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 contacting Girish C. Barua, Ph.D., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7056 ext. 263; fax: 301/402-0220; e-mail: BaruaG@od.nih.gov. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Compositions and Methods for Treatment of Breast Cancer—the Synergistic Effect of Farnesyl Transferase Inhibitors and Tamoxifen Combination Therapy

Geoffrey J. Clark, Joanne Zujewski (NCI)

Serial No. 60/171,928 filed 22 Dec 1999

This invention discloses compositions that act in a synergistic manner to inhibit and or prevent breast cancer cell growth. Specifically, this invention discloses methods for treating and preventing breast cancer using a combination of selective estrogen receptor modulators (SERMs) and farnesyl transferase inhibitors (FTIs). The combination therapy comprising of at least one SERM and at least one FTI has shown enhanced therapeutic efficacy in killing cancer cells. Thus the combination therapy may lead to enhance efficacy of Tamoxifen or other SERM treatment regimes. For example, it is contemplated that the present invention will find use in a treatment therapy using lower doses of SERMs for a shorter duration. In some embodiments of the invention, therapeutic agents are administered to subjects suspected of having cancer or being susceptible to cancer, subjects with cancer, subjects experiencing a recurrence of cancer, or subjects who are post-operative for cancer. Additionally, the treatment agents could be administered prophylactically to patients at risk for development of cancer.

Tyrosyl-DNA Phosphodiesterases (TDP) and Related Polypeptides, Nucleic Acids, Vectors, TDP-Producing Host Cell, Antibodies and Methods of Use

Jeffrey J Pouliot, Howard A Nash (NIMH)

Serial No. 60/157,690, filed 05 Oct 1999

Topisomerases are cellular enzymes that are vital for replication of the genome. However, if topisomerase and DNA form covalent complexes that prevent the resealing of DNA, this may lead to cell death. Essentially, this invention consists of a new isolated and cloned enzyme, tyrosyl-DNA phosphodiesterase (TDP1), that is capable of hydrolyzing the covalent complexes between topisomerase and DNA, allowing the DNA to reseal. The mechanism that defines topisomerases is their capacity to break DNA and, after an interval in which topological changes may occur, to reseal the break without the intervention of a high energy cofactor. The breakage of the DNA is accompanied by the formation of a covalent bond between topisomerase and DNA to create an intermediate that is resolved during the resealing step. However, if the resealing step fails, the covalent intermediates between topisomerase I and DNA can become complexes that lead to cell death. The failure of the resealing is increased by some chemotherapies such as camptothecin. Thus, this technology has many potential commercial uses including: a method for screening camptothecin analogues or other compounds for their resistance to repair by this enzyme or to prescreen patients for their sensitivity to topisomerase inhibitors which could identify patients most likely to respond to camptothecin therapy. Further, this invention provides for a vector comprising of the nucleic acid molecule for TDP1 as well as the method of altering the level of TDP1 in a cell, a tissue, an organ or an organism. Finally, this invention consists of a method for identifying a compound that stabilizes a covalent bond complex that forms between DNA and topisomerase I, wherein the covalent bond cannot be cleaved.

Novel Vacuolar-Type (H+)-V-ATPase-Inhibitory Compounds, Compositions and Methods of Use

Michael R. Boyd (NCI)

Serial No. 60/122,953 filed 05 Mar 1999 and Serial No. 60/169,564 filed 08 Dec 1999

The present invention relates to a new class of vacuolar-type (H⁺)-ATPase-inhibitory compounds. Vacuolar-type (H⁺)-ATPases (V-ATPases) have been described as a universal proton pump which are present in many tissues and cells of the human body. Vacuolar-type (H⁺)-ATPases are present intracellularly within certain organelles and are responsible for maintaining internal acidity thereof; V-ATPases are also located within specialized plasma membranes of certain cells, e.g. kidney intercated cells, osteoclasts and sperm cells. V-ATPases are important for a myriad of physiological functions such as: sorting of membrane and organellar proteins; proinsulin conversion; neurotransmitter uptake; receptor recycling; and cellular degradative processes. V-ATPase isoform-specific inhibitors may preferentially modulate V-ATPase activities in different cells and tissues, and may thereby provide diverse and distinctive pharmacological utilities. Accordingly, the disclosed compounds and compositions may be used to inhibit such biological processes as: intra-organellar acidification, urinary acidification; bone resorption; fertility; tumor cell proliferation; and, drug resistance of tumor cells.