[Federal Register Volume 77, Number 79 (Tuesday, April 24, 2012)]
[Notices]
[Pages 24497-24499]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-9776]
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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.
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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.
FOR FURTHER INFORMATION CONTACT: Licensing information and copies of
the U.S. patent applications listed below may be obtained by writing 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.
Small-Molecule Modulators of Lipid Storage for Treatment of Obesity,
Atherosclerosis, Metabolic Syndrome and Lipid Storage Diseases
Description of Technology: Lipid droplets are key organelles
involved in lipid homeostasis. In normal physiology, these droplets are
formed in response to elevated fatty acid levels, and are broken down
when needed for energy production. Imbalances in lipid homeostasis
trigger compensatory alterations in metabolism that can lead to
diseases such as obesity, atherosclerosis, and metabolic syndrome.
There are also a number of inherited lipid storage diseases that result
in harmful buildup of various lipids, such as Gaucher disease, Fabry
disease, and others. Reducing the accumulation of lipid droplets is a
promising potential strategy for treatment of such disorders.
This technology describes three novel structural classes of small-
molecule compounds that significantly reduce the accumulation of lipid
droplets. These compounds hold promise for the treatment of diseases
associated with aberrant lipid deposition.
Potential Commercial Applications:
Treatment of inherited metabolic diseases such as Gaucher
disease, Fabry disease, and Tay Sachs disease.
Treatment of obesity and metabolic disease.
Treatment of atherosclerosis.
Competitive Advantages: Modulation of lipid droplet accumulation is
a novel mechanism for treatment of lipid storage diseases.
Development Stage:
Early-stage
In vitro data available
Inventors: Matthew Boxer et al. (NCATS).
Intellectual Property: HHS Reference No. E-277-2011/0--U.S.
Provisional Patent Application No. 61/562,894 filed 22 Nov 2011.
Licensing Contact: Tara L. Kirby, Ph.D.; 301-435-4426;
[email protected].
A Broadly Neutralizing Human Anti-HIV Monoclonal Antibody (10E8)
Capable of Neutralizing Most HIV-1 Strains
Description of Technology: This Human Anti-HIV Monoclonal Antibody
(10E8) has great potential to provide passive protection from
infection, as a therapeutic vaccine, or as a tool for the development
of vaccine immunogens. 10E8 is one of the most potent HIV-neutralizing
antibodies isolated thus far and it can potently neutralize up to 98%
of genetically diverse HIV-1 strains. 10E8 is specific to the membrane-
proximal external region (MPER) of the HIV envelope protein, GP41. It
is anticipated that 10E8 could be used in combination with another
human anti-HIV-1 monoclonal antibody to provide an antibody response
that neutralizes nearly all strains of HIV-1. Additionally, 10E8 is a
useful tool for the design of vaccine immunogens that can elicit an
adaptive immune response to produces 10E8 like antibodies. This
technology also includes monoclonal antibodies from the same germ line
as 10E8.
Potential Commercial Applications:
Passive protection to prevent HIV infection
Passive protection to prevent mother-to-infant HIV
transmission
Topical microbicide to prevent HIV infection
Gene-based vectors for anti-gp41 antibody expression
Therapeutic for the elimination of HIV infected cells that are
actively producing virus
Competitive Advantages:
[[Page 24498]]
One of the most potent Human broadly-neutralizing anti HIV
antibodies isolated to date
Broad reactivity and high affinity to most HIV-1 strains
Activity is highly complementary to existing broadly
neutralizing antibodies, such as CD4 binding site antibodies
Capable of neutralizing all HIV-1 strains, if used in
combination with another anti-HIV monoclonal antibody
Development Stage:
Pre-clinical
In vitro data available
In vivo data available (animal)
Publication: In press.
Intellectual Property: HHS Reference No. E-253-2011/0--US
Provisional Application No. 61/556,660 filed 07 Nov 2011.
Related Technologies:
HHS Reference No. E-123-2005/1--PCT Application No. PCT/
US2006/005613 filed 17 Feb 2006
HHS Reference No. E-291-2008/0--US Application No. 13/057,414
filed 03 Feb 2011
Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., MBA; 301-435-
4507; [email protected].
Collaborative Research Opportunity: The National Institute of
Allergy and Infectious Diseases is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate or commercialize vaccine immunogens capable of
eliciting a 10E8-like adaptive immune response. For collaboration
opportunities, please contact Bill Ronnenberg at 301-451-3522 or
[email protected].
Cytochromes P450 CYP2J and CYP2C Polyclonal Antibodies and Recombinant
Proteins
Description of Technology: The National Institutes of Health
announces polyclonal antibodies against mouse cytochrome P450s CYP2J
and CYP2C. Cytochrome P450s catalyze the metabolism of a wide range of
exogenous compounds, including drugs, industrial chemicals,
environmental pollutants, and carcinogens. The 2C family of cytochrome
P450 metabolizes an extensive number of drugs which include
tolbutamide, S-Warfarin, mephenytoin, diazepam and taxol. Many of the
P450 enzymes are also active in the NADPH-dependent oxidation of
arachidonic acid to various eicosanoids found in several species. The
2J family is expressed at high levels in the heart and has been shown
to metabolize both arachidonic acid and linoleic acid. The CYP2J and
CYP2C subfamily members have a wide tissue distribution and may be
useful as model systems for studies of cardiovascular disease, drug
metabolism and toxicity.
Recombinant proteins of mouse cytochrome P450s CYP2C and CYP2J have
also been expressed and can be used as controls in immunoblotting, as
well as for metabolism studies.
Potential Commercial Applications:
These antibodies can be used to study the expression of
the P450s in various tissues by immunohistochemistry and
immunoblotting.
The recombinant proteins can be used as controls in
immunoblotting as well as for metabolism studies.
Competitive Advantages: The CYP2J and CYP2C subfamily members have
a wide tissue distribution and may be useful as model systems for
studies of cardiovascular disease, drug metabolism and toxicity.
Development Stage: In vitro data available.
Inventors: Darryl C. Zeldin (NIEHS) et al.
Publications: Manuscripts in preparation.
Intellectual Property: HHS Reference No. E-153-2011/0--Research
Material. Patent protection has not been pursued for this technology.
Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521;
[email protected].
Collaborative Research Opportunity: The NIEHS is seeking statements
of capability or interest from parties interested in collaborative
research to further develop, evaluate or commercialize antibodies
against mouse cytochrome P450s CYP2J and CYP2C. For collaboration
opportunities, please contact Elizabeth M. Denholm, Ph.D. at
[email protected].
Monoclonal Antibodies Targeting Human DNA Polymerase beta, a DNA Repair
Enzyme
Description of Technology: Available for licensing are monoclonal
antibodies targeting human DNA polymerase beta (Pol B). Pol B is a
constitutively expressed ``housekeeping'' enzyme that plays a role in
base excision repair (BER), a cellular defense mechanism that repairs
DNA base damage and loss. Aberrant Pol B expression is associated with
genomic instability indicating that Pol B is required for DNA
maintenance, replication and recombination.
These antibodies can be utilized to elucidate BER's mechanism of
action and Pol B's structure and function. Moreover, the antibodies can
be used to detect Pol B in samples with a variety of techniques
including immunoblotting, ELISA, immunoprecipitation, and
immunohistochemistry.
Potential Commercial Applications:
Research tool to elucidate the mechanism of base excision
repair
Research reagents
Competitive Advantages: Can be utilized in a variety of
applications to study Pol B.
Development Stage:
Early-stage
In vitro data available
Inventors: Samuel Wilson and Rajendra Prasad (NIEHS).
Publications:
1. Srivastava DK, et al. Phorbol ester abrogates up-regulation of DNA
polymerase beta by DNA-alkylating agents in Chinese hamster ovary
cells. J Biol Chem. 1995 Jul 7;270(27):16402-8. [PMID 7608211]
2. Singhal R, et al. DNA polymerase beta conducts the gap-filling step
in uracil-initiated base excision repair in a bovine testis nuclear
extract. J Biol Chem. 1995 Jan 13;270(2):949-57. [PMID 7822335]
3. Prasad R, et al. Specific interaction of DNA polymerase beta and DNA
ligase I in a multiprotein base excision repair complex from bovine
testis. J Biol Chem. 1996 Jul 5;271(27):16000-7. [PMID 8663274]
4. Piersen C, et al. Evidence for an imino intermediate in the DNA
polymerase beta deoxyribose phosphate excision reaction. J Biol Chem.
1996 Jul 26;271(30):17811-5. [PMID 8663612]
5. Sobol R, et al. Regulated over-expression of DNA polymerase beta
mediates early onset cataract in mice. DNA Repair (Amst). 2003 May
13;2(5):609-22. [PMID 12713817]
6. Poltoratsky V, et al. Down-regulation of DNA polymerase beta
accompanies somatic hypermutation in human BL2 cell lines. DNA Repair
(Amst). 2007 Feb 4;6(2):244-53. [PMID 17127106]
Intellectual Property: HHS Reference No. E-036-2008/0--Research
Tool. Patent protection is not being pursued for this technology.
Licensing Contact: Jennifer Wong; 301-435-4633;
[email protected].
Collaborative Research Opportunity: The NIEHS is seeking statements
of capability or interest from parties interested in collaborative
research to further develop, evaluate or commercialize these monoclonal
antibodies. For collaboration
[[Page 24499]]
opportunities, please contact Elizabeth M. Denholm, Ph.D. at
[email protected].
Treatment of Acute and Chronic Neurological Disorders Using GLP-1,
Exendin-4 and Analogs
Description of Technology: Glucagon-like peptide-1 (GLP-1) and
related peptides, including exendin-4 and liraglutide, are incretin
mimetics that enhance glucose-dependent insulin secretion following
food ingestion as a regulator of glucose homeostasis. Exendin-4 and
liraglutide are used clinically in the safe and effective treatment of
type 2 diabetes to enhance insulin secretion and maintain a euglycemic
state. These actions are primarily mediated at the level of the GLP-1
receptor in the pancreas; however, these compounds are known to enter
the brain where the GLP-1 receptor also is expressed.
Researchers at the NIH have discovered the novel use of GLP-1 and
exendin-4 analogs in the treatment of acute and chronic neurological
disorders and neurodegenerative diseases. Studies conducted in
extensive cell culture and in mouse models using these analogs have
demonstrated significant neurotrophic and neuroprotective actions in
models of several disorders, including Alzheimer's disease, Parkinson's
disease, Huntington's disease, ALS, stroke, head trauma and peripheral
neuropathy. These studies have now been extensively published and
independently validated by other scientific groups. Furthermore,
clinical studies are ongoing to evaluate the use of GLP-1 receptor
agonists for the treatment of early Alzheimer's disease, Parkinson's
disease and diabetic neuropathy by several groups within the US and
Europe.
Potential Commercial Applications: Therapeutics for:
Neurodegenerative diseases--Alzheimer's, Huntington's,
Parkinson's, ALS
Stroke
Head trauma (traumatic brain injury)
Peripheral neuropathies
Competitive Advantages:
Compounds reduce neuronal cell death, amyloid deposition
and neuroinflammation while promoting neurogenesis.
Compounds in this class have already been shown to be safe
and effective for other indications.
Extensive in vitro and animal data are available, and
clinical studies are ongoing.
There are extensive publications in the literature, both
from the inventors and independent groups.
Development Stage:
Pre-clinical
Clinical
In vitro data available
In vivo data available (animal)
In vivo data available (human)
Inventors: Nigel Greig, Harold Halloway, Maire Doyle, Josephine
Egan (all of NIA).
Publications:
1. Li Y, et al. Exendin-4 ameliorates motor neuron degeneration in
cellular and animal models of amyotrophic lateral sclerosis. PLoS One.
2012;7(2):e32008. [PMID 22384126]
2. Li Y, et al. Enhancing the GLP-1 receptor signaling pathway leads to
proliferation and neuroprotection in human neuroblastoma cells. J
Neurochem. 2010 Jun;113(6):1621-1631. [PMID 20374430]
3. Li Y, et al. GLP-1 receptor stimulation reduces amyloid-beta peptide
accumulation and cytotoxicity in cellular and animal models of
Alzheimer's disease. J Alzheimers Dis. 2010;19(4):1205-1219. [PMID
20308787]
4. Li Y, et al. GLP-1 receptor stimulation preserves primary cortical
and dopaminergic neurons in cellular and rodent models of stroke and
Parkinsonism. Proc Natl Acad Sci USA. 2009 Jan 27;106(4):1285-1290.
[PMID 19164583]
5. Martin B, et al. Exendin-4 improves glycemic control, ameliorates
brain and pancreatic pathologies and extends survival in a mouse model
of Huntington's disease. Diabetes. 2009 Feb;58(2):318-328.
[PMID:18984744]
6. Perry T, et al. Evidence of GLP-1-mediated neuroprotection in an
animal model of pyridoxine-induced peripheral sensory neuropathy. Exp
Neurol. 2007 Feb;203(2):293-301. [PMID 17125767]
7. Perry T, Greig NH. Enhancing central nervous system endogenous GLP-1
receptor pathways for intervention in Alzheimer's disease. Curr
Alzheimers Res. 2005 Jul;2(3):377-385. [PMID 15974903]
8. Greig NH, et al. New therapeutic strategies and drug candidates for
neurodegenerative diseases: p53 and TNF-alpha inhibitors, and GLP-1
receptor agonists. Ann NY Acad Sci. 2004 Dec;1035:290-315. [PMID
15681814]
9. Perry TA, Greig NH. A new Alzheimer's disease interventive strategy:
GLP-1. Curr Drug Targets. 2004 Aug;5(6):565-571. [PMID 15270203]
Listing of additional related publications available upon request.
Intellectual Property: HHS Reference No. E-049-2001/0--
U.S. Patent 7,576,050 issued 18 Aug 2009
U.S. Patent Application No. 12/317,042 filed 18 Dec 2008
Foreign counterparts in Australia, Canada, Europe, India, and
Japan
Licensing Contact: Tara L. Kirby, Ph.D.; 301-435-4426;
[email protected].
Collaborative Research Opportunity: The National Institute on
Aging, Drug Design and Development Section, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate or commercialize this technology.
For collaboration opportunities, please contact Vio Conley at
[email protected].
Dated: April 18, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-9776 Filed 4-23-12; 8:45 am]
BILLING CODE 4140-01-P