E6-21037. 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.

ARH3, a Therapeutic Target for Cancer, Ischemia, and Inflammation

Description of Technology: ADP-ribosylation is important in many cellular processes, including DNA replication and repair, maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis. Poly-ADP-ribose is important in a number of critical physiological processes such as DNA repair, cellular differentiation, and carcinogenesis. Until recently, only one human enzyme, PARG, had been identified that degrades the ADP-ribose polymer. Another ADP-ribose, O-acetyl-ADP ribose, is formed via the deacetylation of proteins, such as acetyl-histone, by proteins in the Sir2 family. Sir2 proteins have been implicated in regulation of chromatin structure and longevity.

The NIH announces the discovery of a novel PARG-like enzyme, ARH3. ARH3 possesses PARG activity, yet is structurally distinct from PARG. ARH3 also hydrolyzes O-acetyl-ADP-ribose, and is the only protein recognized to date with such activity. ARH3 thus appears to function in two important signaling pathways, serving to regulate both poly-ADP-ribose and O-acetyl-ADP-ribose levels. It may affect chromatin structure through effects on both pathways. Since ARH3 structures differs from PARG or other enzymes that participate in these pathways, it may be possible to design specific inhibitors to target both the poly-ADP-ribose and Sir2 pathways. These drugs may be used as anticancer agents, radiosensitizers or antiviral agents, or for treating disorders involving oxidative damage, such as acute tissue injury, ischemia, and inflammation.

Applications: (1) Development of therapeutics for cancer or disorders associated with excessive DNA damage; (2) Development of therapeutics for diseases involving oxidative damage, such as acute tissue injury, ischemia and inflammation.

Market: (1) Patients with chemotherapy-resistant tumors, or with cancers that are genetically deficient in DNA repair; (2) Patients with inflammatory or ischemia/reperfusion diseases, particularly those associated with acute cardiovascular disease.

Development Status: Early stage.

Inventors: Joel Moss et al. (NHLBI).

Related Publications:

1. S Oka, J Kato, J Moss. Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase. J Biol Chem. 2006 Jan 13;281(2):705-713.

2. T Ono, A Kasamatsu, S Oka, J Moss. The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases. Proc Natl Acad Sci USA 2006 Nov 7;103(45):16687-16691. Epub 2006 Oct 30, doi 10.1073/pnas.0607911103.

Patent Status: U.S. Provisional Application No. 60/716,807 filed 12 Sep 2005 (HHS Reference No. E-347-2004/0-US-01); PCT Application No. PCT/US2006/035771 filed 12 Sep 2006 (HHS Reference No. E-347-2004/0-PCT-02).

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

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

Collaborative Research Opportunity: The Pulmonary Critical Care Medicine Branch in the National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the invention. Please contact Marianne Lynch in the NHLBI Office of Technology Transfer and Development by phone [phone]) or e-mail ([e-mail]) for more information.

Antisera To Detect Phosphorylated Phosphoinositide-Dependent Kinase 1 (PDK-1)

Description of Technology: PDK-1 phosphorylates and activates a number of cellular kinases, and plays a major role in insulin and growth factor signaling. PDK-1 also represents a promising drug target for a number of cancers. Autophosphorylation at Ser244 (mouse) or Ser241 (human) is critical for PDK-1 activity.

Available for licensing are polyclonal rabbit antisera that specifically detect mouse PDK-1 protein phosphorylated at Ser244. These antisera are also expected to be specific for the human PDK-1 protein phosphorylated at Ser241.

Applications: (1) Tool for screening PDK-1 autophosphorylation inhibitors for cancer and other indications; (2) Tool for studying insulin and growth factor signaling.

Inventor: Michael J. Quon (NCCAM).

Publication: MJ Wick, FJ Ramos, H Chen, MJ Quon, LQ Dong, F Liu. Mouse 3-phosphoinositide-dependent protein kinase-1 undergoes dimerization and trans-phosphorylation in the activation loop. J Biol Chem. 2003 Oct 31;278(44):42913-42919.

Patent Status: HHS Reference No. E-330-2003/0—Research Tool.

Licensing Status: This technology is available as a research tool under a Biological Materials License.

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

Collaborative Research Opportunity: The NIH, NCCAM, Diabetes Unit is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize phospho-specific PDK-1 antibody and insulin signaling. Please contact Michael J. Quon, Chief, Diabetes Unit, NCCAM, NIH at [e-mail] for more information.

Dated: December 6, 2006.

Steven M. Ferguson,

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