E6-18885. 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 Lacking Expression of Chemokine Receptor CCR9 Generated by Gene Targeting (CCR9 KO Mice)

Description of Technology: Chemokines and their receptors are key regulators of thymocytes migration and maturation in normal and inflammation conditions. The chemokine CCL25 is highly expressed in the thymus and small intestine. CCR9, the receptor for CCL25, is expressed on the majority of thymocytes, indicating that CCR9 and its ligand may play an important role in thymocyte development. To investigate the role of CCR9 during lymphocyte development, CCR9 knockout mice were developed. Knockout mice had increased numbers of peripheral γδ-T cells but reduced numbers of αβ-T cells. In competitive transplantation experiments bone marrow from CCR9 knockout mice was much less efficient at repopulating the thymus than control (wild type) bone marrow. Thus, CCR9 KO mice are a model for studying thymocyte development and trafficking in the body. Additionally, as the ligand for CCR9 is highly expressed in the small intestine, CCR9 potentially plays a role in the specialization of immune responses in the gastrointestinal tract.

Applications: (1) Evaluate drugs aimed at blocking or augmenting lymphocyte trafficking; (2) A model for studying T cell development; (3) A model for studying immunological based gastrointestinal disorders.

Inventors: Paul E. Love (NICHD), Joshua M. Farber (NIAID), Shoji Uehara (NICHD).

Publications:

1. S Uehara et al. A role for CCR9 in T lymphocyte development and migration. J Immunol. 2002 Mar 15;168(6):2812-2819.

2. S Uehara et al. Characterization of CCR9 expression and CCL25/thymus-expressed chemokine responsiveness during T cell development: CD3^high CD69+ thymocytes and γδ TCR+ thymocytes preferentially respond to CCL25. J Immunol. 2002 Jan 1;168(1):134-142.

Patent Status: HHS Reference No. E-328-2006/0—Research Tool.

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

Licensing Contact: Jennifer Wong; 301/435-4633; [e-mail].

mFPR2 Transgenic and Knockout Mouse Models for Alzheimer's and Other Inflammatory Diseases

Description of Technology: Human Formyl Peptide-Like Receptor 1 (hFPLR1) has been implicated in host defense for disease processes including Alzheimer's disease, infection, and other inflammatory diseases. hFPLR1 and its mouse homologue Formyl Peptide Receptor 2 (mFPR2) are G-protein coupled receptors that are expressed at high levels on phagocytic leukocytes, mediating leukocyte chemotaxis and activation in response to a number of pathogen- and host-derived peptides. Activation of hFPRL1/mFPR2 by lipoxin A4 may play a role in preventing and resolving inflammation. Also, hFPRL1/mFPR2 has been shown to mediate the chemotactic activity of amyloid β 1-42, a key pathogenic peptide in Alzheimer's disease.

Available for licensing are mice expressing the mFPR2 transgene on either the FVB or C58BL background, as well as mFPR2 knockout mice on the C57BL background. These mice are anticipated to be highly useful in the study of a wide variety of inflammatory, infectious, immunologic and neurodegenerative diseases.

Applications: (1) Drug development model for Alzheimer's disease and other inflammatory diseases; (2) Tool to probe the role of hFPRL1/mFPR2 in host responses in a variety of disease processes, including inflammatory, infectious, immunologic, and neurodegenerative disease.

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

Related Publications:

1. K Chen, P Iribarren, J Hu, J Chen, W 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):3651-3659.

2. H Yazawa, ZX Yu, Takeda, Y Le, W Gong, VJ Ferrans, JJ Oppenheim, CC Li, and JM Wang. Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. FASEB J. 2001 Nov;15(13):2454-2462.

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):434-442.

Patent Status: HHS Reference No. E-303-2006/0—Research Tool.

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

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

Collaborative Research Opportunity: The National Cancer Institute—Frederick, Laboratory of Molecular Immunoregulation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize mFPR2 Transgenic and Knockout Mouse Models for Alzheimer's and Other Inflammatory Diseases. Please contact Betty Tong, Ph.D. at 301-594-4263 or [e-mail] for more information.

Vaccine Production Strain for Acellular Pertussis Vaccine

Description of Technology: Available for licensing from the NIH is a vaccine production strain of Bordetella bronchiseptica that produces Bordetella pertussis toxin in high yield. The Bordetella bronchiseptica strain has been modified to eliminate expression of filamentous hemagglutinin, which typically has to be removed in purification of the toxin, thereby reducing the yield of the active vaccine component. Immediately available for licensing is a strain that encodes a mutated pertussis toxin, which does not have to be chemically detoxified.

Application: Production of Bordatella pertussis toxin for acellular vaccine use.

Inventors: Tod Merkel, Jerry Keith, and Xiaoming Yang (NIDCR).

Patent Status: U.S. Patent No. 7,101,558 issued 05 Sep 2006 (HHS Reference No. E-159-1999/0-US-03).

Licensing Status: Available for non-exclusive licensing.

Licensing Contact: Susan Ano, Ph.D.; 301/435-5515; [e-mail].

HSV-2 Diagnostic

Description of Technology: The present invention relates to novel diagnostic methods for Herpes Simplex Virus Type 2 (HSV-2). HSV-2 infects approximately one fifth of adults in the United States and is the most common cause of genital ulceration. The invention relates to the detection of HSV-2 based on a transforming nucleic acid sequence and its protein product. This DNA sequence harbors the potential to induce the tumorigenic transformation of normal cells in in vitro and in vivo assays and thus will be useful as a means of prognostic evaluation in predicting the development of genital or cervical cancer. Current HSV-2 diagnostic tests relying on tedious viral culture and/or immunoassays that do not have the sensitivity and the specificity essential for diagnosis. Using PCR, the current invention will provide a superior method for viral detection and subtyping.

Application: HSV-2 diagnostic.

Inventors: Joseph A. DiPaolo (NCI-)

Publication: JA DiPaolo et al. Relationship of stable integration of herpes simplex virus-2 Bg/II N subfragment Xho2 to malignant transformation of human papillomavirus-immortalized cervical keratinocytes. Int J Cancer 1998 Jun 10;76(6):865-871.

Patent Status: U.S. Patent 6,617,103 issued 09 Sep 2003 (HHS Reference No. E-091-1999/0-US-03); CA Application 2,259,657 filed 30 Jun 1997 (HHS Reference No. E-091-1999/0-CA-04).

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

Licensing Contact: Susan Ano, Ph.D.; 301/435-5515; [e-mail].

Collaborative Research Opportunity: The NCI Division of Basic Science is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HSV-2 Diagnostic. Please contact Betty Tong, Ph.D. at 301-594-4263 or [e-mail] for more information.

Dated: October 24, 2006.

Steven M. Ferguson,

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