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Government-Owned Inventions; Availability for Licensing

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National Institutes of Health, Public Health Service, HHS.




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 Start Printed Page 56474for companies and may also be available for licensing.


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.

Methods for Introducing Homologous Recombination in a Wide Variety of Bacteria Using Plasmids and Prophage

Donald L. Court (NCI).

U.S. Provisional Application No. 60/573,504 filed 21 May 2004 (HHS Reference No. E-207-2004/0-US-01; U.S. Provisional Application No. 60/653,259 filed 14 Feb 2005 (HHS Reference No. E-207-2004/1-US-01); U.S. Provisional Application No. 60/655,729 filed 22 Feb 2005 (HHS Reference No. E-207-2004/2-US-01); U.S. Patent Application filed 20 May 2005 (HHS Reference No. E-207-2004/3-US-01).

Licensing Contact: Norbert Pontzer; 301/435-5502;

Homologous recombination is the process of exchanging DNA between two DNA molecules through regions of identical sequence. Homologous recombination provides an alternative to using restriction endonucleases and ligases for producing recombinant DNA. Although the background level of homologous recombination in native E. coli is very low even with long homology arms, it is possible to modify or clone nucleic acids using homologous recombination in specific genetically modified strains of E. coli. Whereas, a defective prophage used in these recombineering strains is optimally suited for expression of the lambda RED functions for homologous recombination it is hard for experimenters not familiar with E. coli genetics to move the defective prophage from strain to strain. Thus, methods of introducing the defective prophage and its recombineering functions into other strains of E. coli and other bacteria, including other gram negative bacteria, are also needed.

This invention provides plasmids and methods of use that confer the recombineering function to a variety of cells, including strains like DH10B of E. coli, as well as other species like Salmonella, Pseudomonas, Cyanobacteria, and Yeresinia, among others. These plasmids can be isolated in vitro and can be used to transform bacterial cells, such as gram negative bacteria.

This research is described, in part, in: Thomason, L.C., Costantino, N., Sawitzke, JA., Datta, S., Bubunenko, M., Court, DL., Myers, R.S., Oppenheim, AB. 2005. Recombineering in Prokaryotes. In Phages: Their Role in Bacterial Pathogenesis and Biotechnology. pp. 383-399. (MK. Waldor, DI. Friedman, and SL. Adhya) ASM Press, Herndon, VA.

Also provided are Lambda phages and methods of use for their introduction as prophages to provide recombineering functions into E. coli cells (Virology 319: 185-189, 2004). These phages include appropriate amber mutations in genes to prevent cell death and allow high expression of lambda RED recombination functions. The phage also carry a selectable drug marker used to make lysogens. The phages can be used to infect an E. coli cell that includes a suppressor of the amber mutations which allows the phage to reproduce, lyse the infected cell, and produce high titers of the phage. However, the phage will not be able to destroy cells that do not carry the suppressor mutations and in these cells the phage can lysogenise and be used as a defective prophage to generate recombination activity in those cells. Such cells lacking the suppressor are DH10B cells in which genomic libraries of BACs are cloned. Such random libraries can be lysogenized in mass (or individually) with these phages by selecting for the drug marker they carry. These lysogens can then be manipulated for homologous recombination in the same way as BAC containing derivatives off DY380 described elsewhere.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Regulation of INS (3456) P4 Signalling by a Reversible Kinase/Phosphatase and Methods and Compositions Related Thereto

Stephen Shears (NIEHS) et al.

U.S. Patent Application No. 10/508,363 filed 16 Sep 2004 (HHS Reference No. E-105-2002/0-US-03), claiming priority to 18 Mar 2002.

Licensing Contact: Marlene Shinn-Astor; 301/435-4426;

Receptor-dependent changes in Ins (3,4,5,6) P4 levels is a topic of general biological significance, since this regulates the activities of chloride channels that in turn regulate salt and fluid and mucus secretion from epithelial cells, cell volume homeostasis, and electrical excitability in neurons and smooth muscle.

The NIH announces new treatment methods for asthma, bronchitis and cystic fibrosis. The treatments consist of either increasing or decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a patient, thereby controlling Ins (3,4,5,6) P4-signaling which in turn affects the chloride channels, ultimately regulating salt, fluid and mucus secretion. This modulation of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase is accomplished by either pharmacological or genetic intervention.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Cancer Therapy Using Vasoactive Intestinal Peptide Antagonists

T. Moody (NCI), D. Brenneman (NICHD), et al.

U.S. Patent No. 5,217,953 issued 08 Jun 1993 (HHS Reference No. E-009-1991/0-US-01); U.S. Patent No. 5,565,424 issued 15 Oct 1996 (HHS Reference No. E-009-1991/1-US-01); U.S. Patent No. 6,630,124 issued 07 Oct 2003 (HHS Reference No. E-301-1998/2-US-06); Worldwide IP coverage.

Licensing Contact: Susan Carson; 301/435-5020;

The second leading cause of death in the United States is cancer and more than one million Americans are diagnosed with cancer each year, with this number likely to increase as the population ages. There remains a need for effective therapeutics with improved safety profiles, and promising results can be obtained through targeting receptors which are highly expressed on specific cancers. Vasoactive Intestinal Peptide (VIP) is a 28 amino-acid peptide hormone and one of several small neuropeptides that can function as autocrine growth factors. VIP mediates a variety of physiological responses and has been shown to exert stimulating and trophic effects on neoplastic cells inducing its own receptors by feedback mechanisms. Studies have shown that VIP receptors are present in many epithelial cancers including breast, colon, non-small cell lung carcinoma, and pancreatic and prostate cancers. Work by NIH scientists and their collaborators has shown that VIP receptor antagonists such as the lipophilic VIP antagonist SNH inhibit the growth of cancer cell lines in vitro and in vivo and potentiate the cytotoxicity of chemotherapeutic drugs. For example, results have shown that Start Printed Page 56475SNH and taxol are synergistic at inhibiting breast cell cancer growth and can potentiate the cytotoxicity of taxol in an in vivo human xenograft breast cancer mouse model.

Combination therapy using these agents may therefore greatly enhance the response rate of different cancers to these drugs and may significantly reduce side effects by permitting a lower therapeutic dose to be administered. Available for licensing are compositions of matter and methods of use of VIP receptor antagonists.

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Dated: September 15, 2005.

Steven M. Ferguson,

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

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[FR Doc. 05-19172 Filed 9-26-05; 8:45 am]