[Federal Register Volume 71, Number 179 (Friday, September 15, 2006)]
[Notices]
[Pages 54504-54505]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-15294]


-----------------------------------------------------------------------

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 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.

Human Protein Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) Derived 
Anti-Angiogenic Peptides

    Description of Technology: Cancer is the second leading cause of 
death in United States and it is estimated that there will be 
approximately 600,000 deaths caused by cancer in 2006. A major drawback 
of the existing chemotherapies is the cytotoxic side-effects that are 
associated with them. Thus, there is a need to develop new therapeutic 
approaches with reduced side-effects.
    Anti-angiogenic therapy is a recent approach in cancer therapeutics 
targeting the formation of blood vessels that are necessary for tumor 
growth. Recently, the anti-angiogenic molecule bevacizumab (Avastin) 
has gained approval from the FDA for the first-line treatment of 
metastatic colon cancer in combination with standard chemotherapy.
    Human protein tissue inhibitor of metalloproteinases-2 (TIMP-2) has 
been shown to inhibit angiogenesis in vivo independent of 
metalloproteinase inhibition. This technology discloses new peptide 
sequences derived from TIMP-2. They retain their in vivo anti-
angiogenic property acting via the same mechanism as TIMP-2 and some of 
them have significantly higher activity than TIMP-2. Anti-angiogenic 
peptidomimetics based on this technology can be developed for the 
treatment of angiogenesis associated diseases.
    Applications:
    1. Novel human TIMP-2 derived peptide sequences.
    2. Novel human TIMP-2 derived peptide sequences with considerable 
anti-angiogenic activity in vivo.
    3. Human TIMP-2 derived peptides with high anti-angiogenic activity 
that can be used for the treatment of several cancers.
    4. Human TIMP-2 derived peptides with high anti-angiogenic activity 
that can be used for the treatment of several other angiogenesis 
associated diseases such as retinopathy and rheumatoid arthritis.
    Market:
    1. 600,000 deaths from cancer related diseases estimated in 2006.
    2. The technology platform involving novel anti-angiogenic cancer 
therapy technology has a potential market of more than 2 billion U.S. 
dollars.
    3. The technology platform has additional market in treating 
several other clinical problems such as autoimmune diseases.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: William G. Stetler-Stevenson and Dong-Wan Seo (NCI) 
(Lead Inventor Web page: http://ccr.cancer.gov/staff/staff.asp?profileid=5853)
    Related Publications:
    1. DW Seo, et al. TIMP-2 mediated inhibition of angiogenesis: an 
MMP-independent mechanism. Cell 2003 Jul 25; 114(2):171-180.
    2. WG Stetler-Stevenson, et al. Tissue inhibitor of 
metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and 
human tumor tissues. J Biol Chem. 1990 Aug 15; 265(23):13933-13938.
    3. WG Stetler-Stevenson and DW Seo. TIMP-2: an endogenous inhibitor 
of angiogenesis. Trends Mol Med. 2005 Mar; 11(3):97-103.
    4. DW Seo, et al. Shp-1 mediates the antiproliferative activity of 
tissue inhibitor of metalloproteinase-2 in human microvascular 
endothelial cells. J Biol Chem. 2006 Feb 10; 281(6):3711-3721.
    5. H Chang, et al. TIMP-2 promotes cell spreading and adhesion via 
upregulation of RAP1 signaling. Biochem. Biophys. Res. Comm. 2006 Jul 
7; 345(3):1201-1206.
    6. J Oh, et al. TIMP-2 upregulates RECK expression via 
dephosphorylation of paxillin tyrosine residues 31 and 118. Oncogene 
2006 Jul 13; 25(30):4230-4234.
    Patent Status: U.S. Provisional Application No. 60/728,146 filed 18 
Oct 2005, entitled ``Angio-inhibitory Peptides Derived from TIMP-2'' 
(HHS Reference No. E-186-2005/0-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Thomas P. Clouse, J.D.; 301/435-4076; 
[email protected].
    Collaborative Research Opportunity: The NCI Cell and Cancer Biology 
Branch is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize TIMP-2 derived anti-angiogenic peptides. Please contact 
Betty Tong at 301-496-0477 or [email protected] for more information.

Novel Chemoattractant-Based Toxins To Improve Vaccine Immune Responses 
for Cancer and Infectious Diseases

    Description of Technology: Cancer is one of the leading causes of 
death in United States and it is estimated that there will be more than 
half a million deaths caused by cancer in 2006. A major drawback of the 
current chemotherapy-based therapeutics is the cytotoxic side-effects 
associated with them. Thus there is a dire need to develop new 
therapeutic strategies with fewer side-effects. Immuno-therapy has 
taken a lead among the new therapeutic approaches. Enhancing the innate 
immune response of an individual has been a key approach for the 
treatment against different diseases such as cancer and infectious 
diseases.
    This technology involves the generation of novel chemoattractant 
toxins that deplete the T regulatory cells (Treg) or other 
immunosuppressive or hyperactivated cells locally. Treg controls 
activation of immune responses by suppressing the induction of adaptive 
immune responses, particularly T cell responses. Immunosuppressive 
cells such as tumor infiltrating macrophages or NKT and other cells 
down regulate antitumor immune responses. The chemoattractant toxins 
consist of a toxin moiety fused

[[Page 54505]]

with a chemokine receptor ligand, chemokines and other chemoattractants 
that enables specific targeting and delivery to the Treg cells. This 
technology is advantageous over the more harmful antibodies and 
chemicals that are currently used for the systemic depletion of Treg 
cells. The current technology can be used therapeutically in a variety 
of ways. They can be used together with vaccines to increase efficacy 
of the vaccine for the treatment of cancer, and can used to locally 
deplete Treg cells or other immuno suppressive cells to induce 
cytolytic cell responses at the tumor site or to eliminate chronic 
infectious diseases such as HIV and tuberculosis.
    Applications:
    1. New chemoattractant based toxins targeted towards Treg cells.
    2. New chemoattractant based toxins targeted towards 
immunosuppressive NKT, and macrophages.
    3. New chemoattractant based toxins targeted towards local 
depletion of hyperactivated CD4 T cells to treat autoimmune diseases.
    4. Chemoattractant based toxins depleting Treg cells or other 
immunosuppressive cells causing enhanced vaccine immune responses.
    5. Novel immunotherapy by increasing vaccine efficacy against 
cancer and infectious diseases.
    Market:
    1. 600,000 deaths from cancer related diseases estimated in 2006.
    2. The technology platform involving novel chemo-attractant based 
toxins can be used to improve vaccine immune responses. The vaccine 
market is believed to reach $10bn in 2006.
    3. The technology platform has additional market in treating 
several other clinical problems such as autoimmune diseases.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Arya Biragyn (NIA), Dolgor Bataar (NIA), et al. (Lead 
Inventor Web page: http://www.grc.nia.nih.gov/branches/irp/abiragyn.htm).
    Related Publications:
    1. Copy of manuscript from this technology can be provided once 
accepted for publication.
    2. M Coscia, A Biragyn. Cancer immunotherapy with chemoattractant 
peptides. Semin Cancer Biol 2004 Jun; 14(3):209-218.
    3. R Schiavo et al. Chemokine receptor targeting efficiently 
directs antigens to MHC class I pathways and elicits antigen-specific 
CD8+ T-cell responses. Blood 2006 Jun 15; 107 (12):4597-4605. Epub 2006 
Mar 2, doi 10.1182/blood-2005-08-3207.
    Patent Status: U.S. Provisional Application No. 60/722,675 filed 30 
Sep 2005, entitled ``Methods and Compositions for Modulating Immune 
Tolerance'' (HHS Reference No. E-027-2005/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Thomas P. Clouse, J.D.; 301/435-4076; 
[email protected].
    Collaborative Research Opportunity: The NIA Laboratory of 
Immunology is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize novel chemoattractant-based toxins. Please contact Betty 
Tong at 301-496-0477 or [email protected] for more information.

    Dated: September 8, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E6-15294 Filed 9-14-06; 8:45 am]
BILLING CODE 4140-01-P