E9-978. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Mice With a Conditional LoxP-Flanked Glucosylceramide Synthase Allele Controlling Glycosphingolipid Synthesis

Description of Technology: Glycosphingolipids are organizational building blocks of plasma membranes that participate in key cellular functions, such as signaling and cell-to-cell interactions. Glucosylceramide synthase—encoded by the Ugcg gene—controls the first committed step in the major pathway of glycosphingolipid synthesis. Global disruption of the Ugcg gene in mice is lethal during gastrulation. The inventors have established a Ugcg allele flanked by loxP sites (floxed). When cre recombinase was expressed in the nervous system under control of the nestin promoter, the floxed gene underwent recombination, resulting in a substantial reduction of Ugcg expression and of glycosphingolipid ganglio-series levels. The mice deficient in Ugcg expression in the nervous system show a striking loss of Purkinje cells and abnormal neurologic sphingo-lipid behavior.

The Research Tools available are mice with a floxed Ugcg allele that can be deleted in a conditional manner. These mice carrying floxed Ugcg alleles will be useful for delineating the functional roles of glycosphingolipid synthesis in the nervous system and in other physiologic systems.

Applications

• Study of the functional roles of glycosphingolipid synthesis in the nervous system and other physiologic systems.
• The floxed Ugcg allele will facilitate analysis of the function of glycosphingolipids in development, physiology, and in diseases such as diabetes and cancer.

Development Status: Ready to Use.

Inventors: Richard L. Proia (NIDDK).

Publication: T Yamashita, ML Allende, DN Kalkofen, N Werth, K Sandhoff, RL Proia. Conditional LoxP-flanked glucosylceramide synthase allele controlling glycosphingolipid synthesis. Genesis 2005 Dec;43(4):175-180.

Patent Status: HHS Reference No. E-320-2007/0—Research Material. Patent protection is not being pursued for this technology.

Licensing Status: Available for licensing under a Biological Materials license agreement.

Licensing Contact: Suryanarayana (Sury) Vepa, PhD, J.D.; 301-435-5020; [e-mail].

Collaborative Research Opportunity: The NIDDK Genetics of Development and Disease Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the sphingolipid metabolism in physiology and disease. Please contact Dr. Proia at [e-mail] for more information.

Mutant Nuclear Orphan Receptor for Drug Metabolism Assays

Description of Technology: The constitutively active nuclear orphan receptor (CAR) activates transcription of genes encoding various drug-metabolizing enzymes, such as cytochrome P450, in response to drug exposure. While the direct activation of CAR in response to various drugs has been observed in vivo, CAR is always active in cell-based transfection assays, even in the absence of activating drugs. This constitutive activity of CAR makes it difficult to perform accurate in vitro assays to measure drug metabolism.

The NIH has obtained patent protection for modified CAR proteins that can be directly activated by drugs in vitro. This technology may potentially be used in the development of more efficient and cost-effective cell-based drug metabolism assays.

Applications: Development of improved in vitro assays to measure drug metabolism.

Inventors: Masahiko Negishi et al. (NIEHS).

Publications

1. T Sueyoshi, T Kawamoto, I Zelko, P Honkakoski, M Negishi. The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. J Biol Chem. 1999 Mar 5;274(10):6043-6046.

2. T Kawamoto, S Kakizaki, K Yoshinari, M Negishi. Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene. Mol Endocrinol. 2000 Nov;14(11):1897-1905.

Patent Status: U.S. Patent No. 7,365,160 issued 29 Apr 2008 (HHS Reference No. E-034-2002/0-US-03).

Licensing Status: Available for exclusive and non-exclusive licensing.

Licensing Contact: Tara L. Kirby, PhD; 301-435-4426; [e-mail].

Dated: January 8, 2009.

Richard U. Rodriguez,

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