00-33086. 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.

Transgenic Zebrafish with Vascular Specific Expression of Exogenous Genes Driven by the Zebrafish Fli-1 Promoter

Brant M. Weinstein, Nathan N. Lawson (NICHD)

DHHS Reference No. E-003-01/0

Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; email: [e-mail]

The technology portrayed in this invention is available through a Biological Materials License for research tools and diagnostic tests. Zebrafish are an important and valuable model system for high-throughput mutational or pharmacological screens for genes or molecules with important roles in blood vessel growth or differentiation. This invention consists of germline transgenic zebrafish lines in which the expression of green fluorescent protein (EGFP) is driven by zebrafish Fli-1 promoter sequences. These transgenic lines display bright, uniform, and persistent expression of EGFP protein throughout the vascular system. The Fli promoter also drives transient EGFP expression in cranial neural crest and its derivatives. The transgenics allow straightforward, noninvasive fluorescent visualization of virtually all blood vessels in the animal throughout embryonic and early larval development.

These Fli-EGFP transgenics have a number of potential applications. They can be used to help identify endogenous genes important for blood vessel formation, either by screening mutagenized transgenic embryos for vascular specific mutants or by preparing vascular specific cDNA libraries for use in novel gene discovery. They also provide an efficient method for performing high-throughput in vivo screening for antiangiogenic or proangiogenic drugs and other compounds. Using transgenic zebrafish for these screens has the added benefit of simultaneously revealing toxic and teratogenic effects of the tested agents on a whole, developing organism.

Transcranial Magnetic Stimulation Coil for Specific Non-Invasive Deep Brain Stimulation

Abraham Zangen (NIDA), Roy Wise (NIDA), Mark Hallett (NINDS), Yiftach Roth (EM), Pedro Miranda (NINDS)

DHHS Reference No. E-223-00/0 filed 20 Oct 2000

Licensing Contact: Dale Berkley; 301/496-7735 ext. 223; e-mail: [e-mail]

The invention is a magnetic stimulator that is placed in contact with the head of a subject to magnetically stimulate the brain. The invention has applications in the treatment of neurophysiological or cardiovascular conditions, and may be of particular utility in the treatment of disorders associated with deep regions of the brain, such as drug addiction and depression. The unique coil shape of the stimulator is designed to target deep brain regions like the nucleus accumbens, which are associated with the biological mechanism underlying drug abuse. Deep regions of the brain are also implicated in depressive disorders, and this coil is likely to offer an improvement in the transcranial magnetic stimulation therapy currently being tested for treatment of depression.

Peroxynitrite Generators, Compositions Comprising Same, and Methods for Treating Biological Disorders Using Same

Challice L. Bonifant, Joseph E. Saavedra and Larry K. Keefer (NCI)

DHHS Reference No. E-175-00/0 filed 02 June 2000

Licensing Contact: Norbert Pontzer; 301/496-7735, ext. 284; e-mail: [e-mail]

Diazeniumdiolates are a class of compounds which release nitric oxide (NO) under physiological conditions. Nitric oxide performs a number of regulatory functions in vivo such as controlling vascular tone and platelet function, but it can also combine with superoxide ion to produce peroxynitrite ion, as especially reactive species. Peroxynitrite-mediated cellular toxicity may have several therapeutic applications. Because of the relatively low amounts of superoxide ion present in some cells, the peroxynitrite mechanism of diazeniumdiolate toxicity is not uniformly available. In order to generate peroxynitrite ions in tissues or other media lacking adequate levels of superoxide ion, this invention provides a new class of compounds which release NO and superoxide ion simultaneously to generate peroxynitrite ions.

Molecules of this invention can be designed to generate peroxynitrite ion at specific biochemical targets. For one type of targeting, the release of NO is designed to be triggered by nucleophilic attack on the diazeniumdiolate drug while superoxide generation is simultaneously occurring at a quinone moiety elsewhere in the molecule. If the required nucleophilic attack is designed to be specifically catalyzed in the active site of glutathione S-transferase-pi, a cytoprotective enzyme overexpressed by certain tumors to render them drug-resistant, compounds of this invention could restore the susceptibility of tumor cells to chemotherapy by knocking out the excess enzyme, thereby preventing the tumor cells from inactivating the chemotherapeutic agents. Attachment of the compounds to polymeric compositions would physically localize the peroxynitrite activity. Physical localization in vivo may have utility against the recently recognized chronic infections caused by biofilms, and generation of peroxynitrite ions in vitro may have utility against infectious bilfilms on medical devices.

Dated: December 20, 2000.

Jack Spiegel,

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