[Federal Register Volume 65, Number 79 (Monday, April 24, 2000)]
[Notices]
[Pages 21771-21772]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-10178]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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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: [email protected]. 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;

[[Page 21772]]

tumor cell proliferation; and, drug resistance of tumor cells.

    Dated: April 17, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-10178 Filed 4-21-00; 8:45 am]
BILLING CODE 4140-01-P