[Federal Register Volume 73, Number 31 (Thursday, February 14, 2008)]
[Notices]
[Pages 8705-8707]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-2752]


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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.

New Inhibitors of Multidrug Resistant Proteins Such as ABCG2

    Description of Technology: Drug resistance plays a significant role 
in the failure of cancer chemotherapy. Some proteins such as ABCG2, Pgp 
and MRP1 that belong to the superfamily of ATP-binding cassette 
transporters contribute to this process.
    Two categories of ABCG2 protein inhibitors--botryllamides, isolated 
from a marine sponge, and naphthopyrones, isolated from marine sea 
stars--have been obtained by high-throughput screening of 89,000 
natural product extracts from the Natural Products Repository at NCI.
    These new compounds serve as potential therapeutic agents for 
cancer chemotherapy either exclusively or in combination with 
conventional regimens. The study of structure-activity relationships 
will help delineate features that would enhance activity and 
specificity to multiple drug resistant proteins.
    Advantages: Increase bioavailability of orally administered drugs; 
Enhance drug delivery to certain tissues.
    Applications: Cancer therapeutics; Cancer stem cell research; Study 
of structure, function and relevance of MDR in cancer.
    Market: Cancer is the second leading cause of death in America, 
after heart disease. Multiple drug resistance is a significant 
impediment in the treatment of cancers resulting in poor prognosis. 
Some cancers with demonstrated high levels of MDR are leukemia, colon, 
renal, liver, adrenocortical, and pancreatic. Breast, ovarian, sarcoma 
and small-cell lung cancer show increased MDR on treatment.
    This new technology has the potential to increase the effectiveness 
of conventional chemotherapy and prognosis of cancer.
    Developmental Status: Early stage.
    Inventors: Curtis J. Henrich et al. (NCI).
    Patent Status: U.S. Provisional Application No. 60/018,758 filed 03 
Jan 2008 (HHS Reference No. E-315-2007/0-US-01).
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: John Stansberry, PhD; 301/435-5236; 
[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.

[[Page 8706]]

    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 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: Snorri Thorgeirsson (NCI) and Cedric Coulouaran (NCI).
    Relevant Publication: Manuscript in press Hepatology 2008.
    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 Fold-Back Diabody Format for Diphtheria Toxin-Based Immunotoxins That 
Can Increase Binding and Potency

    Description of Technology: NIH inventors, in collaboration with 
Scott and White Memorial Hospital inventors, have developed new 
immunotoxins comprising a mutant diphtheria toxin linked to an anti-
prostate specific membrane antigen (PSMA) fold-back diabody. The fold-
back diabody construct has a shortened linker region between the heavy 
and light chains of the antibody variable domain. This construct allows 
interactions between the longer-linked variable domains while 
preventing interactions between the shorter-linked variable domains. 
This results in increased efficiency of epitope recognition and 
delivery to the appropriate target cells. These immunotoxins can be 
used for the treatment of cancers that overexpress PMSA, with specific 
application against prostate cancer.
    Applications:
    Treatment of primary prostate tumors.
    Treatment of metastatic prostate tumors, for which no currently 
effective treatment exists.
    Application against other tumors expressing the PSMA epitope on the 
tumor neovasculature such as breast cancer.
    Advantages:
    Increased potency of 10-40-fold resulting from the use of the fold-
back diabody construct.
    First treatment with applications to metastatic prostate cancer.
    Pichia pastoris production process of the fold-back immunotoxin can 
be used to scale up for GMP production.
    Benefits:
    Significant social benefit for successfully treating the second 
leading cause of cancer-related deaths among males in the United 
States.
    Approximately 8 billion USD per year are spent on prostate cancer 
treatment; a new treatment could procure a significant financial 
position.
    Opportunity to occupy a strong market position through the 
development of the first treatment of metastatic prostate cancer.
    Inventors: David Neville (NIMH) et al.
    Patent Status: U.S. Patent Application No. 60/953,416 filed 01 Aug 
2007 (HHS Reference No. E-268-2007/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Mental Health, Laboratory of Molecular Biology, is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize anti-PSMA fold-
back immunotoxins. Please contact David Neville by phone at 301-496-
6807 or e-mail [email protected] for more information.

Ribosomal Protein S3 (RPS3), an Essential Component of NF-kB is a Novel 
and Selective Drug Target

    Description of Technology: NF-kB, represented by the p50-p65 
heterodimer, is a DNA binding protein complex that has well documented 
functions in inflammatory or autoimmune diseases. Its potential as a 
drug target is currently being explored by the pharmaceutical industry.
    The present invention describes that ribosomal protein S3 (RPS3) is 
a novel component of the p65 homodimer and p65-p50 heterodimer DNA 
binding complex. Experiments confirmed that RPS3 is essential for 
normal expression of specific NF-kB target genes, including key 
physiological events that require p65.
    Advantages and Applications: A novel and selective target for drug 
candidates targeting the NF-kB pathway.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Michael J. Lenardo and Fengyi Wan (NIAID).
    Patent Status: U.S. Provisional Application No. 60/913,336 filed 23 
Apr 2007 (HHS Reference No. E-162-2007/0-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Mojdeh Bahar, J.D.; 301-435-2950; 
[email protected].
    Collaborative Research Opportunity: The NIAID Laboratory of 
Immunology is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize this technology. Please contact Dr. Michael Lenardo at 
301-496-6754 for more information.

A New Technology for Identification of Genes Expressed in Hypoxia 
Conditions

    Description of Technology: Low concentrations of oxygen (hypoxia) 
are a major pathophysiological condition conducive for angiogenesis, 
necessary for tumor growth and metastasis of cancer cells.
    A new technology comprising of a vector DNA (pGL2-TK-HRE) that 
expresses the luciferase gene under the influence of a hypoxia 
inducible promoter sequence from the nitric oxide synthase gene has 
been used to transform various human tumor cell lines such as U251-HRE 
and PC3-HRE. These cells express little to no luciferase under normal 
oxygen levels, but stably express significantly higher levels under low 
oxygen levels.
    The transformed cell lines can be used to screen and develop drugs 
and small molecules that inhibit angiogenesis, an attractive target for 
cancer therapy. The technology can also be used in gene therapy where 
the therapeutic gene is being expressed under a hypoxia inducible 
promoter.
    Advantages: Quantitative; Robust, stably express luciferase; Can be 
used in vivo.
    Applications: Early detection of angiogenesis; Cancer therapeutics; 
Gene therapy.
    Market: Cancer is the second leading cause of death in America, 
after heart disease. Every year, more than a million people are 
diagnosed with cancer. Over 50% of the cases reported in the U.S. 
affect the lung, breast, prostate and colorectal. Although the number 
of

[[Page 8707]]

deaths reported is declining 553,888 cancer deaths in 2004 compared to 
556,902 in 2003, the total number of all cancer deaths among women is 
rising.
    With the help of the new technology early detection, therapy and 
monitoring of cancer combating efforts would be possible.
    Development Status: Developed.
    Inventor: Giovanni Melillo (NCI)
    Patent Status: HHS Reference No. E-220-2003/0--Research Tool. 
Patent protection is not being sought for this technology.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: John Stansberry, PhD; 301/435-5236; 
[email protected].

    Date: February 6, 2008.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E8-2752 Filed 2-13-08; 8:45 am]
BILLING CODE 4140-01-P