01-3604. 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 agencies 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.

Potentiation of Antineoplastic Agents Using Sigma 2 Ligands

Keith W. Crawford, Wayne D. Bowen (NIDDK)

DHHS Reference No. E-165-99/0 filed 11 May 2000

Licensing Contact: Catherine Joyce; 301/496-7735 ext. 244; e-mail: [e-mail].

The inventors have developed a therapeutic method of treating cancer through the administration of a sigma-2 receptor ligand, such as CB-184, in combination with the anti-neoplastic drugs, doxorubicin or actinomycin D. The novel combination produces marked tumor cell death at concentrations that produce little or no cytotoxicity when cells are exposed to the drugs alone. The protocol may be effective in treating tumors that are resistant to antineoplastics alone as a result of mutations of the p53 tumor suppressor gene.

Tumor Markers in Ovarian Cancer

Patrice J. Morin, Colleen D. Hough, Cheryl A. Sherman-Baust, Ellen S. Pizer (NIA)

DHHS Reference No. E-138-00/0 filed 03 Apr 2000

Licensing Contact: Catherine Joyce; 301/496-7735 ext. 244; e-mail: [e-mail].

This invention relates generally to the identification of ovarian tumor markers and diagnostic, prognostic and therapeutic methods for their use. The invention is based on the identification of a series of ovarian tumor marker genes that are highly expressed in ovarian epithelial tumor cells and are minimally expressed in normal ovarian epithelial cells.

Imidazoacridones With Anti-Tumor Activity

Cholody et al. (NCI)

DHHS Reference No. E-289-99/0 filed 07 March 2000

Licensing Contact: Girish Barua; 301/496-7735 ext. 263; e-mail: [e-mail].

The present invention relates to novel bifunctional molecules with anti-tumor activity. These agents are composed of an imidazoacridone moiety linked by a nitrogen containing aliphatic chain of various length and rigidity to another aromatic ring system capable of intercalation to DNA.

Previous studies on related symmetrical bis-imidazoacridones revealed that only one planar imidazoacridone moiety intercalates into DNA. The second aromatic moiety which is crucial for biological activity resides in DNA groove, and is believed to interact with DNA-binding proteins (most likely, transcription factors). It was hypothesized that action of bis-imidazoacridone constitute a new paradigm of how small molecules can interfere with gene transcription.

To enhance the biological activity, the inventors have developed unsymmetrical compounds in which one imidazoacridone system with relatively poor DNA-intercalating properties was replaced with much stronger intercalators, such as 3-chloro-7-methoxyacridine or naphthalimide moieties. These new compounds, especially those containing naphthalimide moiety are extremely cytotoxic against variety of tumor cells in vitro ( IC50 at low nanomolar range) and kill tumor cells by inducing apoptosis. In vivo, in nude mice xenografted with human tumors, the compounds significantly inhibited growth of such tumors as colon tumor HCT116 and Colo205 as well pancreatic tumors (lines 6.03 and 10.05 freshly established from a patient).

Dated: February 6, 2001.

Jack Spiegel,

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