[Federal Register Volume 70, Number 186 (Tuesday, September 27, 2005)]
[Notices]
[Pages 56473-56475]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-19172]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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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

[[Page 56474]]

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.

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; 
<a href="/cdn-cgi/l/email-protection#bfcfd0d1cbc5dacdd1ffd2ded6d391d1d6d791d8d0c9"><span class="__cf_email__" data-cfemail="93e3fcfde7e9f6e1fdd3fef2faffbdfdfafbbdf4fce5">[email protected]</span></a>.

    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; 
<a href="/cdn-cgi/l/email-protection#1f6c77767171725f727e76733171767731787069"><span class="__cf_email__" data-cfemail="56253e3f38383b163b373f3a78383f3e78313920">[email protected]</span></a>.

    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; <a href="/cdn-cgi/l/email-protection#d5b6b4a7a6babba6a095b8b4bcb9fbbbbcbdfbb2baa3"><span class="__cf_email__" data-cfemail="d6b5b7a4a5b9b8a5a396bbb7bfbaf8b8bfbef8b1b9a0">[email protected]</span></a>.

    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

[[Page 56475]]

SNH 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.

    Dated: September 15, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-19172 Filed 9-26-05; 8:45 am]
BILLING CODE 4140-01-P


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