Government-Owned Inventions; Availability for Licensing, 20858-20862 [E7-7933]
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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.
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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;
Major Neutralization Site of Hepatitis E clingmac@mail.nih.gov.
Virus and Use of This Neutralization
Collaborative Research Opportunity:
Site in Methods of Vaccination
The NIAID Laboratory of Infectious
Description of Technology: Hepatitis E Diseases is seeking statements of
capability or interest from parties
is endemic in many countries
interested in collaborative research to
throughout the developing world, in
further develop, evaluate, or
particular on the continents of Africa
commercialize these antibodies or
and Asia. The disease generally affects
structures they interact with. For more
young adults and has a very high
information, please contact Robert H.
mortality rate, up to 20%, in pregnant
Purcell, M.D., Co-chief, Laboratory of
women. This invention relates to the
Infectious Diseases, National Institute of
identification of a neutralization site of
hepatitis E virus (HEV) and neutralizing Allergy and Infectious Diseases,
National Institutes of Health, 50 South
antibodies that react with it. The
Drive, Bldg. 50, Rm. 6523, Bethesda, MD
neutralization site is located on a
polypeptide from the ORF2 gene (capsid 20892–8009; Phone (301) 496–5090; Fax
(301) 402–0524.
gene) of HEV. This neutralization site
was identified using a panel of
Dated: April 17, 2007.
chimpanzee monoclonal antibodies that Steven M. Ferguson,
are virtually identical to human
Director, Division of Technology Development
antibodies. Since this neutralization site and Transfer, Office of Technology Transfer,
is conserved among genetically
National Institutes of Health.
divergent strains of HEV, the
[FR Doc. E7–7930 Filed 4–25–07; 8:45 am]
neutralizing monoclonal antibodies may BILLING CODE 4140–01–P
be useful in the diagnosis, treatment
and/or prevention of hepatitis E.
Furthermore, immunogens that
DEPARTMENT OF HEALTH AND
encompass this neutralization site may
HUMAN SERVICES
be used in vaccination to effectively
National Institutes of Health
prevent, and/or reduce the incidence of
HEV infection. Polypeptides containing
this neutralization site may be useful in Government-Owned Inventions;
Availability for Licensing
evaluating vaccine candidates for the
production of neutralizing antibodies to AGENCY: National Institutes of Health,
HEV.
Public Health Service, HHS.
Inventors: Suzanne U. Emerson
ACTION: Notice.
(NIAID), Robert H. Purcell (NIAID), et
al.
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
Related Publications:
Government and are available for
1. YH Zhou et al. A truncated ORF2
protein contains the most immunogenic licensing in the U.S. in accordance with
35 U.S.C. 207 to achieve expeditious
site on ORF2: antibody responses to
commercialization of results of
non-vaccine sequences following
federally-funded research and
challenge of vaccinated and nondevelopment. Foreign patent
vaccinated macaques with HEV.
applications are filed on selected
Vaccine 2005 May 2;23(24):3157–3165.
inventions to extend market coverage
2. DJ Schofield et al. Monoclonal
for companies and may also be available
antibodies that neutralize HEV
for licensing.
recognize an antigenic site at the
carboxyterminus of an ORF2 protein
ADDRESSES: Licensing information and
vaccine. Vaccine 2003 Dec
copies of the U.S. patent applications
12;22(2):257–267.
listed below may be obtained by writing
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.
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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
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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
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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
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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).
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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
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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
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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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Federal Register / Vol. 72, No. 80 / Thursday, April 26, 2007 / Notices
rwilkins on PROD1PC63 with NOTICES
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
VerDate Aug<31>2005
18:59 Apr 25, 2007
Jkt 211001
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.
PO 00000
Frm 00049
Fmt 4703
Sfmt 4703
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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DATES: Application forms should reach
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[Federal Register Volume 72, Number 80 (Thursday, April 26, 2007)]
[Notices]
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From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-7933]
-----------------------------------------------------------------------
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
[[Page 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 beta-thalassemia, 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 beta-thalassemia
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 beta-thalassemia; 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 insulin-like 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.
[[Page 20860]]
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 non-exclusive 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 high-throughput in vitro screens to
select anti-epileptics and cognitive enhancing drugs for continued drug
development. Because avalanches represent scale-invariant 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 Androutsellis-Theotokis and Ronald D.G. McKay
(NINDS).
Publication: A Androutsellis-Theotokis et al. Notch signalling
[[Page 20861]]
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 non-exclusive 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 17beta-
carbonates
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 non-exclusive 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 crest-melanocyte (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 neural-crest
melanocyte genes are expressed at embryonic stages of neural crest-
melanocyte 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 pigment-
producing 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:
[[Page 20862]]
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 delta- and 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 blood-brain barriers. Finally, the
inventors have prepared various fluorescent Dmt-Tic 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 P-
glycoprotein 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 mu-opioid 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 *elta-opioid 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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