[Federal Register Volume 74, Number 130 (Thursday, July 9, 2009)]
[Notices]
[Pages 32937-32940]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-16300]


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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.

Immunogenic Peptide from NGEP Protein for Developing Prostate Cancer 
Vaccines

    Description of Technology: The NGEP protein is only present in the 
prostate and is typically overexpressed on prostate cancer cells. 
Hence, as a novel prostate tumor-associated antigen (TAA) it is a good 
target for developing active immunotherapies to kill prostate cancer 
cells. For example, NGEP could be used in a vaccine to activate an 
individual's immune system to recognize and kill NGEP-expressing 
prostate cancer cells. However, TAAs typically are not very effective 
in inciting an immune response. This can be overcome by identifying 
portions (epitopes) of the

[[Page 32938]]

TAA that are more immunologically active.
    Investigators at the NIH have identified a small peptide fragment 
of the NGEP protein (NGEP CTL peptide epitope) that is very effective 
in activating cytotoxic lymphocytes, causing them to destroy prostate 
cancer cells and has great potential for development of a variety of 
active immunotherapy strategies, such as vector-based cancer vaccines, 
to treat and prevent prostate cancer. In addition, it could be used for 
developing sensitive immunoassays for measuring the immune response of 
a prostate cancer patient during immunotherapy.
    Applications:
     Peptide cancer vaccine.
     Vector-based cancer vaccine.
     Liposome-based cancer vaccine.
     Cellular cancer vaccine.
     In vitro diagnostic for monitoring the immune response of 
prostate cancer patients during cancer vaccine trials.
    Advantages:
     Small biologic therapeutic.
     Can be chemically synthesized or produced recombinantly.
     DNA encoded peptide allows molecular engineering.
     Can be used as a tumor antigen with the clinically proven 
TRICOM-based vaccine technology.
    Development Status: Early stage.
    Market: Prostate cancer is the second-leading cause of cancer death 
in men. It is estimated that in the United States there will be 192,280 
new cases of prostate cancer and 27,360 deaths due to prostate cancer 
in 2009.
    Inventors: Jeffrey Schlom et al. (NCI).
    Publications: No publications directly related to this technology.
    Patent Status: U.S. Provisional Application No. 61/170,900 filed 20 
Apr 2009 (HHS Reference No. E-042-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Sabarni Chatterjee, PhD; 301-435-5587; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Tumor Immunology and Biology, 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize this technology. Please contact Kevin Brand, J.D. at 301-
451-4566 or [email protected] for more information.

Gene Expression Signature Predictive of Response to Chemotherapy

    Description of Technology: Combination cisplatin and fluorouracil 
(CF) is a reference chemotherapy regimen for metastatic gastric cancer. 
However, to date, no genome-wide studies have identified distinctions 
in gene expression that predict which subjects with metastatic disease 
will benefit from this therapy and which subjects will not exhibit a 
therapeutic response to chemotherapy. Given the toxicity of 
chemotherapy, however, defining parameters that identify those subjects 
who will likely benefit from chemotherapy is of paramount importance. 
Early identification of non-responders would provide opportunities to 
explore alternate or novel therapeutic approaches. Thus, a need exists 
to identify methods of predicting a subject's response to chemotherapy 
prior to receiving the treatment.
    Scientists at the National Institutes of Health have discovered a 
three-gene signature that can be used to determine the chemotherapy 
response in patients with cancer. By measuring the expression of three 
cancer-specific genes it can be determined if a patient with an 
epithelial cancer such as gastric, bladder, head and neck, esophageal 
or cervical cancers, will respond to CF treatment. The inventors have 
demonstrated that examining these expression levels has high fidelity 
in identifying CF treatment non-responders. Further, the invention 
describes a mechanism that can help patients identified as non-
responders become responsive to treatment. Therefore these methods have 
the potential to reduce fatalities caused by metastatic gastric cancer 
by identifying patients early on who are non-responsive to standard CF 
treatment and customizing a new treatment plan which may be better 
suited to their individual needs.
    Applications:
     Prognostic testing of epithelial cancer patients.
     Customized treatment for gastric cancer patients 
identified as CF treatment non-responders.
    Advantages:
     Expression levels of cancer-specific genes can be used to 
determine if metastatic gastric cancer patients are responsive to 
combination cisplatin and fluorouracil (CF) treatment.
     Fatalities due to metastatic gastric cancer may be reduced 
by customizing the treatment of non-responders.
    Market: In 2008, it is estimated that there will be 21,500 new 
cases and 10,880 deaths from gastric cancer in the United States.
    Development Status: Patient tissue sample data available.
    Inventors: Jeffrey E. Green and Hark Kyun Kim (NCI).
    Patent Status: U.S. Provisional Application No. 61/195,123 filed 03 
Oct 2008 (HHS Reference No. E-282-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Cancer Biology and Genetics, 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize Gene Expression Signature Predictive of Response to 
Chemotherapy. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Therapeutic Applications of a p53 Isoform in Regenerative Medicine, 
Aging, and Cancer

    Description of Technology: p53 plays a critical role in 
carcinogenesis and aging as a key regulator of cell cycle progression, 
senescence and apoptosis. The inventors have discovered that a natural 
variant of p53 ([Delta]133p53) inhibits p53-dependent cell senescence. 
Utilizing [Delta]133p53 siRNAs, the inventors have data demonstrating 
that siRNA-treated human fibroblast undergo cell senescence, thereby 
indicating that [Delta]133p53 inhibition could be a novel approach for 
cell senescence-mediated anti-proliferative therapy, including anti-
cancer treatments. Alternatively, enhanced expression with 
[Delta]133p53 can extend the replicative lifespan of normal human 
cells. This technology may provide a new method in the field of 
regenerative medicine for aging-related degenerative disease.
    Also available for licensing are [Delta]133p53 siRNAs and shRNA 
vectors, as well as a [Delta]133p53 overexpression vector, which can be 
used for cancer and age-related degenerative therapeutics. The shRNA 
can be stably integrated into the cellular genome for long-term 
[Delta]133p53 inhibition.
    The inventors have also discovered that another p53 variant 
(p53[beta]) accelerates p53-dependent cell senescence, and developed a 
vector for overexpressing p53[beta], which could be used for cell 
senescence-mediated anti-proliferative therapy.
    Applications:
     Method to treat cancer.
     Method to treat aging related disorders.
     Method to promote tissue regeneration.

[[Page 32939]]

     Pharmaceutical compositions to inhibit cancer or promote 
cell regeneration.
    Advantages:
     Ability to treat a wide variety of cancers and age-related 
diseases as p53 is present in normal cells.
     shRNA therapeutics are stably integrated into genome for 
long-term treatment.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Market:
     An estimated 1,479,350 new cancer diagnoses in the U.S. in 
2009.
     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: Curtis C. Harris (NCI) et al.
    Relevant Publications:
    1. K Fujita et al. p53 isoforms, [Delta]133p53 and p53[beta], are 
endogenous regulators of replicative cellular senescence. Nat Cell 
Biol., in press.
    2. International Agency Research on Cancer Conference, Lyon, 
France, November 13, 2007.
    Patent Status:
     U.S. Provisional Application No. 60/987,340 filed 12 Nov 
2007 (HHS Reference No. E-033-2008/0-US-01).
     PCT Application No. PCT/US2008/080648 filed 21 Oct 2008 
(HHS Reference No. E-033-2008/0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[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 this technology. Please 
contact [email protected] for more information.

Novel Compounds that Specifically Kill Multi-Drug Resistant Cancer 
Cells

    Description of Invention: One of the major hindrances to successful 
cancer chemotherapy is the development of multi-drug resistance (MDR) 
in cancer cells. MDR is frequently caused by the increased expression 
or activity of ABC transporter proteins in response to the toxic agents 
used in chemotherapy. Research has generally been directed to 
overcoming MDR by inhibiting the activity of ABC transporters. However, 
compounds that inhibit ABC transporter activity often elicit strong and 
undesirable side-effects, restricting their usefulness as therapeutics.
    Investigators at the NIH previously identified that the compound 
NSC73306 had the ability to specifically kill cancer cells that 
overexpressed an ABC transporter responsible for MDR. Importantly, this 
``MDR-selective compound'' is not an inhibitor of ABC transporters, 
reducing the likelihood of undesirable side-effects if used as a 
therapeutic.
    Using NSC 73306 as a model, new MDR-selective compounds have been 
created with improved solubility and selectivity. These new MDR-
selective compounds can also selectively kill MDR cancer cells, with 
their efficacy correlating directly with the level of ABC transporter 
expression. Recent evidence also shows that these new MDR-selective 
compounds have the ability to decrease the expression of ABC 
transporters, potentially re-sensitizing the cancer cells to 
chemotherapeutic agents. Thus, MDR-selective compounds represent a 
powerful strategy for treating multi-drug resistant cancers as a direct 
chemotherapeutic and as agents that can re-sensitize MDR cancer cells 
for treatment with additional chemotherapeutic agents.
    Applications:
     Treatment of cancers associated with multi-drug 
resistance, either alone or in combination with other therapeutics.
     Development of a pharmacophore for improved effectiveness 
in treating cancers associated with multi-drug resistance.
     Re-sensitization of multi-drug resistant cancer cells to 
chemotherapeutic agents.
    Advantages:
     MDR-selective compounds capitalize on one of the most 
common drawbacks to cancer therapies (MDR) by using it as an advantage 
for treating cancer.
     The compositions do not inhibit the activity of ABC 
transporters, thereby reducing the chance of undesired side-effects 
during treatment.
     The effects of MDR-selective compounds correlate with the 
level of ABC transporter expression, allowing healthy cells which do 
not express high levels of ABC transporters to better survive 
treatments.
     Increased specificity allows the new MDR-selective 
compounds to be tailored to treating cancers associated with the 
overexpression and hyperactivity of particular ABC transporters.
     Increased solubility of the new MDR-selective compounds 
allows greater access to cancer cells, thereby increasing therapeutic 
effectiveness.
    Development Status: Preclinical stage of development.
    Patent Status: PCT Application No. PCT/US2009/000861 (HHS Reference 
No. E-017-2008/0-PCT-02).
    Inventors: Matthew D. Hall et al. (NCI).
    For more information, see:
     MD Hall et al. Synthesis, activity, and pharmacophore 
development for isatin-beta-thiosemicarbazones with selective activity 
toward multidrug-resistant cells. J Med Chem. 2009 May 28;52(10):3191-
3204.
     US Patent Application Publication 20080214606 A1 (US 
Patent Application 11/629,233).
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Cell Biology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize the agents described here. Please 
contact John D. Hewes, PhD at 301-435-3121 or [email protected] for 
more information.

Methods for Treating Cancer in Humans Using IL-21

    Description of Invention: The present invention discloses the use 
of IL-21 for cancer therapy, cancer prevention, and method to induce 
apoptosis. When compared to similar cytokines, IL-21 has shown 
substantial anticancer activity and reduced toxicity in murine models.
    IL-21 belongs to the class I family of cytokines and is closely 
related to IL-2 and IL-15. Some cancer patients have shown significant 
response to administration of IL-2. However, IL-2 has also been 
associated with severe toxicity leading to a variety of undesirable 
side effects. This invention attempts to resolve the toxicity concerns 
and presents a new therapy for cancer prevention and treatment.
    Applications: Method to treat and prevent cancer.
    Advantages: Targeted therapy to minimize negative side effects of 
IL-2 cancer therapeutics.
    Development Status: Pre-clinical.
    Inventors: Patrick Hwu (formerly NCI), Gang Wang (formerly NCI), 
Warren J. Leonard (NHLBI), Rosanne Spolski (NHLBI), et al.
    Related Publications:
    1. R Spolsi and WJ Leonard. Interleukin-21: Basic biology and 
implications for cancer and

[[Page 32940]]

autoimmunity. Annu Rev Immunol. 2008;26:57-79.
    2. WJ Leonard and R Spolski. Interleukin-21: A modulator of 
lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol. 
2005 Sep;5(9):688-698.
    3. G Wang et al. In vivo antitumor activity of interleukin 21 
mediated by natural killer cells. Cancer Res. 2003 Dec15;63(24):9016-
9022.
    Patent Status: U.S. Patent Application No. 10/508,978 filed 19 Nov 
2004 (HHS Reference No. E-137-2002/0-US-03).
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].

    Dated: July 1, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-16300 Filed 7-8-09; 8:45 am]
BILLING CODE 4140-01-P