[Federal Register Volume 74, Number 223 (Friday, November 20, 2009)]
[Notices]
[Pages 60276-60277]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-27925]


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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 
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.

Phage Display Plasmids With Improved Expression Properties for Human 
and Chimeric Nonhuman/Human Fab Libraries

    Description of Invention: The Fab molecule was the first generated 
antibody fragment and still dominates basic research and clinical 
applications. New phage display vectors were designed to generate and 
select Fab libraries with human constant domains. These vectors 
facilitate bacterial expression of human, humanized, and chimeric 
nonhuman/human Fab antibody fragments. They differ from currently 
available pComb3H and pComb3X phage display vectors by assembling human 
and chimeric nonhuman/human Fab libraries in two rather than three PCR 
steps. As a result, these novel constructs retain the initial variable 
light and heavy chain sequences and improve the resulting Fab library's 
complexity in terms of number, diversity, and affinity. These 
constructs were developed with and without a His tag and yield 
approximately 100 [mu]g to 2 mg of protein, which can be used for 
evaluation and characterization of Fab binding properties such as 
affinity and specificity. Notably, the His tag provides a handle to 
easily purify Fab.

Applications

     Generation of human, humanized, and chimeric nonhuman/
human Fab antibody fragments.
     Research tool to characterize Fab antibody fragments.

Advantages

     Improved Fab library with complexity and number, 
diversity, and affinity.
     His tag construct allows for simplified purification 
assays.
    Inventor: Christoph Rader (NCI).

Relevant Publications

    1. KY Kwong and C Rader. E. coli expression and purification of Fab 
antibody fragments. Curr Protoc Protein Sci. 2009 Feb;Chapter 6:Unit 
6.10.
    2. T Hofer et al. Chimeric rabbit/human Fab and IgG specific for 
members of the Nogo-66 receptor family selected for species cross-
reactivity with an improved phage display vector. J Immunol Methods. 
2007 Jan 10;318(1-2):75-87.
    Patent Status: HHS Reference No. E-008-2010/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].

Potent and Selective Inhibitors of Human Lipoxygenase for Prostate 
Cancer Therapy

    Description of Invention: With more than $2 billion in revenues in 
the US in 2007, the market for diagnostic and therapeutic products for 
prostate cancer is substantial. More than 2,000,000 American men 
currently live with prostate cancer and more than 200,000 new cases are 
diagnosed each year.
    Researchers led by Dr. David Maloney at the National Human Genome 
Research Institute (NHGRI) have discovered several novel compounds that 
selectively and potently inhibit lipoxygenase (LOX), an enzyme that 
metabolizes polyunsaturated fatty acids which has been implicated in 
the pathogenesis of prostate cancers. These novel compounds are small 
molecules, and as such have an advantage over antibody-based 
technologies in this market. As prostate cancer is the most commonly 
diagnosed malignancy among men in the USA and Europe, the significant 
need for new therapies suggests that these novel LOX inhibitor 
compounds have a strong potential of reaching the marketplace.

Applications

     Therapeutics for prostate cancer.
     Therapeutics for several other LOX-associated pathologies 
including atherosclerosis, asthma, other cancers, glomerulonephritis, 
osteoporosis, and Alzheimer's disease.

Advantages

     Potent and selective inhibitory activity to reduce 
negative side effects.
     Compounds are small molecules (less immunogenic than 
antibodies).
    Development Status: Pre-clinical.
    Inventors: David Maloney et al. (NHGRI).

Relevant Publications

    1. V Kenyon et al. Novel human lipoxygenase inhibitors discovered 
using virtual screening with homology models. J Med Chem. 2006 Feb 
23;49(4):1356-1363.
    2. JD Deschamps et al. Baicalein is a potent in vitro inhibitor 
against both reticulocyte 15-human and platelet 12-human lipoxygenases. 
Bioorg Med Chem. 2006 Jun 15;14(12):4295-4301.
    3. Y Vasquez-Martinez et al. Structure-activity relationship 
studies of flavonoids as potent inhibitors of human platelet 12-hLO, 
reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. Bioorg Med 
Chem. 2007 Dec 1;15(23):7408-7425.
    4. J Inglese et al. Quantitative high-throughput screening: a 
titration-based approach that efficiently identifies biological 
activities in large chemical libraries. Proc Natl Acad Sci USA. 2006 
Aug 1;103(31): 11473-11478.
    Patent Status: U.S. Provisional Application No. 61/238,972 filed 01 
Sep 2009 (HHS Reference No. E-252-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Patrick P. McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The NIH Chemical Genomics 
Center, NHGRI, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize this technology. Please

[[Page 60277]]

contact Claire Driscoll at [email protected] or 301-594-2235 for 
more information.

    Dated: November 13, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-27925 Filed 11-19-09; 8:45 am]
BILLING CODE 4140-01-P