product type vs. Product form]]

==== Patents by target diseases ====
{| border="1" cellpadding="16", style="#008080"
!width="800" bgcolor=DodgerBlue|'''Target disease/ disorder'''
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="150" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|Alopecia areata, alopecia pityrodes or alopecia seborrheica, or androgenic alopecia (i.e. male pattern baldness)
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
|bgcolor=LightCyan|1
|-
|bgcolor=LightCyan|Alopecia areata, male pattern baldness and female pattern baldness
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
|bgcolor=LightCyan|2
|-
|bgcolor=LightCyan|Androgenic alopecia (i.e. male pattern baldness), prostatic hyperplasia or both.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
|bgcolor=LightCyan|3
|-
|bgcolor=LightCyan|Inappropriate activation of the androgen receptor, acne, oily skin, alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
|bgcolor=LightCyan|4
|-
|bgcolor=LightCyan|Prostatic hyperplasia, prostatic cancer, hirsutism, acne, male pattern baldness, seborrhea, and other diseases related to androgen hyperactivity
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
|bgcolor=LightCyan|5
|-
|bgcolor=LightCyan|Alopecia, acne, oily skin, prostrate cancer, hirsutism, and benign prostate hyperplasia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|6
|-
|bgcolor=LightCyan|Androgen-associated hair loss and androgen-skin related disorders.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
|bgcolor=LightCyan|7
|-
|bgcolor=LightCyan|Androgenetic or androgenic alopecia or androgeno-genetic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
|bgcolor=LightCyan|8
|-
|bgcolor=LightCyan|Diseases caused by testosterone (male-pattern alopecia)
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
|bgcolor=LightCyan|9
|-
|bgcolor=LightCyan|Alopecia areata, female pattern hair loss, hair loss secondary to chemotherapy or radiation treatment, stress-related hair loss, self-induced hair loss, scarring alopecia, and alopecia in non-human mammal
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
|bgcolor=LightCyan|10
|-
|bgcolor=LightCyan|Male pattern alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
|bgcolor=LightCyan|11
|-
|bgcolor=LightCyan|Alopecia, androgenic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
|bgcolor=LightCyan|12
|-
|bgcolor=LightCyan|Hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
|bgcolor=LightCyan|13
|-
|bgcolor=LightCyan|Male pattern alopecia
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
|bgcolor=LightCyan|14
|-
|bgcolor=LightCyan|Androgenetic, androgenic or androgenogenetic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
|bgcolor=LightCyan|15
|-
|bgcolor=LightCyan|Curing other scalp related problems
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050244362%22.PGNR.&OS=DN/20050244362&RS=DN/20050244362 US20050244362]
|bgcolor=LightCyan|16
|}

==== Patents by application ====
[[Image:application.jpg|thumb|center|700px|Distribution of patents based on application]]

==== [[List of patents]] ====

== Pathways and linkages ==

=== Pathways associated with hair matrix cell activation===

'''Molecular mediators of hair follicle embryogenesis:''' Identification of the molecular pathways controlling differentiation and proliferation in mammalian hair follicles provides the crucial link to understanding the regulation of normal hair growth, the basis of hereditary hair loss diseases, and the origin of follicle-based tumors. Homeobox (hox), hedgehog (hh), patched (ptc), wingless (wg}/wnt, disheveled (dsh), engrailed (en), Notch 1 and armadillo/B-catenin genes are all critical for hair follicle.

* '''Wnt pathway:''' Maintains hair-inducing activity of the dermal papilla.
* '''Hedgehog pathway:''' Sonic hedgehog (SHH) signaling plays a critical role in hair follicle development. Sonic hedgehog gene. Sonic hedgehog, SHH for short, helps guide hair follicles from a resting stage into growth activity. SHH is particularly important in the embryonic formation of hair follicles.
* '''STAT pathway'''
* '''TGF beta/BMP Pathway:''' Bone morphogenetic protein (BMP) signaling have been implicated in the regulation of both proliferation and differentiation in the hair follicle. BMP2 is expressed in the embryonic ectoderm, but then localizes to the early hair follicle placode and underlying mesenchyme. BMP4 is expressed in the early dermal condensate. Research results show that BMPs are a key component of the signaling network controlling hair development and are required to induce the genetic program regulating hair shaft differentiation in the anagen hair follicle. Transforming growth factor beta (TGF-beta), inhibits mitogen - induced dermal papilla cell proliferation
* '''FGF Pathway:''' Fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) potentiate the growth of dermal papilla cells. It is proposed that these proteins increase the synthesis of stromelysin (an enzyme, matrix metalloproteinase) which acts on the papilla cells and accelerates their growth.
* '''MAPK Pathway:''' Mitogen-activated protein kinase (MAPK) activation, increases keratinocyte turnover.
* '''NOTCH Pathway''': Notch-1 is expressed in ectodermal-derived cells of the follicle, in the inner cells of the embryonic placode and the follicle bulb, and in the suprabasal cells of the mature outer root sheath. Delta-1, one of the three ligands is only expressed during embryonic follicle development and is exclusive to the mesenchymal cells of the pre-papilla located beneath the follicle placode, and appears to promote and accelerate placode formation, while suppressing placode formation in surrounding cells. Other ligands, Serrate 1 and Serrate 2, are expressed in matrix cells destined to form the inner root sheath and hair shaft.

=== Pathways associated with Anti Androgen===
[[Image:Slide1.GIF|thumb|center|700 px|Alopecia pathways]]

==== Players of WNT inhibition Pathway ====
[[Image:wnt.jpg|thumb|right|200 px|Wnt inhibition]]
{| border="1" cellpadding="15", style="#008080"
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="200" bgcolor=DodgerBlue|'''Key compound'''
!width="200" bgcolor=DodgerBlue|'''Players of inhibition'''
|- style="height:10px"
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|GSK3
|-
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6989385.PN.&OS=PN/6989385&RS=PN/6989385 US6989385]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|GSK3
|-
|bgcolor=lightyellow|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|CDK,GSK3
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6974819.PN.&OS=PN/6974819&RS=PN/6974819 US6974819]
|bgcolor=LightCyan|Pyrimidine derivative
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6743791.PN.&OS=PN/6743791&RS=PN/6743791 US6743791]
|bgcolor=LightCyan|Heterocyclic compounds
|bgcolor=LightCyan|AKT3, GSK-3, ERK2
|-
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050277773%22.PGNR.&OS=DN/20050277773&RS=DN/20050277773 US20050277773]
|bgcolor=LightCyan|Pyrrolo[3,2-d]pyrimidine derivatives
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040072836%22.PGNR.&OS=DN/20040072836&RS=DN/20040072836 US20040072836]
|bgcolor=LightCyan|Aza-oxindole derivatives
|bgcolor=LightCyan|GSK3, AKT, PKC
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP1477489&F=0 EP1477489]
|bgcolor=LightCyan|Pyrrolopyrimidine derivatives
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO0056710&F=0 WO0056710]
|bgcolor=LightCyan|3-(Anilinomethylene) oxindoles
|bgcolor=LightCyan|GSK3, AKT, PKC
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO03011287&F=0 WO2003011287]
|bgcolor=LightCyan|Pyrazolon derivatives
|bgcolor=LightCyan|GSK3, β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6924141.PN.&OS=PN/6924141&RS=PN/6924141 US6924141]
|bgcolor=LightCyan|Lithium chloride, Wnt3/4/ 7
|bgcolor=LightCyan|β-catenin, GSK3, Wnt
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6706685.PN.&OS=PN/6706685&RS=PN/6706685 US6706685]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6683048.PN.&OS=PN/6683048&RS=PN/6683048 US6683048]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|α-catenin, β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6677116.PN.&OS=PN/6677116&RS=PN/6677116 US6677116]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6303576.PN.&OS=PN/6303576&RS=PN/6303576 US6303576]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|β-catenin
|}

==== Role of Pyrazole compounds in Wnt Pathway====
'''Pyrazole'''
* '''Pyrazole''' (C3H4N2) refers both to the class of simple aromatic ring organic compounds of the heterocyclic series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions and to the unsubstituted parent compound. Being so composed and having pharmacological effects on humans, they are classified as alkaloids although they are not known to occur in nature.
* Pyrazoles are produced synthetically through the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation
[[Image:pyrazole1.jpg|thumb|center|500px|Pyrazole (C3H4N2)]]
* Pyrazoles are used for their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, tranquilizing, muscle relaxing, psychoanaleptic, anticonvulsant, monoamineoxidase inhibiting, antidiabetic and antibacterial activities.
* Structurally related compounds are pyrazoline and pyrazolidine.
[[Image:pyrazole2.jpg|thumb|center|500px|Structurally related compounds]]

==== GSK3 inhibition by pyrazole compounds ====
[[Image:bold3.jpg]]
{| border="1" cellpadding="2", style="#008080"
!width="350"|[http://patft1.uspto.gov/netacgi/nph-Parser?TERM1=6989385+&Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=0&f=S&l=50 US6989385]
[[Image:US6989385.jpg]]
!width="350"|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
[[Image:US6664247.jpg]]
!width="350"|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
[[Image:WO2005012256.jpg]]
|-
|bgcolor=lightcyan|R1=T-Ring D, wherein
T is a valence bond and
Ring D = 5-6 membered aryl or heteroaryl ring;

R2 = hydrogen or C1-4 aliphatic and
R2'= hydrogen;

R3 = -R, -OR, or -N(R4)2, wherein
R = hydrogen, C1-6 aliphatic, 5-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl, and
L is -O-, -S-, or -NH-; and
Ring D is substituted by up to three substituents selected from -halo, -CN, -NO2, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R<4>), -N(R4)COR, -N(R4)CO2R, -SO2N(R4)2, -N(R4)SO2R, -N(R6)COCH2N(R4)2, -N(R6)COCH2CH2N(R4)2, or -N(R6)COCH2CH2CH2N(R4)2, wherein R = hydrogen, C1-6 aliphatic, phenyl, 5-6 membered heteroaryl ring, or 5-6 membered heterocyclic ring

|bgcolor=lightcyan|X = R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, S02, C=O, NRg(C=O) or O(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;

R1 is hydrogen; carbocyclic or heterocyclic group having from 3 to 12 ring members; or C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from 0, S, NH, SO, S02;

R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and

R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

|bgcolor=lightcyan|X is a groupR1-A-NR4-or a 5-or 6-membered carbocyclic or heterocyclic ring;
A is a bond,SO2, C=O, NRg (C=O) or O(C=O) wherein Rg is hydrogen orC14 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;Y is a bond or an alkylene chain of 1,2 or 3 carbon atoms in length;R'is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e. g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono-ordi-Cl 4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected fromO, S, NH, SO, SO2 ;R2 is hydrogen; halogen;C14 alkoxy (e. g. methoxy); or aC14 hydrocarbyl group optionally substituted by halogen (e. g. fluorine), hydroxyl orC14 alkoxy (e. g. methoxy);R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; andR4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e. g. fluorine), hydroxyl or C1-4 alkoxy (e. g. methoxy).
|}
==== Inhibition by amine derivatives ====

'''Patent Number''': US6989385
'''Applicant''': ''Vertex Pharmaceuticals Incorporated''
'''Title''': Pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure''':

[[Image:pyrazol1.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6989385 patent]]

'''Patent Number''': US7008948
'''Applicant''': Vertex Pharmaceuticals Incorporated
'''Title''': Fused pyrimidyl pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure'''

[[Image:pyrazol2.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US7008948 patent]]

'''Patent Number''': US6977262
'''Assignee''': Mitsubishi Pharma Corporation
'''Title''': Dihydropyrazolopyridine compounds and pharmaceutical use thereof

'''Basic Structure''':

[[Image:pyrazol3.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6977262 patent]]

----
'''Patent Number''': US6664247
'''Assignee''': Vertex Pharmaceuticals Incorporated
'''Title''': Pyrazole compounds useful as protein kinase inhibitors'''

'''Basic Structure''':

[[Image:pyrazol4.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US6664247 patent]]

----
'''Patent Number''': US2004224944
'''Assignee''': VERTEX PHARMACEUTICALS INC
'''Title''': Pyrazole compounds useful as protein kinase inhibitors

'''Basic Structure''':

[[Image:pyrazol5.jpeg]]

[[Derivatives of pyrimidine-pyrazole amine disclosed in US2004224944 patent]]

[[Other derivates for alopecia]]

==== GSK-3 Inhibition Mechanism - Phosphorylation====
* ''GSK-3 inhibition targets treatment of chemotherapy-induced alopecia'' [http://www.biomedcentral.com/1471-2199/5/15 source]
* In the canonical Wnt signaling cascade, adenomatous polyposis coli (APC), axin, and GSK3 constitute the so-called destruction complex, which controls the stability of beta-catenin. It is generally believed that four conserved Ser/Thr residues in the N terminus of beta-catenin are the pivotal targets for the constitutively active serine kinase GSK3. GSK3 covalently modifies beta-catenin by attaching phosphate groups (from ATP) to serine, and threonine residues. In so doing, the functional properties of the protein kinase’s substrate (beta-catenin) are modified.

* In the absence of Wnt signals, glycogen synthase kinase (GSK) is presumed to phosphorylate the N-terminal end of beta-catenin, thus promote degradation of beta-catenin and subsequent ubiquitination and proteasomal targeting.

* Exposure of cells to Wnts leads to inactivation of GSK-3 through an as yet unclear mechanism.The phosphoprotein Dishevelled is required, after receptor-ligand interaction, to transduce the signal that results in the inactivation of GSK-3. As a result, beta-catenin is dephosphorylated and escapes the ubiqduitylation-dependent destruction machinery.

* Unphosphorylated beta-catanin accumulates in the cytoplasm and translocates to the nucleus, where it can associate with the TCF/LEFs and become a transcriptional transactivator.

'''[[More details on GSK-3]]'''

'''Key points'''

* Beta-catenin phosphorylation at serine 45 (Ser45), threonine 41 (Thr41), Ser37, and Ser33 is critical for beta-catenin degradation. [http://jb.oxfordjournals.org/cgi/content/abstract/132/5/697 source]
* Regulation of beta-catenin phosphorylation is a central part of the canonical Wnt signaling pathway. [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=223838&ArtikelNr=66755&filename=66755.pdf source]
* Ser-X-X-X-Ser (X is any amino acid) motif is obligatory for beta-catenin phosphorylation by GSK3.[http://lib.bioinfo.pl/auth:He,X source]
* Beta-catenin phosphorylation/degradation and its regulation by Wnt can occur normally in the absence of Thr41 as long as the Ser-X-X-X-Ser motif/spacing is preserved. [httSp://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2006/45/i16/abs/bi0601149.html source]

'''GK3 Inhibition:'''

* GSK3 is regulated by phosphorylation.
* Phosphorylation of GSK3beta on Ser9 (Ser21 in GSK3alpha) by protein kinase B (PKB) causes its inactivation is the primary mechanism responsible for growth factor inhibition of this kinase. Activation of GSK3beta is dependent upon the phosphorylation of Tyr216 (Tyr279 in GSK3alpha). Upon activation, it has been shown to phosphorylate a number of different cellular proteins, including p53, c-Myc, c-Jun, heat shock factor-1 (HSF-1), beta-catenin and cyclin D1. [http://www.bioreagents.com/index.cfm/fuseaction/products.detail/CatNbr/OPA1-03082 source]
* GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3beta and GSK3alpha, respectively. [http://lib.bioinfo.pl/auth:Friedman,AB source]
* GSK3’s substrate specificity is unique in that phosphorylation of substrate only occurs if a phosphoserine or phosphotyrosine is present four residues C-terminal to the site of GSK phosphorylation. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11430833&dopt=Abstract source]
* A phosphorylation cascade starts from GSK3 itself and initiates it in beta-catenin. [http://www.genesdev.org/cgi/content/full/16/16/2073 source]
* Thus our goal is to stop the phosphorylation of the serine and threonine residue of GSK3.
* The figure below illustrates the phosphorylation mechanism of serine and threonine by ATP.

[[image:GSK3_phosphorylation.jpg|400 px|center|thumb|Phosphorylation mechanism [http://images.google.com/images?q=tbn:DGnhgZ7y7pSejM:bass.bio.uci.edu/~hudel/bs99a/lecture26/phosphoaa.gif source]]]

* We can't stop conversion of ADP to ATP that relaseas Phosphorous group causing Phosphorylation.
* We can only block the oxygen atom on serine and threonine as a result which will in turn stop Phosphorylation.
* The two probable ways of blocking the oxygen atom are (a) As oxygen is a Lewis acid with strong electron donating capacity, so usually a strong electron pair acceptor can easily bind to oxygen atom and preventing phosphorylation or (b) breaking of the -OH bond with the carbon atom.

'''Serine - pyrazole reaction'''

[[image:serine-pyrazol.jpg|600 px|center|thumb|Serine and Pyrazole reaction [http://www.genome.ad.jp/dbget-bin/www_bget?rn+R03134 source]]]

* The T-loop of GSK-3 is tyrosine phosphorylated at Y216 and Y279 in GSK-3b and GSK-3a, respectively, but not threonine phosphorylated. Y216/Y279 phosphorylation could play a role in forcing open the substrate (e.g, beta-catanin)-binding site.

* Thus, T-loop tyrosine might facilitate substrate phosphorylation but is not strictly required for kinase activity.

* Stimulation of cells with pyrazole compounds cause inactivation of GSK-3 through phosphorylation (S9 of GSK-3 beta and S21 of GSK-3 alpha), which inhibits GSK-3 activity. Thus leading to dephosphorylation of substrates (e.g., beta-catanin) resulting in their functional activation and consequent increased hair follicle morphogenisis.

* Phosphorylation of S9/S21 creates a primed pesudosubstrate that binds intramolecularly to the positively charged pocket of the GSK-3. This folding precludes phosphorylation of substrates (eg., beta-catanin) because the catalytic groove is occupied. The mechanism of inhibition is competitive.

* A consequence of this is that primed substrates, in high enough concentrations, out-compete the pesudosubstrate and thus become phosphorylated.

* Thus, small molecule inhibitors modeled to fit in the positively charged pocket of the GSK-3 kinease domain could potentially be very effective for selective inhibition of primed substrates.

'''Proposed mechanisms to regulate GSK-3''' [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12615961 source]

# inactivation of GSK-3 through serine phosphorylation
# activation of GSK-3 through tyrosine phosphorylation
# inactivation of GSK-3 through tyrosine dephosphorylation
# Covalant modifications of substrates through priming phosphorylation
# inhibition or facilation of GSK-3 mediated substrate phosphorylation thriugh interation of GSK-3 with binding or scaffolding proteins
# targeting of GSK-3 to different subcellular localizations
# differential usage of isoforms or splice variants to alter subcellular localization or substrate specificity
# integration of parellel signals conveyed by a signal stimulus.

'''Key Finding'''
* '''Pyrazole compounds with inhibition constant (Ki) of <0.1 mM''' are a good starting point for developing molecules that can inhibit serine/threonine protein kinase (such as GSK-3) and the proteins they help to regulate. [http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html?DOC=patentwatch%5Carchive%5C011204_patentwatch.html source]

=== Pathway associated with anti-androgen ===

* Dihydrotestosterone
** Formed by peripheral conversion of testosterone by 5-alpha reductase
** Binds to androgen receptor on susceptible hair follicles
* Hormone-receptor complex activates genes responsible for gradual transformation of large terminal follicles to miniaturized (progressive diminution of hair shaft diameter and length in response to systemic androgens) follicles

[[Image:5-alpha-reductase inhibition.jpeg|center|500 px]]

Alopecia - Hair Loss

2007-08-17T03:46:55Z

67.180.82.65:

{{TOCrightEx}}
== Rationale ==
* "Medication for men plagued by hair loss has become a topic of interest in Japan since a drug company began marketing it at the end of last year." March 5th, 2006 – [http://stophair.setupmyblog.com/?p=55 source]

* "An increasing number of companies are apparently turning the Chinese fear of a bald spot into big bucks with some doing so well they are branching out into other countries." February 16, 2006 – [http://stophair.setupmyblog.com/]

* "There is something in the air, or should we say in the hair, these days. Scientific research into hair loss remedies has never been more active or more exciting." June 7, 2006 - [http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/06-07-2005/0003821470&EDATE=]

== Alopecia IPMap ==
[http://www.dolcera.com/client/d8r3/hairloss_map.htm Dolcera IPMap for Alopecia]

== Introduction ==

=== Hair basics ===
* Hair is a complex and delicate part of the body.
* Keeping it healthy and beautiful is a challenge.
* Hair grows everywhere on the body with the exception of lips, eyelids, palms of the hands and soles of the feet.
* Hair is basically a form of skin.
* Hair is made up of a protein called keratin.
* Each shaft of hair is made of two or three inter-twined layers of keratin which grow from a follicle beneath the skin.
* Hair Structure - [http://www.pg.com/science/haircare/hair_twh_12.htm]
* Hair Cycle - [http://www.follicle.com/hair-structure-life-cycle.html]

[[Image:Hairbasics.jpg|center|400px|Structure of Hair root and Hair bulb]]

=== What causes hair loss? ===
* Decrease in growth of hair
* Increase in shedding of hair
* Breakage of hair
* Conversion of thick terminal hairs to thin vellus hairs
[[Image:Facts.jpg|thumb|right|250px|Survey results from Japan]]
Both men and women lose hair for similar reasons. Hair loss in men is often more dramatic, and follows a specific pattern of loss, one of which has been termed “Male Pattern Baldness" or "Androgenetic Alopecia".

=== Types of alopecia===

* Alopecia Areata (AA): Hair loss occurring in patches anywhere on the body.
* Alopecia Totalis (AT): Total loss of the hair on the scalp.
* Alopecia Universalis (AU): Total loss of all hair on the body.
* Alopecia Barbae: Loss of facial hair (for a man) especially in the beard area.
* Alopecia Mucinosa: A type of alopecia which results in scaley patches.
* Androgenetic Alopecia (AGA): Also known as male pattern baldness. It is a thinning of the hair to an almost transparent state, in both men or women. It is thought to be a hereditary form of hair loss.
* Traction Alopecia: Traction alopecia is usually due to excessive pulling or tension on hair shafts as a result of certain hair styles. It is seen more often in women, particularly those of East Indian and Afro-Caribbean origin. Hair loss depends on the way the hair is being pulled. Prolonged traction alopecia can stop new hair follicles from developing and leads to permanent hair loss.
* Anagen Effluvium: This hair loss is generally caused by chemicals such as those used to treat cancer. Initially it causes patchy hair loss, which often then leads to total hair loss. The good news is that when you stop using these chemicals the hair normally grows back (usually about 6 months later). Other drugs also can cause hair loss. Many medicines used to treat even common diseases can cause hair loss.
* Scarring Alopecia: A form of alopecia which leaves scarring on the area of hair loss.
* Telogen Effluvium: A form of hair loss where more than normal numbers of hair fall out. There is a general 'thinning' of the hair. Unlike some other hair and scalp conditions, it is temporary and the hair growth usually recovers. ([http://www.alopeciaonline.org.uk/about/types.asp Source])

=== Androgenetic alopecia ===
* Gradual onset
* Transition from large, thick, pigmented terminal hairs to thinner, shorter, indeterminate hairs and finally to short, wispy, non-pigmented vellus hairs in the involved areas
* Characterized by a receding hairline and/or hair loss on the top of the head

'''Main causes'''
* Genetic predisposition
* Hormonal effect of androgen
* Reduction of blood circulation around hair follicle
* Deactivation of hair matrix cells

'''Some facts from Japan'''

* Market size: ¥ 30 Billion
* Number of products: more than 100

(JICST-EPlus - Japanese Science & Technology)

== IP activity over the years ==
The graph indicates:
* Number of patents filed every 5 years (except for first 7 years).
* First solution proposed in 1973
* Filing trend indicates steep rise in activity recently.
[[Image:Year1.jpg|thumb|center|400px|IP Activity over years]]

== Major players ==
[[Image:players.jpg|thumb|left|400px|Assignees with more than 20 patents ]]
[[Image:players1.jpg|thumb|center|400px|Assignees with fewer than 20 patents ]] 

* '''Active assignees'''
Assignees currently active with more than 5 patents to their credit during 2000-2005.
* Warner with 9 patents,
* Bristol with 6 and
* Abbott with 5.

[[Image:Active.jpg|thumb|center|500px|Active Assignees]]

== Treatment Approaches==
Composition of treatment for causes are identified and categorized as follows:

* Anti-androgens (Finasteride) [http://www.emedicine.com/DERM/topic21.htm source]
* Vasodilators (Minoxidil) [http://www.emedicine.com/DERM/topic21.htm source]
* Double action (Anti-androgen + Vasodilator)
* Hair matrix cells activator

{|border="1" cellpadding="2", style="#008080" align="center"
|- style="font-weight:bold" valign="top"
! Cause !! Treatment approach !! Pathways affected

|- valign="top"
| Hormonal effect of androgen || Anti-androgens || Testosterone pathway

|- valign="top"
| Reduction of blood circulation around hair follicle || Vasodilators (eg. Minoxidil) || NO/cGMP Pathway

|- valign="top"
| Deactivation of hair matrix cells || Hair matrix cells activator
|
* Wnt pathway
* STAT pathway
* TGF beta/BMP Pathway
* FGF Pathway
* MAPK Pathway
* NOTCH Pathway
* Hedgehog Pathway
|}

=== Anti-androgens ===
* Anti-androgens are used in hormone therapy.
* Anti-androgens are designed to affect the hormones made in the adrenal glands. They don't stop the hormones from being made, but they stop them from having an effect leading to hair loss.

'''What causes hair loss?'''
* Testosterone is reduced to its active metabolite, Dihydrotestosterone (DHT) by the enzyme 5 alpha reductase.
* DHT attaches to androgen receptor sites at the hair follicle.
* DHT causes gradual miniaturization of the follicle, which eventually results in hair loss.

'''How do anti-androgens treat hair loss?'''
* Anti-androgens compete with DHT to bind to the androgen receptor.
* Upon binding of anti-androgen in place of DHT, follicle miniaturization is lowered and hair loss prevented.

==== Functions of Anti-androgen ====
[http://www.revivogen.com/revivogen/work.html Anti-androgen]

[[Image:Andogen1.jpg|thumb|center|500px|Functions of Anti-androgen]]

==== IP Map for anti-androgen ====

{| border="1" cellpadding="0", style="#008080"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="100" bgcolor=DodgerBlue|'''Nature'''
!width="450" bgcolor=DodgerBlue|'''Composition'''
!width="400" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
BLOTECH (2004)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Palmetto berry extract (fatty acids & sterols), Pumpkin seed extract (Vitamins-B, alpha-linolenic acid, amino acids and phytosterols), Quercetin (Flavonoids) and Beta-sitosterol (Rice bran, wheat germ, corn oils and soybeans)
|bgcolor=LightCyan|Fatty acids – Inhibit testosterone
Sterols - Mechanism of action unknown.

Quercetin results in cell growth cycle.

Beta-sitosterol reduce inflammation on scalp
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
WARNER LAMBERT(2004)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 4-cycloalkoxy benzonitrile derivatives and salts
|bgcolor=LightCyan|Acts as androgen receptor modulator and blocks formation of DHT.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
WARNER LAMBERT(2004)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 6-sulfonamido-quinolin-2-one and 6-sulfonamido-2-oxo-chromene derivatives.
|bgcolor=LightCyan|The compounds inhibit, or decrease, activation of androgen receptor by androgens.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
APHIOS Corp (2003)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Supercritical fluid isolate of Saw Palmetto and Sperol (Serenoa repens berry) and their analogs or derivatives.
|bgcolor=LightCyan|Modulates androgenic activity by inhibiting 5.alpha.-reductase activity.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
Fundacion Pablo Cassara (2003)
|bgcolor=LightCyan|Nucleotide
|bgcolor=LightCyan|Pharmacologically active oligonucleotides (encompass both DNA and S-DNA bond)
|bgcolor=LightCyan|Oligonucleotides inhibit androgen receptor (AR) expression at very low concentrations in skin and hair follicle
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
PFIZER INC (2001)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|Thyromimetic compounds (structurally similar to thyronine) with finasteride, or cyproterone acetate
|bgcolor=LightCyan|Activates thyroid hormone receptors in hair follicle which in turn promote elasticisation of follicle walls and hair follicle
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
N/A (1995)
|bgcolor=LightCyan|Peptides/nucleic acid
|bgcolor=LightCyan|Bradykinin antagonist (peptide of plasma origin from kininogen precursor-kallikrein)
|bgcolor=LightCyan|Inhibits synthesis of bradykinin receptors or compounds by binding to B2 receptor
|- style="height:20px"
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
KAO Corp (1987)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Walnut extract (leaves/pericarps) with an organic solvent
|bgcolor=LightCyan|Blocks formation of DHT
|}

=== Minoxidil (Vasodilators) ===
* Minoxidil is a "potassium channel opener" that leads to vasodilation.
* The drug is available in two forms. Oral minoxidil is used to treat high blood pressure and the topical solution form is used to treat hair loss and baldness.

'''What causes hair loss?'''
* A thick network of tiny veins and arteries line the outer wall of the follicle. Blood pumps through the bulb and hair via this network.
* DHT accumulates in the hair follicles and roots, constricting the blood supply of oxygen and nutrients to the hair roots; which is also seen to possibly contribute towards hair loss.

'''How does Minoxidil treat hair loss?'''
* Minoxidil is applied to the scalp topically, where it dilates blood vessels in the scalp and sustains the hair follicles for longer period of time.
* Minoxidil is thought to have a direct mitogenic effect on epidermal cells, as has been observed both in vitro and in vivo. Though the mechanism of its action for causing cell proliferation is not very clear, minoxidil is thought to prevent intracellular calcium entry. Calcium normally enhances epidermal growth factors to inhibit hair growth, and Minoxidil by getting converted to minoxidil sulfate acts as a potassium channel agonist and enhances potassium ion permeability to prevent calcium ions from entering into cells. ([http://www.hairtransplantadvice.com/medical-hair-restoration.php Source])
* Minoxidil sulfate (MS) appears to be the active metabolite responsible for hair growth stimulation.

==== Functions of Vasodilators ====

[[Image:minoxidil1.jpg|thumb|center|500px|Functions of Monoxidil [http://www.nurseminerva.co.uk/diagrams.htm#Diagram%201 source]]]

==== IP Map for Vasodilators ====

{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75" bgcolor=DodgerBlue|'''Nature'''
!width="600" bgcolor=DodgerBlue|'''Composition'''
!width="300" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
WARNER LAMBERT(2002)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|Benzopyran compounds
|bgcolor=LightCyan|Rapidly metabolizes, and causes reduced cardiovascular effects as compared to other known potassium channel openers
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
LG HOUSEHOLD & HEALTH CARE(2001)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Sophora flavescens extract (alkaloids & flavonoids, luteolin-7-glucose and cytosine) Hinokitiol (Taiwan hinoki oil, Aomori, Western Red Cedar oil) and Nicotinamide (Vitamin B complex)
|bgcolor=LightCyan|Promotes function of cell activity and dilates blood vessels
|}

=== Double action (Anti-androgen + Vasodilator) ===
* Combination of Vasodilator + Anti-androgen (double action) composition for effective treatment of Male-Pattern Baldness.

'''What is the problem with using only Anti-androgen therapy?'''
* Anti-androgen is not effective in addressing the issue of vasocontriction around hair follicles due to sebum oil build up.
* Anti-androgen only prevents binding of DHT to androgen receptors. However, the effects of improper oxygen and nutrient supply to the brain due to vasocontriction still remains and gradually causes hair loss.

'''What is the problem with using only Vasodilator (or Minoxidil only) therapy?'''
* Vasodilator or Minoxidil-based products are generally not effective in stopping hair loss as vasodilators (or Minoxidil) do not block the harmful effects of DHT in the scalp and hair follicles.
* Vasodilators or Minoxidil simply dilate blood vessels in the scalp. However, the harmful DHT still gets produced in the body, enters the scalp and hair follicles causing hair loss.

'''How is the combination of Anti-androgens and Vasodilator (or Minoxidil) effective?'''
* Anti-androgens target the problem of DHT binding to androgen receptors and prevents follicle miniaturization.
* Vasodilators like Minoxidil cause vasodilation and therefore improve supply of oxygen and nutrients to the hair follicle and roots.
* Combination therapy therefore proves to be much more effective than individual therapy.

==== Functions of (Anti-androgen + Vasodilators) ====
[http://www.revivogen.com/revivogen/work.html Anti-androgen ]and [http://www.xandrox.net/articles/article01.htm Minoxidil]
[[Image:Doubleaction1.jpg|thumb|center|500px|Functions of (Anti-androgen + Vasodilators)]]

==== IP Map for (Anti-androgen + Vasodilators) ====
{| border="1" cellpadding="3"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75" bgcolor=DodgerBlue|'''Nature'''
!width="500" bgcolor=DodgerBlue|'''Composition'''
!width="500" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
N/A(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Testosterone blocker or vascular toner (Flutamide, cyproterone acetate, spironolactone, progesterone, or analogs or derivatives) and minoxidil mixed along with non-retinoid penetration enhancer and sunscreen
|bgcolor=LightCyan|Inhibits 5.alpha.-reductase activity (block DHT) and increase blood flow on the scalp
|- style="height:100px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
L'OREAL(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Prostaglandin (polyunsaturated fatty acids) EP-2, EP-3 EP-4 receptor agonist with Minoxidil, 2,4-diaminopyrimidine 3-oxide, and Aminexil, cyclic AMP
|bgcolor=LightCyan|Minoxidil (designed to mimic nitric oxide's effects) grows hair via prostaglandin-H synthase stimulation. EP-3 and EP-4 are expressed in anagen hair follicles which induce a reduction in the level of cAMP
|- style="height:100px"
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
COLOMER GROUP(1999)
|bgcolor=LightCyan|Natural extract
|bgcolor=LightCyan|Hop extract (oil contains terpenes and humulene), Rosemary extract (hydroalcohol), Swertia extract (glycol with a swertiamarin), Silanodiol salicylate (biologically active silicon compound)
|bgcolor=LightCyan|Inhibits activity of 5-alpha-reductase, protects follicular cell membranes by neutralizing action of oxidation reaction in tissues, stimulates hair follicles and blood circulation to the hair root, supplies oxygen and nutrients to base of follicle, retains humidity, avoids dehydration of scalp
|}

=== Hair matrix cell activator ===
Hair matrix cell activator is a substance that acts at the matrix cells in the hair follicle preventing their degradation.

'''What causes hair loss?'''
* Stem cells are interspersed within the basal layer of the outer root sheath and in an area called the bulge.
* Stem cells migrate to hair matrix where they start to divide and differentiate, under the influence of substances produced by cells of the dermal papilla.
* Perifollicular matrix cells undergo slow degradation which prevents follicle stimulation.
* Hair follicle activation is required for hair growth and thus inhibition of follicle activation eventually leads to hair loss.

'''How does hair cell matrix activator treat hair loss?'''
* Hair cell matrix activator slows down and inhibits degradation of the perifollicular matrix.
* This leads to an increase in hair follicle matrix cells that differentiate from progenitor stem cells.
* Matrix activator allows activation of hair matrix cells and therefore follicle stimulation leading to hair growth.

==== Functions of Hair matrix cell activator ====
[http://www.ijdb.ehu.es/fullaccess/fulltext.04023/ft163.pdf Hair matrix cell activator]
[[Image:Hair matrix.jpg|thumb|center|500px|Functions of Hair matrix cell activator ]]

==== IP Map for Hair matrix cell activator ====
{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="100" bgcolor=DodgerBlue|'''Nature'''
!width="200" bgcolor=DodgerBlue|'''Composition'''
!width="600" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
SHISEIDO(1999)
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|(2-substituted oxyphenyl) alkanamide derivative and its salt
|bgcolor=LightCyan|Mechanism of action has not been made clear, having excellent hair follicle activating action and regrowth promoting effect
|- style="height:50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
L'OREAL(1998)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Metalloprotease (MMP-9) inhibitor (thiol or a hydroxamate) other than chelating calcium ions
|bgcolor=LightCyan|Reducing the expression of MMPs (Metalloproteases) in the scalp - slows down or inhibits the degradation of the perifollicular matrix (extracellular matrix surrounding the hair follicle)
|}

== Technology mapping based on patents analyzed ==

=== IPMap: Composition nature matrix ===

{| border="1" cellpadding="11", style="#008080"
!width="120" bgcolor=DodgerBlue|'''Year'''
!width="200" bgcolor=DodgerBlue|'''Organic Compound'''
!width="200" bgcolor=DodgerBlue|'''Natural extracts'''
!width="200" bgcolor=DodgerBlue|'''Peptides'''
!width="200" bgcolor=DodgerBlue|'''Nucleotides'''
!width="200" bgcolor=DodgerBlue|'''Natural extract + Organic comp'''
|- style="height:10px"
|bgcolor=LightCyan|2005
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|UNILEVER (1)
|-
|bgcolor=LightCyan|2004
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|BLOTECH (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|KAO (1)
|-
|bgcolor=LightCyan|2003
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|APHIOS (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|FUNDACION (1)
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2002
|bgcolor=LightCyan|WARNER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2001
|bgcolor=LightCyan |PFIZER (1)
|bgcolor=LightCyan|LG HEALTH-CARE (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|2000
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|L’OREAL (1) / N/A (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1999
|bgcolor=LightCyan|SHISEDIO (1)
|bgcolor=LightCyan|COLOMER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1998
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|L’OREAL (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1995
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|N/A (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1987
|bgcolor=LightCyan|....
|bgcolor=LightCyan|KAO (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|-
|bgcolor=LightCyan|1982
|bgcolor=LightCyan|UNILEVER (1)
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|bgcolor=LightCyan|....
|}

=== Focus of patents ===

{| border="1" cellpadding="17", style="#008080"
!width="800" bgcolor=DodgerBlue|'''Focus of patents'''
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="100" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|2-substituted oxyphenyl alkanamide derivative having excellent hair growth effect.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
|bgcolor=LightCyan|1
|-
|bgcolor=LightCyan|Thyromimetic compounds, and its role in treating hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
|bgcolor=LightCyan|2
|-
|bgcolor=LightCyan|Saw Palmetto berry extract, pumpkin seed extract, sitosterol and quercetin for the treatment and prevention of the biologically detrimental effects of DHT
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
|bgcolor=LightCyan|3
|-
|bgcolor=LightCyan|4-cycloalkoxy benzonitriles and its use as androgen receptor modulators
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
|bgcolor=LightCyan|4
|-
|bgcolor=LightCyan|Supercritical fluid isolate of Saw Palmetto, Sperol for inhibition of 5-.alpha.-reductase activity
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
|bgcolor=LightCyan|5
|-
|bgcolor=LightCyan|New class of quinolin-2-ones and chromen-2-ones andtheir use as androgen receptor antagonists
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|6
|-
|bgcolor=LightCyan|Antiandrogen oligonucleotides usable for the treatment of dermatological androgen-related disorders
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
|bgcolor=LightCyan|7
|-
|bgcolor=LightCyan|Bradykinin antagonists for stimulating or inducing hair growth and/or arresting hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
|bgcolor=LightCyan|8
|-
|bgcolor=LightCyan|Extract from walnut leaves and/or pericarps as 5 alpha -reductase inhibitor
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
|bgcolor=LightCyan|9
|-
|bgcolor=LightCyan|Stimulating hair growth using benzopyrans
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
|bgcolor=LightCyan|10
|-
|bgcolor=LightCyan|Sophora flavescens extract, Coicis semen extract, clove extract, etc for promoting hair growth, function of cell activity and dilating peripheral blood vessels.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
|bgcolor=LightCyan|11
|-
|bgcolor=LightCyan|Compositions to prevent or reduce hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
|bgcolor=LightCyan|12
|-
|bgcolor=LightCyan|Prostaglandin EP-3 receptor antagonists for reducing hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
|bgcolor=LightCyan|13
|-
|bgcolor=LightCyan|Synergic effect arising from the interaction of active ingredients, consisting of three plant extracts and a synthetic organosilicic compound for prevent hair loss and stimulate hair growth
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
|bgcolor=LightCyan|14
|-
|bgcolor=LightCyan|Metalloprotease inhibitors to induce and/or stimulate the growth
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
|bgcolor=LightCyan|15
|-
|bgcolor=LightCyan|Method of decreasing sebum production and pore size
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050277699%22.PGNR.&OS=DN/20050277699&RS=DN/20050277699 US20050277699 ]
|bgcolor=LightCyan|16
|-
|bgcolor=LightCyan|Method for reducing sebum on the hair and skin
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=4529587.PN.&OS=PN/4529587&RS=PN/4529587 US4529587]
|bgcolor=LightCyan|17
|}

=== Technology focus===
[[Image:Technologyfocus2.jpg|thumb|center|700px|Technology focus]]

=== Distribution of patents ===

==== By patent types ====
[[Image:Didtribution.jpg|thumb|center|700px|Distribution based on patent types ]]

==== By key ingredients ====
[[Image:key1.jpg|thumb|center|700px|Distribution of key ingredients]]

==== By target disease ====
[[Image:target.jpg|thumb|center|700px|Distribution based on target diseases]]

==== Key ingredients vs. Target disease ====
[[Image:key&target1.jpg|thumb|center|1000px|Key ingredients vs. Target disease]]

==== Target species ====
[[Image:Species.jpg|thumb|center|700px|Target species]]

==== Mode of administration ====
[[Image:Mode.jpg|thumb|center|700px|Mode of administration]]

==== Product type vs. Product form ====
[[Image:prod.jpg|thumb|center|700px|Product type vs. Product form]]

==== Patents by target diseases ====
{| border="1" cellpadding="16", style="#008080"
!width="800" bgcolor=DodgerBlue|'''Target disease/ disorder'''
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="150" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|Alopecia areata, alopecia pityrodes or alopecia seborrheica, or androgenic alopecia (i.e. male pattern baldness)
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
|bgcolor=LightCyan|1
|-
|bgcolor=LightCyan|Alopecia areata, male pattern baldness and female pattern baldness
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030007941%22.PGNR.&OS=DN/20030007941&RS=DN/20030007941 US20030007941]
|bgcolor=LightCyan|2
|-
|bgcolor=LightCyan|Androgenic alopecia (i.e. male pattern baldness), prostatic hyperplasia or both.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 US20060009430]
|bgcolor=LightCyan|3
|-
|bgcolor=LightCyan|Inappropriate activation of the androgen receptor, acne, oily skin, alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009427%22.PGNR.&OS=DN/20060009427&RS=DN/20060009427 US20060009427]
|bgcolor=LightCyan|4
|-
|bgcolor=LightCyan|Prostatic hyperplasia, prostatic cancer, hirsutism, acne, male pattern baldness, seborrhea, and other diseases related to androgen hyperactivity
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050118282%22.PGNR.&OS=DN/20050118282&RS=DN/20050118282 US20050118282]
|bgcolor=LightCyan|5
|-
|bgcolor=LightCyan|Alopecia, acne, oily skin, prostrate cancer, hirsutism, and benign prostate hyperplasia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|6
|-
|bgcolor=LightCyan|Androgen-associated hair loss and androgen-skin related disorders.
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009429%22.PGNR.&OS=DN/20060009429&RS=DN/20060009429 US20060009429]
|bgcolor=LightCyan|7
|-
|bgcolor=LightCyan|Androgenetic or androgenic alopecia or androgeno-genetic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220030073616%22.PGNR.&OS=DN/20030073616&RS=DN/20030073616 US20030073616]
|bgcolor=LightCyan|8
|-
|bgcolor=LightCyan|Diseases caused by testosterone (male-pattern alopecia)
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
|bgcolor=LightCyan|9
|-
|bgcolor=LightCyan|Alopecia areata, female pattern hair loss, hair loss secondary to chemotherapy or radiation treatment, stress-related hair loss, self-induced hair loss, scarring alopecia, and alopecia in non-human mammal
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040157856%22.PGNR.&OS=DN/20040157856&RS=DN/20040157856 US20040157856]
|bgcolor=LightCyan|10
|-
|bgcolor=LightCyan|Male pattern alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050053572%22.PGNR.&OS=DN/20050053572&RS=DN/20050053572 US20050053572]
|bgcolor=LightCyan|11
|-
|bgcolor=LightCyan|Alopecia, androgenic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060052405%22.PGNR.&OS=DN/20060052405&RS=DN/20060052405 US20060052405]
|bgcolor=LightCyan|12
|-
|bgcolor=LightCyan|Hair loss
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050123577%22.PGNR.&OS=DN/20050123577&RS=DN/20050123577 US20050123577]
|bgcolor=LightCyan|13
|-
|bgcolor=LightCyan|Male pattern alopecia
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6447762.PN.&OS=PN/6447762&RS=PN/6447762 US6447762]
|bgcolor=LightCyan|14
|-
|bgcolor=LightCyan|Androgenetic, androgenic or androgenogenetic alopecia
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
|bgcolor=LightCyan|15
|-
|bgcolor=LightCyan|Curing other scalp related problems
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050244362%22.PGNR.&OS=DN/20050244362&RS=DN/20050244362 US20050244362]
|bgcolor=LightCyan|16
|}

==== Patents by application ====
[[Image:application.jpg|thumb|center|700px|Distribution of patents based on application]]

==== [[List of patents]] ====

== Pathways and linkages ==

=== Pathways associated with hair matrix cell activation===

'''Molecular mediators of hair follicle embryogenesis:''' Identification of the molecular pathways controlling differentiation and proliferation in mammalian hair follicles provides the crucial link to understanding the regulation of normal hair growth, the basis of hereditary hair loss diseases, and the origin of follicle-based tumors. Homeobox (hox), hedgehog (hh), patched (ptc), wingless (wg}/wnt, disheveled (dsh), engrailed (en), Notch 1 and armadillo/B-catenin genes are all critical for hair follicle.

* '''Wnt pathway:''' Maintains hair-inducing activity of the dermal papilla.
* '''Hedgehog pathway:''' Sonic hedgehog (SHH) signaling plays a critical role in hair follicle development. Sonic hedgehog gene. Sonic hedgehog, SHH for short, helps guide hair follicles from a resting stage into growth activity. SHH is particularly important in the embryonic formation of hair follicles.
* '''STAT pathway'''
* '''TGF beta/BMP Pathway:''' Bone morphogenetic protein (BMP) signaling have been implicated in the regulation of both proliferation and differentiation in the hair follicle. BMP2 is expressed in the embryonic ectoderm, but then localizes to the early hair follicle placode and underlying mesenchyme. BMP4 is expressed in the early dermal condensate. Research results show that BMPs are a key component of the signaling network controlling hair development and are required to induce the genetic program regulating hair shaft differentiation in the anagen hair follicle. Transforming growth factor beta (TGF-beta), inhibits mitogen - induced dermal papilla cell proliferation
* '''FGF Pathway:''' Fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) potentiate the growth of dermal papilla cells. It is proposed that these proteins increase the synthesis of stromelysin (an enzyme, matrix metalloproteinase) which acts on the papilla cells and accelerates their growth.
* '''MAPK Pathway:''' Mitogen-activated protein kinase (MAPK) activation, increases keratinocyte turnover.
* '''NOTCH Pathway''': Notch-1 is expressed in ectodermal-derived cells of the follicle, in the inner cells of the embryonic placode and the follicle bulb, and in the suprabasal cells of the mature outer root sheath. Delta-1, one of the three ligands is only expressed during embryonic follicle development and is exclusive to the mesenchymal cells of the pre-papilla located beneath the follicle placode, and appears to promote and accelerate placode formation, while suppressing placode formation in surrounding cells. Other ligands, Serrate 1 and Serrate 2, are expressed in matrix cells destined to form the inner root sheath and hair shaft.

=== Pathways associated with Anti Androgen===
[[Image:Slide1.GIF|thumb|center|700 px|Alopecia pathways]]

==== Players of WNT inhibition Pathway ====
[[Image:wnt.jpg|thumb|right|200 px|Wnt inhibition]]
{| border="1" cellpadding="15", style="#008080"
!width="150" bgcolor=DodgerBlue|'''Patent no.'''
!width="200" bgcolor=DodgerBlue|'''Key compound'''
!width="200" bgcolor=DodgerBlue|'''Players of inhibition'''
|- style="height:10px"
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|GSK3
|-
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6989385.PN.&OS=PN/6989385&RS=PN/6989385 US6989385]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|GSK3
|-
|bgcolor=lightyellow|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
|bgcolor=lightyellow|Pyrazole compounds
|bgcolor=lightyellow|CDK,GSK3
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6974819.PN.&OS=PN/6974819&RS=PN/6974819 US6974819]
|bgcolor=LightCyan|Pyrimidine derivative
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6743791.PN.&OS=PN/6743791&RS=PN/6743791 US6743791]
|bgcolor=LightCyan|Heterocyclic compounds
|bgcolor=LightCyan|AKT3, GSK-3, ERK2
|-
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050277773%22.PGNR.&OS=DN/20050277773&RS=DN/20050277773 US20050277773]
|bgcolor=LightCyan|Pyrrolo[3,2-d]pyrimidine derivatives
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040072836%22.PGNR.&OS=DN/20040072836&RS=DN/20040072836 US20040072836]
|bgcolor=LightCyan|Aza-oxindole derivatives
|bgcolor=LightCyan|GSK3, AKT, PKC
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP1477489&F=0 EP1477489]
|bgcolor=LightCyan|Pyrrolopyrimidine derivatives
|bgcolor=LightCyan|GSK3
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO0056710&F=0 WO0056710]
|bgcolor=LightCyan|3-(Anilinomethylene) oxindoles
|bgcolor=LightCyan|GSK3, AKT, PKC
|-
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO03011287&F=0 WO2003011287]
|bgcolor=LightCyan|Pyrazolon derivatives
|bgcolor=LightCyan|GSK3, β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6924141.PN.&OS=PN/6924141&RS=PN/6924141 US6924141]
|bgcolor=LightCyan|Lithium chloride, Wnt3/4/ 7
|bgcolor=LightCyan|β-catenin, GSK3, Wnt
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6706685.PN.&OS=PN/6706685&RS=PN/6706685 US6706685]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6683048.PN.&OS=PN/6683048&RS=PN/6683048 US6683048]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|α-catenin, β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6677116.PN.&OS=PN/6677116&RS=PN/6677116 US6677116]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|β-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6303576.PN.&OS=PN/6303576&RS=PN/6303576 US6303576]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|β-catenin
|}

==== Role of Pyrazole compounds in Wnt Pathway====
'''Pyrazole'''
* '''Pyrazole''' (C3H4N2) refers both to the class of simple aromatic ring organic compounds of the heterocyclic series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions and to the unsubstituted parent compound. Being so composed and having pharmacological effects on humans, they are classified as alkaloids although they are not known to occur in nature.
* Pyrazoles are produced synthetically through the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation
[[Image:pyrazole1.jpg|thumb|center|500px|Pyrazole (C3H4N2)]]
* Pyrazoles are used for their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, tranquilizing, muscle relaxing, psychoanaleptic, anticonvulsant, monoamineoxidase inhibiting, antidiabetic and antibacterial activities.
* Structurally related compounds are pyrazoline and pyrazolidine.
[[Image:pyrazole2.jpg|thumb|center|500px|Structurally related compounds]]

==== GSK3 inhibition by pyrazole compounds ====
[[Image:bold3.jpg]]
{| border="1" cellpadding="2", style="#008080"
!width="350"|[http://patft1.uspto.gov/netacgi/nph-Parser?TERM1=6989385+&Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=0&f=S&l=50 US6989385]
[[Image:US6989385.jpg]]
!width="350"|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
[[Image:US6664247.jpg]]
!width="350"|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
[[Image:WO2005012256.jpg]]
|-
|bgcolor=lightcyan|R1=T-Ring D, wherein
T is a valence bond and
Ring D = 5-6 membered aryl or heteroaryl ring;

R2 = hydrogen or C1-4 aliphatic and
R2'= hydrogen;

R3 = -R, -OR, or -N(R4)2, wherein
R = hydrogen, C1-6 aliphatic, 5-6 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl, and
L is -O-, -S-, or -NH-; and
Ring D is substituted by up to three substituents selected from -halo, -CN, -NO2, -N(R4)2, optionally substituted C1-6 aliphatic group, -OR, -C(O)R, -CO2R, -CONH(R<4>), -N(R4)COR, -N(R4)CO2R, -SO2N(R4)2, -N(R4)SO2R, -N(R6)COCH2N(R4)2, -N(R6)COCH2CH2N(R4)2, or -N(R6)COCH2CH2CH2N(R4)2, wherein R = hydrogen, C1-6 aliphatic, phenyl, 5-6 membered heteroaryl ring, or 5-6 membered heterocyclic ring

|bgcolor=lightcyan|X = R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, S02, C=O, NRg(C=O) or O(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;

R1 is hydrogen; carbocyclic or heterocyclic group having from 3 to 12 ring members; or C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from 0, S, NH, SO, S02;

R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and

R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

|bgcolor=lightcyan|X is a groupR1-A-NR4-or a 5-or 6-membered carbocyclic or heterocyclic ring;
A is a bond,SO2, C=O, NRg (C=O) or O(C=O) wherein Rg is hydrogen orC14 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;Y is a bond or an alkylene chain of 1,2 or 3 carbon atoms in length;R'is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e. g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono-ordi-Cl 4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected fromO, S, NH, SO, SO2 ;R2 is hydrogen; halogen;C14 alkoxy (e. g. methoxy); or aC14 hydrocarbyl group optionally substituted by halogen (e. g. fluorine), hydroxyl orC14 alkoxy (e. g. methoxy);R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; andR4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e. g. fluorine), hydroxyl or C1-4 alkoxy (e. g. methoxy).
|}

Alopecia - Hair Loss

2007-08-17T03:46:03Z

67.180.82.65:

Main Page

2007-08-02T15:03:02Z

67.180.82.65:

__NOTOC__
== Technology ==
==== Landscape Reports ====
* [[Hybrid Electric Vehicle Battery System]]
* [[Supply Chain RFID Applications]]
* [[Insurance sector]]
* [[Quality of Service on CDMA platforms]]
* [[Solar cells]]
* [[OLED - Organic Light Emitting Diode]]

==== Dashboard ====
* [http://client.dolcera.com/dash_auto/dashboard.html Automotive dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/rfid_model.swf RFID dashboard]

==== Innovation Explorer ====
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics Innovation Explorer]

==== IPMaps ====
* [http://www.dolcera.com/ipmapdemo/satellite_antenna/ipmap.html Satellite Antenna IPMap]
* [http://www.dolcera.com/ipmapdemo/rfid/ipmap.html RFID IPMap]
* [http://www.dolcera.com/ipmapdemo/multimodal_apps/ipmap.html Multimodal Applications IPMap]

===Subscription service===
[[4G Subscription]]

== Life sciences and Chemistry ==
==== Landscape reports ====
* [[Alopecia - Hair Loss]]
* [[Diabetes products and services]]
* [[Inflammation and cardiovascular drugs]]
* [[Non-wovens]]

==== Dashboard ====
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]

==== IPMap ====
* [http://dolcera.com/client/d8r3/hairloss_map.htm Alopecia/Hair loss IPMap]

== Finance ==
* [[Innovative personal finance products]]

== Dolcera Offerings summary ==
* [[Dolcera Offerings|Dolcera offerings summary]]

== Dolcera Training ==
* [[Training Manual]]

== Chinese Page ==
* [[Home Page]]
* [[Service Page]]
* [[About]]

Main Page

2007-07-29T21:46:24Z

67.180.82.65: /* Innovation Explorer */

__NOTOC__
== Technology ==
==== Landscape Reports ====
* [[Hybrid Electric Vehicle Battery System]]
* [[Supply Chain RFID Applications]]
* [[Insurance sector]]
* [[Quality of Service on CDMA platforms]]
* [[Solar cells]]
* [[OLED - Organic Light Emitting Diode]]

==== Innovation Explorer ====
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics Innovation Explorer]

==== IPMaps ====
* [http://www.dolcera.com/ipmapdemo/satellite_antenna/ipmap.html Satellite Antenna IPMap]
* [http://www.dolcera.com/ipmapdemo/rfid/ipmap.html RFID IPMap]
* [http://www.dolcera.com/ipmapdemo/multimodal_apps/ipmap.html Multimodal Applications IPMap]

===Subscription service===
[[4G Subscription]]

== Life sciences and Chemistry ==
==== Landscape reports ====
* [[Alopecia - Hair Loss]]
* [[Diabetes products and services]]
* [[Inflammation and cardiovascular drugs]]
* [[Non-wovens]]

==== Dashboard ====
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard] '''New!'''
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]

==== IPMap ====
* [http://dolcera.com/client/d8r3/hairloss_map.htm Alopecia/Hair loss IPMap]

== Finance ==
* [[Innovative personal finance products]]

== Dolcera Offerings summary ==
* [[Dolcera Offerings|Dolcera offerings summary]]

== Dolcera Training ==
* [[Training Manual]]

== Chinese Page ==
* [[Home Page]]
* [[Service Page]]
* [[About]]

Solar cells

2007-07-01T17:18:03Z

67.180.82.65:

===Summary===

The project is about manufacturing procedures for solar cells. Based on the details given by the client and based on our study, we have conducted patent search and prepared the taxonomy

===Taxonomy===

The patent documents will be clustered based on following taxonomy. More nodes could be added during patent analysis.

[[Image:Estimation_of_solar_cell.jpg|thumb|center|800 px|]]

=== Patent search strategy===

'''Database''': Micropat (full-text)

'''Years:''' 1836 to date

'''Limitations:''' '''''Assignee/Applicant''''':- Sunpower OR Sanyo OR Sharp OR Q-Cells OR Suntech OR Motech OR BP Solar OR Kyocera OR Schott Solar OR RWE Schott OR ASE America OR Mobil Solar OR Solarworld OR Shell Solar OR Ersole OR Advent OR Isophoton OR Photowatt OR Mitsubishi Electric OR Honda

{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#808080"|Query <nowiki> </nowiki>
|align = "center" bgcolor = "#808080"|Search queries
|align = "center" bgcolor = "#808080"|Hits
|-
|1
| (((solar adj1 cell) or photovoltaic) and black and appearance)
|align = "center"|10
|-
|2
|(((solar adj1 cell) or photovoltaic) and ((Back adj1 junction) or (Back adj1 contact)))
|align = "center"|75
|-
|3
|(((solar adj1 cell) or photovoltaic) and ((Doped or APCVD) and oxid<nowiki>*</nowiki>))
|align = "center"|328
|-
|4
|(((solar adj1 cell) or photovoltaic) and ((Plated or Interdigitated) or metallization or seed layer))
|align = "center"|189
|-
|5
|(((solar adj1 cell) or photovoltaic) and ((Tunnel adj1 junction) or PolySilicon or (Amorphous adj1 silicon) or (Silicon adj1 Nitride) or (Oxy adj1 nitride) or TiO2 or (titanium adj1 oxide)))
|align = "center"|970
|-
|6
|(((solar adj1 cell) or photovoltaic) and (((inkjet or (screen adj1 print)) and pattern<nowiki>*</nowiki>) or resist))
|align = "center"|228
|-
|7
|(((solar adj1 cell) or photovoltaic) and ((Silicon adj1 Heterojunction<nowiki>*</nowiki>) or heterojunction<nowiki>*</nowiki> or (hetero adj1 junction<nowiki>*</nowiki>)))
|align = "center"|102
|-
|8
|(((solar adj1 cell) or photovoltaic) and ((Random or Upright or Tilted) and Textur<nowiki>*</nowiki>))
|align = "center"|26
|-
|9
|(((solar adj1 cell) or photovoltaic) and ((Light adj1 Trapping) or (Internal and (reflection or refraction or optics))))
|align = "center"|91
|-
|10
|(((solar adj1 cell) or photovoltaic) and ((Single adj1 sided adj1 etching) or Photoluminescence or Electroluminescence))
|align = "center"|15
|-
|11
|(((solar adj1 cell) or photovoltaic) and (Characterization or (Rapid adj1 Thermal adj1 Processing) or (auto adj1 lines) or ((surface or hydrogen) and passivation)))
|align = "center"|120
|-
|12
|(((solar adj1 cell) or photovoltaic) and (LED or (light adj1 emiting adj1 diode) or LCD or (liquid adj1 crystal adj1 diode) or TFT or (thin adj1 film adj1 transistor)))
|align = "center"|199
|-
|13
|(((solar adj1 cell) or photovoltaic) and (((Poly adj1 Silicon or polysilicon or silicon or tunnel adj1 oxide) and deposition) or LPCVD or (Low adj1 Pressure adj1 Chemical adj1 Vapour adj1 Deposition) or PECVD or (Plasma adj1 Enhanced adj1 Chemical adj1 Vapor adj1 Deposition) or (hot adj1 wire) or APCVD or (Atmospheric adj1 pressure adj1 chemical adj1 vapor adj1 deposition) or disaline or reliability))
|align = "center"|730
|-
|14
|Final query = 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13
|align = "center"|1007
|-
|}

Total number to patents = 1007 (After removing patent families)

----

===Scientific Literature Search===
'''Database''' 
'''Scitation''' is the re-launch of the Online Journal Publishing Service (OJPS), a leader in online sci-tech publishing and journal hosting since 1996 - American Institute of Physics 

'''Search Date''' 
01-Jan-2007 till 15 May 2007

'''Search string''' 

(((solar cell <IN> (abstract,title,keywords)) <accrue>(photovoltaic <IN> (abstract,title,keywords)))) <AND> usdate >=1-jan-2000 <AND> usdate <=15-may-2007 - '''[http://scitation.aip.org/vsearch/servlet/VerityServlet?KEY=FREESR&possible1=&possible1zone=article&bool1=and&possible2=solar+cell&possible2zone=multi&bool4=accrue&possible4=photovoltaic&possible4zone=multi&sort=chron&maxdisp=25&threshold=0&frommonth=Jan&fromday=1&fromyear=2000&tomonth=May&today=15&toyear=2007&fromvolume=&fromissue=&tovolume=&toissue=&%5Bsearch%5D.x=45&%5Bsearch%5D.y=18&smode=strresults&ver=&sti=&page=1&origquery=&vdk_query=&chapter=0&docdisp=0 2040 Hits]'''

Main Page

2007-07-01T17:17:52Z

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4G wireless technology developments

2007-07-01T16:58:51Z

67.180.82.65: /* The Dolcera 4G Wireless Standards Subscription Service */

{{TOCrightEx}}
== The Dolcera 4G Wireless Standards Subscription Service ==
Dolcera will track the following information for all 4G wireless standards continuously:
* Standards development (major milestones, announcements, specifications releases)
* Patent filings
* Products
* Spectrum availability, allocation and auctions around the world

To subscribe, please email [mailto:info@dolcera.com info@dolcera.com].

==Definition of 4G==

The 4G will be a fully IP-based integrated system of systems and network of networks achieved after the convergence of wired and wireless networks as well as computer, consumer electronics, communication technology, and several other convergences that will be capable of providing 100 Mbit/s and 1 Gbit/s, respectively, in outdoor and indoor environments with end-to-end QoS and high security, offering any kind of services anytime, anywhere, at affordable cost and one billing.

According to the 4G working groups, the infrastructure and the terminals will have almost all the standards from 2G to 3G implemented. The infrastructure will however only be packet based, all-IP. The system will also serve as an open platform where the new innovations can go with it.

'''Standards supported by 4G:'''

* WiMax
* WiBro
* 3GPP Long Term Evolution
* HSOPA
* 3GPP2 Ultra Mobile Broadband

'''Services where 4G is used:'''

*Wireless broadband access
*Multimedia Messaging Service
*Video chat
*Mobile TV
*High definition TV content,
*DVB
*Minimal service like voice and data

'''Objectives of the 4G wireless communication standard:'''

* A spectrally efficient system (in bits/s/Hz and bit/s/Hz/site)
* High network capacity
* A nominal data rate of 100 Mbit/s at high speeds and 1 Gbit/s at stationary conditions as defined by the ITU-R
* A data rate of at least 100 Mbit/s between any two points in the world
* Smooth handoff across heterogeneous network
* Seamless connectivity and global roaming across multiple networks
* High quality of service for next generation multimedia support (real time audio, high speed data, HDTV video content, mobile TV, etc)
* Interoperability with the existing wireless standards
* An all IP, packet switched network

'''Access schemes:'''

* OFDMA
* Single Carrier FDMA
* MC-CDMA
===Technology overview===
Mindmap below shows the overview of emerging technologies in 4G

[[Image:4Gmindmap1.jpg|800px|center|thumb|Overview]]
===Mobile technology roadmap===
[[Image:roadmap.jpg|700px|center|thumb|Roadmap]]

==WiMax==
WiMAX is defined as "Worldwide Interoperability for Microwave Access" by the WiMAX Forum, formed in June 2001 to promote conformance and interoperability of the IEEE 802.16 standard, officially known as WirelessMAN. WiMAX aims to provide wireless data over long distances, in a variety of different ways, from point to point links to full mobile cellular type access. In practical terms this enables a user, for example, to browse the Internet on a laptop computer without physically connecting the laptop to a wall jack.

=== Spectrum coverage by geography ===
Image below shows the spectrum for WiMax users World wide.
[[Image:Spectrum1.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]
Image below shows the sample of country wise spectrum allocation data. This information is form '''[http://maravedis-bwa.com Maravadis: Telecom market research & and analysis] '''.
[[Image:Spectrum-geography.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]

[[More information on Maravadis]]

===Standards===
# [http://standards.ieee.org/getieee802/download/802.16.2-2004.pdf IEEE 802.16-2004 (802.16d)] addresses only fixed systems
# [http://standards.ieee.org/getieee802/download/802.16e-2005.pdf IEEE Std 802.16e-2005], also called mobile WiMax
#* 802.16e also bring Multiple Antenna Support through Multiple-input multiple-output communications. This brings potential benefits in terms of coverage, self installation, power consumption, frequency re-use and bandwidth efficiency. 802.16e also adds a capability for full mobility support.
# WiMAX II, 802.16m will be proposed for IMT-Advanced 4G (future development)
#* 3GPP LTE and WiMAX-m are concentrating much effort on MIMO-AAS, mobile multi-hop relay networking and related developments needed to deliver 10X and higher Co-Channel reuse multiples.

IEEE 802.16e-2005 improves upon IEEE 802.16-2004 by:

* Scaling of the Fast Fourier Transform (FFT) to the channel bandwidth in order to keep the carrier spacing constant across different channel bandwidths (1.25-20 MHz). Constant carrier spacing results in a higher spectrum efficiency in wide channels, and a cost reduction in narrow channels. Also known as Scalable OFDMA (SOFDMA).
* Improving NLOS coverage by utilizing advanced antenna diversity schemes, and hybrid-Automatic Retransmission Request (hARQ)
* Improving coverage by introducing Adaptive Antenna Systems (AAS) and Multiple Input Multiple Output (MIMO) technology
* Increasing system gain by use of denser sub-channelization, thereby improving indoor penetration
* Introducing high-performance coding techniques such as Turbo Coding and Low-Density Parity Check (LDPC), enhancing security and NLOS performance
* Introducing downlink sub-channelization, allowing administrators to trade coverage for capacity or vice versa
* Enhanced Fast Fourier Transform algorithm can tolerate larger delay spreads, increasing resistance to multipath interference
* Adding an extra QoS class (enhanced real-time Polling Service) more appropriate for VoIP applications.
* Adding support for mobility (soft and hard handover between base stations). This is seen as one of the most important aspects of 802.16e-2005, and is the very basis of 'Mobile WiMAX'.

[http://en.wikipedia.org/wiki/WiMAX Source]

'''Market research data:'''
* Worldwide WiMAX equipment revenues are forecast to reach $3.26 billion in 2009
* Worldwide outdoor wireless mesh access node sales are forecast to reach $1.17 billion in 2009
* Samsung leads overall WiMAX equipment revenue share in 3Q06, ahead of Alvarion, Airspan, and Aperto Networks
* Strix Systems leads overall outdoor mesh revenue market share in 3Q06, just ahead of Tropos Networks and BelAir Networks
* 35% of WiMAX equipment sales come from Asia Pacific, 30% from EMEA, 20% from North America, and 14% from CALA
* 49% of wireless mesh access node sales come from North America, 25% from EMEA, 18% from Asia Pacific, and 8% from CALA

[http://www.bbwexchange.com/pubs/2006/12/05/page1421-371393.asp Source]

===Companies===
*[[List of companies]]
===Products===
Table below shows some of the products using WiMax technology.
{|border="2" cellspacing="0" cellpadding="4" width="70%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "2"|[http://www.alvarion-usa.com/products/breezemax/ Alvarion]
|align = "center" rowspan = "2"|BreezeMAX WiMax - base station
|BreezeMAX Macro Base
| 
[[Image:Document2_1.jpg]]

|-
|BreezeMAX Micro Base Station
| 
[[Image:Document2_2.jpg]]

|-
|[http://www.wimax-industry.com/sp/wcm/axc/emap.htm Axxcelera]
|Base station
|EXCELMAX BASE STATION
| 
[[Image:Document2_3.jpg]]

|-
|[http://www.proxim.com/terabeam/products/teramax/index.html Proxim]
|TeraMax P2MP systems comprise base stations and clients, and include mounting hardware, Power over Ethernet (POE), and system management software.
|TeraMax P2MP
| 
[[Image:Document2_4.jpg]]

|-
|align = "center" rowspan = "3"|[http://www.airspan.com/products_group.aspx?ProductGroupID=1 Airspan]
|align = "center" rowspan = "3"|AS.MAX - base stations
|Hiper MAX
|Not available
|-
|Macro MAX
|Not available
|-
|Micro MAX
|Not available
|-

|}

===IP information===
Search query and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Claims, Title or Abstract Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiMax OR (Wi ADJ1 Max))
|align = "center"|328
|-
|}

==WiBro==
WiBro is an acronym for wireless broadband and is actually a term that is in the process of being phased out in favor of the more collaborative and generic Mobile WiMAX.
* Korean standards makers early on adopted the term to describe their initiatives towards adopting a version of the 802.16e standard.
* Basically, the Korean standard chose to accept a specific mobile WiMAX iteration of 802.16e, rather than any future version that included backwards compatibility to fixed wireless 802.16 systems.
* Korea enjoys probably the most extensive 3G deployments in the world already, and its fixed broadband access per capita is the highest in the world. What it needed was an improved mobile broadband. In fact, the Korean government issued the first three deployment licenses for WiBro/Mobile WiMAX in January of 2005.
* WiBro/Mobile WiMAX in many respects is driving the mobile side of WiMAX at least from the point of view of vendors eager to provide products to these early deployments. This decision however, results in a backwards compatibility problem with Fixed WiMAX standards or 802.16-2004.
* The smooth interoperability of previous WiBro gear from Samsung with other vendors such as Motorola should be cemented this year as these two companies along with Intel have been chosen as the primary vendor for Sprint Nextel’s WiMAX deployment. The two companies clearly have a powerful incentive for their products to work seamlessly.

===Standards===
* WiBro is an integral part of IEEE 802.16e

'''WiBro vs. 802.16e/Mobile WiMax'''

[[Image:wibro1.jpg|center|600px|thumb|WiBro vs. 802.16e/Mobile WiMax]]

[http://www.postech.ac.kr/department/cse/linus/home_kor/seminar/sin-posdata.pdf Source]
===Companies===
* [[List of companies supporting WiBro technology]]
Industry news:
* South Korean telco SK Telecom and Wavesat, a Canadian developer of a WiMAX chipset, software and development platform have signed an agreement to cooperate in the development of WiBro/OFDMA technology for next generation mobile devices.
* Wavesat will work with SK Telecom (SKT) to develop WiBro/OFDMA systems-on-chips (SoCs), system tools and a development kit based on the WiBro 802.16e S-OFDMA profile. The U-mobile product portfolio from Wavesat will allow WiMax wireless system providers (OEMs/ODMs) worldwide to develop and deploy fully mobile WiMAX and WiBro solutions.[http://www.digitalmediaasia.com/default.asp?ArticleID=12523 Source]

===Products Overview===
{|border="2" cellspacing="0" width="100%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "4"|Samsung
|align = "center" rowspan = "3"|Mobile Station
|align = "center"|[http://www.3g.co.uk/PR/Jan2006/2427.htm M8000 WiBro handset ]
|align = "center"| 
[[Image:Document5_01.jpg]]

|-
|align = "center"|[http://uk.gizmodo.com/2005/12/28/samsungs_super_wibro_phone.html Super WiBro Phone ]
|align = "center"| 
[[Image:Document5_02.jpg]]

|-
|align = "center"|[http://aving.net/usa/news/default.asp?mode=read&c_num=28705&c_code=02&sp_code=0&btb_num=2747 WiBro-enabled notebook pc]
|align = "center"| 
[[Image:Document5_03.jpg]]

|-
|align = "center"|Access control Router
|align = "center"|[http://www.etopiamedia.net/ybw/pages/ybw2-5551212.html Access control Router]
|align = "center"| 
[[Image:Document5_04.jpg]]

|-
|align = "center"|Kisan Telecom
|align = "center"|Base station
|align = "center"|[http://www.kisantel.co.kr/eng/products/sub02.asp WiBro Repeater]
|align = "center"| 
[[Image:Document5_05.jpg]]

|-
|align = "center"|i-River
|align = "center"|Mobile Station
|align = "center"|[http://www.mobilecomms-technology.com/projects/kt-corp/kt-corp2.html G10 games console]
|align = "center"| 
[[Image:Document5_06.jpg]]

|-
|align = "center"|Korea Telekom
|align = "center"|USB modem
|align = "center"|[http://www.kt.co.kr/eng/New/pr_news_kt_view.jsp iPlug Premium ]
|align = "center"| 
[[Image:Document5_07.jpg]]

|-
|}

===IP information===
Search terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007 Any Classification: G06F OR G06Q OR G08G OR H04B OR H04K OR H04L OR H04N OR H04Q
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiBro OR (Wi ADJ1 Bro))
|align = "center"|180
|-
|}

==3GPP Long Term Evolution==
3GPP LTE (Long Term Evolution) is the name given to a project within the Third Generation Partnership Project to improve the UMTS mobile phone standard to cope with future requirements.

* LTE focus is on Enhancement of the Universal Terrestrial Radio Access (UTRA) and Optimisation of the UTRAN architecture.
* Downlink based on OFDMA (OFDMA offers improved spectral efficiency, capacity, etc)
* Uplink based on SC-FDMA (single carrier) (SC-FDMA is technically similar to OFDMA but is better suited for uplink from hand-held devices- more considerations on battery power)

'''Goals of 3GPP Long Term Evolution'''
* Download rates of 100 Mbit/s, and upload rates of 50 Mbit/s for every 20 MHz of spectrum
* At least 200 active users in every 5 MHz cell. (ie 200 active phone calls)
* Sub-5ms latency for small IP packets
* Increased spectrum flexibility, with spectrum slices as small as 1.25 MHz (and as large as 20 MHz) supported (W-CDMA requires 5 MHz slices, leading to some problems with roll-outs of the technology in countries where 5 MHz is a commonly allocated amount of spectrum, and is frequently already in use with legacy standards such as 2G GSM and cdmaOne.) Limiting sizes to 5 MHz also limited the amount of bandwidth per handset
* Optimal cell size of 5 km, 30 km sizes with reasonable performance, and up to 100 km cell sizes supported with acceptable performance
* Co-existence with legacy standards (users can transparently start a call or transfer of data in an area using an LTE standard, and, should coverage be unavailable, continue the operation without any action on their part using GSM/GPRS or W-CDMA-based UMTS)

===Companies===
* [[List of companies supporting 3GPP technology and HSOPA]]
===Products===
=== IP information===
Search (Companied search for 3GPP LTE and HSOPA (super 3G) ) terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((3GPP ADj1 (LTE OR (Long ADJ1 Term ADJ1 Evolution))) OR (super ADJ1 3G))
|align = "center"|47
|-
|}

==HSOPA==
High Speed OFDM Packet Access (HSOPA) is a proposed part of 3GPP's Long Term Evolution (LTE) upgrade path for UMTS systems. HSOPA is also often referred to as Super 3G. If adopted, HSOPA succeeds HSDPA and HSUPA technologies specified in 3GPP releases 5 and 6. Unlike HSDPA or HSUPA, HSOPA is an entirely new air interface system, unrelated to and incompatible with W-CDMA.
Features of HSOPA
HSOPA has the following features:
* Flexible bandwidth usage with 1.25 MHz to 20 MHz bandwidths. By comparison, W-CDMA uses fixed size 5 MHz chunks of spectrum.
* Increased spectral efficiency at 2-4 times more than in 3GPP release 6, peak transfer rates of 100 Mbit/s for downlink and 50 Mbit/s for uplink.
* Latency times of around 20 ms for round trip time from user terminal to RAN, approximately the same as a combined HSDPA/HSUPA system, but much better than "classic" W-CDMA.

'''Design'''

HSOPA uses Orthogonal Frequency Division Multiplexing (OFDM) and multiple-input multiple-output (MIMO) antenna technology to support up to 10 times as many users as W-CDMA based systems, with lower processing power required on each handset.[1]. Still in development, experimental performance is 37 Mbit/s in the downlink over a 5 MHz channel, close to the theoretical maximum of 40 Mbit/s.

'''Difference: HOSPA - WiMax'''

While both WiMAX and the HSOPA use OFDM/OFDMA, HSOPA enhanced UMTS will most likely be optimized for wide area mobile voice communications. HSOPA will use OFDMA for the down-link and Single Carrier FDMA (SC-FDMA) for the up-link. WiMAX/802.16e-2005 uses OFDMA for both the up and down links.
SC-OFDM can maintain connections at longer distance but has lower bandwidth than OFDMA. However, WiMAX advocates perceive evolution of WBB as also shifting the 'architectural evolution' of wireless networks to more granular, symmetrical, higher bandwidth micro-cell and mobile multi-hop relay network topologies.
Multi-mode WiMAX plus CDMA and other technologies can work together to fulfill both long range, low bandwidth and shorter range, high bandwidth requirements on the basis of providing the user with 'always best connected' experience.

==3GPP2 Ultra Mobile Broadband==
UMB (Ultra Mobile Broadband) is the brand name for the project within 3GPP2 to improve the CDMA2000 mobile phone standard for next generation applications and requirements.The system employs OFDMA technology along with advanced antenna techniques to provide peak rates of up to 280 Mbit/s.

Goals for UMB:
* Improving system capacity
* Greatly increasing user data rates throughout the cell
* Lowering costs
* Enhancing existing services
* Making possible new applications, and
* Making use of new spectrum opportunities.

The technology will provide users with concurrent IP-based services in a full mobility environment. The UMB standardization is expected to be completed in mid 2007, with commercialization taking place around mid-2009.

'''Technology overview'''
* OFDMA-based air interface
* Frequency Division Duplex
* Scalable bandwidth between 1.25-20 MHz (OFDMA systems are especially well suited for wider bandwidths larger than 5 MHz)
* Supports mixed cell sizes, e.g., macro-cellular, micro-cellular & pico-cellular.
* IP network architecture
* Supports flat, centralized and mixed topologies
* Data speeds over 275 Mbit/s downstream and over 75 Mbit/s upstream

[http://en.wikipedia.org/wiki/Ultra_Mobile_Broadband Source]

[http://www.3gpp2.org/Public_html/Misc/AboutHome.cfm More infromation]

'''Key features'''
* Multiple radio and advanced antenna techniques
*# Sophisticated control and signaling mechanisms (minimized) combine the best aspects of CDMA, TDM, OFDM, and OFDMA into a single air interface
*# Multiple Input Multiple Output (MIMO) and Space Division Multiple Access (SDMA)
*# Improved interference management techniques
* Ultra-high mobile broadband peak data rates
*# Up to 280Mbps peak data rate on forward link
*# Up to 68Mbps peak data rate on reverse link
* Ultra-low network latency
*# An average of 16.8 msec (32-byte, RTT) end-to-end network latency
* Enhanced VoIP capacity and user experience
*# Up to 500 simultaneous VoIP users (10 MHz FDD allocations)
* Scalable IP-based flat or hierarchical architecture
*# Greater service deployment flexibility, improved performance, and lower cost of ownership
* Flexible spectrum allocations
*# Scalable, non-contiguous and dynamic channel (bandwidth) allocations
*# Support for bandwidth allocations of 1.25 MHz, 5 MHz, 10 MHz and 20 MHz
* Less power consumption
*# Improved battery life

[http://www.cdg.org/technology/3g_umb.asp Source]
===Companies===
These are some of the companies working in this particular area.
* Nokia
* LG
* RES in Motion
* Qualcomm
* Motorola
* Ericsson
* Samsung
* Interdigital
* Infineon Technologie

QUALCOMM has announced next generation chips. [http://ultramobileblog.com/category/ultra-mobile-broadband/ Source]

===IP information===
Search terms and results
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Claims, Title or Abstract
|align = "center"|76
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Title or Abstract
|align = "center"|22
|-
|}

4G wireless technology developments

2007-07-01T16:58:18Z

67.180.82.65: /* The Dolcera 4G Wireless Standards Subscription Service */

{{TOCrightEx}}
== The Dolcera 4G Wireless Standards Subscription Service ==
Dolcera will track the following information for all 4G wireless standards continuously:
* Standards development (major milestones, announcements, specifications releases)
* Patent filings
* Spectrum availability, allocation and auctions around the world

To subscribe, please email [mailto:info@dolcera.com info@dolcera.com].

==Definition of 4G==

The 4G will be a fully IP-based integrated system of systems and network of networks achieved after the convergence of wired and wireless networks as well as computer, consumer electronics, communication technology, and several other convergences that will be capable of providing 100 Mbit/s and 1 Gbit/s, respectively, in outdoor and indoor environments with end-to-end QoS and high security, offering any kind of services anytime, anywhere, at affordable cost and one billing.

According to the 4G working groups, the infrastructure and the terminals will have almost all the standards from 2G to 3G implemented. The infrastructure will however only be packet based, all-IP. The system will also serve as an open platform where the new innovations can go with it.

'''Standards supported by 4G:'''

* WiMax
* WiBro
* 3GPP Long Term Evolution
* HSOPA
* 3GPP2 Ultra Mobile Broadband

'''Services where 4G is used:'''

*Wireless broadband access
*Multimedia Messaging Service
*Video chat
*Mobile TV
*High definition TV content,
*DVB
*Minimal service like voice and data

'''Objectives of the 4G wireless communication standard:'''

* A spectrally efficient system (in bits/s/Hz and bit/s/Hz/site)
* High network capacity
* A nominal data rate of 100 Mbit/s at high speeds and 1 Gbit/s at stationary conditions as defined by the ITU-R
* A data rate of at least 100 Mbit/s between any two points in the world
* Smooth handoff across heterogeneous network
* Seamless connectivity and global roaming across multiple networks
* High quality of service for next generation multimedia support (real time audio, high speed data, HDTV video content, mobile TV, etc)
* Interoperability with the existing wireless standards
* An all IP, packet switched network

'''Access schemes:'''

* OFDMA
* Single Carrier FDMA
* MC-CDMA
===Technology overview===
Mindmap below shows the overview of emerging technologies in 4G

[[Image:4Gmindmap1.jpg|800px|center|thumb|Overview]]
===Mobile technology roadmap===
[[Image:roadmap.jpg|700px|center|thumb|Roadmap]]

==WiMax==
WiMAX is defined as "Worldwide Interoperability for Microwave Access" by the WiMAX Forum, formed in June 2001 to promote conformance and interoperability of the IEEE 802.16 standard, officially known as WirelessMAN. WiMAX aims to provide wireless data over long distances, in a variety of different ways, from point to point links to full mobile cellular type access. In practical terms this enables a user, for example, to browse the Internet on a laptop computer without physically connecting the laptop to a wall jack.

=== Spectrum coverage by geography ===
Image below shows the spectrum for WiMax users World wide.
[[Image:Spectrum1.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]
Image below shows the sample of country wise spectrum allocation data. This information is form '''[http://maravedis-bwa.com Maravadis: Telecom market research & and analysis] '''.
[[Image:Spectrum-geography.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]

[[More information on Maravadis]]

===Standards===
# [http://standards.ieee.org/getieee802/download/802.16.2-2004.pdf IEEE 802.16-2004 (802.16d)] addresses only fixed systems
# [http://standards.ieee.org/getieee802/download/802.16e-2005.pdf IEEE Std 802.16e-2005], also called mobile WiMax
#* 802.16e also bring Multiple Antenna Support through Multiple-input multiple-output communications. This brings potential benefits in terms of coverage, self installation, power consumption, frequency re-use and bandwidth efficiency. 802.16e also adds a capability for full mobility support.
# WiMAX II, 802.16m will be proposed for IMT-Advanced 4G (future development)
#* 3GPP LTE and WiMAX-m are concentrating much effort on MIMO-AAS, mobile multi-hop relay networking and related developments needed to deliver 10X and higher Co-Channel reuse multiples.

IEEE 802.16e-2005 improves upon IEEE 802.16-2004 by:

* Scaling of the Fast Fourier Transform (FFT) to the channel bandwidth in order to keep the carrier spacing constant across different channel bandwidths (1.25-20 MHz). Constant carrier spacing results in a higher spectrum efficiency in wide channels, and a cost reduction in narrow channels. Also known as Scalable OFDMA (SOFDMA).
* Improving NLOS coverage by utilizing advanced antenna diversity schemes, and hybrid-Automatic Retransmission Request (hARQ)
* Improving coverage by introducing Adaptive Antenna Systems (AAS) and Multiple Input Multiple Output (MIMO) technology
* Increasing system gain by use of denser sub-channelization, thereby improving indoor penetration
* Introducing high-performance coding techniques such as Turbo Coding and Low-Density Parity Check (LDPC), enhancing security and NLOS performance
* Introducing downlink sub-channelization, allowing administrators to trade coverage for capacity or vice versa
* Enhanced Fast Fourier Transform algorithm can tolerate larger delay spreads, increasing resistance to multipath interference
* Adding an extra QoS class (enhanced real-time Polling Service) more appropriate for VoIP applications.
* Adding support for mobility (soft and hard handover between base stations). This is seen as one of the most important aspects of 802.16e-2005, and is the very basis of 'Mobile WiMAX'.

[http://en.wikipedia.org/wiki/WiMAX Source]

'''Market research data:'''
* Worldwide WiMAX equipment revenues are forecast to reach $3.26 billion in 2009
* Worldwide outdoor wireless mesh access node sales are forecast to reach $1.17 billion in 2009
* Samsung leads overall WiMAX equipment revenue share in 3Q06, ahead of Alvarion, Airspan, and Aperto Networks
* Strix Systems leads overall outdoor mesh revenue market share in 3Q06, just ahead of Tropos Networks and BelAir Networks
* 35% of WiMAX equipment sales come from Asia Pacific, 30% from EMEA, 20% from North America, and 14% from CALA
* 49% of wireless mesh access node sales come from North America, 25% from EMEA, 18% from Asia Pacific, and 8% from CALA

[http://www.bbwexchange.com/pubs/2006/12/05/page1421-371393.asp Source]

===Companies===
*[[List of companies]]
===Products===
Table below shows some of the products using WiMax technology.
{|border="2" cellspacing="0" cellpadding="4" width="70%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "2"|[http://www.alvarion-usa.com/products/breezemax/ Alvarion]
|align = "center" rowspan = "2"|BreezeMAX WiMax - base station
|BreezeMAX Macro Base
| 
[[Image:Document2_1.jpg]]

|-
|BreezeMAX Micro Base Station
| 
[[Image:Document2_2.jpg]]

|-
|[http://www.wimax-industry.com/sp/wcm/axc/emap.htm Axxcelera]
|Base station
|EXCELMAX BASE STATION
| 
[[Image:Document2_3.jpg]]

|-
|[http://www.proxim.com/terabeam/products/teramax/index.html Proxim]
|TeraMax P2MP systems comprise base stations and clients, and include mounting hardware, Power over Ethernet (POE), and system management software.
|TeraMax P2MP
| 
[[Image:Document2_4.jpg]]

|-
|align = "center" rowspan = "3"|[http://www.airspan.com/products_group.aspx?ProductGroupID=1 Airspan]
|align = "center" rowspan = "3"|AS.MAX - base stations
|Hiper MAX
|Not available
|-
|Macro MAX
|Not available
|-
|Micro MAX
|Not available
|-

|}

===IP information===
Search query and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Claims, Title or Abstract Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiMax OR (Wi ADJ1 Max))
|align = "center"|328
|-
|}

==WiBro==
WiBro is an acronym for wireless broadband and is actually a term that is in the process of being phased out in favor of the more collaborative and generic Mobile WiMAX.
* Korean standards makers early on adopted the term to describe their initiatives towards adopting a version of the 802.16e standard.
* Basically, the Korean standard chose to accept a specific mobile WiMAX iteration of 802.16e, rather than any future version that included backwards compatibility to fixed wireless 802.16 systems.
* Korea enjoys probably the most extensive 3G deployments in the world already, and its fixed broadband access per capita is the highest in the world. What it needed was an improved mobile broadband. In fact, the Korean government issued the first three deployment licenses for WiBro/Mobile WiMAX in January of 2005.
* WiBro/Mobile WiMAX in many respects is driving the mobile side of WiMAX at least from the point of view of vendors eager to provide products to these early deployments. This decision however, results in a backwards compatibility problem with Fixed WiMAX standards or 802.16-2004.
* The smooth interoperability of previous WiBro gear from Samsung with other vendors such as Motorola should be cemented this year as these two companies along with Intel have been chosen as the primary vendor for Sprint Nextel’s WiMAX deployment. The two companies clearly have a powerful incentive for their products to work seamlessly.

===Standards===
* WiBro is an integral part of IEEE 802.16e

'''WiBro vs. 802.16e/Mobile WiMax'''

[[Image:wibro1.jpg|center|600px|thumb|WiBro vs. 802.16e/Mobile WiMax]]

[http://www.postech.ac.kr/department/cse/linus/home_kor/seminar/sin-posdata.pdf Source]
===Companies===
* [[List of companies supporting WiBro technology]]
Industry news:
* South Korean telco SK Telecom and Wavesat, a Canadian developer of a WiMAX chipset, software and development platform have signed an agreement to cooperate in the development of WiBro/OFDMA technology for next generation mobile devices.
* Wavesat will work with SK Telecom (SKT) to develop WiBro/OFDMA systems-on-chips (SoCs), system tools and a development kit based on the WiBro 802.16e S-OFDMA profile. The U-mobile product portfolio from Wavesat will allow WiMax wireless system providers (OEMs/ODMs) worldwide to develop and deploy fully mobile WiMAX and WiBro solutions.[http://www.digitalmediaasia.com/default.asp?ArticleID=12523 Source]

===Products Overview===
{|border="2" cellspacing="0" width="100%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "4"|Samsung
|align = "center" rowspan = "3"|Mobile Station
|align = "center"|[http://www.3g.co.uk/PR/Jan2006/2427.htm M8000 WiBro handset ]
|align = "center"| 
[[Image:Document5_01.jpg]]

|-
|align = "center"|[http://uk.gizmodo.com/2005/12/28/samsungs_super_wibro_phone.html Super WiBro Phone ]
|align = "center"| 
[[Image:Document5_02.jpg]]

|-
|align = "center"|[http://aving.net/usa/news/default.asp?mode=read&c_num=28705&c_code=02&sp_code=0&btb_num=2747 WiBro-enabled notebook pc]
|align = "center"| 
[[Image:Document5_03.jpg]]

|-
|align = "center"|Access control Router
|align = "center"|[http://www.etopiamedia.net/ybw/pages/ybw2-5551212.html Access control Router]
|align = "center"| 
[[Image:Document5_04.jpg]]

|-
|align = "center"|Kisan Telecom
|align = "center"|Base station
|align = "center"|[http://www.kisantel.co.kr/eng/products/sub02.asp WiBro Repeater]
|align = "center"| 
[[Image:Document5_05.jpg]]

|-
|align = "center"|i-River
|align = "center"|Mobile Station
|align = "center"|[http://www.mobilecomms-technology.com/projects/kt-corp/kt-corp2.html G10 games console]
|align = "center"| 
[[Image:Document5_06.jpg]]

|-
|align = "center"|Korea Telekom
|align = "center"|USB modem
|align = "center"|[http://www.kt.co.kr/eng/New/pr_news_kt_view.jsp iPlug Premium ]
|align = "center"| 
[[Image:Document5_07.jpg]]

|-
|}

===IP information===
Search terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007 Any Classification: G06F OR G06Q OR G08G OR H04B OR H04K OR H04L OR H04N OR H04Q
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiBro OR (Wi ADJ1 Bro))
|align = "center"|180
|-
|}

==3GPP Long Term Evolution==
3GPP LTE (Long Term Evolution) is the name given to a project within the Third Generation Partnership Project to improve the UMTS mobile phone standard to cope with future requirements.

* LTE focus is on Enhancement of the Universal Terrestrial Radio Access (UTRA) and Optimisation of the UTRAN architecture.
* Downlink based on OFDMA (OFDMA offers improved spectral efficiency, capacity, etc)
* Uplink based on SC-FDMA (single carrier) (SC-FDMA is technically similar to OFDMA but is better suited for uplink from hand-held devices- more considerations on battery power)

'''Goals of 3GPP Long Term Evolution'''
* Download rates of 100 Mbit/s, and upload rates of 50 Mbit/s for every 20 MHz of spectrum
* At least 200 active users in every 5 MHz cell. (ie 200 active phone calls)
* Sub-5ms latency for small IP packets
* Increased spectrum flexibility, with spectrum slices as small as 1.25 MHz (and as large as 20 MHz) supported (W-CDMA requires 5 MHz slices, leading to some problems with roll-outs of the technology in countries where 5 MHz is a commonly allocated amount of spectrum, and is frequently already in use with legacy standards such as 2G GSM and cdmaOne.) Limiting sizes to 5 MHz also limited the amount of bandwidth per handset
* Optimal cell size of 5 km, 30 km sizes with reasonable performance, and up to 100 km cell sizes supported with acceptable performance
* Co-existence with legacy standards (users can transparently start a call or transfer of data in an area using an LTE standard, and, should coverage be unavailable, continue the operation without any action on their part using GSM/GPRS or W-CDMA-based UMTS)

===Companies===
* [[List of companies supporting 3GPP technology and HSOPA]]
===Products===
=== IP information===
Search (Companied search for 3GPP LTE and HSOPA (super 3G) ) terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((3GPP ADj1 (LTE OR (Long ADJ1 Term ADJ1 Evolution))) OR (super ADJ1 3G))
|align = "center"|47
|-
|}

==HSOPA==
High Speed OFDM Packet Access (HSOPA) is a proposed part of 3GPP's Long Term Evolution (LTE) upgrade path for UMTS systems. HSOPA is also often referred to as Super 3G. If adopted, HSOPA succeeds HSDPA and HSUPA technologies specified in 3GPP releases 5 and 6. Unlike HSDPA or HSUPA, HSOPA is an entirely new air interface system, unrelated to and incompatible with W-CDMA.
Features of HSOPA
HSOPA has the following features:
* Flexible bandwidth usage with 1.25 MHz to 20 MHz bandwidths. By comparison, W-CDMA uses fixed size 5 MHz chunks of spectrum.
* Increased spectral efficiency at 2-4 times more than in 3GPP release 6, peak transfer rates of 100 Mbit/s for downlink and 50 Mbit/s for uplink.
* Latency times of around 20 ms for round trip time from user terminal to RAN, approximately the same as a combined HSDPA/HSUPA system, but much better than "classic" W-CDMA.

'''Design'''

HSOPA uses Orthogonal Frequency Division Multiplexing (OFDM) and multiple-input multiple-output (MIMO) antenna technology to support up to 10 times as many users as W-CDMA based systems, with lower processing power required on each handset.[1]. Still in development, experimental performance is 37 Mbit/s in the downlink over a 5 MHz channel, close to the theoretical maximum of 40 Mbit/s.

'''Difference: HOSPA - WiMax'''

While both WiMAX and the HSOPA use OFDM/OFDMA, HSOPA enhanced UMTS will most likely be optimized for wide area mobile voice communications. HSOPA will use OFDMA for the down-link and Single Carrier FDMA (SC-FDMA) for the up-link. WiMAX/802.16e-2005 uses OFDMA for both the up and down links.
SC-OFDM can maintain connections at longer distance but has lower bandwidth than OFDMA. However, WiMAX advocates perceive evolution of WBB as also shifting the 'architectural evolution' of wireless networks to more granular, symmetrical, higher bandwidth micro-cell and mobile multi-hop relay network topologies.
Multi-mode WiMAX plus CDMA and other technologies can work together to fulfill both long range, low bandwidth and shorter range, high bandwidth requirements on the basis of providing the user with 'always best connected' experience.

==3GPP2 Ultra Mobile Broadband==
UMB (Ultra Mobile Broadband) is the brand name for the project within 3GPP2 to improve the CDMA2000 mobile phone standard for next generation applications and requirements.The system employs OFDMA technology along with advanced antenna techniques to provide peak rates of up to 280 Mbit/s.

Goals for UMB:
* Improving system capacity
* Greatly increasing user data rates throughout the cell
* Lowering costs
* Enhancing existing services
* Making possible new applications, and
* Making use of new spectrum opportunities.

The technology will provide users with concurrent IP-based services in a full mobility environment. The UMB standardization is expected to be completed in mid 2007, with commercialization taking place around mid-2009.

'''Technology overview'''
* OFDMA-based air interface
* Frequency Division Duplex
* Scalable bandwidth between 1.25-20 MHz (OFDMA systems are especially well suited for wider bandwidths larger than 5 MHz)
* Supports mixed cell sizes, e.g., macro-cellular, micro-cellular & pico-cellular.
* IP network architecture
* Supports flat, centralized and mixed topologies
* Data speeds over 275 Mbit/s downstream and over 75 Mbit/s upstream

[http://en.wikipedia.org/wiki/Ultra_Mobile_Broadband Source]

[http://www.3gpp2.org/Public_html/Misc/AboutHome.cfm More infromation]

'''Key features'''
* Multiple radio and advanced antenna techniques
*# Sophisticated control and signaling mechanisms (minimized) combine the best aspects of CDMA, TDM, OFDM, and OFDMA into a single air interface
*# Multiple Input Multiple Output (MIMO) and Space Division Multiple Access (SDMA)
*# Improved interference management techniques
* Ultra-high mobile broadband peak data rates
*# Up to 280Mbps peak data rate on forward link
*# Up to 68Mbps peak data rate on reverse link
* Ultra-low network latency
*# An average of 16.8 msec (32-byte, RTT) end-to-end network latency
* Enhanced VoIP capacity and user experience
*# Up to 500 simultaneous VoIP users (10 MHz FDD allocations)
* Scalable IP-based flat or hierarchical architecture
*# Greater service deployment flexibility, improved performance, and lower cost of ownership
* Flexible spectrum allocations
*# Scalable, non-contiguous and dynamic channel (bandwidth) allocations
*# Support for bandwidth allocations of 1.25 MHz, 5 MHz, 10 MHz and 20 MHz
* Less power consumption
*# Improved battery life

[http://www.cdg.org/technology/3g_umb.asp Source]
===Companies===
These are some of the companies working in this particular area.
* Nokia
* LG
* RES in Motion
* Qualcomm
* Motorola
* Ericsson
* Samsung
* Interdigital
* Infineon Technologie

QUALCOMM has announced next generation chips. [http://ultramobileblog.com/category/ultra-mobile-broadband/ Source]

===IP information===
Search terms and results
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Claims, Title or Abstract
|align = "center"|76
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Title or Abstract
|align = "center"|22
|-
|}

4G wireless technology developments

2007-07-01T16:58:05Z

67.180.82.65:

{{TOCrightEx}}
== The Dolcera 4G Wireless Standards Subscription Service ==
Dolcera will track the following information for all 4G wireless standards continuously:
* Standards development (major milestones, announcements, specifications releases)
* Patent filings
* Spectrum availability, allocation and auctions around the world

To subscribe, please email [mailto:info@dolcera.com info@dolcera.com]

==Definition of 4G==

The 4G will be a fully IP-based integrated system of systems and network of networks achieved after the convergence of wired and wireless networks as well as computer, consumer electronics, communication technology, and several other convergences that will be capable of providing 100 Mbit/s and 1 Gbit/s, respectively, in outdoor and indoor environments with end-to-end QoS and high security, offering any kind of services anytime, anywhere, at affordable cost and one billing.

According to the 4G working groups, the infrastructure and the terminals will have almost all the standards from 2G to 3G implemented. The infrastructure will however only be packet based, all-IP. The system will also serve as an open platform where the new innovations can go with it.

'''Standards supported by 4G:'''

* WiMax
* WiBro
* 3GPP Long Term Evolution
* HSOPA
* 3GPP2 Ultra Mobile Broadband

'''Services where 4G is used:'''

*Wireless broadband access
*Multimedia Messaging Service
*Video chat
*Mobile TV
*High definition TV content,
*DVB
*Minimal service like voice and data

'''Objectives of the 4G wireless communication standard:'''

* A spectrally efficient system (in bits/s/Hz and bit/s/Hz/site)
* High network capacity
* A nominal data rate of 100 Mbit/s at high speeds and 1 Gbit/s at stationary conditions as defined by the ITU-R
* A data rate of at least 100 Mbit/s between any two points in the world
* Smooth handoff across heterogeneous network
* Seamless connectivity and global roaming across multiple networks
* High quality of service for next generation multimedia support (real time audio, high speed data, HDTV video content, mobile TV, etc)
* Interoperability with the existing wireless standards
* An all IP, packet switched network

'''Access schemes:'''

* OFDMA
* Single Carrier FDMA
* MC-CDMA
===Technology overview===
Mindmap below shows the overview of emerging technologies in 4G

[[Image:4Gmindmap1.jpg|800px|center|thumb|Overview]]
===Mobile technology roadmap===
[[Image:roadmap.jpg|700px|center|thumb|Roadmap]]

==WiMax==
WiMAX is defined as "Worldwide Interoperability for Microwave Access" by the WiMAX Forum, formed in June 2001 to promote conformance and interoperability of the IEEE 802.16 standard, officially known as WirelessMAN. WiMAX aims to provide wireless data over long distances, in a variety of different ways, from point to point links to full mobile cellular type access. In practical terms this enables a user, for example, to browse the Internet on a laptop computer without physically connecting the laptop to a wall jack.

=== Spectrum coverage by geography ===
Image below shows the spectrum for WiMax users World wide.
[[Image:Spectrum1.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]
Image below shows the sample of country wise spectrum allocation data. This information is form '''[http://maravedis-bwa.com Maravadis: Telecom market research & and analysis] '''.
[[Image:Spectrum-geography.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]

[[More information on Maravadis]]

===Standards===
# [http://standards.ieee.org/getieee802/download/802.16.2-2004.pdf IEEE 802.16-2004 (802.16d)] addresses only fixed systems
# [http://standards.ieee.org/getieee802/download/802.16e-2005.pdf IEEE Std 802.16e-2005], also called mobile WiMax
#* 802.16e also bring Multiple Antenna Support through Multiple-input multiple-output communications. This brings potential benefits in terms of coverage, self installation, power consumption, frequency re-use and bandwidth efficiency. 802.16e also adds a capability for full mobility support.
# WiMAX II, 802.16m will be proposed for IMT-Advanced 4G (future development)
#* 3GPP LTE and WiMAX-m are concentrating much effort on MIMO-AAS, mobile multi-hop relay networking and related developments needed to deliver 10X and higher Co-Channel reuse multiples.

IEEE 802.16e-2005 improves upon IEEE 802.16-2004 by:

* Scaling of the Fast Fourier Transform (FFT) to the channel bandwidth in order to keep the carrier spacing constant across different channel bandwidths (1.25-20 MHz). Constant carrier spacing results in a higher spectrum efficiency in wide channels, and a cost reduction in narrow channels. Also known as Scalable OFDMA (SOFDMA).
* Improving NLOS coverage by utilizing advanced antenna diversity schemes, and hybrid-Automatic Retransmission Request (hARQ)
* Improving coverage by introducing Adaptive Antenna Systems (AAS) and Multiple Input Multiple Output (MIMO) technology
* Increasing system gain by use of denser sub-channelization, thereby improving indoor penetration
* Introducing high-performance coding techniques such as Turbo Coding and Low-Density Parity Check (LDPC), enhancing security and NLOS performance
* Introducing downlink sub-channelization, allowing administrators to trade coverage for capacity or vice versa
* Enhanced Fast Fourier Transform algorithm can tolerate larger delay spreads, increasing resistance to multipath interference
* Adding an extra QoS class (enhanced real-time Polling Service) more appropriate for VoIP applications.
* Adding support for mobility (soft and hard handover between base stations). This is seen as one of the most important aspects of 802.16e-2005, and is the very basis of 'Mobile WiMAX'.

[http://en.wikipedia.org/wiki/WiMAX Source]

'''Market research data:'''
* Worldwide WiMAX equipment revenues are forecast to reach $3.26 billion in 2009
* Worldwide outdoor wireless mesh access node sales are forecast to reach $1.17 billion in 2009
* Samsung leads overall WiMAX equipment revenue share in 3Q06, ahead of Alvarion, Airspan, and Aperto Networks
* Strix Systems leads overall outdoor mesh revenue market share in 3Q06, just ahead of Tropos Networks and BelAir Networks
* 35% of WiMAX equipment sales come from Asia Pacific, 30% from EMEA, 20% from North America, and 14% from CALA
* 49% of wireless mesh access node sales come from North America, 25% from EMEA, 18% from Asia Pacific, and 8% from CALA

[http://www.bbwexchange.com/pubs/2006/12/05/page1421-371393.asp Source]

===Companies===
*[[List of companies]]
===Products===
Table below shows some of the products using WiMax technology.
{|border="2" cellspacing="0" cellpadding="4" width="70%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "2"|[http://www.alvarion-usa.com/products/breezemax/ Alvarion]
|align = "center" rowspan = "2"|BreezeMAX WiMax - base station
|BreezeMAX Macro Base
| 
[[Image:Document2_1.jpg]]

|-
|BreezeMAX Micro Base Station
| 
[[Image:Document2_2.jpg]]

|-
|[http://www.wimax-industry.com/sp/wcm/axc/emap.htm Axxcelera]
|Base station
|EXCELMAX BASE STATION
| 
[[Image:Document2_3.jpg]]

|-
|[http://www.proxim.com/terabeam/products/teramax/index.html Proxim]
|TeraMax P2MP systems comprise base stations and clients, and include mounting hardware, Power over Ethernet (POE), and system management software.
|TeraMax P2MP
| 
[[Image:Document2_4.jpg]]

|-
|align = "center" rowspan = "3"|[http://www.airspan.com/products_group.aspx?ProductGroupID=1 Airspan]
|align = "center" rowspan = "3"|AS.MAX - base stations
|Hiper MAX
|Not available
|-
|Macro MAX
|Not available
|-
|Micro MAX
|Not available
|-

|}

===IP information===
Search query and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Claims, Title or Abstract Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiMax OR (Wi ADJ1 Max))
|align = "center"|328
|-
|}

==WiBro==
WiBro is an acronym for wireless broadband and is actually a term that is in the process of being phased out in favor of the more collaborative and generic Mobile WiMAX.
* Korean standards makers early on adopted the term to describe their initiatives towards adopting a version of the 802.16e standard.
* Basically, the Korean standard chose to accept a specific mobile WiMAX iteration of 802.16e, rather than any future version that included backwards compatibility to fixed wireless 802.16 systems.
* Korea enjoys probably the most extensive 3G deployments in the world already, and its fixed broadband access per capita is the highest in the world. What it needed was an improved mobile broadband. In fact, the Korean government issued the first three deployment licenses for WiBro/Mobile WiMAX in January of 2005.
* WiBro/Mobile WiMAX in many respects is driving the mobile side of WiMAX at least from the point of view of vendors eager to provide products to these early deployments. This decision however, results in a backwards compatibility problem with Fixed WiMAX standards or 802.16-2004.
* The smooth interoperability of previous WiBro gear from Samsung with other vendors such as Motorola should be cemented this year as these two companies along with Intel have been chosen as the primary vendor for Sprint Nextel’s WiMAX deployment. The two companies clearly have a powerful incentive for their products to work seamlessly.

===Standards===
* WiBro is an integral part of IEEE 802.16e

'''WiBro vs. 802.16e/Mobile WiMax'''

[[Image:wibro1.jpg|center|600px|thumb|WiBro vs. 802.16e/Mobile WiMax]]

[http://www.postech.ac.kr/department/cse/linus/home_kor/seminar/sin-posdata.pdf Source]
===Companies===
* [[List of companies supporting WiBro technology]]
Industry news:
* South Korean telco SK Telecom and Wavesat, a Canadian developer of a WiMAX chipset, software and development platform have signed an agreement to cooperate in the development of WiBro/OFDMA technology for next generation mobile devices.
* Wavesat will work with SK Telecom (SKT) to develop WiBro/OFDMA systems-on-chips (SoCs), system tools and a development kit based on the WiBro 802.16e S-OFDMA profile. The U-mobile product portfolio from Wavesat will allow WiMax wireless system providers (OEMs/ODMs) worldwide to develop and deploy fully mobile WiMAX and WiBro solutions.[http://www.digitalmediaasia.com/default.asp?ArticleID=12523 Source]

===Products Overview===
{|border="2" cellspacing="0" width="100%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "4"|Samsung
|align = "center" rowspan = "3"|Mobile Station
|align = "center"|[http://www.3g.co.uk/PR/Jan2006/2427.htm M8000 WiBro handset ]
|align = "center"| 
[[Image:Document5_01.jpg]]

|-
|align = "center"|[http://uk.gizmodo.com/2005/12/28/samsungs_super_wibro_phone.html Super WiBro Phone ]
|align = "center"| 
[[Image:Document5_02.jpg]]

|-
|align = "center"|[http://aving.net/usa/news/default.asp?mode=read&c_num=28705&c_code=02&sp_code=0&btb_num=2747 WiBro-enabled notebook pc]
|align = "center"| 
[[Image:Document5_03.jpg]]

|-
|align = "center"|Access control Router
|align = "center"|[http://www.etopiamedia.net/ybw/pages/ybw2-5551212.html Access control Router]
|align = "center"| 
[[Image:Document5_04.jpg]]

|-
|align = "center"|Kisan Telecom
|align = "center"|Base station
|align = "center"|[http://www.kisantel.co.kr/eng/products/sub02.asp WiBro Repeater]
|align = "center"| 
[[Image:Document5_05.jpg]]

|-
|align = "center"|i-River
|align = "center"|Mobile Station
|align = "center"|[http://www.mobilecomms-technology.com/projects/kt-corp/kt-corp2.html G10 games console]
|align = "center"| 
[[Image:Document5_06.jpg]]

|-
|align = "center"|Korea Telekom
|align = "center"|USB modem
|align = "center"|[http://www.kt.co.kr/eng/New/pr_news_kt_view.jsp iPlug Premium ]
|align = "center"| 
[[Image:Document5_07.jpg]]

|-
|}

===IP information===
Search terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007 Any Classification: G06F OR G06Q OR G08G OR H04B OR H04K OR H04L OR H04N OR H04Q
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiBro OR (Wi ADJ1 Bro))
|align = "center"|180
|-
|}

==3GPP Long Term Evolution==
3GPP LTE (Long Term Evolution) is the name given to a project within the Third Generation Partnership Project to improve the UMTS mobile phone standard to cope with future requirements.

* LTE focus is on Enhancement of the Universal Terrestrial Radio Access (UTRA) and Optimisation of the UTRAN architecture.
* Downlink based on OFDMA (OFDMA offers improved spectral efficiency, capacity, etc)
* Uplink based on SC-FDMA (single carrier) (SC-FDMA is technically similar to OFDMA but is better suited for uplink from hand-held devices- more considerations on battery power)

'''Goals of 3GPP Long Term Evolution'''
* Download rates of 100 Mbit/s, and upload rates of 50 Mbit/s for every 20 MHz of spectrum
* At least 200 active users in every 5 MHz cell. (ie 200 active phone calls)
* Sub-5ms latency for small IP packets
* Increased spectrum flexibility, with spectrum slices as small as 1.25 MHz (and as large as 20 MHz) supported (W-CDMA requires 5 MHz slices, leading to some problems with roll-outs of the technology in countries where 5 MHz is a commonly allocated amount of spectrum, and is frequently already in use with legacy standards such as 2G GSM and cdmaOne.) Limiting sizes to 5 MHz also limited the amount of bandwidth per handset
* Optimal cell size of 5 km, 30 km sizes with reasonable performance, and up to 100 km cell sizes supported with acceptable performance
* Co-existence with legacy standards (users can transparently start a call or transfer of data in an area using an LTE standard, and, should coverage be unavailable, continue the operation without any action on their part using GSM/GPRS or W-CDMA-based UMTS)

===Companies===
* [[List of companies supporting 3GPP technology and HSOPA]]
===Products===
=== IP information===
Search (Companied search for 3GPP LTE and HSOPA (super 3G) ) terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((3GPP ADj1 (LTE OR (Long ADJ1 Term ADJ1 Evolution))) OR (super ADJ1 3G))
|align = "center"|47
|-
|}

==HSOPA==
High Speed OFDM Packet Access (HSOPA) is a proposed part of 3GPP's Long Term Evolution (LTE) upgrade path for UMTS systems. HSOPA is also often referred to as Super 3G. If adopted, HSOPA succeeds HSDPA and HSUPA technologies specified in 3GPP releases 5 and 6. Unlike HSDPA or HSUPA, HSOPA is an entirely new air interface system, unrelated to and incompatible with W-CDMA.
Features of HSOPA
HSOPA has the following features:
* Flexible bandwidth usage with 1.25 MHz to 20 MHz bandwidths. By comparison, W-CDMA uses fixed size 5 MHz chunks of spectrum.
* Increased spectral efficiency at 2-4 times more than in 3GPP release 6, peak transfer rates of 100 Mbit/s for downlink and 50 Mbit/s for uplink.
* Latency times of around 20 ms for round trip time from user terminal to RAN, approximately the same as a combined HSDPA/HSUPA system, but much better than "classic" W-CDMA.

'''Design'''

HSOPA uses Orthogonal Frequency Division Multiplexing (OFDM) and multiple-input multiple-output (MIMO) antenna technology to support up to 10 times as many users as W-CDMA based systems, with lower processing power required on each handset.[1]. Still in development, experimental performance is 37 Mbit/s in the downlink over a 5 MHz channel, close to the theoretical maximum of 40 Mbit/s.

'''Difference: HOSPA - WiMax'''

While both WiMAX and the HSOPA use OFDM/OFDMA, HSOPA enhanced UMTS will most likely be optimized for wide area mobile voice communications. HSOPA will use OFDMA for the down-link and Single Carrier FDMA (SC-FDMA) for the up-link. WiMAX/802.16e-2005 uses OFDMA for both the up and down links.
SC-OFDM can maintain connections at longer distance but has lower bandwidth than OFDMA. However, WiMAX advocates perceive evolution of WBB as also shifting the 'architectural evolution' of wireless networks to more granular, symmetrical, higher bandwidth micro-cell and mobile multi-hop relay network topologies.
Multi-mode WiMAX plus CDMA and other technologies can work together to fulfill both long range, low bandwidth and shorter range, high bandwidth requirements on the basis of providing the user with 'always best connected' experience.

==3GPP2 Ultra Mobile Broadband==
UMB (Ultra Mobile Broadband) is the brand name for the project within 3GPP2 to improve the CDMA2000 mobile phone standard for next generation applications and requirements.The system employs OFDMA technology along with advanced antenna techniques to provide peak rates of up to 280 Mbit/s.

Goals for UMB:
* Improving system capacity
* Greatly increasing user data rates throughout the cell
* Lowering costs
* Enhancing existing services
* Making possible new applications, and
* Making use of new spectrum opportunities.

The technology will provide users with concurrent IP-based services in a full mobility environment. The UMB standardization is expected to be completed in mid 2007, with commercialization taking place around mid-2009.

'''Technology overview'''
* OFDMA-based air interface
* Frequency Division Duplex
* Scalable bandwidth between 1.25-20 MHz (OFDMA systems are especially well suited for wider bandwidths larger than 5 MHz)
* Supports mixed cell sizes, e.g., macro-cellular, micro-cellular & pico-cellular.
* IP network architecture
* Supports flat, centralized and mixed topologies
* Data speeds over 275 Mbit/s downstream and over 75 Mbit/s upstream

[http://en.wikipedia.org/wiki/Ultra_Mobile_Broadband Source]

[http://www.3gpp2.org/Public_html/Misc/AboutHome.cfm More infromation]

'''Key features'''
* Multiple radio and advanced antenna techniques
*# Sophisticated control and signaling mechanisms (minimized) combine the best aspects of CDMA, TDM, OFDM, and OFDMA into a single air interface
*# Multiple Input Multiple Output (MIMO) and Space Division Multiple Access (SDMA)
*# Improved interference management techniques
* Ultra-high mobile broadband peak data rates
*# Up to 280Mbps peak data rate on forward link
*# Up to 68Mbps peak data rate on reverse link
* Ultra-low network latency
*# An average of 16.8 msec (32-byte, RTT) end-to-end network latency
* Enhanced VoIP capacity and user experience
*# Up to 500 simultaneous VoIP users (10 MHz FDD allocations)
* Scalable IP-based flat or hierarchical architecture
*# Greater service deployment flexibility, improved performance, and lower cost of ownership
* Flexible spectrum allocations
*# Scalable, non-contiguous and dynamic channel (bandwidth) allocations
*# Support for bandwidth allocations of 1.25 MHz, 5 MHz, 10 MHz and 20 MHz
* Less power consumption
*# Improved battery life

[http://www.cdg.org/technology/3g_umb.asp Source]
===Companies===
These are some of the companies working in this particular area.
* Nokia
* LG
* RES in Motion
* Qualcomm
* Motorola
* Ericsson
* Samsung
* Interdigital
* Infineon Technologie

QUALCOMM has announced next generation chips. [http://ultramobileblog.com/category/ultra-mobile-broadband/ Source]

===IP information===
Search terms and results
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Claims, Title or Abstract
|align = "center"|76
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Title or Abstract
|align = "center"|22
|-
|}

4G wireless technology developments

2007-06-26T07:02:59Z

67.180.82.65:

{{TOCrightEx}}
==Definition of 4G==

The 4G will be a fully IP-based integrated system of systems and network of networks achieved after the convergence of wired and wireless networks as well as computer, consumer electronics, communication technology, and several other convergences that will be capable of providing 100 Mbit/s and 1 Gbit/s, respectively, in outdoor and indoor environments with end-to-end QoS and high security, offering any kind of services anytime, anywhere, at affordable cost and one billing.

According to the 4G working groups, the infrastructure and the terminals will have almost all the standards from 2G to 3G implemented. The infrastructure will however only be packet based, all-IP. The system will also serve as an open platform where the new innovations can go with it.

'''Standards supported by 4G:'''

* WiMax
* WiBro
* 3GPP Long Term Evolution
* HSOPA
* 3GPP2 Ultra Mobile Broadband

'''Services where 4G is used:'''

*Wireless broadband access
*Multimedia Messaging Service
*Video chat
*Mobile TV
*High definition TV content,
*DVB
*Minimal service like voice and data

'''Objectives of the 4G wireless communication standard:'''

* A spectrally efficient system (in bits/s/Hz and bit/s/Hz/site)
* High network capacity
* A nominal data rate of 100 Mbit/s at high speeds and 1 Gbit/s at stationary conditions as defined by the ITU-R
* A data rate of at least 100 Mbit/s between any two points in the world
* Smooth handoff across heterogeneous network
* Seamless connectivity and global roaming across multiple networks
* High quality of service for next generation multimedia support (real time audio, high speed data, HDTV video content, mobile TV, etc)
* Interoperability with the existing wireless standards
* An all IP, packet switched network

'''Access schemes:'''

* OFDMA
* Single Carrier FDMA
* MC-CDMA
===Technology overview===
Mindmap below shows the overview of emerging technologies in 4G

[[Image:4Gmindmap1.jpg|800px|center|thumb|Overview]]
===Mobile technology roadmap===
[[Image:roadmap.jpg|700px|center|thumb|Roadmap]]

==WiMax==
WiMAX is defined as "Worldwide Interoperability for Microwave Access" by the WiMAX Forum, formed in June 2001 to promote conformance and interoperability of the IEEE 802.16 standard, officially known as WirelessMAN. WiMAX aims to provide wireless data over long distances, in a variety of different ways, from point to point links to full mobile cellular type access. In practical terms this enables a user, for example, to browse the Internet on a laptop computer without physically connecting the laptop to a wall jack.

=== Spectrum coverage by geography ===
Image below shows the spectrum for WiMax users World wide.
[[Image:Spectrum1.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]
Image below shows the sample of country wise spectrum allocation data. This information is form '''[http://maravedis-bwa.com Maravadis: Telecom market research & and analysis] '''.
[[Image:Spectrum-geography.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]

[[More information on Maravadis]]

===Standards===
# [http://standards.ieee.org/getieee802/download/802.16.2-2004.pdf IEEE 802.16-2004 (802.16d)] addresses only fixed systems
# [http://standards.ieee.org/getieee802/download/802.16e-2005.pdf IEEE Std 802.16e-2005], also called mobile WiMax
#* 802.16e also bring Multiple Antenna Support through Multiple-input multiple-output communications. This brings potential benefits in terms of coverage, self installation, power consumption, frequency re-use and bandwidth efficiency. 802.16e also adds a capability for full mobility support.
# WiMAX II, 802.16m will be proposed for IMT-Advanced 4G (future development)
#* 3GPP LTE and WiMAX-m are concentrating much effort on MIMO-AAS, mobile multi-hop relay networking and related developments needed to deliver 10X and higher Co-Channel reuse multiples.

IEEE 802.16e-2005 improves upon IEEE 802.16-2004 by:

* Scaling of the Fast Fourier Transform (FFT) to the channel bandwidth in order to keep the carrier spacing constant across different channel bandwidths (1.25-20 MHz). Constant carrier spacing results in a higher spectrum efficiency in wide channels, and a cost reduction in narrow channels. Also known as Scalable OFDMA (SOFDMA).
* Improving NLOS coverage by utilizing advanced antenna diversity schemes, and hybrid-Automatic Retransmission Request (hARQ)
* Improving coverage by introducing Adaptive Antenna Systems (AAS) and Multiple Input Multiple Output (MIMO) technology
* Increasing system gain by use of denser sub-channelization, thereby improving indoor penetration
* Introducing high-performance coding techniques such as Turbo Coding and Low-Density Parity Check (LDPC), enhancing security and NLOS performance
* Introducing downlink sub-channelization, allowing administrators to trade coverage for capacity or vice versa
* Enhanced Fast Fourier Transform algorithm can tolerate larger delay spreads, increasing resistance to multipath interference
* Adding an extra QoS class (enhanced real-time Polling Service) more appropriate for VoIP applications.
* Adding support for mobility (soft and hard handover between base stations). This is seen as one of the most important aspects of 802.16e-2005, and is the very basis of 'Mobile WiMAX'.

[http://en.wikipedia.org/wiki/WiMAX Source]

'''Market research data:'''
* Worldwide WiMAX equipment revenues are forecast to reach $3.26 billion in 2009
* Worldwide outdoor wireless mesh access node sales are forecast to reach $1.17 billion in 2009
* Samsung leads overall WiMAX equipment revenue share in 3Q06, ahead of Alvarion, Airspan, and Aperto Networks
* Strix Systems leads overall outdoor mesh revenue market share in 3Q06, just ahead of Tropos Networks and BelAir Networks
* 35% of WiMAX equipment sales come from Asia Pacific, 30% from EMEA, 20% from North America, and 14% from CALA
* 49% of wireless mesh access node sales come from North America, 25% from EMEA, 18% from Asia Pacific, and 8% from CALA

[http://www.bbwexchange.com/pubs/2006/12/05/page1421-371393.asp Source]

===Companies===
*[[List of companies]]
===Products===
Table below shows some of the products using WiMax technology.
{|border="2" cellspacing="0" cellpadding="4" width="70%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "2"|[http://www.alvarion-usa.com/products/breezemax/ Alvarion]
|align = "center" rowspan = "2"|BreezeMAX WiMax - base station
|BreezeMAX Macro Base
| 
[[Image:Document2_1.jpg]]

|-
|BreezeMAX Micro Base Station
| 
[[Image:Document2_2.jpg]]

|-
|[http://www.wimax-industry.com/sp/wcm/axc/emap.htm Axxcelera]
|Base station
|EXCELMAX BASE STATION
| 
[[Image:Document2_3.jpg]]

|-
|[http://www.proxim.com/terabeam/products/teramax/index.html Proxim]
|TeraMax P2MP systems comprise base stations and clients, and include mounting hardware, Power over Ethernet (POE), and system management software.
|TeraMax P2MP
| 
[[Image:Document2_4.jpg]]

|-
|align = "center" rowspan = "3"|[http://www.airspan.com/products_group.aspx?ProductGroupID=1 Airspan]
|align = "center" rowspan = "3"|AS.MAX - base stations
|Hiper MAX
|Not available
|-
|Macro MAX
|Not available
|-
|Micro MAX
|Not available
|-

|}

===IP information===
Search query and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Claims, Title or Abstract Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiMax OR (Wi ADJ1 Max))
|align = "center"|328
|-
|}

==WiBro==
WiBro is an acronym for wireless broadband and is actually a term that is in the process of being phased out in favor of the more collaborative and generic Mobile WiMAX.
* Korean standards makers early on adopted the term to describe their initiatives towards adopting a version of the 802.16e standard.
* Basically, the Korean standard chose to accept a specific mobile WiMAX iteration of 802.16e, rather than any future version that included backwards compatibility to fixed wireless 802.16 systems.
* Korea enjoys probably the most extensive 3G deployments in the world already, and its fixed broadband access per capita is the highest in the world. What it needed was an improved mobile broadband. In fact, the Korean government issued the first three deployment licenses for WiBro/Mobile WiMAX in January of 2005.
* WiBro/Mobile WiMAX in many respects is driving the mobile side of WiMAX at least from the point of view of vendors eager to provide products to these early deployments. This decision however, results in a backwards compatibility problem with Fixed WiMAX standards or 802.16-2004.
* The smooth interoperability of previous WiBro gear from Samsung with other vendors such as Motorola should be cemented this year as these two companies along with Intel have been chosen as the primary vendor for Sprint Nextel’s WiMAX deployment. The two companies clearly have a powerful incentive for their products to work seamlessly.

===Standards===
* WiBro is an integral part of IEEE 802.16e

'''WiBro vs. 802.16e/Mobile WiMax'''

[[Image:wibro1.jpg|center|600px|thumb|WiBro vs. 802.16e/Mobile WiMax]]

[http://www.postech.ac.kr/department/cse/linus/home_kor/seminar/sin-posdata.pdf Source]
===Companies===
* [[List of companies supporting WiBro technology]]
Industry news:
* South Korean telco SK Telecom and Wavesat, a Canadian developer of a WiMAX chipset, software and development platform have signed an agreement to cooperate in the development of WiBro/OFDMA technology for next generation mobile devices.
* Wavesat will work with SK Telecom (SKT) to develop WiBro/OFDMA systems-on-chips (SoCs), system tools and a development kit based on the WiBro 802.16e S-OFDMA profile. The U-mobile product portfolio from Wavesat will allow WiMax wireless system providers (OEMs/ODMs) worldwide to develop and deploy fully mobile WiMAX and WiBro solutions.[http://www.digitalmediaasia.com/default.asp?ArticleID=12523 Source]

===Products Overview===
{|border="2" cellspacing="0" width="100%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "4"|Samsung
|align = "center" rowspan = "3"|Mobile Station
|align = "center"|[http://www.3g.co.uk/PR/Jan2006/2427.htm M8000 WiBro handset ]
|align = "center"| 
[[Image:Document5_01.jpg]]

|-
|align = "center"|[http://uk.gizmodo.com/2005/12/28/samsungs_super_wibro_phone.html Super WiBro Phone ]
|align = "center"| 
[[Image:Document5_02.jpg]]

|-
|align = "center"|[http://aving.net/usa/news/default.asp?mode=read&c_num=28705&c_code=02&sp_code=0&btb_num=2747 WiBro-enabled notebook pc]
|align = "center"| 
[[Image:Document5_03.jpg]]

|-
|align = "center"|Access control Router
|align = "center"|[http://www.etopiamedia.net/ybw/pages/ybw2-5551212.html Access control Router]
|align = "center"| 
[[Image:Document5_04.jpg]]

|-
|align = "center"|Kisan Telecom
|align = "center"|Base station
|align = "center"|[http://www.kisantel.co.kr/eng/products/sub02.asp WiBro Repeater]
|align = "center"| 
[[Image:Document5_05.jpg]]

|-
|align = "center"|i-River
|align = "center"|Mobile Station
|align = "center"|[http://www.mobilecomms-technology.com/projects/kt-corp/kt-corp2.html G10 games console]
|align = "center"| 
[[Image:Document5_06.jpg]]

|-
|align = "center"|Korea Telekom
|align = "center"|USB modem
|align = "center"|[http://www.kt.co.kr/eng/New/pr_news_kt_view.jsp iPlug Premium ]
|align = "center"| 
[[Image:Document5_07.jpg]]

|-
|}

===IP information===
Search terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007 Any Classification: G06F OR G06Q OR G08G OR H04B OR H04K OR H04L OR H04N OR H04Q
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiBro OR (Wi ADJ1 Bro))
|align = "center"|180
|-
|}

==3GPP Long Term Evolution==
3GPP LTE (Long Term Evolution) is the name given to a project within the Third Generation Partnership Project to improve the UMTS mobile phone standard to cope with future requirements.

* LTE focus is on Enhancement of the Universal Terrestrial Radio Access (UTRA) and Optimisation of the UTRAN architecture.
* Downlink based on OFDMA (OFDMA offers improved spectral efficiency, capacity, etc)
* Uplink based on SC-FDMA (single carrier) (SC-FDMA is technically similar to OFDMA but is better suited for uplink from hand-held devices- more considerations on battery power)

'''Goals of 3GPP Long Term Evolution'''
* Download rates of 100 Mbit/s, and upload rates of 50 Mbit/s for every 20 MHz of spectrum
* At least 200 active users in every 5 MHz cell. (ie 200 active phone calls)
* Sub-5ms latency for small IP packets
* Increased spectrum flexibility, with spectrum slices as small as 1.25 MHz (and as large as 20 MHz) supported (W-CDMA requires 5 MHz slices, leading to some problems with roll-outs of the technology in countries where 5 MHz is a commonly allocated amount of spectrum, and is frequently already in use with legacy standards such as 2G GSM and cdmaOne.) Limiting sizes to 5 MHz also limited the amount of bandwidth per handset
* Optimal cell size of 5 km, 30 km sizes with reasonable performance, and up to 100 km cell sizes supported with acceptable performance
* Co-existence with legacy standards (users can transparently start a call or transfer of data in an area using an LTE standard, and, should coverage be unavailable, continue the operation without any action on their part using GSM/GPRS or W-CDMA-based UMTS)

===Companies===
* [[List of companies supporting 3GPP technology and HSOPA]]
===Products===
=== IP information===
Search (Companied search for 3GPP LTE and HSOPA (super 3G) ) terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((3GPP ADj1 (LTE OR (Long ADJ1 Term ADJ1 Evolution))) OR (super ADJ1 3G))
|align = "center"|47
|-
|}

==HSOPA==
High Speed OFDM Packet Access (HSOPA) is a proposed part of 3GPP's Long Term Evolution (LTE) upgrade path for UMTS systems. HSOPA is also often referred to as Super 3G. If adopted, HSOPA succeeds HSDPA and HSUPA technologies specified in 3GPP releases 5 and 6. Unlike HSDPA or HSUPA, HSOPA is an entirely new air interface system, unrelated to and incompatible with W-CDMA.
Features of HSOPA
HSOPA has the following features:
* Flexible bandwidth usage with 1.25 MHz to 20 MHz bandwidths. By comparison, W-CDMA uses fixed size 5 MHz chunks of spectrum.
* Increased spectral efficiency at 2-4 times more than in 3GPP release 6, peak transfer rates of 100 Mbit/s for downlink and 50 Mbit/s for uplink.
* Latency times of around 20 ms for round trip time from user terminal to RAN, approximately the same as a combined HSDPA/HSUPA system, but much better than "classic" W-CDMA.

'''Design'''

HSOPA uses Orthogonal Frequency Division Multiplexing (OFDM) and multiple-input multiple-output (MIMO) antenna technology to support up to 10 times as many users as W-CDMA based systems, with lower processing power required on each handset.[1]. Still in development, experimental performance is 37 Mbit/s in the downlink over a 5 MHz channel, close to the theoretical maximum of 40 Mbit/s.

'''Difference: HOSPA - WiMax'''

While both WiMAX and the HSOPA use OFDM/OFDMA, HSOPA enhanced UMTS will most likely be optimized for wide area mobile voice communications. HSOPA will use OFDMA for the down-link and Single Carrier FDMA (SC-FDMA) for the up-link. WiMAX/802.16e-2005 uses OFDMA for both the up and down links.
SC-OFDM can maintain connections at longer distance but has lower bandwidth than OFDMA. However, WiMAX advocates perceive evolution of WBB as also shifting the 'architectural evolution' of wireless networks to more granular, symmetrical, higher bandwidth micro-cell and mobile multi-hop relay network topologies.
Multi-mode WiMAX plus CDMA and other technologies can work together to fulfill both long range, low bandwidth and shorter range, high bandwidth requirements on the basis of providing the user with 'always best connected' experience.

==3GPP2 Ultra Mobile Broadband==
UMB (Ultra Mobile Broadband) is the brand name for the project within 3GPP2 to improve the CDMA2000 mobile phone standard for next generation applications and requirements.The system employs OFDMA technology along with advanced antenna techniques to provide peak rates of up to 280 Mbit/s.

Goals for UMB:
* Improving system capacity
* Greatly increasing user data rates throughout the cell
* Lowering costs
* Enhancing existing services
* Making possible new applications, and
* Making use of new spectrum opportunities.

The technology will provide users with concurrent IP-based services in a full mobility environment. The UMB standardization is expected to be completed in mid 2007, with commercialization taking place around mid-2009.

'''Technology overview'''
* OFDMA-based air interface
* Frequency Division Duplex
* Scalable bandwidth between 1.25-20 MHz (OFDMA systems are especially well suited for wider bandwidths larger than 5 MHz)
* Supports mixed cell sizes, e.g., macro-cellular, micro-cellular & pico-cellular.
* IP network architecture
* Supports flat, centralized and mixed topologies
* Data speeds over 275 Mbit/s downstream and over 75 Mbit/s upstream

[http://en.wikipedia.org/wiki/Ultra_Mobile_Broadband Source]

[http://www.3gpp2.org/Public_html/Misc/AboutHome.cfm More infromation]

'''Key features'''
* Multiple radio and advanced antenna techniques
*# Sophisticated control and signaling mechanisms (minimized) combine the best aspects of CDMA, TDM, OFDM, and OFDMA into a single air interface
*# Multiple Input Multiple Output (MIMO) and Space Division Multiple Access (SDMA)
*# Improved interference management techniques
* Ultra-high mobile broadband peak data rates
*# Up to 280Mbps peak data rate on forward link
*# Up to 68Mbps peak data rate on reverse link
* Ultra-low network latency
*# An average of 16.8 msec (32-byte, RTT) end-to-end network latency
* Enhanced VoIP capacity and user experience
*# Up to 500 simultaneous VoIP users (10 MHz FDD allocations)
* Scalable IP-based flat or hierarchical architecture
*# Greater service deployment flexibility, improved performance, and lower cost of ownership
* Flexible spectrum allocations
*# Scalable, non-contiguous and dynamic channel (bandwidth) allocations
*# Support for bandwidth allocations of 1.25 MHz, 5 MHz, 10 MHz and 20 MHz
* Less power consumption
*# Improved battery life

[http://www.cdg.org/technology/3g_umb.asp Source]
===Companies===
These are some of the companies working in this particular area.
* Nokia
* LG
* RES in Motion
* Qualcomm
* Motorola
* Ericsson
* Samsung
* Interdigital
* Infineon Technologie

QUALCOMM has announced next generation chips. [http://ultramobileblog.com/category/ultra-mobile-broadband/ Source]

===IP information===
Search terms and results
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Claims, Title or Abstract
|align = "center"|76
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Title or Abstract
|align = "center"|22
|-
|}

4G wireless technology developments

2007-06-26T07:02:35Z

67.180.82.65:

{{TOCRightEx}}
==Definition of 4G==

The 4G will be a fully IP-based integrated system of systems and network of networks achieved after the convergence of wired and wireless networks as well as computer, consumer electronics, communication technology, and several other convergences that will be capable of providing 100 Mbit/s and 1 Gbit/s, respectively, in outdoor and indoor environments with end-to-end QoS and high security, offering any kind of services anytime, anywhere, at affordable cost and one billing.

According to the 4G working groups, the infrastructure and the terminals will have almost all the standards from 2G to 3G implemented. The infrastructure will however only be packet based, all-IP. The system will also serve as an open platform where the new innovations can go with it.

'''Standards supported by 4G:'''

* WiMax
* WiBro
* 3GPP Long Term Evolution
* HSOPA
* 3GPP2 Ultra Mobile Broadband

'''Services where 4G is used:'''

*Wireless broadband access
*Multimedia Messaging Service
*Video chat
*Mobile TV
*High definition TV content,
*DVB
*Minimal service like voice and data

'''Objectives of the 4G wireless communication standard:'''

* A spectrally efficient system (in bits/s/Hz and bit/s/Hz/site)
* High network capacity
* A nominal data rate of 100 Mbit/s at high speeds and 1 Gbit/s at stationary conditions as defined by the ITU-R
* A data rate of at least 100 Mbit/s between any two points in the world
* Smooth handoff across heterogeneous network
* Seamless connectivity and global roaming across multiple networks
* High quality of service for next generation multimedia support (real time audio, high speed data, HDTV video content, mobile TV, etc)
* Interoperability with the existing wireless standards
* An all IP, packet switched network

'''Access schemes:'''

* OFDMA
* Single Carrier FDMA
* MC-CDMA
===Technology overview===
Mindmap below shows the overview of emerging technologies in 4G

[[Image:4Gmindmap1.jpg|800px|center|thumb|Overview]]
===Mobile technology roadmap===
[[Image:roadmap.jpg|700px|center|thumb|Roadmap]]

==WiMax==
WiMAX is defined as "Worldwide Interoperability for Microwave Access" by the WiMAX Forum, formed in June 2001 to promote conformance and interoperability of the IEEE 802.16 standard, officially known as WirelessMAN. WiMAX aims to provide wireless data over long distances, in a variety of different ways, from point to point links to full mobile cellular type access. In practical terms this enables a user, for example, to browse the Internet on a laptop computer without physically connecting the laptop to a wall jack.

=== Spectrum coverage by geography ===
Image below shows the spectrum for WiMax users World wide.
[[Image:Spectrum1.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]
Image below shows the sample of country wise spectrum allocation data. This information is form '''[http://maravedis-bwa.com Maravadis: Telecom market research & and analysis] '''.
[[Image:Spectrum-geography.jpg|center|800px|thumb|Spectrum for WiMax users World wide]]

[[More information on Maravadis]]

===Standards===
# [http://standards.ieee.org/getieee802/download/802.16.2-2004.pdf IEEE 802.16-2004 (802.16d)] addresses only fixed systems
# [http://standards.ieee.org/getieee802/download/802.16e-2005.pdf IEEE Std 802.16e-2005], also called mobile WiMax
#* 802.16e also bring Multiple Antenna Support through Multiple-input multiple-output communications. This brings potential benefits in terms of coverage, self installation, power consumption, frequency re-use and bandwidth efficiency. 802.16e also adds a capability for full mobility support.
# WiMAX II, 802.16m will be proposed for IMT-Advanced 4G (future development)
#* 3GPP LTE and WiMAX-m are concentrating much effort on MIMO-AAS, mobile multi-hop relay networking and related developments needed to deliver 10X and higher Co-Channel reuse multiples.

IEEE 802.16e-2005 improves upon IEEE 802.16-2004 by:

* Scaling of the Fast Fourier Transform (FFT) to the channel bandwidth in order to keep the carrier spacing constant across different channel bandwidths (1.25-20 MHz). Constant carrier spacing results in a higher spectrum efficiency in wide channels, and a cost reduction in narrow channels. Also known as Scalable OFDMA (SOFDMA).
* Improving NLOS coverage by utilizing advanced antenna diversity schemes, and hybrid-Automatic Retransmission Request (hARQ)
* Improving coverage by introducing Adaptive Antenna Systems (AAS) and Multiple Input Multiple Output (MIMO) technology
* Increasing system gain by use of denser sub-channelization, thereby improving indoor penetration
* Introducing high-performance coding techniques such as Turbo Coding and Low-Density Parity Check (LDPC), enhancing security and NLOS performance
* Introducing downlink sub-channelization, allowing administrators to trade coverage for capacity or vice versa
* Enhanced Fast Fourier Transform algorithm can tolerate larger delay spreads, increasing resistance to multipath interference
* Adding an extra QoS class (enhanced real-time Polling Service) more appropriate for VoIP applications.
* Adding support for mobility (soft and hard handover between base stations). This is seen as one of the most important aspects of 802.16e-2005, and is the very basis of 'Mobile WiMAX'.

[http://en.wikipedia.org/wiki/WiMAX Source]

'''Market research data:'''
* Worldwide WiMAX equipment revenues are forecast to reach $3.26 billion in 2009
* Worldwide outdoor wireless mesh access node sales are forecast to reach $1.17 billion in 2009
* Samsung leads overall WiMAX equipment revenue share in 3Q06, ahead of Alvarion, Airspan, and Aperto Networks
* Strix Systems leads overall outdoor mesh revenue market share in 3Q06, just ahead of Tropos Networks and BelAir Networks
* 35% of WiMAX equipment sales come from Asia Pacific, 30% from EMEA, 20% from North America, and 14% from CALA
* 49% of wireless mesh access node sales come from North America, 25% from EMEA, 18% from Asia Pacific, and 8% from CALA

[http://www.bbwexchange.com/pubs/2006/12/05/page1421-371393.asp Source]

===Companies===
*[[List of companies]]
===Products===
Table below shows some of the products using WiMax technology.
{|border="2" cellspacing="0" cellpadding="4" width="70%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "2"|[http://www.alvarion-usa.com/products/breezemax/ Alvarion]
|align = "center" rowspan = "2"|BreezeMAX WiMax - base station
|BreezeMAX Macro Base
| 
[[Image:Document2_1.jpg]]

|-
|BreezeMAX Micro Base Station
| 
[[Image:Document2_2.jpg]]

|-
|[http://www.wimax-industry.com/sp/wcm/axc/emap.htm Axxcelera]
|Base station
|EXCELMAX BASE STATION
| 
[[Image:Document2_3.jpg]]

|-
|[http://www.proxim.com/terabeam/products/teramax/index.html Proxim]
|TeraMax P2MP systems comprise base stations and clients, and include mounting hardware, Power over Ethernet (POE), and system management software.
|TeraMax P2MP
| 
[[Image:Document2_4.jpg]]

|-
|align = "center" rowspan = "3"|[http://www.airspan.com/products_group.aspx?ProductGroupID=1 Airspan]
|align = "center" rowspan = "3"|AS.MAX - base stations
|Hiper MAX
|Not available
|-
|Macro MAX
|Not available
|-
|Micro MAX
|Not available
|-

|}

===IP information===
Search query and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Claims, Title or Abstract Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiMax OR (Wi ADJ1 Max))
|align = "center"|328
|-
|}

==WiBro==
WiBro is an acronym for wireless broadband and is actually a term that is in the process of being phased out in favor of the more collaborative and generic Mobile WiMAX.
* Korean standards makers early on adopted the term to describe their initiatives towards adopting a version of the 802.16e standard.
* Basically, the Korean standard chose to accept a specific mobile WiMAX iteration of 802.16e, rather than any future version that included backwards compatibility to fixed wireless 802.16 systems.
* Korea enjoys probably the most extensive 3G deployments in the world already, and its fixed broadband access per capita is the highest in the world. What it needed was an improved mobile broadband. In fact, the Korean government issued the first three deployment licenses for WiBro/Mobile WiMAX in January of 2005.
* WiBro/Mobile WiMAX in many respects is driving the mobile side of WiMAX at least from the point of view of vendors eager to provide products to these early deployments. This decision however, results in a backwards compatibility problem with Fixed WiMAX standards or 802.16-2004.
* The smooth interoperability of previous WiBro gear from Samsung with other vendors such as Motorola should be cemented this year as these two companies along with Intel have been chosen as the primary vendor for Sprint Nextel’s WiMAX deployment. The two companies clearly have a powerful incentive for their products to work seamlessly.

===Standards===
* WiBro is an integral part of IEEE 802.16e

'''WiBro vs. 802.16e/Mobile WiMax'''

[[Image:wibro1.jpg|center|600px|thumb|WiBro vs. 802.16e/Mobile WiMax]]

[http://www.postech.ac.kr/department/cse/linus/home_kor/seminar/sin-posdata.pdf Source]
===Companies===
* [[List of companies supporting WiBro technology]]
Industry news:
* South Korean telco SK Telecom and Wavesat, a Canadian developer of a WiMAX chipset, software and development platform have signed an agreement to cooperate in the development of WiBro/OFDMA technology for next generation mobile devices.
* Wavesat will work with SK Telecom (SKT) to develop WiBro/OFDMA systems-on-chips (SoCs), system tools and a development kit based on the WiBro 802.16e S-OFDMA profile. The U-mobile product portfolio from Wavesat will allow WiMax wireless system providers (OEMs/ODMs) worldwide to develop and deploy fully mobile WiMAX and WiBro solutions.[http://www.digitalmediaasia.com/default.asp?ArticleID=12523 Source]

===Products Overview===
{|border="2" cellspacing="0" width="100%"
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Company'''
|align = "center" bgcolor = "#99CCFF" colspan = "2"|'''Product'''
|align = "center" bgcolor = "#99CCFF" rowspan = "2"|'''Image'''
|-
|align = "center" bgcolor = "#99CCFF"|'''Main category'''
|align = "center" bgcolor = "#99CCFF"|'''Sub category'''
|-
|align = "center" rowspan = "4"|Samsung
|align = "center" rowspan = "3"|Mobile Station
|align = "center"|[http://www.3g.co.uk/PR/Jan2006/2427.htm M8000 WiBro handset ]
|align = "center"| 
[[Image:Document5_01.jpg]]

|-
|align = "center"|[http://uk.gizmodo.com/2005/12/28/samsungs_super_wibro_phone.html Super WiBro Phone ]
|align = "center"| 
[[Image:Document5_02.jpg]]

|-
|align = "center"|[http://aving.net/usa/news/default.asp?mode=read&c_num=28705&c_code=02&sp_code=0&btb_num=2747 WiBro-enabled notebook pc]
|align = "center"| 
[[Image:Document5_03.jpg]]

|-
|align = "center"|Access control Router
|align = "center"|[http://www.etopiamedia.net/ybw/pages/ybw2-5551212.html Access control Router]
|align = "center"| 
[[Image:Document5_04.jpg]]

|-
|align = "center"|Kisan Telecom
|align = "center"|Base station
|align = "center"|[http://www.kisantel.co.kr/eng/products/sub02.asp WiBro Repeater]
|align = "center"| 
[[Image:Document5_05.jpg]]

|-
|align = "center"|i-River
|align = "center"|Mobile Station
|align = "center"|[http://www.mobilecomms-technology.com/projects/kt-corp/kt-corp2.html G10 games console]
|align = "center"| 
[[Image:Document5_06.jpg]]

|-
|align = "center"|Korea Telekom
|align = "center"|USB modem
|align = "center"|[http://www.kt.co.kr/eng/New/pr_news_kt_view.jsp iPlug Premium ]
|align = "center"| 
[[Image:Document5_07.jpg]]

|-
|}

===IP information===
Search terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007 Any Classification: G06F OR G06Q OR G08G OR H04B OR H04K OR H04L OR H04N OR H04Q
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|(WiBro OR (Wi ADJ1 Bro))
|align = "center"|180
|-
|}

==3GPP Long Term Evolution==
3GPP LTE (Long Term Evolution) is the name given to a project within the Third Generation Partnership Project to improve the UMTS mobile phone standard to cope with future requirements.

* LTE focus is on Enhancement of the Universal Terrestrial Radio Access (UTRA) and Optimisation of the UTRAN architecture.
* Downlink based on OFDMA (OFDMA offers improved spectral efficiency, capacity, etc)
* Uplink based on SC-FDMA (single carrier) (SC-FDMA is technically similar to OFDMA but is better suited for uplink from hand-held devices- more considerations on battery power)

'''Goals of 3GPP Long Term Evolution'''
* Download rates of 100 Mbit/s, and upload rates of 50 Mbit/s for every 20 MHz of spectrum
* At least 200 active users in every 5 MHz cell. (ie 200 active phone calls)
* Sub-5ms latency for small IP packets
* Increased spectrum flexibility, with spectrum slices as small as 1.25 MHz (and as large as 20 MHz) supported (W-CDMA requires 5 MHz slices, leading to some problems with roll-outs of the technology in countries where 5 MHz is a commonly allocated amount of spectrum, and is frequently already in use with legacy standards such as 2G GSM and cdmaOne.) Limiting sizes to 5 MHz also limited the amount of bandwidth per handset
* Optimal cell size of 5 km, 30 km sizes with reasonable performance, and up to 100 km cell sizes supported with acceptable performance
* Co-existence with legacy standards (users can transparently start a call or transfer of data in an area using an LTE standard, and, should coverage be unavailable, continue the operation without any action on their part using GSM/GPRS or W-CDMA-based UMTS)

===Companies===
* [[List of companies supporting 3GPP technology and HSOPA]]
===Products===
=== IP information===
Search (Companied search for 3GPP LTE and HSOPA (super 3G) ) terms and result:
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Full patent spec. Years: 1991-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((3GPP ADj1 (LTE OR (Long ADJ1 Term ADJ1 Evolution))) OR (super ADJ1 3G))
|align = "center"|47
|-
|}

==HSOPA==
High Speed OFDM Packet Access (HSOPA) is a proposed part of 3GPP's Long Term Evolution (LTE) upgrade path for UMTS systems. HSOPA is also often referred to as Super 3G. If adopted, HSOPA succeeds HSDPA and HSUPA technologies specified in 3GPP releases 5 and 6. Unlike HSDPA or HSUPA, HSOPA is an entirely new air interface system, unrelated to and incompatible with W-CDMA.
Features of HSOPA
HSOPA has the following features:
* Flexible bandwidth usage with 1.25 MHz to 20 MHz bandwidths. By comparison, W-CDMA uses fixed size 5 MHz chunks of spectrum.
* Increased spectral efficiency at 2-4 times more than in 3GPP release 6, peak transfer rates of 100 Mbit/s for downlink and 50 Mbit/s for uplink.
* Latency times of around 20 ms for round trip time from user terminal to RAN, approximately the same as a combined HSDPA/HSUPA system, but much better than "classic" W-CDMA.

'''Design'''

HSOPA uses Orthogonal Frequency Division Multiplexing (OFDM) and multiple-input multiple-output (MIMO) antenna technology to support up to 10 times as many users as W-CDMA based systems, with lower processing power required on each handset.[1]. Still in development, experimental performance is 37 Mbit/s in the downlink over a 5 MHz channel, close to the theoretical maximum of 40 Mbit/s.

'''Difference: HOSPA - WiMax'''

While both WiMAX and the HSOPA use OFDM/OFDMA, HSOPA enhanced UMTS will most likely be optimized for wide area mobile voice communications. HSOPA will use OFDMA for the down-link and Single Carrier FDMA (SC-FDMA) for the up-link. WiMAX/802.16e-2005 uses OFDMA for both the up and down links.
SC-OFDM can maintain connections at longer distance but has lower bandwidth than OFDMA. However, WiMAX advocates perceive evolution of WBB as also shifting the 'architectural evolution' of wireless networks to more granular, symmetrical, higher bandwidth micro-cell and mobile multi-hop relay network topologies.
Multi-mode WiMAX plus CDMA and other technologies can work together to fulfill both long range, low bandwidth and shorter range, high bandwidth requirements on the basis of providing the user with 'always best connected' experience.

==3GPP2 Ultra Mobile Broadband==
UMB (Ultra Mobile Broadband) is the brand name for the project within 3GPP2 to improve the CDMA2000 mobile phone standard for next generation applications and requirements.The system employs OFDMA technology along with advanced antenna techniques to provide peak rates of up to 280 Mbit/s.

Goals for UMB:
* Improving system capacity
* Greatly increasing user data rates throughout the cell
* Lowering costs
* Enhancing existing services
* Making possible new applications, and
* Making use of new spectrum opportunities.

The technology will provide users with concurrent IP-based services in a full mobility environment. The UMB standardization is expected to be completed in mid 2007, with commercialization taking place around mid-2009.

'''Technology overview'''
* OFDMA-based air interface
* Frequency Division Duplex
* Scalable bandwidth between 1.25-20 MHz (OFDMA systems are especially well suited for wider bandwidths larger than 5 MHz)
* Supports mixed cell sizes, e.g., macro-cellular, micro-cellular & pico-cellular.
* IP network architecture
* Supports flat, centralized and mixed topologies
* Data speeds over 275 Mbit/s downstream and over 75 Mbit/s upstream

[http://en.wikipedia.org/wiki/Ultra_Mobile_Broadband Source]

[http://www.3gpp2.org/Public_html/Misc/AboutHome.cfm More infromation]

'''Key features'''
* Multiple radio and advanced antenna techniques
*# Sophisticated control and signaling mechanisms (minimized) combine the best aspects of CDMA, TDM, OFDM, and OFDMA into a single air interface
*# Multiple Input Multiple Output (MIMO) and Space Division Multiple Access (SDMA)
*# Improved interference management techniques
* Ultra-high mobile broadband peak data rates
*# Up to 280Mbps peak data rate on forward link
*# Up to 68Mbps peak data rate on reverse link
* Ultra-low network latency
*# An average of 16.8 msec (32-byte, RTT) end-to-end network latency
* Enhanced VoIP capacity and user experience
*# Up to 500 simultaneous VoIP users (10 MHz FDD allocations)
* Scalable IP-based flat or hierarchical architecture
*# Greater service deployment flexibility, improved performance, and lower cost of ownership
* Flexible spectrum allocations
*# Scalable, non-contiguous and dynamic channel (bandwidth) allocations
*# Support for bandwidth allocations of 1.25 MHz, 5 MHz, 10 MHz and 20 MHz
* Less power consumption
*# Improved battery life

[http://www.cdg.org/technology/3g_umb.asp Source]
===Companies===
These are some of the companies working in this particular area.
* Nokia
* LG
* RES in Motion
* Qualcomm
* Motorola
* Ericsson
* Samsung
* Interdigital
* Infineon Technologie

QUALCOMM has announced next generation chips. [http://ultramobileblog.com/category/ultra-mobile-broadband/ Source]

===IP information===
Search terms and results
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#99CCFF"|Search scope: US Granted US Applications EP-A EP-B WO JP (bibliographic data only) DE-C,B DE-A DE-T DE-U GB-A FR-A; Years: 2001-2007
|align = "center" bgcolor = "#99CCFF"|Patents
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Claims, Title or Abstract
|align = "center"|76
|-
|align = "center"|((Ultra ADJ1 Mobile ADJ1 Broadband) OR 3GPP2) Title or Abstract
|align = "center"|22
|-
|}