[Federal Register Volume 76, Number 172 (Tuesday, September 6, 2011)]
[Notices]
[Pages 55071-55073]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-22694]


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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.

ADDRESSES: 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

[[Page 55072]]

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.

Antibodies Against TL1A, a TNF-Family Cytokine, for the Treatment and 
Diagnosis of Autoimmune Inflammatory Diseases

    Description of Technology: Autoimmune inflammatory diseases occur 
in greater than five percent of the United States population; this 
disease group includes asthma, multiple sclerosis, rheumatoid 
arthritis, and lupus. Treatments generally include immunosuppressants 
or anti-inflammatory drugs, which can have serious side effects; 
recently, more specific immunomodulatory therapies such as TNF-alpha 
antagonists have been developed.
    In experiments with mice, NIAMS inventors have shown that the 
interaction between the TNF family ligand TL1A with its receptor, DR3, 
is critical for development of disease in asthma, inflammatory bowel 
disease and multiple sclerosis. They have also developed anti-TL1A 
antibodies that prevent disease in mouse models of rheumatoid arthritis 
and inflammatory bowel disease.
    This technology describes anti-mouse TL1A and anti-human TL1A 
monoclonal antibodies that may be useful for the development of 
diagnostics and therapeutics for autoimmune inflammatory disease, as 
well as methods of treating such disease by blocking the interaction 
between TL1A and DR3.
    Potential Commercial Applications:
     Antibody-based therapeutics for autoimmune inflammatory 
disease.
     Diagnostics for autoimmune inflammatory disease.
     Research tools to probe the role of TL1A-DR3 interactions 
in the development of autoimmune disease.
    Competitive Advantages:
     Specific immunomodulatory effect provides potential for 
potent therapy without inducing global immunosuppression.
     Anti-TL1A monoclonal antibodies available for further 
development.
    Development Stage:
     Early-stage.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Richard M. Siegel, Francoise Meylan, Yun-Jeong Song 
(NIAMS).
    Publication: Meylan F, et al. The TNF-family cytokine TL1A drives 
IL-13-dependent small intestinal inflammation. Mucosal Immunol. 2011 
Mar;4(2):172-185. [PMID 20980995].
    Intellectual Property:
     HHS Reference No. E-011-2007/0--U.S. Application No. 11/
972,395 filed 10 Jan 2008.
     HHS Reference No. E-073-2011/0--U.S. Application No. 61/
488,671 filed 20 May 2011.
    Related Technology: HHS Reference No. E-072-2011/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Contact: Tara L. Kirby, PhD; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Arthritis and Musculoskeletal and Skin Diseases is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the anti-mouse 
TL1A and anti-human TL1A monoclonal antibodies. For collaboration 
opportunities, please contact Cecilia Pazman at [email protected].

TL1A Transgenic Mice for the Study of Inflammatory Bowel Disease (IBD) 
and Allergic-Type Immune Responses

    Description of Technology: TL1A is a TNF family cytokine that co-
stimulates T-cell proliferation and cytokine production through its 
interactions with the TNF family receptor DR3. TL1A-DR3 interactions 
have been shown to be important for the development of autoimmune 
inflammatory diseases, including inflammatory bowel disease (IBD).
    In order to probe the role of TL1A-DR3 interactions in IBD, NIAMS 
inventors have developed transgenic mice that constitutively express 
TL1A in T cells or in dendritic cells. These mice spontaneously develop 
inflammatory small bowel pathology that is IL-13 dependent, and that 
closely resembles intestinal responses to allergens and to nematode 
infection.
    These mice represent a unique model for the study of IBD, and in 
particular, the role of IL-13 in the development of this disease. They 
may also be used as a platform for investigating agents that block 
TL1A-DR3 interactions and the pathology associated with chronic TL1A 
expression.
    Potential Commercial Applications:
     Studies of small bowel inflammation/IBD.
     Studies of the role of TL1A-DR3 interactions in the 
development of autoimmune inflammatory disease.
     Investigation of TL1A-DR3 blocking agents for the 
treatment of IBD or other TL1A-DR3 dependent diseases.
    Competitive Advantages:
     Lines available with transgene expressed in T cells (under 
CD2 promoter) or dendritic cells (CD11c promoter).
     Models are IL-13 dependent.
     No major defects in systemic immunity.
    Development Stage: In vivo data available (animal).
    Inventors: Richard M. Siegel and Francoise Meylan (NIAMS).
    Publications:
    1. Meylan F, et al. The TNF-family cytokine TL1A drives IL-13-
dependent small intestinal inflammation. Mucosal Immunol. 2011 
Mar;4(2):172-185. [PMID 20980995].
    2. Meylan F, et al. The TNF-family receptor DR3 is essential for 
diverse T cell-mediated inflammatory diseases. Immunity. 2008 Jul 
18;29(1):79-89. [PMID 18571443].
    Intellectual Property: HHS Reference No. E-072-2011/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Related Technologies:
     HHS Reference No. E-011-2007/0--U.S. Application No. 11/
972,395 filed 10 Jan 2008.
     HHS Reference No. E-073-2011/0--U.S. Application No. 61/
488,671 filed 20 May 2011.
    Licensing Contact: Tara L. Kirby, PhD; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Arthritis and Musculoskeletal and Skin Diseases is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize TL1A Transgenic 
Mice. For collaboration opportunities, please contact Cecilia Pazman at 
[email protected].

Human Monoclonal Antibodies Cross-reacting to Insulin-like Growth 
Factors IGF-I and IGF-II as Potential Anti-tumor Agents

    Description of Technology: The type 1 insulin-like growth factor 
(IGF) receptor (IGF1R) is over-expressed by many tumors and mediates 
proliferation, motility, and protection from apoptosis. Agents that 
inhibit IGF1R expression or function can potentially block tumor growth 
and metastasis. Its major ligands, IGF-I, and IGF-II are over-expressed 
by multiple tumor types. Previous studies indicate that inhibition of 
IGF-I, and/or IGF-II binding to its cognizant receptor negatively 
modulates signal transduction through the IGF pathway and concomitant 
cell proliferation and growth. Therefore, use of humanized or fully 
human antibodies against IGFs

[[Page 55073]]

represents a valid approach to inhibit tumor growth.
    The present invention discloses the identification and 
characterization of a fully human monoclonal antibody designated m708.5 
that has been affinity maturated against IGF-I and IGF-II and displays 
extremely high affinities for IGF-I and IGF-II in the picoM range. The 
m708.5 antibody potently inhibited signal transduction mediated by the 
IGF-1R interaction with IGF-I and IGF-II and blocked phosphorylation of 
IGF-IR and the insulin receptor. Further, this antibody inhibited 
migration in the MCF-7 breast cancer cell line at the picoM range. 
Therefore, this antibody can be used to prevent binding of IGF-I and/or 
IGF-II to its concomitant receptor IGFIR, consequently, modulating 
diseases such as cancer.
    Potential Commercial Applications:
     Therapeutic for the treatment of various human diseases 
associated with aberrant cell growth and motility such as breast, 
prostate, and leukemia carcinomas.
     Research regent to study IGF-I and/or IGF-II binding and 
its association with tumor growth.
    Competitive Advantages:
     Antibodies against the ligands IGF-I and IGF-II, such as 
this invention, inhibit the interaction with IGF-IR yet likely do not 
have the type of toxicity associated with IGF-1R antibodies.
     High concentrations of IGF-II are found in cancer 
patients, on average several fold higher than IGF-I, thus this cross-
reacting IGF-I/IGF-II antibody could be more effective than existing 
IGF-IR and/or IGF-I currently in the clinic.
     This novel IGF antibody may provide therapeutic 
intervention for multiple carcinomas.
    Development Stage:
     Pre-clinical.
     In vitro data available.
    Inventors: Dimiter Dimitrov, Zhongyu Zhu, and Qi Zhao (NCI).
    Publications:
    1. Zhao Q, et al. Human monoclonal antibody fragments binding to 
insulin-like growth factors 1 and 2 with picomolar affinity. Mol Cancer 
Ther. 2011 Jul 12; Epub ahead of print. [PMID 21750218].
    2. Feng Y, et al. Novel human monoclonal antibodies to insulin-like 
growth factor (IGF)-II that potently inhibit the IGF receptor type I 
signal transduction function. Mol Cancer Ther. 2006;5(1):114-120. [PMID 
18283605].
    3. Kimura T, et al. Targeting of bone-derived insulin-like growth 
factor-II by a human neutralizing antibody suppresses the growth of 
prostate cancer cells in a human bone environment. Clin Cancer Res. 
2010 Jan 1;16(1): 121-129. [PMID 20028742].
    Intellectual Property: HHS Reference No. E-068-2011/0--U.S. 
Provisional Application No. 61/474,664 filed 12 April 2011.
    Related Technologies:
     HHS Reference No. E-336-2005/0--U.S. Patent Application 
No. 12/296,328 filed 07 Oct 2008; Antibody Compositions and Methods for 
Treatment of Neoplastic Disease.
     HHS Reference No. E-217-2005/0--U.S. Patent No. 7,824,681 
issued 02 Nov 2010; Human Monoclonal Antibodies that Specifically Bind 
IGF-II.
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The NCI CCR Nanobiology 
Program, Protein Interaction Group, 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 John Hewes, PhD at 
[email protected].

Transgenic Mice Expressing Human Arginase II Gene in Endothelium: 
Useful for Studying Atherosclerosis and Other Vasculopathies

    Description of Technology: Cardiovascular disorders associated with 
endothelial dysfunction, like atherosclerosis, have decreased 
endothelial nitric oxide (NO) bioavailability. L-arginine, the primary 
substrate for endothelial nitric oxide synthase (eNOS), is important in 
the regulation of NO production. Arginase competes with eNOS for L-
arginine and has been implicated in the endothelial dysfunction. NIH 
investigators have generated transgenic mice with human ArgII (hArgII) 
gene under control of endothelial-specific Tie2 promoter. In these 
mice, hArgII was expressed at very high levels in all tissues except 
liver. Analysis has shown that expression of hArgII was endothelium-
specific. Overexpression of hArgII neither led to significant changes 
in plasma level of arginine, citrulline, NOHA, ADMA, SDMA and 
ornithine, nor to changes in plasma lipid levels. Level of arginase 
activity in peritoneal macrophages isolated from the transgenic mice 
also was also unchanged. However, ArgII overexpression induced signs of 
endothelial dysfunction. In apoE-knockout mice hArgII led to 2-fold 
increasing in aortic area with atherosclerotic lesions. The Tie2hArgII 
transgenic mouse can be useful as a new model for investigating the 
role of ArgII in endothelial function and development of 
atherosclerosis.
    Potential Commercial Applications:
     Useful to study the role of arginase II gene in 
endothelium.
     Useful for testing the drugs for treatment of the 
endothelial dysfunction related to eNOS insufficiency, including 
hypertension.
     Useful to study mechanisms of atherosclerosis.
    Competitive Advantages: Better model system to study functional 
significance of arginase II.
    Development Stage:
     Early-stage.
     Pre-clinical.
     In vivo data available (animal).
    Inventors: Boris L. Vaisman and Alan T. Remaley (NHLBI).
    Publication: Vaisman BL, et al. Abstract 3636: The Effects of 
Arginase II Overexpression on Endothelial Function in Transgenic Mouse 
Model. Circulation. 2008 Oct 28;118:S--455.
    Intellectual Property: HHS Reference No. E-255-2010/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Suryanarayana (Sury) Vepa, PhD; 301-435-5020; 
[email protected].

    Dated: August 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-22694 Filed 9-2-11; 8:45 am]
BILLING CODE 4140-01-P