E9-31284. 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.

Method of Preventing and Treating Metastatic Disease

Description of Technology: Cancer that recurs as metastatic disease many years after primary tumor resection and adjuvant therapy appears to arise from tumor cells that disseminated early in the course of disease but did not develop into clinically apparent lesions. These long-term surviving, disseminated tumor cells maintain a state of dormancy, but may be triggered to proliferate through largely unknown factors. Inventors at the National Institutes of Health have discovered agents that prevent or treat recurrent metastatic cancer by inhibiting type I collagen production and downstream signaling through beta 1 integrin activation. Blocking activation of beta-1 integrin signaling using pharmacological approaches or using RNA interference was found to prevent reorganization of the cytoskeleton that is associated with proliferation of the dormant tumor cells. The technology provides compositions and methods for modulating the switch from tumor cell dormancy to proliferation clinical metastatic disease in a patient by administering beta-1 integrin signaling inhibitors.

Applications

• Method of treating metastatic disease by targeting components of the beta-1 integrin signaling pathway.
• Method of preventing metastatic disease after removal of primary tumors.

Advantage: Discovery of beta-1 integrin signaling pathway involvement provides a number of therapeutic targets for development of novel cancer therapeutics.

Market: In the U.S., it is estimated that 192,370 women will be diagnosed with and 40,170 women will die of cancer of the breast in 2009. Although improved detection and treatment of primary tumors has raised the rate of survival there remains a high probability of recurrence of metastatic disease leading to mortality.

Inventors: Dalit Barkan and Jeffrey E. Green (NCI).

Publications: None related to this technology.

Patent Status: U.S. Provisional Application No. 61/179,641 filed 19 May 2009 (HHS Reference No. E-192-2009/0-US-01).

Licensing Status: Available for licensing.

Licensing Contact: Surekha Vathyam, PhD, 301-435-4076; [e-mail].

Collaborative Research Opportunity: The Center for Cancer Research, Laboratory of Cancer Biology and Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, PhD at 301-435-3121 or [e-mail] for more information.

Diamidine Inhibitors of Tdp1 as Anti-Cancer Agents

Description of Technology: Available for licensing and commercial development are methods and compositions for treating cancer, using novel compounds derived from diamidine. Diamidine and its derivatives are potent inhibitors of tyrosyl-DNA-phosphodiesterase (Tdp1). which may be useful in chemotherapy.

Camptothecins are effective Topoisomerase I (Top1) inhibitors, and two derivatives (Topotecan® and Camptosar®) are currently approved for treatment of ovarian and colorectal cancer. Camptothecins damage DNA by trapping covalent complexes between the Top1 catalytic tyrosine and the 3′-end of the broken DNA. Tdp1 repairs Top1-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. Thus, the presence and activity of Tdp1 can reduce the effectiveness of camptothecins as anticancer agents. In addition, Tpd1 repairs free-radical-mediated DNA breaks.

Inhibition of Tpd1 using diamidine or its derivatives. may reduce repair of DNA breaks and increase the rate of apoptosis in cancer cells. In addition. diamidine derivatives have the potential to enhance the anti-neoplastic activity of Top1 inhibitors, by reducing repair of Top1-DNA lesions through inhibition of Tdp1.

Development Status: Pre-clinical stage.

Inventors: Yves G. Pommier and Christoph Marchand (NCI).

Publications

1. Z Liao et al. Inhibition of human tyrosyl-DNA phosphodiesterase by aminoglycoside antibiotics and ribosome inhibitors. Mol Pharmacol. 2006 Jul:70(1):366-372.

2. Y Pommier. Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints. Curr Med Chem Anticancer Agents. 2004 Sep; 4(5):429-434. Review.

3. Y Pommier et al. Repair of and checkpoint response to topoisomerase I mediated DNA damage. Mutat Res. 2003 Nov 27;532(1-2):173-203. Review.

Patent Status: U.S. Patent Application No. 12/225,672 filed 26 Sep 2008 (HHS Reference No. E-165-2006/0-US-04).

Licensing Status: Available for licensing.

Licensing Contact: Betty Tong, PhD; 301-594-6565; [e-mail].

Collaborative Research Opportunity: The Laboratory of Molecular Pharmacology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Tdp1 inhibitors for the treatment of cancers. Please contact John D. Hewes, PhD at 301-435-3121 or [e-mail] for more information.

Dated: December 23, 2009.

Richard U. Rodriguez,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.