[Federal Register Volume 69, Number 20 (Friday, January 30, 2004)]
[Notices]
[Pages 4521-4522]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-1994]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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.

[[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; [email protected].

    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; [email protected].

    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; [email protected].

    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.

    Dated: January 23, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-1994 Filed 1-29-04; 8:45 am]
BILLING CODE 4140-01-P