E6-13191. 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.

Amyloid Beta Is a Ligand for FPR Class Receptors

Description of Technology: Alzheimer's disease is the most important dementing illness in the United States because of its high prevalence. Five to ten percent of the United States population 65 years and older are afflicted with the disease. In 1990 there were approximately 4 million individuals with Alzheimer's, and this number is expected to reach 14 million by the year 2050. It is the fourth leading cause of death for adults, resulting in more than 100,000 deaths annually. Amyloid beta has been identified as playing an important role in the neurodegeneration of Alzheimer's disease. However, the mechanism by which this occurred was unknown, but has been postulated to be either direct or indirect through an induction of inflammatory responses.

The NIH announces the identification of the 7-transmembrane, G-protein-coupled receptor, FPRL-1, in the cellular uptake and fibrillar aggregation of amyloid ββ(Aββ) peptides. The Aββ peptides use the FPRL-1 receptor to attract and activate human monocytes and mouse microglial cells (publications referenced below), and have been identified as a principal component of the amyloid plaques associated with Alzheimer's disease. In addition, the known anti-inflammatory drug, Colchicine, has been shown to inhibit the FPRL1 activation by amyloid ββ** and the internalization of FPRL1/amyloid beta complexes.

Inventors: Ji Ming Wang et al. (NCI).

Publications:

1. Y Le, W Gong, L Tiffany, A Tumanov, S Nedospasov, W Shen, NM Dunlop, J-L Gao, PM Murphy, JJ Oppenheim, and JM Wang, “Amyloid (beta)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1,” J. Neuroscience 2001 Jan 15; 21(2):RC123.

2. HL Tiffany, MC Lavigne, YH Cui, JM Wang, TL Leto, JL Gao, and PM Murphy, “Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain,” J Biol Chem. 2001 Jun 29;276(26):23645-52.

3. YH Cui, Y Le, W Gong, P Proost, J Van Damme, WJ Murphy, and JM Wang, “Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine microglial cells,” J Immunol. 2002 Jan 1;168(1):434-42.

4. H Yazawa., Z-X Yu, K Takeda, Y Le, W Gong, VJ Ferrans, JJ Oppenheim, CC Li, and JM Wang, “Beta amyloid peptide (Ab42) is internalized via the G-protein coupled receptor FPRL1 and forms fibrillar aggregates in macrophages,” FASEB J. 2001 Nov; 15(13):2454-2642.

5. P Iribarren, K Chen, J Hu, G Gong, EH Cho, S Lockett, B Uranchimeg, and JM Wang, “CpG-containing oligodeoxynucleotide promotes microglial the up-take of amyloid beta 1-42 by up-regulating the expression of the G-protein coupled receptor mFPR2,”.FASEB J. 2005 Dec;19(14):2032-4.

6. K Chen, P Iribarren, J Hu, J Chen, G Gong, EH Cho, S Lockett, NM Dunlop, and JM Wang, “Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid beta peptide,” J Biol Chem. 2006 Feb 10;281(6):3651-9.

Patent Status: U.S. Patent Application No. 10/831,524 filed 23 Apr 2004 (HHS Reference No. E-336-01/0-US-02), claiming priority to 26 Oct 2001.

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

Licensing Contact: 301/496-7057; [e-mail]

Collaborative Research Opportunity: The National Cancer Institute, Laboratory of Molecular Immunoregulation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialized siRNA delivery development. Please contact Diana Bialozor at 301/846-5465 or [e-mail] for more information.

Dated: August 1, 2006.

Steven M. Ferguson,

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