E8-17506. 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.

Protein-tyrosine Phosphotase Inhibitors as Inhibitors of Human Tyrosyl-DNA Phosphodiesterase (Tdp1) and Methods of Treating Disorders

Description of Technology: Tyrosyl-DNA phosphodiesterase (Tdp1) is an enzyme that repairs topoisomerase I (Top1)-mediated DNA damage induced by chemotherapeutic agents (such as camptothecins) and ubiquitous DNA lesions that interfere with transcription and replication. Tdp1 is a relevant target for anticancer therapies due to its role in repairing Top1-mediated DNA damage and DNA damage associated with DNA strand breaks. Tdp1 inhibitors are expected to be effective in cancer treatment when used in combination with Top1 inhibitors.

The current invention is Me-3,4 dephostatin, and more generally protein-tyrosine phosphatase inhibitors, which is a Tdp1 inhibitor. Me-3,4 dephostatin could potentiate the pharmacological action of Top1 inhibitors.

Applications and Modality

• It is anticipated that Tdp1 inhibitors in association with Top1 inhibitors can have selective activity toward tumor tissues.
• Tdp1 inhibitors may exhibit antitumor activity by themselves because tumors have excess free radicals.

Market

• An estimated 1,444,920 new cancer diagnoses in the U.S. in 2007.
• 600,000 deaths caused by cancer in the U.S. in 2006.
• Cancer is the second leading cause of death in the U.S.
• Cancer drug market will likely double to $50 billion in 2010 from $25 billion in 2006.

Development Status: The technology is currently in the pre-clinical stage of development.

Inventors: Yves Pommier (NCI) et al.

Relevant Publication: S Antony et al. Novel high-throughput electrochemiluminescent assay for identification of human tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors and characterization for furamidine (NSC 305831) as an inhibitor of Tdp1. Nucleic Acid Res. 2007;35(13):4474-4484.

Patent Status: U.S. Provisional Application No. 61/042,706 filed 04 Apr 2008 (HHS Ref. No. E-121-2008/0-US-01).

Licensing Status: Available for exclusive and non-exclusive licensing.

Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; [e-mail].

Steroid Derivatives as Inhibitors of Human Tyrosyl-DNA Phosphodiesterase (Tdp1)

Description of Technology: Tyrosyl-DNA phosphodiesterase (Tdp1) is an enzyme that repairs topoisomerase I (Top1)-mediated DNA damage induced by chemotherapeutic agents and ubiquitous DNA lesions that interfere with transcription. The current technology are steroid derivatives that human inhibit Tdp1.

Currently, there are various types of Top1 inhibitors used in chemotherapy, e.g., camptothecin. However, Tdp1 inhibitors are expected to be effective in combination therapy with Top1 inhibitors for the treatment of cancers. Combining Tdp1 inhibitors with Top1 inhibitors would allow Tdp1 to potentiate the antiproliferative activity of Top1 inhibitors. In addition to Tdp1's effect on Top1, Tdp1 inhibitors can also exhibit antitumor activity independently, as tumors are shown to have excess free radicals, and Tdp1 repairs DNA damage by oxygen radicals.

Applications and Modality: It is anticipated that Tdp1 inhibitors in association with Top1 inhibitors can have selective activity toward tumor tissues. Tdp1 inhibitors may exhibit antitumor activity by themselves because tumors have excess free radicals.

Market: 600,000 deaths from cancer related diseases were estimated in 2006. In 2006, cancer drug sales were estimated to be $25 billion.

Development Status: The technology is currently in the pre-clinical stage of development.

Inventors: Yves Pommier et al. (NCI).

Patent Status:

• U.S. Provisional Application No. 61/000,430 filed 24 Oct 2007 (HHS Reference No. E-130-2007/1-US-01).
• PCT Application No. PCT/US2008/004541 filed 05 Apr 2008, claiming priority to 05 Apr 2007 (HHS Reference No. E-130-2007/2-PCT-01).

Licensing Status: Available for exclusive and non-exclusive licensing.

Licensing Contact: Adaku Nwachukwu, J.D.; 301/435-5560; [e-mail].

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

Dated: July 22, 2008.

Richard U. Rodriguez,

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