Skip to Content

Notice

Government-Owned Inventions; Availability for Licensing

Document Details

Information about this document as published in the Federal Register.

Published Document

This document has been published in the Federal Register. Use the PDF linked in the document sidebar for the official electronic format.

Start Preamble

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: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.Start Printed Page 4522

Analogs of Thalidomide as Potential Angiogenesis Inhibitors

William D. Figg, Erin Lepper (NCI)

U.S. Provisional Application No. 60/486,515 filed 11 Jul 2003 (DHHS Reference No. E-272-2003/0-US-01)

Licensing Contact: Matthew Kiser; 301/435-5236; kiserm@mail.nih.gov.

The present disclosure relates to anti-angiogenesis compositions and methods, and particularly thalidomide analogs that actively inhibit angiogenesis in humans and animals.

Angiogenesis is the formation of new blood vessels from pre-existing vessels. Angiogenesis is prominent in solid tumor formation and metastasis. A tumor requires formation of a network of blood vessels to sustain the nutrient and oxygen supply for continued growth. Some tumors in which angiogenesis is important include most solid tumors and benign tumors, such as acoustic neuroma, neurofibroma, trachoma, and pyogenic granulomas. Prevention of angiogenesis could halt the growth of these tumors and the resultant damage due to the presence of the tumor.

The subject application discloses active thalidomide analogs that exhibit enhanced potency in the inhibition of undesirable angiogenesis, and methods for using these compounds to treat angiogenesis and solid tumors. In particular, the presently disclosed method provides for inhibiting unwanted angiogenesis in a human or animal by administering to the human or animal with the undesired angiogenesis a composition comprising an effective amount of the active thalidomide analogs. According to a more specific aspect, the method involves inhibiting angiogenesis by exposing a mass having the undesirable angiogenesis to an angiogenesis inhibiting amount of one or more compounds, or pharmaceutically acceptable salts of such compounds.

Serine Protease Inhibitors

Peter P. Roller, Peng Li (NCI)

U.S. Provisional Application No. 60/507,583 filed 30 Sep 2003 (DHHS Reference No. E-272-2002/0-US-01)

Licensing Contact: Matthew Kiser; 301/435-5236; kiserm@mail.nih.gov.

This disclosure concerns novel serine protease inhibitors and methods for using the inhibitors to reduce tumor progression and/or metastasis. Embodiments of the inhibitors are highly effective, selective inhibitors of matriptase, which has been implicated in tissue remodeling associated with the growth of cancerous tumors and cancer metastasis.

Angiogenesis and tumor invasion require that the normal tissue surrounding the tumor be broken down in a process referred to as tissue remodeling. Tissue remodeling is accomplished by a host of enzymes that break down the proteins in the normal tissue barriers comprising the extracellular matrix. Among the enzymes associated with degradation of the extracellular matrix and tissue remodeling are a number of proteases. The expression of some of these proteases has been correlated with tumor progression.

The disclosed compounds can be used to inhibit matriptase, MTSP1, or both, in vitro and in vivo and thus can be used in the prevention or treatment of conditions characterized by abnormal or pathological serine protease activity. For example, the compounds are useful for prevention or treatment of conditions characterized by the pathological degradation of the extracellular matrix, such as conditions characterized by neovascularization or angiogenesis, including cancerous conditions, particularly metastatic cancerous conditions where matriptase is implicated. The disclosed compounds can be used to decrease the degradation of the cellular matrix and thereby reduce concomitant tumor progression and metastasis. Conditions characterized by abnormal or pathological serine protease activity that can be treated according to the disclosed method include those characterized by abnormal cell growth and/or differentiation, such as cancers and other neoplastic conditions. Typical examples of cancers that may be treated according to the disclosed inhibitors and method include colon, pancreatic, prostate, head and neck, gastric, renal, and brain cancers.

Methods for Inhibiting Chaperone Proteins

Monica Marcu, Leonard Neckers, Theodor Schulte (NCI)

U.S. Patent Application No. 09/936,449 filed 20 Dec 2001 (DHHS Reference No. E-084-1999/0-US-07), with priority to 12 Mar 1999

Licensing Contact: George Pipia; 301/435-5560; pipiag@mail.nih.gov.

This invention is directed to depletion of the Heat Shock Protein (HSP)-90 with novobiocin. Hsp90 is an essential and abundant chaperone in eukaryotes. It is considered today an exciting molecular target for cancer therapy. NIH inventors demonstrated previously that the gyrase-B inhibitor, novobiocin, and its related coumarin derivatives interact with Hsp90, causing in vitro and in vivo depletion of key regulatory Hsp90-dependent proteins. Using deletion/mutation analysis, the inventors have identified the novobiocin binding domain on Hsp90 and demonstrated that it overlaps a functional ATP binding site, which was previously unknown. These results identify a second site on Hsp90 where the binding of small molecule inhibitors can significantly impact this chaperone's function, and thus support the hypothesis that both N- and C-terminal domains of Hsp90 interact to modulate chaperone activity. The inventors have performed preliminary in vivo experiments, treating mice carrying tumor xenografts with novobiocin encapsulated in Alzet pumps (slow, constant release for one month). The treated mice exhibited significantly slower tumor growth. Results of these studies demonstrated a significantly slower growth of tumors.

Start Signature

Dated: January 23, 2004.

Steven M. Ferguson,

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

End Signature End Preamble

[FR Doc. 04-1994 Filed 1-29-04; 8:45 am]

BILLING CODE 4140-01-P