E6-15294. 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: [phone]; fax: [phone]. 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; [e-mail].

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 [e-mail] 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 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; [e-mail].

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 [e-mail] 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.