[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