[Federal Register Volume 77, Number 192 (Wednesday, October 3, 2012)]
[Notices]
[Pages 60442-60444]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-24251]


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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.

A Novel Immortalized Human Adrenal Cell Line With Inactive Protein 
Kinase A for Studies on cAMP Signaling and Endocrine Tumorigenesis

    Description of Technology: The first known immortalized cell line 
with a naturally-occurring inactivating mutation in PRKAR1A, the 
regulatory subunit type 1A (R1alpha) of protein kinase A (PKA), which 
is associated with tumor formation.
    PKA isozyme balance is critical for the control of cAMP signaling 
and related cell cycle and proliferation changes. Aberrant cAMP 
signaling has been linked to adrenocortical and other, mostly 
endocrine, tumors. Inactivating mutations in the PRKAR1A gene are a 
known cause of Carney Complex--an autosomal dominant multiple neoplasia 
syndrome associated with skin, heart, and other myxomas and a variety 
of endocrine tumors.
    Potential Commercial Applications:
     Studies on multiple tumor formation associated with Carney 
Complex.
     Characterization of cAMP-mediated mechanisms of endocrine 
tumor formation.
     Studies of a large variety of cAMP-mediated processes in 
normal physiology and disease.
    Competitive Advantages: First known immortalized cell line with a 
naturally-occurring inactivating mutation in the PRKAR1A gene.
    Development Stage: In vitro data available.
    Inventor: Constantine A. Stratakis (NICHD).
    Publication: Nesterova M, et al. An immortalized human cell line 
bearing a PRKAR1A-inactivating mutation: effects of overexpression of 
the wild-type

[[Page 60443]]

Allele and other protein kinase A subunits. J Clin Endocrinol Metab. 
2008 Feb;93(2):565-71. [PMID 18056771].
    Intellectual Property: HHS Reference No. E-267-2012/0--Research 
Material. Patent protection is not being pursued for this technology.
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The Eunice Kennedy Shriver 
National Institute of Child Health and Human Development 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 Joseph 
Conrad III, Ph.D. at [email protected].

Modulation of Regulatory T-Cell and B-Cell Lymphocytes for the 
Treatment of Autoimmune and Other Disease Indications

    Description of Technology: A method of modulating the immune 
response by affecting the activity of the regulatory lymphocytes 
through targeting of the Hepatitis A Virus receptor 1 (HAVCR1) 
receptor. This methodology can be developed for the treatment of 
autoimmune diseases, allergies, prevention of transplant rejection, and 
incorporated into therapeutic strategies for cancer.
    Regulatory lymphocytes, such as regulatory T-cells (Tregs) and B-
cells (Bregs), play a significant role in suppressing and controlling 
immune responses to antigens, including allergens and self-antigens 
that induce autoimmune diseases. The Tregs and Bregs also control the 
immune responses to microbial pathogens thereby limiting excessive 
damage to tissue. HAVCR1 is expressed on these regulatory lymphocytes 
and functions as a master regulator of these cells.
    Potential Commercial Applications:
     Treatment of Autoimmune Diseases.
     Treatment of Allergies.
     Prevention of Rejection of Allogenic Transplants.
     Cancer Therapy.
     Immunotherapies.
     Stimulate Response to Vaccines (adjuvant).
    Competitive Advantages: Can be used to target multiple disease 
states.
    Development Stage:
     Early-stage.
     Pre-clinical.
     In vitro data available.
    Inventors: Gerardo Kaplan, Mohanraj Manangeeswaran, Jerome Jacques, 
Krishnamurthy Konduru (all of FDA).
    Publication: Manangeeswaran M, et al. Binding of hepatitis A virus 
to its cellular receptor 1 inhibits T-regulatory cell functions in 
humans. Gastroenterology. 2012 Jun;142(7):1516-25.e3. [PMID 22430395].
    Intellectual Property: HHS Reference No. E-095-2012/0--U.S. 
Provisional Application No. 61/611,437 filed 15 Mar 2012.
    Related Technology: HHS Reference No. E-150-1994/0--U.S. Patent 
5,622,861 issued 22 Apr 1997 (Hepatitis A Virus Receptor).
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected].
    Collaborative Research Opportunity: The Center for Biologics 
Evaluation and Research, Laboratory of Emerging Pathogens, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
targeting of HAVCR1 to control Treg and Breg function in human 
diseases. For collaboration opportunities, please contact Gerardo 
Kaplan at [email protected].

A Method To Expand a Population of Regulatory T Cells Optimal for the 
Treatment of Autoimmune Diseases

    Description of Technology: The transfusion of regulatory T cells 
(Tregs) has been used in the clinic to successfully prevent graft vs. 
host disease and is currently being evaluated in the treatment of other 
autoimmune diseases, such as organ graft rejection, type 1 diabetes and 
multiple sclerosis. Prior to transfusion, adoptive regulatory T cell 
transfer requires the expansion of regulatory T cells in culture; this 
results in a mixed population of regulatory T cells that limits the 
effectiveness of the transferred cells.
    Scientists at the NIH have developed a method that promotes the 
expansion of regulatory T cells that are longer lived, more stable, and 
more suppressive of the autoimmune response. By supplementing T cell 
cultures with DNA oligonucleotides, the inventors were able to enrich 
the regulatory T cell population that enhanced the suppression of the 
autoimmune response. This method has the potential to more effectively 
generate regulatory T cells for the treatment of autoimmune diseases.
    Potential Commercial Applications: Treatment of autoimmune 
diseases, such as Graft vs. Host Disease, Organ Graft Rejection Type 1 
Diabetes, Multiple Sclerosis.
    Competitive Advantages:
     More effective therapy when compared to traditional T cell 
expansion methods.
     Expansion method is inexpensive and similar to current 
methods.
    Development Stage: In vitro data available.
    Inventors: Yong Chan Kim and Ethan M. Shevach (NIAID).
    Publication: Kim Y, et al. Oligodeoxynucleotides stabilize Helios-
expressing Foxp3+ human T regulatory cells during in vitro expansion. 
Blood. 2012 Mar 22;119(12):2810-8. [PMID 22294730].
    Intellectual Property: HHS Reference No. E-279-2011/0--U.S. 
Provisional Application No. 61/576,837 filed 16 Dec 2011.
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].

Peptides for Treatment of Tumor Necrosis Factor Alpha Mediated 
Inflammatory Disease

    Description of Technology: Tumor Necrosis Factor alpha (TNF-alpha) 
is a multifunctional cytokine that mediates inflammation, immune 
regulation, and cellular proliferation. This cytokine is converted to 
its active form by TNF-alpha converting enzyme (TACE). Pathological 
increases in TNF-alpha activity have been associated with a wide 
variety of inflammatory diseases, including inflammatory bowel disease, 
rheumatoid arthritis, and cancer. Inhibiting the conversion of TNF-
alpha to its active form by inhibiting TACE represents a potential 
treatment for these diseases.
    The current technology provides peptides, derived from an N-
terminal fragment of the TACE protein, that inhibit TACE activity. Also 
described are methods of using these peptides to lower levels of active 
TNF-alpha. These peptides could be used as a treatment for TNF-alpha-
mediated inflammatory diseases.
    Potential Commercial Applications: Treatment of TNF-alpha mediated 
inflammatory diseases.
    Competitive Advantages: Inhibition of TACE activity represents a 
novel mechanism to treat inflammatory disease.
    Development Stage:
     Early-stage.
     In vitro data available.
    Inventors: Stewart J. Levine et al. (NHLBI).
    Publication: Buckley CA, et al. Amino-terminal TACE prodomain 
attenuates TNFR2 cleavage independently of the cysteine switch. Am J 
Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1132-8. [PMID 
15749738].

[[Page 60444]]

    Intellectual Property: HHS Reference No. E-208-2003/0--U.S. Patent 
No. 7,655,752 issued 02 Feb 2010.
    Licensing Contact: Tara Kirby, Ph.D.; 301-435-4426; 
[email protected].

Human Antibodies and Fusion Proteins With Potent and Broad HIV-1 
Neutralizing Activity

    Description of Technology: The inventions listed below provide 
multiple novel human anti-HIV-1 domain antibodies (m36 and its 
affinity- matured versions) and their fusion proteins with two-domain 
or single-domain human soluble CD4 (sCD4) that can potentially be used 
alone or synergistically with other anti-HIV-1 antibodies and 
antiretroviral drugs as therapeutics and/or preventatives for infection 
by different HIV-1 strains.
    Some of the inventions listed below also describe some fusion 
proteins as vaccine immunogens that could elicit broadly neutralizing 
antibodies against HIV-isolates from different clades. One invention 
also describes the methods to prepare and use the immunogens in the 
vaccination for prevention of HIV-1 infections. More specifically, the 
later invention provides a vaccine composed of a primary immunogen and 
a secondary immunogen, and a method for making the vaccine which could 
be effective in eliciting desired broadly neutralizing antibodies. The 
primary immunogen could be effective in activating B cell receptors 
(BCRs) that are on the maturational pathways of the desired antibodies 
and have an intermediate degree of somatic mutational diversity. The 
secondary immunogen contains epitopes of the desired antibodies and 
could be effective in further diversifying the BCRs sufficiently to 
form mature BCRs that have the identical or substantially identical 
sequence as the desired antibodies.
    Potential Commercial Applications: Treatment and prevention of HIV-
1 infections.
    Competitive Advantages:
     Elicits broadly neutralizing antibodies against HIV-1 
isolates from different clades.
     Potentially elicits antibodies that are not regulated by 
tolerance mechanisms.
     Novel methods to design vaccines for HIV-1 treatment and 
prevention.
     May also be used for designing vaccines for cancer 
treatment.
     Relatively small size allows for potential penetration 
into lymphoid tissues.
    Development Stage:
     In vitro data available.
     In vivo data available (animal).
    Inventors: Dimiter Dimitrov and Weizao Chen (NCI).
    Publications:
    1. Chen W, et al. Human domain antibodies to conserved sterically 
restricted regions on gp120 as exceptionally potent cross-reactive HIV-
1 neutralizers. Proc Natl Acad Sci USA. 2008 Nov 4;105(44):17121-6. 
[PMID 18957538].
    2. Chen W, et al. Engineered single human CD4 domains as potent 
HIV-1 inhibitors and components of vaccine immunogens. J Virol. 2011 
Sep;85(18):9395-405. [PMID 21715496].
    3. Chen W, et al. Bifunctional fusion proteins of the human 
engineered antibody domain m36 with human soluble CD4 are potent 
inhibitors of diverse HIV-1 isolates. Antiviral Res. 2010 
Oct;88(1):107-15. [PMID 20709110].
    4. Chen W, Dimitrov DS. Human monoclonal antibodies and engineered 
antibody domains as HIV entry inhibitors. Curr Opin HIV AIDS. 2009 
Mar;4(2):112-7. [PMID 19339949].
    Intellectual Property:
     HHS Reference No. E-043-2008/0--U.S. Patent Application 
No. 12/811,998 filed 07 Jul 2010; related international applications.
     HHS Reference No. E-322-2008/0--U.S. Patent Application 
No. 13/123,659 filed 11 Apr 2011.
     HHS Reference No. E-103-2010/1--PCT Application No. PCT/
US2011/037439 filed 20 May 2011, which published as WO 2011-146891 on 
31 May 2012.
    Licensing Contact: Sally Hu, Ph.D.; 301-435-5606; [email protected].
    Collaborative Research Opportunity: The NCI CCR Nanobiology Program 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate or commercialize 
m36, single domain sCD4, and related fusion proteins as candidate 
therapeutics against HIV-1. For collaboration opportunities, please 
contact John Hewes, Ph.D. at [email protected].

    Dated: September 27, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-24251 Filed 10-2-12; 8:45 am]
BILLING CODE 4140-01-P