03-29492. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

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.

Geldanamycin Derivatives With Methyl Substituted Hydrogen Atom at the N22 Position as Anti Cancer Agents

Yong-Sok Lee, Leonard Neckers, Monica Marcu (NCI).

U.S. Provisional Patent Application No. 60/508,752 filed 03 Oct 2003 (DHHS Reference Nos. E-169-2003/0-US-01).

Licensing Contact: George Pipia; 301/435-5560; [e-mail].

This invention is directed to an N22-methyl substituted derivatives of geldanamycin. Modeling studies have shown that providing a methyl substituent in the N22 position of geldanamycin derivatives stabilizes the cis-conformation of the compounds. From computer modeling and mutational studies inventors concluded that the active form of geldanamycin interacting with heat shock protein 90 (Hsp90) has the amid bond in cis-configuration, which is energetically less stable than in trans-configuration. Using computer-modeling investigators have further demonstrated that methyl substitution at the N22 position of geldanamycin stabilizes the cis-derivatives of geldanamycin. These compounds are currently being synthesized at NCI. These compounds are expected to have an increased binding to and inhibition of Hsp90. Inhibition of Hsp90 is being investigated in the treatment of many cancers.

Degradation and Transcriptional Inhibition of HIF-2alpha Protein by 17-AAG

Jennifer Isaacs, Leonard Neckers (NCI).

U.S. Provisional Patent Application No. 60/508,795 filed 03 Oct 2003 (DHHS Reference No. E-064-2003/0-US-01).

Licensing Contact: George Pipia; 301/435-5560; [e-mail].

The technology is directed to the use of 17-allylaminogeldanamycin (17-AAG) and, by analogy, other geldanamycin derivatives to inhibit the activity of hypoxia inducible factor-2a (HIF-2a). HIF-2a is thought to play an important role in tumor growth in the lung and endothelium, and is overexpressed in a majority of renal carcinomas. Accordingly, the technology suggests the use of 17-AAG and other geldanamycin derivatives to reduce levels of HIF-2a in cells that overexpress the protein, for example to treat cancer. According to the lead inventor, HIF-2a plays a central role behind the mechanism of action of geldanamycin in renal cancer. The inventors also predict that certain geldanamycin derivatives will have therapeutic benefit in tumors overexpressing HIF-2a, and that those derivatives could also find therapeutic utility in clinical conditions involving hypervascularization.

Dated: November 13, 2003.

Steven M. Ferguson,

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