20858 Federal Register / Vol. 72, No. 80 / Thursday, April 26, 2007 / Notices 

hewesj@mail.nih.gov for more 

information. 

Monoclonal Antibodies Specific for the 

E2 Glycoprotein of Hepatitis C Virus 

and Their Use in the Diagnosis, 

Treatment and Prevention of 

Hepatitis C 

Description of Technology: Hepatitis 

C virus is an enveloped, single-stranded 

RNA virus, approximately 50 nm in 

diameter, that has been classified as a 

separate genus in the Flaviviridae 

family. Most persons infected with 

hepatitis C virus develop chronic 

infection. These chronically infected 

individuals have a relatively high risk of 

developing chronic hepatitis, liver 

cirrhosis and hepatocellular carcinoma. 

There is currently no vaccine to prevent 

the hepatitis C virus infection. The 

present invention relates to human 

monoclonal antibodies which exhibit 

immunological binding affinity for the 

hepatitis C virus E2 glycoprotein and 

are cross-reactive against different 

hepatitis C virus strains. These 

antibodies may be used in passive 

immunoprophylaxis for the prevention 

of hepatitis C virus infection and/or in 

passive immunotherapy for the 

treatment of hepatitis C. 

Applications: In vitro diagnostic assay 

for identifying patients infected with 

hepatitis C virus and contaminated 

blood samples; method of preventing 

infection using monoclonal antibodies 

that neutralize E2 glycoproteins from 

different genotypes of hepatitis C virus. 

Market: Over 4 million people in the 

U.S. are infected with hepatitis C virus. 

An estimated 150 to 200 million people 

are infected with hepatitis C virus 

worldwide. 

Inventors: Suzanne U. Emerson 

(NIAID), Robert H. Purcell (NIAID), 

Harvey J. Alter (NIAID), et al. 

Related Publication: DJ Schofield et 

al. Human monoclonal antibodies that 

react with the E2 glycoprotein of 

hepatitis C virus and possess 

neutralizing activity. Hepatology. 2005 

Nov;42(5):1055–1062. 

Patent Status: U.S. Provisional 

Application No. 60/250,561, filed 01 

Dec 2000 (HHS Reference No. E–017–

2001/0–US–01); PCT Application No. 

PCT/US01/45221, filed 30 Nov 2001, 

published as WO 02/055560 on 18 Jul 

2002 (HHS Reference No. E–017–2001/ 

0–PCT–02); U.S. Patent Application No. 

10/432,006 filed 16 May 2003, issued as 

U.S. Patent No. 6,924,362 on 02 Aug 

2005 (HHS Reference No. E–017–2001/ 

0–US–03) 

Licensing Contact: Chekesha S. 

Clingman, Ph.D.; 301/435–5018; 

clingmac@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIAID Laboratory of Infectious 

Diseases is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize these monoclonal 

antibodies. For more information, please 

contact Robert H. Purcell, M.D., Cochief, Laboratory of Infectious Diseases, 

National Institute of Allergy and 

Infectious Diseases, National Institutes 

of Health, 50 South Drive, Bldg. 50, Rm. 

6523, Bethesda, MD 20892–8009; Phone 

(301) 496–5090; Fax (301) 402–0524. 

Major Neutralization Site of Hepatitis E 

Virus and Use of This Neutralization 

Site in Methods of Vaccination 

Description of Technology: Hepatitis E 

is endemic in many countries 

throughout the developing world, in 

particular on the continents of Africa 

and Asia. The disease generally affects 

young adults and has a very high 

mortality rate, up to 20%, in pregnant 

women. This invention relates to the 

identification of a neutralization site of 

hepatitis E virus (HEV) and neutralizing 

antibodies that react with it. The 

neutralization site is located on a 

polypeptide from the ORF2 gene (capsid 

gene) of HEV. This neutralization site 

was identified using a panel of 

chimpanzee monoclonal antibodies that 

are virtually identical to human 

antibodies. Since this neutralization site 

is conserved among genetically 

divergent strains of HEV, the 

neutralizing monoclonal antibodies may 

be useful in the diagnosis, treatment 

and/or prevention of hepatitis E. 

Furthermore, immunogens that 

encompass this neutralization site may 

be used in vaccination to effectively 

prevent, and/or reduce the incidence of 

HEV infection. Polypeptides containing 

this neutralization site may be useful in 

evaluating vaccine candidates for the 

production of neutralizing antibodies to 

HEV. 

Inventors: Suzanne U. Emerson 

(NIAID), Robert H. Purcell (NIAID), et 

al. 

Related Publications: 

1. YH Zhou et al. A truncated ORF2 

protein contains the most immunogenic 

site on ORF2: antibody responses to 

non-vaccine sequences following 

challenge of vaccinated and nonvaccinated macaques with HEV. 

Vaccine 2005 May 2;23(24):3157–3165. 

2. DJ Schofield et al. Monoclonal 

antibodies that neutralize HEV 

recognize an antigenic site at the 

carboxyterminus of an ORF2 protein 

vaccine. Vaccine 2003 Dec 

12;22(2):257–267. 

3. YH Zhou et al. An ELISA for 

putative neutralizing antibodies to 

hepatitis E virus detects antibodies to 

genotypes 1, 2, 3, and 4. Vaccine 2004 

Jun 30;22(20):2578–2585. 

Patent Status: U.S. Patent No. 

6,930,176, issued 16 Aug 2005 (HHS 

Reference No. E–043–2000/0–US–04); 

EP Application 00982311.3, filed on 30 

Nov 2000, published as 1235862 on 04 

Sept 2002 (HHS Reference No. E–043–

2000/0–EP–03); U.S. Patent No. 

7,148,323, issued 12 Dec 2006 (HHS 

Reference No. E–043–2000/0–US–05) 

Licensing Contact: Chekesha S. 

Clingman, Ph.D.; 301/435–5018; 

clingmac@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIAID Laboratory of Infectious 

Diseases is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize these antibodies or 

structures they interact with. For more 

information, please contact Robert H. 

Purcell, M.D., Co-chief, Laboratory of 

Infectious Diseases, National Institute of 

Allergy and Infectious Diseases, 

National Institutes of Health, 50 South 

Drive, Bldg. 50, Rm. 6523, Bethesda, MD 

20892–8009; Phone (301) 496–5090; Fax 

(301) 402–0524. 

Dated: April 17, 2007. 

Steven M. Ferguson, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E7–7930 Filed 4–25–07; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Government-Owned Inventions; 

Availability for Licensing 

AGENCY: National Institutes of Health, 

Public Health Service, HHS. 

ACTION: Notice. 

SUMMARY: The inventions listed below 

are owned by an agency of the U.S. 

Government and are available for 

licensing in the U.S. in accordance with 

35 U.S.C. 207 to achieve expeditious 

commercialization of results of 

federally-funded research and 

development. Foreign patent 

applications are filed on selected 

inventions to extend market coverage 

for companies and may also be available 

for licensing. 

ADDRESSES: Licensing information and 

copies of the U.S. patent applications 

listed below may be obtained by writing 


rwilkins on PROD1PC63 with NOTICES
Federal Register / Vol. 72, No. 80 / Thursday, April 26, 2007 / Notices 20859 

to the indicated licensing contact at the 

Office of Technology Transfer, National 

Institutes of Health, 6011 Executive 

Boulevard, Suite 325, Rockville, 

Maryland 20852–3804; telephone: 301/ 

496–7057; fax: 301/402–0220. A signed 

Confidential Disclosure Agreement will 

be required to receive copies of the 

patent applications. 

GDF15, a Marker and Cause of 

Morbidity in Thalassemia 

Description of Technology: The 

invention includes methods for the 

measurement of Growth Differentiation 

Factor 15 (GDF15, also known as MIC–

1 or NAG–1) levels in order to diagnose 

or predict disease severity in patients 

with thalassemia and with related 

complications, as well as methods for 

treating thalassemia by administration 

of a GDF15 antagonist. Also disclosed is 

a method to reduce hepcidin levels by 

administration of GDF15, a GDF15 

substitute, or GDF15 agonist. 

GDF15 is a member of the TGF-Beta 

superfamily of proteins, which are 

known to control cell proliferation, 

differentiation, and apoptosis in 

numerous cell types. The inventors are 

additionally interested in investigating 

the role of GDF15 in other disorders 

characterized by ineffective 

erythropoiesis, as well as the role of 

GDF15 in the regulation of iron 

metabolism. 

Thalassemia consists of a group of 

inherited diseases of the red blood cells, 

arising from deficient or absent 

production of globin chains. In betathalassemia, also known as Cooley’s 

anemia or Mediterranean anemia, 

defective globin production reduces the 

number and viability of red blood cells, 

causing anemia and subsequent 

expansion of bone marrow. As a result 

of marrow expansion distorted bone 

formation ensues. Beta thalassemia, the 

most severe form of thalassemia, also 

results in iron overload, which is the 

major cause of beta-thalassemia 

mortality worldwide. As a result of iron 

overload, the patient may develop 

hypropituitarism, hypothyroidism, 

hypoparathyrodism, diabetes, 

arthropathy, cirrhosis and 

cardiopulmonary disease. Treatment of 

beta-thalassemia involves frequent 

blood transfusions and chelation 

therapy to remove excess iron from the 

blood. 

In thalassemia, the patient’s hepcidin 

expression is pathologically suppressed. 

Hepcidin is a protein synthesized in the 

liver, which reduces iron absorption in 

the body. 

The inventors have identified GDF15 

as a hepcidin-suppressing cytokine that 

is overexpressed in thalassemia. GDF15 

levels in blood plasma have been found 

to be dramatically elevated in betathalassemia patients compared to 

healthy donors and patients with 

hereditary hemochromatosis, another 

form of iron overload disease. 

Applications: 

1. Diagnostic test to detect increased 

risk for thalassemia-related 

complications. 

2. Treatment of thalassemia by 

administration of a GDF15 antagonist. 

3. Treatment of iron-dysregulated 

diseases. 

4. Treatment of ineffective 

erythropoiesis. 

5. Treatment of anemia of chronic 

disease. 

Market: Thalassemia is a growing 

global public health problem. It is 

estimated that seven percent of the 

world’s population are carriers, with 

about 400,000 affected babies born each 

year. Approximately 1,000 people in the 

United States currently have betathalassemia; however, the number of 

patients is expected to grow. Prevalence 

of the disease is higher in those of 

Mediterranean descent and those from 

China, India and other Asian countries. 

The U.S. Food and Drug Administration 

classifies thalassemia as a rare or orphan 

disease. 

Development Status: Early stage. 

Inventors: Jeffery L. Miller and 

Toshihiko Tanno (NIDDK). 

Publications: In Review. 

Patent Status: U.S. Provisional 

Application No. 60/864,705 filed 07 

Nov. 2006 (HHS Reference No. E–022–

2007/0-US–01). 

Licensing Status: Available for 

exclusive or nonexclusive licensing. 

Licensing Contact: Tara L. Kirby, PhD; 

301/435–4426; tarak@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIDDK’s Molecular Medicine 

Branch is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize the role of GDF15 in 

other disorders characterized by 

ineffective erythropoiesis, as well as the 

role of GDF15 in the regulation of iron 

metabolism. Please contact Dr. Jeffery L. 

Miller at Jeff.Miller1@nih.hhs.gov or 

301/402–2373 for more information. 

Methods for Treating Autoimmune 

Inflammatory Disease by Blocking 

DR3–TL1A Interactions 

Description of Technology: As a 

group, autoimmune inflammatory 

diseases occur in greater than five 

percent of the United States population, 

and represent the fourth-largest cause of 

disability among women. This disease 

group includes asthma, multiple 

sclerosis, rheumatoid arthritis, and 

lupus, among others. Treatments 

generally include immunosuppressants 

or anti-inflammatory drugs; recently, 

more specific immunomodulatory 

therapies such as TNF-alpha antagonists 

have been developed. 

The invention discloses methods for 

treatment of autoimmune inflammatory 

disease by blocking the interaction 

between one particular TNF family 

ligand, TL1A (or TNFSF15), and its 

receptor, DR3 (or TNFRSF25). The 

inventors have shown that the DR3–

TL1A interaction is critical for 

development of disease in mouse 

models of asthma and multiple 

sclerosis. Additionally, mice lacking the 

DR3 receptor have normal immune 

system development and response to 

immune challenge. Thus, a treatment for 

autoimmune disease that blocks the 

DR3–TL1A interaction may provide a 

potent therapy without inducing global 

immunosuppression. 

Applications: Development of 

therapeutics for autoimmune 

inflammatory disease. 

Market: More than five percent of the 

United States population has an 

autoimmune disease; The market size 

for rheumatoid arthritis is predicted to 

be $10 billion by 2008. 

Development Status: Early stage. 

Inventors: Richard M. Siegel and 

Francoise Meylan (NIAMS). 

Patent Status: U.S. Provisional 

Application No. 60/879,668 filed 10 Jan 

2007 (HHS Reference No. E–011–2007/ 

0–US–01). 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Tara Kirby, PhD; 

301/435–4426; tarak@mail.nih.gov. 

Genetic Markers for Body Size in Dogs 

Description of Technology: Dogs 

exhibit the greatest diversity in body 

size of any mammalian species. To 

explore the genetic basis for size 

variation among dogs, the inventors 

compared the DNA of various small dog 

breeds to larger dog breeds. They found 

that variation in one gene, IGF–1, which 

codes for the protein hormone insulinlike growth factor 1, is very strongly 

associated with small stature across all 

dog breeds studied. An important 

determinant of body size in mammals, 

IGF–1 induces cell growth and 

differentiation and is a potent inhibitor 

of apoptosis. Analysis of DNA from over 

3,000 dogs and 143 breeds revealed a 

specific IGF–1 gene sequence variant, or 

haplotype, associated with small size in 

the canine genetic code. 

The invention discloses markers 

defining chromosomal haplotypes 

associated with adult body size in dogs. 


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Also claimed are methods and kits for 

predicting adult body size in dogs using 

these markers. A genetic test based on 

this invention would be of use to 

breeders wishing to predict a dog’s size, 

and thus its conformance to the breed 

standard, at adulthood. 

Applications: Canine genetic test to 

predict adult body size. 

Market: In 2006, over 1.7 million 

purebred dogs competed in American 

Kennel Club-sanctioned conformance 

shows in the United States. 

Development Status: Early stage. 

Inventors: Elaine A. Ostrander and 

Nathaniel B. Sutter (NHGRI). 

Publication: N Sutter et al. A single 

IGF1 allele is a major determinant of 

small size in dogs. Science 2007 Apr 

6;316(5821):112–115, doi: 10.1126/ 

science.1137045. 

Patent Status: U.S. Provisional 

Application No. 60/856,411 filed 02 

Nov 2006 (HHS Reference No. E–009–

2007/0–US–01). 

Licensing Status: Available for nonexclusive licensing. 

Licensing Contact: Tara L. Kirby, 

PhD.; 301/435–4426; 

tarak@mail.nih.gov. 

A Neuronal Avalanche Size (NAS) 

Assay to Screen for Cognitive 

Enhancers and Anti-Epileptics 

Description of Technology: Currently 

available methods of detecting and 

measuring EEG activity only crudely 

classify normal and abnormal activity or 

distinguish epileptic activity early in 

the onset of its deviation from normal 

activity. Available for licensing are 

methods for recognizing a new pattern 

of EEG activity called neuronal 

avalanche size (NAS) that has been 

correlated with cognitive function and 

epilepsy. The NAS uses extracellular 

field potentials to measure the 

distribution of synchronized neurons in 

the cortex (neuronal avalanches) and 

thus the state of the cortical network. 

When the avalanche size reaches a 

power law with a slope of ¥3⁄2, the 

system is in the critical state and the 

cortical network is functioning 

optimally to spread information 

throughout the network. If the system 

slope deviates from ¥3⁄2, the system is 

outside the critical state and is either 

epileptic or sub-critical. In animal 

studies measurement of NAS quantified 

a drug’s potential to increase cognitive 

functioning and induce or reduce 

epilepsy. 

The NAS assay may thus enable highthroughput in vitro screens to select 

anti-epileptics and cognitive enhancing 

drugs for continued drug development. 

Because avalanches represent scaleinvariant dynamics they can also be 

recorded using surface (EEG) electrodes. 

This technology may thus be useful in 

assessing cognitive function, epileptic 

pathology and in selecting and 

monitoring drug therapy for epileptic 

patients. 

Applications: 

1. In vitro screen to assess drugs for 

potential use as anti-epileptics for drugs 

with the propensity to cause epilepsy. 

2. In vitro screen to assess drugs with 

the ability to enhance cognitive 

function, and ultimately, relieve 

cognitive defects associated with 

psychiatric illnesses and neurological 

disorders. 

3. EEG monitoring of patients for 

diagnosis and drug selection and 

monitoring. 

Market: 

1. Epilepsy affects approximately 2.7 

million people in the United States, and 

over 50 million people worldwide. 

2. The cost of epilepsy in the United 

States is $12.8 billion per year, where 

eighty percent of this cost is due to 

patients with intractable seizures. 

3. The cost for developing and 

commercializing new drugs is 

approximately $1 billion. 

4. Schizophrenia affects about 1 out of 

100 people in the United States, 

resulting in a public health burden of 

$40 billion per year in the U.S. alone. 

5. Atypical neuroleptics alleviate 

cognitive deficits in schizophrenia and 

are now prescribed to more than 70 

percent of all schizophrenic patients, 

totaling annual sales of $8.7 billion in 

2003. 

6. Atypical neuroleptics have variable 

efficacy in alleviating symptoms, and 

act on multiple, poorly understood 

pathways simultaneously resulting in 

many side effects. 

7. The proposed in vitro screen could 

tremendously facilitate the development 

of more efficient and selective 

psychotropic drugs to alleviate cognitive 

deficits in schizophrenia. 

Development Status: In vivo and in 

vitro data are available. 

Inventors: Dietmar Plenz (NIMH). 

Publications: 

1. JM Beggs, D Plenz. Neuronal 

avalanches in neocortical circuits. J 

Neurosci. 2003 Dec 3;23(35):11167–77. 

2. CV Stewart, D Plenz. Inverted-U 

profile of dopamine-NMDA-mediated 

spontaneous avalanche recurrence in 

superficial layers of rat prefrontal 

cortex. J Neurosci. 2006 Aug 

2;26(31):8148–59. 

Patent Status: U.S. Provisional 

Application No. 60/707,651 filed 12 

Aug 2005 (HHS Reference No. E–294–

2005/0–US–01); PCT Application No. 

PCT/US2006/031884 filed 14 Aug 2006 

(HHS Reference No. E–294–2005/1–

PCT–01). 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Norbert Pontzer, 

J.D., Ph.D.; 301/435–5502; 

pontzern@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIMH/Section of Neural Network 

physiology is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize the NAS assay. Please 

contact Dietmar Plenz at 

plenzd@mail.nih.gov for more 

information. 

Method for Promoting Stem Cell 

Proliferation and Survival 

Description of Technology: This 

technology describes a method to 

promote stem cell survival and 

proliferation by manipulating the 

phosphorylation state of Stat3 protein. 

This method has been shown to 

enhance survival and proliferation in 

stem cell cultures in vitro, and also in 

neuronal precursor cells in vivo. The 

methods include use of a Notch ligand 

and growth factors such as FGF 2 or 

insulin to promote neural stem cell 

survival and proliferation. The 

technology is also directed to a 

population of stem cells expressing 

STAT3 phosphorylated at serine 727. 

Applications: 

1. Clinical treatment for stroke and 

other neurodegenerative diseases by 

administration of agents that promote 

stem cell survival and proliferation. 

2. Increased generation of stem cells 

in vitro. 

3. Screening assays for agents that 

promote proliferation of stem cells or 

inhibit proliferation of cancer cells. 

4. Diagnostic assay for cancer to 

determine the phosphorylation state of 

the protein in tumors. 

Market: 

1. Prognostic marker to help 

determine response of individuals with 

cancer. 

2. Commercial suppliers or large-scale 

users of stem cells. 

Development Status: 

1. A method of increasing 

proliferation and survival of stem cells 

or precursor cells in vitro has been 

developed. The cells produced by this 

method have been described in an 

article in Nature 2006 Aug 

17;442(7104):823–826. 

2. The method of increasing 

proliferation and survival of stem cells 

is efficacious in in vivo rodent models 

of Parkinson’s disease and stroke. 

Inventors: Andreas AndroutsellisTheotokis and Ronald D.G. McKay 

(NINDS). 

Publication: A AndroutsellisTheotokis et al. Notch signalling 


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regulates stem cell numbers in vitro and 

in vivo. Nature 2006 Aug 

17;442(7104):823–826. 

Patent Status: 

1. U.S. Provisional Application No. 

60/715,935 filed 08 Sep 2005 (HHS 

Reference No. E–239–2005/0–US–01). 

2. PCT Application No. PCT/US2006/ 

034988 filed 07 Sep 2006 (HHS 

Reference No. E–239–2005/0–PCT–02). 

Licensing Status: Available for nonexclusive or exclusive licensing. 

Licensing Contact: Fatima Sayyid, 

M.H.P.M.; 301/435–4521; 

sayyidf@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Neurological 

Disorders and Stroke, Laboratory of 

Molecular Biology, is seeking statements 

of capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize agents that inhibit or 

induce phosphorylation of STAT3 

protein and survival of stem cells and 

precursor cells. Please contact Martha 

Lubet at 301/435–3120 or 

lubetm@mail.nih.gov. 

Preparation and Use of Androgenic 

Compounds: Nandrolone 17betacarbonates 

Description of Invention: 

Hypogonadism is defined as deficient or 

absent male gonadal function that 

results in insufficient testosterone 

secretion. Hypogonadism can be caused 

by surgery; radiation; genetic and 

developmental disorders; liver and 

kidney disease; infection; and certain 

auto-immune disorders. The most 

common genetic disorders are 

Klinefelter syndrome found in men and 

Turner syndrome in women. 

Hypogonadism affects an estimated 4 

to 5 million men in the United States, 

and although it may occur in men at any 

age, low testosterone levels are 

especially common in older males. More 

than 60% of men over age 65 have free 

testosterone levels below the normal 

values of men aged 30 to 35. Studies 

suggest that hypogonadism in adult men 

is often underdiagnosed and under 

treated. This may be because the 

symptoms are easily attributed to aging 

or other medical causes, or ignored by 

patients and physicians. In fact, only 

about 5% of hypogonadal men receive 

testosterone replacement. Some experts 

also believe that we need to reevaluate 

normal testosterone levels and lower the 

diagnostic cutoff for hypogonadism. By 

doing so, many patients who we now 

consider to be ‘‘low-normal’’ would 

probably be considered candidates for 

androgen replacement. 

The inventors have discovered 

androgenic compounds, the lead 

compound being 17beta-carbonates of 

nandrolone derivatives. These 

compounds can be used to treat 

hypogonadism, as hormonal therapy 

and as a male contraceptive. The 

disclosed carbonates have potent 

activity when administered as an oral 

composition. In addition, long-lasting 

activity has also been observed with 

subcutaneous administration in 

laboratory animals. It is foreseen that 

these androgens can be utilized in 

hormonal replacement therapy for both 

men and women, which constitute a 

huge market both in the United States 

and abroad. 

Inventors: Richard P. Blye and Hyun 

K. Kim (NICHD). 

Patent Status: U.S. Provisional 

Application No. 60/650,376 filed 04 Feb 

2005 (HHS Reference No. E–181–2004/ 

0–US–01); PCT Application No. PCT/ 

US2006/02436 filed 24 Jan 2006 (HHS 

Reference No. E–181–2004/0–PCT–02). 

Licensing Status: Available for nonexclusive or exclusive licensing. 

Licensing Contact: Tara L. Kirby, PhD; 

301/435–4426; tarak@mail.nih.gov. 

Collaborative Research Opportunity: 

The NICHD Contraception & 

Reproductive Health Branch is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize this technology. Please 

contact John D. Hewes, Ph.D. at 301–

435–3121 or hewesj@mail.nih.gov for 

more information. 

Neural Crest-Melanocyte cDNA Based 

Microarray Analysis for Human Skin 

Pigmentation Research 

Description of Technology: 

Microarrays have wide applications in 

basic research and are used for the 

discovery of candidate genes as markers 

for disease and for therapeutic 

intervention. This invention pertains to 

the identification of a set of neural crestmelanocyte (NC-M) genes through 

microarray analysis and informatic 

analysis. Utilizing the extensive 

sequence information in the expressed 

sequence tag database (dbEST), the 

specific set of cDNA sequence was 

identified for microarray analysis of 

melanocyte function and diseases. This 

integrated technique of sequencing with 

bioinformatics led to the discovery of 

novel genes. The cDNA sequences 

selected in this invention are differently 

expressed in neural crest melanocyte 

derivates relative to non-neural derived 

samples. Given that many of the neuralcrest melanocyte genes are expressed at 

embryonic stages of neural crestmelanocyte development, the gene set 

identified in this invention should 

provide a useful tool for the analysis of 

patterns of transcriptional regulation of 

NC-M development. Thus, this 

technology will be useful for the 

characterization of altered expression 

patterns in diseases such as melanoma. 

Further, this new microarray research 

tool has been developed using the set of 

genes that are likely to be involved in 

the control of human skin pigmentation. 

The microarray system utilizing these 

genes is of significant importance in 

identifying small molecules that may 

modulate their activity leading to 

alterations in human skin pigmentation. 

Therefore, this invention is significantly 

useful to the researchers to study 

alterations in human skin pigment 

amount and type. 

Inventors: William J. Pavan and Stacie 

K. Loftus (NHGRI). 

Patent Status: HHS Reference No. E–

014–2002/0—Research Tool. 

Licensing Status: Available for 

licensing under a Biological Materials 

License. 

Licensing Contact: Tara L. Kirby, PhD; 

301/435–4426; tarak@mail.nih.gov. 

RAB38, a Target for Treatment of 

Melanoma and Pigmentation Disorders 

Description of Technology: 

Melanocytes are specialized pigmentproducing cells that are responsible for 

coloration of skin, eyes and hair. Using 

cDNA microarray expression profiling, 

the inventors have identified RAB38, a 

small GTP-binding protein, as an 

important gene involved in melanocyte 

function. Human RAB38 was localized 

to the mouse chocolate (cht) locus, and 

mutation of this gene in mice changes 

hair color from black to brown, similar 

to OCAIII mice, which have a mutation 

in TYRP1, another melanosomal gene, 

and are used as a model for 

oculocutaneous albinism. 

The inventors have demonstrated that 

RAB38 is important for trafficking of the 

TYRP1 protein; thus, RAB38 mutant 

mice are genocopies of TYRP1 mutant 

mice. Modulation of RAB38 activity, 

such as by pharmacologic intervention, 

might alter pigmentation in human skin. 

Recently, RAB38 has also been 

identified as a melanocyte 

differentiation antigen that is strongly 

immunogenic, leading to spontaneous 

antibody responses in a significant 

proportion of melanoma patients. Thus, 

RAB38 may also have applications for 

melanoma diagnostics and treatment. 

This invention discloses RAB38 

nucleic acids and protein, and methods 

for detecting mutations in RAB38. Also 

disclosed are methods for screening for 

agents to modulate RAB38 activity, and 

for modulating pigmentation through 

modulation of RAB38 activity. 

Applications: 


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1. Marker protein and target for 

antigen-specific immunotherapy in 

patients with malignant melanoma. 

2. Therapeutics and diagnostics for 

melanin-related disorders. 

Development Status: Early stage. 

Inventors: William J. Pavan and Stacie 

K. Loftus (NHGRI). 

Publications: Stacie K. Loftus, Denise 

M. Larson, Laura L. Baxter, Anthony 

Antonellis, Yidong Chen, Xufeng Wu, 

Yuan Jiang, Michael Bittner, John A. 

Hammer III, and William J. Pavan. 

Mutation of melanosome protein RAB38 

in chocolate mice. Proc Natl Acad Sci 

U.S.A. 2002 Apr 2;99(7):4471–4476. 

Patent Status: 

1. U.S. National Stage Application No. 

10/501,611 filed 20 Nov 2005, claiming 

priority to 18 Jan 2002 (HHS Reference 

No. E–315–2001/0–US–07). 

2. Foreign counterparts pending in 

Australia, Canada, Europe, and Japan. 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Tara L. Kirby, 

Ph.D; 301/435–4426; 

tarak@mail.nih.gov. 

Novel Dmt-Tic Analogues Specific for 

Delta- and Mu-Opioid Receptors 

Description of Technology: Opioid 

receptor modulators, used historically 

for pain control, have more recently 

been shown to possess broader 

therapeutic potential in areas such as 

opiate and alcohol abuse, neurological 

disease or injury, neuropeptide or 

neurotransmitter imbalance, and 

immune system dysfunction. 

Furthermore, their interaction with key 

reward pathways presents interesting 

avenues for exploration in the treatment 

of food as an addictive substance, due 

to the fact that obesity is a major health 

problem in the U.S. Also, evidence of 

modulatory interactions between deltaand mu-opioid receptors has spurred 

interest in new opioid ligands 

possessing mixed and dual specificity 

for these receptors. These bifunctional 

compounds are particularly promising 

for treatment of addiction and treatment 

of pain with the elimination of drug 

tolerance. 

The inventors have developed a wide 

variety of highly selective Dmt-Tic 

analogues with potential therapeutic 

applications. These analogues include 

specific agonists and antagonists of the 

delta- and mu-opioid receptors and 

combinations thereof. 

Some disclosed analogues are di- and 

tri-peptidic derivatives of the Dmt-Tic 

pharmacophore; in addition to opioid 

receptor specificity, two of these 

derivatives have been shown to inhibit 

the activity of human multidrug 

resistance glycoprotein 1 (hMDR1) and 

may represent a novel chemosensitizing 

agent for treating cancer, and may also 

be used for reducing tolerance to 

morphine, the drug of choice in most 

hospitals around the world, thereby 

increasing its effectiveness. Also 

disclosed are compounds produced 

through derivatization of Dmt-Tic 

reference compounds with lysine, 

resulting in an unexpected and broad 

range of delta-and/or mu-opioid 

receptor modulation. The inventors 

have also prepared symmetric and 

asymmetric Dmt-Tic di-peptides that are 

potent dual delta- and mu-opioid 

receptor antagonists and that can pass 

through the gastrointestinal and bloodbrain barriers. Finally, the inventors 

have prepared various fluorescent DmtTic analogs that are useful for study of 

delta- and mu-opioid receptor structure 

and function. 

Applications: 

1. Potential opiate, food, and alcohol 

addiction therapeutics. 

2. Potential therapeutics for pain 

treatment. 

3. Potential therapeutics for cancer. 

4. Tools for screening ligand binding 

activity and differentiating between 

delta- and mu-opioid receptors. 

Market: 

1. In 2004, approximately 22 million 

Americans over the age of 12 required 

treatment for alcohol or illicit drug 

abuse and addiction; 13 million of these 

were classified as alcoholics. 

2. Approximately 50 million 

Americans suffer from pain, and an 

estimated 1.5 billion people suffer from 

moderate to severe pain worldwide. 

3. Two-thirds of the U.S. population 

is overweight, with a quarter designated 

as obese (9 million of whom are 

children); the number of overweight 

Americans doubled between 1980–1999 

and is predicted to increase 20% by 

2013 to 140 million. 

Development Status: In vitro data are 

available. 

Inventors: Lawrence H. Lazarus 

(NIEHS) et al. 

Publications: 

1. G. Balboni et al. Effect of lysine at 

C-terminus of the Dmt-Tic opioid 

pharmacophore. J Med Chem. 2006 Sep 

7;49(18):5610–5617. 

2. T Lovekamp et al. Inhibition of 

human multidrug resistance Pglycoprotein 1 by analogues of a potent 

delta-opioid antagonist. Brain Res. 2001 

May 25;902(1):131–134. 

3. T Li et al. Potent Dmt-Tic 

pharmacophoric delta- and mu-opioid 

receptor antagonists. J Med Chem. 2005 

Dec 15;48(25):8035–8044. 

4. T Li et al. Transformation of a muopioid agonist into biologically potent 

mu-opioid antagonists. Bioorg Med 

Chem. 2007 Feb 1;15(3):1237–1251. 

5. G. Balboni et al. Highly selective 

fluorescent analogue of the potent *eltaopioid receptor antagonist Dmt-Tic. J 

Med Chem. 2004 Dec 16:47(26):6541–

6546. 

Patent Status: 

1. U.S. Patent No. 6,753,317 issued 22 

Jun 2004 (HHS Reference No. E–103–

2000/0–US–02). 

2. U.S. Patent No. 6,916,905 issued 12 

Jul 2005 (HHS Reference No. E–103–

2000/1–US–01). 

3. U.S. Patent Application No. 10/ 

280,752 filed 16 Nov 2005 (HHS 

Reference No. E–103–2000/2–US–02). 

4. U.S. Provisional Application No. 

60/834,438 filed 31 Jul 2006 (HHS 

Reference No. E–103–2000/3–US–01). 

5. PCT Application No. PCT/US06/ 

33560 filed 30 Aug 2006 (HHS 

Reference No. E–305–2005/0–PCT–02). 

Licensing Status: Available for 

exclusive or nonexclusive licensing. 

Licensing Contact: Tara L. Kirby, PhD; 

301/435–4426; tarak@mail.nih.gov. 

Dated: April 17, 2007. 

Steven M. Ferguson, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E7–7933 Filed 4–25–07; 8:45 am] 

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