[Federal Register Volume 73, Number 132 (Wednesday, July 9, 2008)]
[Notices]
[Pages 39319-39321]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-15562]



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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.

Method for Detection and Quantification of PLK1 Expression and Activity

    Description of Technology: Polo-like kinase 1 (Plk1) plays a role 
in the regulation of the cell cycle and control of cellular 
proliferation. Because Plk1 is associated with neoplastic 
transformation of human cells, expression of this protein has been 
proposed as a prognostic marker for many types of malignancies. In 
mammalian cells, four Plks exist, but their expression patterns and 
functions appear to be distinct from each other. Available for 
licensing is a Plk1 ELISA assay using peptide substrates that are 
specific for Plk1, in that they are phosphorylated and bound by Plk1, 
but not by the related polo kinases Plk2, Plk3 and Plk4.
    By exploiting a unique Plk1-dependent phosphorylation and binding 
property, an easy and reliable ELISA assay has been developed to 
quantify Plk1 expression levels and kinase activity. With this highly 
sensitive assay, Plk1 activity can be measured with 2-20 microgram of 
total lysates without immunoprecipitation or purification steps. Since 
deregulated Plk1 expression has been suggested as a prognostic marker 
for a wide range of human malignancies, this assay may provide an 
innovative tool for assessing the predisposition for cancer 
development, monitoring cancer progression, and estimating the 
prognosis of various types of cancer patients.
    Applications: Optimized PBIP1 polypeptides, a natural substrate of 
Plk1, with enhanced specificity and sensitivity over the native PBIP1 
sequence.
    ELISA assay to quantify Plk1 expression and kinase activity.
    Advantages: Rapid, highly sensitive assay that requires lower 
amounts of starting material than conventional immunoprecipitation 
assays.
    Assay that is selective for Plk1.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Market: An estimated 1,444,920 new cancer diagnoses in the U.S. in 
2007. Cancer is the second leading cause of death in United States. It 
is estimated that the cancer therapeutic market would double to $50 
billion a year in 2010 from $25 billion in 2006.
    Inventors: Kyung Lee and Jung-Eun Park (NCI).
    Publications: 1. J-E Park, L Li, K Strebhardt, SH Yuspa, and KS. 
Lee. Direct quantification of polo-like kinase 1 activity in cells and 
tissues using a highly sensitive and specific ELISA assay (about to be 
submitted).
    2. KS Lee et al. Mechanisms of mammalian polo-like kinase 1 (Plk1) 
localization: self-versus non-self-priming. Cell Cycle 2008 Jan;7(2): 
141-145.
    3. KS Lee et al. Self-regulated mechanism of Plk1 localization to 
kinetochores: lessons from the Plk1-PBIP1 interaction. Cell Div. 2008 
Jan 23;3:4.
    4. YH Kang et al. Self-regulated Plk1 recruitment to kinetochores 
by the Plk1-PBIP1 interaction is critical for proper chromosome 
segregation. Mol Cell. 2006 Nov 3;24(3): 409-422.
    Patent Status: U.S. Provisional Application No. 61/054,032 filed 16 
May 2008 (HHS Reference No. E-091-008/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633.; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Metabolism is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize the PLK1 ELISA assay described 
above. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Cripto-1 Represents a Biomarker for Chronic Inflammatory Diseases

    Description of Technology: Chronic inflammatory bowel disease (IBD) 
(e.g. Crohn's disease and ulcerative colitis) and chronic inflammatory 
arthropathy such as rheumatoid arthritis represent an enormous socio-
economic burden due to the cost for long term medication and 
rehabilitation and the decreased productivity due to periods of acute 
recurrences. A major characteristic of these diseases is the tissue 
infiltration of specific CD4+ T cells that sustain inflammation by 
secreting cytokines. One of these cytokines, TNF-alpha, is a current 
therapeutic target for the treatment of these chronic inflammatory 
diseases.
    This technology describes Cripto-1 as a biomarker for chronic 
inflammatory diseases. Cripto-1, an epidermal growth factor (EGF)-
related protein, shows higher expression levels in tissue sections of 
Crohn's disease, ulcerative colitis, and rheumatoid arthritis as 
compared to adjacent unaffected areas. Moreover, the inventors show 
that the response to Cripto-1 is not due to a generic immune response, 
and Cripto-1 expression increases the expression of TNF-alpha in CD4+ T 
cells in tissues affected by chronic inflammatory disease. As a result, 
this technology could be used as a diagnostic biomarker for chronic 
inflammatory diseases as well as a novel therapeutic target to help 
control TNF-alpha in chronic inflammatory diseases.
    Applications: Diagnostic tool for the detection of a chronic 
inflammatory disease.
    Method to inhibit cytokine production in a tissue affected with a 
chronic inflammatory disease.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Luigi Strizzi, David S. Salomon, Monica I. Gonzales 
(NCI).
    Patent Status: U.S. Provisional Application No. 61/045,746 filed 17 
Apr 2008 (HHS Reference No. E-075-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Mammary Biology and Tumorigenesis Laboratory is seeking statements of 
capability or interest from parties interested in collaborative 
research to further

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develop, evaluate, or commercialize Cripto-1 as a biomarker for chronic 
inflammatory diseases. Please contact John D. Hewes, Ph.D. at 301-435-
3121 or [email protected] for more information.

Cripto-1 as a Biomarker for Cardiac Ischemia

    Description of Technology: Ischemic heart disease is a major cause 
of human cardiac morbidity and mortality, affecting over 14 million 
people in the United States alone. Current detection of cardiac 
ischemia relies upon identification of electrocardiographic anomalies 
and the release of cardiac markers from the damaged myocardial tissue. 
Unfortunately, patients with acute myocardial infarction are often 
insensitive to these tests during the early phases of intervention and 
as a result more markers for cardiac ischemic disease are needed.
    This technology describes Cripto-1 as a biomarker for infarcted 
cardiac tissues. Cripto-1 is a member of the epidermal growth factor 
(EGF)-related proteins and is currently thought to play an important 
role in several cancers. The present invention shows that Cripto-1 is 
overexpressed in infarcted myocardial tissue, and not expressed or 
weakly expressed in non-infarct related heart disease tissues and 
normal tissues. Furthermore, the overexpression of Cripto-1 correlates 
with the hypoxia-inducible factor-1-alpha indicating specificity to 
ischemic heart tissue. The expression of Cripto-1 has also been shown 
to be highly expressed in stem cells, which may have an important role 
in the repair of damaged myocardial tissue. Thus, this technology could 
represent a new biomarker for the diagnosis of myocardial infarction as 
well as a surrogate biomarker to monitor the healing process including 
regenerative stem cell activity of the infarcted myocardial tissue.
    Applications:
    Diagnostic tool for the detection of myocardial infarction.
    Method to monitor stem cell activity in damaged myocardial tissue.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Luigi Strizzi, Caterina Bianco, David S. Salomon (NCI).
    Patent Status: U.S. Provisional Application No. 61/046,181 filed 18 
Apr 2008 (HHS Reference No. E-049-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney A. Hastings; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Mammary Biology and Tumorigenesis Laboratory is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize Cripto-1 as a 
biomarker for cardiac ischemia. Please contact John D. Hewes, Ph.D. at 
301-435-3121 or [email protected] for more information.

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 benefit from statins, therefore expanding 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: Dr. Levy Kopelovich (NCI) et al.
    Patent Status: U.S. Provisional Application No. 60/985,587 filed 05 
Nov 2007 (HHS Reference No. E-328-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Betty Tong, PhD; 301-594-6565; 
[email protected].

TGF-beta Gene Expression Signature in Cancer Prognosis

    Description of Technology: Hepatocellular carcinoma (HCC) is the 
third leading cause of cancer death worldwide, and it is very 
heterogeneous in terms of its clinical presentation as well as genomic 
and transcriptomic patterns. This heterogeneity and the lack of 
appropriate biomarkers have hampered patient prognosis and treatment 
stratification.
    Available for licensing is a novel temporal TGF-beta gene 
expression signature that predicts HCC patient clinical outcomes. 
Patients with tumors expressing late TGF-beta responsive genes had a 
malignant prognosis and an invasive tumor phenotype as evaluated by 
decreased survival time, increased tumor recurrence, and vascular 
invasion rate. Additionally, this signature may also be able to 
prognose other cancers, including lung cancer.
    Applications: Method to diagnose cancer.
    Method to monitor cancer progression and aid clinicians to choose 
appropriate therapies.
    Commercial kits to prognose cancer.
    Advantages: Early diagnostic tool to stratify HCC patients to chose 
more effective treatment.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Market: An estimated 1,444,920 new cancer diagnosed in the U.S. in 
2007.
    Cancer is the second leading cause of death in United States.
    It is estimated that the cancer therapeutic market would double to 
$50 billion a year in 2010 from $25 billion in 2006.

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    Inventors: Snorri Thorgeirsson (NCI) and Cedric Coulouaran (NCI)
    Relevant Publication: Coulouaran C, Factor VM, Thorgeirsson SS. 
Transforming growth factor-beta gene expression signature in mouse 
hepatocytes predicts clinical outcome in human cancer. Hepatology 2008 
Jun;47(6):2059-2067.
    Patent Status: U.S. Provisional Application No. 60/981,661 filed 22 
Oct 2007 (HHS Reference No. E-282-2007/0-US-01)
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Experimental Carcinogenesis 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize a novel temporal TGF-beta gene expression signature that 
predicts HCC patient clinical outcomes. Please contact John D. Hewes, 
PhD at 301-435-3121 or [email protected] for more information.

A New Pot1 Variant Gene as a Diagnostic Biomarker for Hereditary Non-
polyposis Colorectal Cancer

    Description of Technology: The diagnosis of Hereditary Nonpolyposis 
Colorectal Cancer (HNPCC) is difficult because the disease lacks 
phenotypic signs that might facilitate its presymptomatic diagnosis. 
This invention is based on the identification of a new splice variant 
of a gene that appears to exist specifically in HNPCC, namely ``Pot1'' 
or ``Protection of Telomeres.'' Pot1 has a critical role in ensuring 
chromosome stability by binding to telomeres. The invention presents a 
variant of Pot1 that is present in mismatch repair-deficient, but not 
proficient, cancer cell lines and primary, non-tumor tissue samples. 
The presence of this variant may be useful both as a diagnostic marker 
for HNPCC, and as a new therapeutic target for the treatment of HNPCC.
    Applications and Modality: Identification of new ``Pot1'' variant 
gene associated with HNPCC
    New gene can be used as a potential diagnostic biomarker for the 
diagnosis of HNPCC.
    Pot1 as a new therapeutic target for the treatment of HNPCC.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Qin Yang and Curtis C. Harris (NCI).
    Related Publications:
    1. P Baumann et al. Human Pot1 (protection of telomeres) protein: 
cytolocalization, gene structure, and alternative splicing. Mol Cell 
Biol. 2002 Nov;22(22):8079-8087.
    2. A Umar et al. Revised Bethesda Guidelines for hereditary 
nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite 
instability. J Natl Cancer Inst. 2004 Feb 18;96(4):261-268.
    3. HT Lynch et al. Hereditary nonpolyposis colorectal carcinoma 
(HNPCC) and HNPCC-like families: Problems in diagnosis, surveillance, 
and management. Cancer. 2004 Jan 1;100(1):53-64.
    4. Q Yang et al. Functional diversity of human protection of 
telomeres 1 isoforms in telomere protection and cellular senescence. 
Cancer Res. 2007 Dec 15;67(24):11677-11686.
    Patent Status: U.S. Provisional Application No. 60/620,754 filed 20 
Oct 2004 (HHS Reference No. E-263-2004/0-US-01), entitled ``POT1 
Alternating Splice Variants''
    International Patent Application No. PCT/US2005/037957 filed 19 Oct 
2005, which published as WO 2006/045062 on 27 Apr 2006 (HHS Reference 
No. E-263-2004/0-PCT-02)
    U.S. Patent Application No. 11/665,944 filed 20 Apr 2007 (HHS 
Reference No. E-263-2004/0-US-03).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Laboratory of Human Carcinogenesis is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize biomarkers of colon cancer. 
Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

    Dated: June 30, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-15562 Filed 7-8-08; 8:45 am]
BILLING CODE 4140-01-P