[Federal Register Volume 74, Number 199 (Friday, October 16, 2009)]
[Notices]
[Pages 53264-53265]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-24877]


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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.

B-cell Surface Reactive Antibodies for the Treatment of B-Cell Chronic 
Lymphocytic Leukemia

    Description of Technology: B-cell chronic lymphocytic leukemia (B-
CLL) is a cancer characterized by a progressive accumulation of 
functionally incompetent lymphocytes. Despite high morbidity and 
mortality, the only available potential cure is allogeneic 
hematopoietic stem cell transplantation (alloHSCST). However, there is 
less than a 50% chance of finding a matching bone marrow or blood donor 
for B-CLL patients. Other clinically tested targeted therapies such as 
rituximab and alemtuzumab target both malignant and normal B cells, 
resulting in immunosuppression.
    Available for licensing are fully human monoclonal antibodies that 
were selected from the first human post-alloHSCT antibody library. The 
library was generated from a time point after transplantation at which 
antibodies to B-CLL cell surface antigens peaked, thus indicating its 
therapeutic value. Utilizing phage display, the investigators generated 
a panel of fully human monoclonal antibodies that strongly bind to the 
same epitope on a B-CLL cell surface antigen. Weaker binding to normal 
B cells, but not to other lymphocytes, was observed. These fully human 
monoclonal antibodies provide readily available treatment that 
selectively targets malignant B cells.
    Applications:
     B-cell chronic lymphocytic leukemia therapeutics.
     Method to inhibit the growth of malignant B-cells.
     Method to detect B-cell tumors.
    Advantages:
     Selective targeting of malignant B-cell surface antigens 
that are minimally non-damaging to non-diseased cells.
     Readily available therapeutics without the need for bone 
marrow or blood transplantation.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Market:
     Monoclonal antibody market has the potential to reach 
$30.3 billion in 2010 largely driven by technological evolution from 
chimeric and humanized to fully human antibodies.
     In the U.S., there is annual incidence of an estimated 
15,000 newly diagnosed cases of B-CLL and the disease is responsible 
for an estimated 4,500 deaths.
    Inventors: Christoph Rader et al. (NCI)
    Publication: S Baskar, JM Suschak, I Samija, R Srinivasan, RW 
Childs, SZ Pavletic, MR Bishop, C Rader. A human monoclonal antibody 
drug and target discovery platform for B-cell chronic lymphocytic 
leukemia based on allogeneic hematopoietic stem cell transplantation 
and phage display. Blood, in press. Epub ahead of print, 2009 Aug 10.
    Patent Status: U.S. Provisional Application No. 61/178,688 filed 15 
May 2009 (HHS Reference No. E-163-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Experimental Transplantation and Immunology Branch, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
fully human monoclonal antibodies selected from post-alloHSCT antibody 
libraries. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

CXCR4 and CCR10 Expressing Cells: Useful for the Study of Cancer Cell 
Survival and Metastasis

    Description of Technology: The chemokine receptor CXCR4 functions 
in normal cells, but has been shown to be the most common chemokine 
receptor expressed on cancer cells, including melanoma, colon, breast, 
and lung cancers. It plays roles in angiogenesis and cancer cell 
survival as well as metastasis. CCR10 has also been shown to be 
expressed by melanoma cells. Like CXCR4, expression of CCR10 can 
enhance cancer cell survival and block immune recognition of cancer 
cells. Antagonists of CXCR4 and CCR10, under various conditions, have 
decreased metastasis or prevented tumor formation after implantation of 
cancer cells in mice.
    These cell lines are based on the widely used B16 murine melanoma 
cell line. The cell lines were transduced with retroviral vectors 
encoding cDNA for either CXCR4 or CCR10 under control of a TET-
dependent promoter. Both lines achieve greater than 10 fold induction 
of the respective genes (proteins), which has been confirmed by surface 
antibody staining using flow cytometry. These cell lines are ideally 
suited for studying the effect of these chemokine receptors in tumor 
growth or metastasis. They are also useful for

[[Page 53265]]

developing a mouse model for studying the effect of down-regulating 
these receptors specifically in melanoma cells. This would mimic the 
effect of antagonists without the confounding effects of systemically 
inhibiting CXCR4 or CCR10. By either adding or removing dietary 
administered doxycycline, receptor expression can be regulated to 
assess the role of these two receptors in a variety of cancer-related 
assays.
    Applications:
     Study the effect of chemokine receptors in tumor growth or 
metastasis.
     Test CXCR4 and CCR10 antagonists in preclinical studies.
     Develop B16 melanoma mouse model mimicking the effect of 
chemokine receptor antagonists.
    Advantages:
     Ability to regulate in vitro and in vivo expression of the 
chemokine receptor.
     Ability to investigate the in vivo role in cancer cells of 
doxycycline control of chemokine receptor expression.
    Development Status: The technology is currently in the preclinical 
stage of development.
    Market: Cancer is the second leading cause of death in the U.S. and 
it is estimated that more than 1 million Americans develop cancer in a 
year.
    Inventors: Sam T. Hwang (NCI).
    Publication: T Kakinuma, ST Hwang. Chemokines, chemokine receptors, 
and cancer metastasis. J Leukoc Biol. 2006 Apr;79(4):639-651.
    Patent Status: HHS Reference No. E-345-2008/0--Research Material. 
Patent protection is not being sought for either technology.
    Licensing Status: Available for non-exclusive licensing under a 
Biological Materials License Agreement.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].

Identification of Persons Likely To Benefit From Statin Mediated Cancer 
Prevention by Pharmacogenetics

    Description of Technology: Inhibitors of 3-hydroxy-3-methylglutaryl 
(HMG) coenzyme A reductase (statins) are a class of well-tolerated 
compounds that are the most widely used cholesterol-lowering drugs in 
the United States. Reduced cancer risk among statin users has also been 
observed as a secondary outcome in randomized controlled clinical 
trials evaluating effects of statins on cardiovascular outcomes. 
However the observed cancer risk reduction varied with different 
clinical studies. Thus there is a need to identify individuals who 
would benefit from treatment with statins.
    The current invention describes a pharmacogenetic method to 
identify candidates who are most likely to benefit from treatment with 
statins to reduce cancer risk, and consequently minimizing any 
unnecessary cost and side effects in individuals who do not benefit. 
Specifically, we discovered that an HMGCR genetic variant rs12654264 is 
associated with significantly lower colorectal cancer risk, with most 
of the benefit seen in HMGCoA reductase inhibitor (statin) users. We 
also discovered that this same HMGCR genetic variant is associated with 
significantly higher serum cholesterol levels in Israeli colorectal 
cancer patients. The same HMGCR genetic variant has also been 
associated with significantly higher serum cholesterol levels in two 
independent groups of individuals of mixed European descent [http://www.broad.mit.edu/diabetes/scandinavs/index.html and N Engl J Med.2008 
March 20;358(12):1240-1249 (http://www.ncbi.nlm.nih.gov/pubmed/18354102?dopt)]. These data suggest that the same genetic variant 
modifies cholesterol metabolism in a manner that affects both 
colorectal cancer risk and cardiovascular risk.
    Applications and Market:
     Statins account for approximately 80% of the cholesterol-
lowering drugs prescribed in the United States, and six statins are 
currently available on the U.S. market. Reduced cancer risk is also 
associated with statin use. This invention provides a method to 
indentify individuals who are most likely to benefit from cancer 
chemopreventive treatment with statins.
     Pharmacogenetic markers can be developed to identify 
patient population that can be benefit from statins, therefore expands 
the markets of stains.
    Development Status: The inventors have discovered several novel 
genetic variants of HMG coenzyme A reductase gene, and are further 
investigating the functional significance of the variants in vitro.
    Inventors: Levy Kopelovich (NCI) et al.
    Patent Status: PCT Application No. PCT/US2008/082359 filed 04 Nov 
2008, which published as WO 2009/061734 on 14 May 2009 (HHS Reference 
No. E-328-2007/0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].

    Dated: October 7, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-24877 Filed 10-15-09; 8:45 am]
BILLING CODE 4140-01-P