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 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: (301) 496-7057; fax: (301) 402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Vectors for Wild-Type DDR1b or DDR1b Mutant, and Production of THP-1 Cell Line Expressing Two DDR1 Isoforms, DDR1a and DDR1b

Teizo Yoshimura (NCI)

DHHS Reference No.: E-243-2004/0—Research Material.

Licensing Contact: Jesse S. Kindra; (301) 435-5559; kindraj@mail.nih.gov.

This technology relates to cloning of cDNAs coding for human discoidin domain receptor (DDR1) cDNAs (clone 11A for DDR1a and Clone 11B for DDR1b) from a human lung cDNA library; a mammalian expression vector for wild-type DDR1b or DDR1b mutant, and a THP-1 cell line expressing two DDR1 isoforms, DDR1a and DDR1b. These materials are useful to study the role and signaling pathways of DDR1 and to identify agonists or antagonists of these receptors.

Additional information regarding these materials is described in: Kamohara et al., “Discoidin domain receptor 1 isoform-a (DDR1a) promotes migration of leukocytes in three-dimensional collagen lattices,” FASEB J, 15:2724-2726, 2001; Matsuyama et al., “Interaction of discoidin receptor 1 isoform b (DDR1b) with collagen activates p38 mitogen-activated protein kinase and promotes differentiation of macrophages,” FASEB J, 17:1286-1288, 2003; Matsuyama et al., “Activation of discoidin receptor 1 facilitates the maturation of human monocyte-derived dendritic cells through the TNF receptor associated factor 6/TGF-beta-activated protein kinase 1 binding protein 1beta/p38alpha mitogen-activated protein kinase signaling cascade,” J. Immunol. 171:3520-3532, 2003; Matsuyama et al., “Activation of discoidin domain receptor 1 isoform b with collagen up-regulates chemokine production in human macrophages: Role of p38 mitogen-activated protein kinase and NF-kB,” J. Immunol. 172:2332-2340, 2004.

Method for Ex-Vivo Selection and Expansion of Stimulus-Responding Primary Cells Using Selective Reversible Immortalization

Eugene Barsov, David Ott (NCI)

U.S. Provisional Application No.: 60/528,244 filed 09 Dec 2003 (DHHS Reference No. E-210-2002/0-US-01).

Licensing Contact: Mojdeh Bahar; (301) 435-2950; baharm@mail.nih.gov.

This invention is a gene transfer technique to immortalize primary cells (e.g. lymphocytes) that respond to a stimulus, such as a viral antigen (e.g. HIV toxoids), a tumor antigen, or a growth factor. The antigen or growth factor stimulates a specific subset of primary cells within a population of cells to proliferate and divide. Murine leukemia virus (MuLV)-based retroviral vectors comprising a gene or genes for immortalization are used to transfect primary cells that have been stimulated to divide. Since MuLV retroviral vectors will only infect dividing cells, only primary cells activated by the antigen or growth factor will be infected by this retroviral vector and immortalized, thereby creating an “antigen-specific trap.” The primary cells to be immortalized can be in targeted tissue or in stimulated ex vivo culture. The transduced cells are expanded to large numbers without differentiating, and brought back to the primary cell stage by removing the introduced genes (e.g. by Cre-lox recombination). The expanded population of primary cells can then be used.

Hybrid Adeno-Retroviral Vector for the Transformation of Cells

Changyu Zheng, Brian O'Connell, Bruce J. Baum (NIDCR)

U.S. Provisional Application No.: 60/265,198 filed 30 Jan 2001 (DHHS Reference No. E-312-2000/0-US-01; PCT Application PCT/US02/02279 filed 25 Jan 2002, which was published as WO 02/061104 on 30 Jul 2002 (DHHS Reference No. E-312-2000/0-PCT-02).

U.S. Patent Application No.: 10/470,784 filed 29 Jul 2003 (DHHS Reference No. E-312-2000/0-US-03).

Licensing Contact: Jesse Kindra; (301) 435-5559; kindraj@mail.nih.gov.

The invention described and claimed in these patent applications provides for novel hybrid vectors which may be used for cell transformation either in vivo, in vitro, or ex vivo. The hybrid vectors, which are capable of integrating into the chromosome of the host cell and are capable of transducing dividing and non-dividing cells, have an adenoviral serotype 5 backbone and two retroviral (Moloney murine leukemia virus) elements upstream and downstream of the transgene. These elements include part of the envelope sequence, the long terminal repeat (LTR) and the packaging signal sequence (upstream), and part of the envelope sequence and LTR (downstream). Due to their hybrid nature, these vectors provide a means of efficient, reliable, long-term gene expression. Furthermore, unlike other chimeric or hybrid vector systems, only a single vector is required to deliver a transgene of interest and retroviral functional proteins are not required. The vectors are packaged and delivered via an adenoviral particle and administered directly to the target cell.

This research is described, in part, in: Zheng et al., “Inclusion of Moloney murine leukemia virus elements upstream of the transgene cassette in an E1-deleted adenovirus leads to an unusual genomic integration in epithelial cells,” Virology 2003 313:460-72, 2003; Zheng et al., “Integration efficiency of a hybrid adenoretroviral vector,” Biochem Biophys Res Commun. 300:115-20, 2003; Zheng & Baum, “Long-term expression after infection by the hybrid vector AdLTR-luc is from integrated transgene,” Biochem Biophys Res Commun. 291:34-40, 2002.