[Federal Register Volume 72, Number 220 (Thursday, November 15, 2007)]
[Notices]
[Pages 64230-64231]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-22302]


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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.

Human T-box Transcription Factor Brachyury as a Target for Cancer 
Immunotherapy: Identification of Epitopes of Human Brachyury as Targets 
for T-cell Mediated Lysis of Tumors

    Description of Technology: Identification of tumor antigens is 
essential in advancing immune-based therapeutic interventions in 
cancer. Transcription factors that control mesoderm have been 
implicated in tumor cell invasion and metastasis. Brachyury, a member 
of the T-box transcription factor family, is a highly conserved protein 
and a fundamental player in mesoderm (epithelial-to-mesenchymal 
transition, i.e. EMT) specification in multicellular organisms.
    This invention describes the identification of the human 
transcription factor Brachyury as a novel target for cancer 
immunotherapy for the treatment of several tumors such as tumors of 
lung, intestine, stomach, kidney, bladder, uterus, ovary, and testis, 
and chronic lymphocytic leukemia. This is the first demonstration that 
(a) a T-box transcription factor and (b) a molecule implicated in 
mesodermal development (EMT) can be a potential target for human T-cell 
mediated cancer immunotherapy.
    Applications:
    1. Brachyury can be targeted for cancer immunotherapy.
    2. Epitopes of the Brachyury protein that could be used to expand 
human T-lymphocytes for T-cell mediated lysis of tumors.
    3. The technology can be developed as a cancer vaccine.
    Advantages:
    1. This technology can be delivered with the U.S. government owned 
fowl pox vector.
    2. In vitro proof of concept data are available.
    Benefits: This is the first demonstration that (a) a T-box 
transcription factor and (b) a molecule implicated in mesodermal 
development (EMT) can be a potential target for human T-cell mediated 
cancer immunotherapy. This technology has the potential of becoming a 
successful therapy for metastatic cancers.
    Inventors: Jeffrey Schlom, et al. (NCI, CCR, LTIB)
    Development Status: In vivo studies are ongoing.
    Relevant Publication: C Palena, DE Polev, KY Tsang, RI Fernando, M 
Litzinger, LL Krukovskaya, AV Baranova, AP Kozlov, J Schlom. The human 
T-box mesodermal transcription factor Brachyury is a candidate target 
for T-cell-mediated cancer immunotherapy. Clin Cancer Res. 2007 Apr 
15;13(8):2471-2478.
    Patent Status: U.S. Provisional Application filed 28 Feb 2007 (HHS 
Reference No. E-074-2007/0-US-01).
    Licensing Status: This technology is available for licensing under 
an exclusive or non-exclusive patent license.
    Licensing Contact: Michelle Booden, PhD.; 301/451-7337; 
[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 cancer vaccines aimed at targeting Brachyury. Please 
contact John D. Hewes, PhD. at 301-435-3121 or [email protected] for 
more information.

Diagnostic Ovarian Cancer Biomarkers

    Description of Technology: Ovarian cancer is one of the most common 
malignancies. Warning symptoms generally do not occur until the tumor 
has already spread beyond the ovary. As a result, patients are 
diagnosed with advanced stages of ovarian cancer and their prognosis is 
poor. Five year

[[Page 64231]]

survival rate for these patients is only fifteen percent and despite a 
clinical response of eighty percent to surgery and chemotherapy, most 
patients experience tumor recurrence within two years of treatment. The 
overwhelming majority of patients will eventually develop 
chemoresistance and lose their batter against cancer.
    The inventors have discovered unique proangiogenic biomarkers 
isolated from ovarian endothelial cells. By targeting tumor 
angiogenesis by inhibiting endothelial cells that support tumor growth, 
this technology provides methods to diagnose ovarian cancer in its 
early stages.
    Available for licensing is a gene profile that is indicative of 
patient survival. Unlike other biomarkers that are determined from 
discrete patient groups at either end of the survival spectrum, this 
profile is based upon expressed genes in late stage, high-grade 
papillary serous ovarian tumors. This predictive patient survival 
profile is based upon the theory that gene expression for advanced late 
stage ovarian cancer is more likely to develop aggressive, recurrent 
disease.
    Also available for licensing is a gene signature that can predict 
whether a patient will respond positively to chemotherapy, show an 
initial response but will relapse within six months of completing 
chemotherapy, or not respond to chemotherapy. This methodology may 
enable clinicians to identify patients who need alternative 
chemotherapy regiment and to recommend cancer treatment appropriately.
    Applications:
    Method to prognose ovarian cancer and likelihood of aggressive, 
recurrent ovarian cancer;
    Method to predict patient survival with advanced stage ovarian 
cancer;
    Method to predict ovarian patient sensitivity to chemotherapeutic 
agents;
    Methods to identify treatment options to enhance patient's response 
to chemotherapeutic agents;
    Methods to treat ovarian cancer patients with inhibitory 
proangiogenic agents;
    Ovarian cancer therapeutics.
    Advantages:
    Rapid, easy to use diagnostics;
    Tool to choose appropriate cancer treatments which may avoid 
patient exposure to negative side effects of chemotherapy.
    Market:
    Ovarian cancer is the fifth most common form of cancer in women in 
the U.S.;
    Ovarian cancer is three times more lethal than breast cancer;
    15,310 deaths in the U.S. in 2006.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Michael J. Birrer, et al. (NCI).
    Publication: C Lu, et al. Gene alterations identified by expression 
profiling in tumor-associated endothelial cells from invasive ovarian 
carcinoma. Cancer Res. 2007 Feb 15;67(4):1757-1768.
    Patent Status:
    U.S. Provisional Application No. 60/951,073 filed 20 Jul 2007 (HHS 
Reference No. E-061-2007/0-US-01);
    U.S. Provisional Application No. 60/899,942 filed 06 Feb 2007 (HHS 
Reference No. E-060-2007/0-US-01);
    U.S. Provisional Application No. 60/901,455 filed 14 Feb 2007 (HHS 
Reference No. E-095-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].
    Collaborative Research Opportunity: The Cell and Cancer Biology 
Branch of the National Cancer Institute is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize a gene 
expression profile that predicts ovarian cancer patient response to 
chemotherapy. Please contact John D. Hewes, Ph.D., NCI Technology 
Transfer Center, Tel. 301-435-3121 or E-mail: [email protected] for 
more information.

A Novel, Inhibitory Platelet Surface Protein (TREM Like Transcript, 
TLT-1): New Target for the Treatment of Cancer, Infectious Diseases, 
Cardiac Diseases, and Platelet-Associated Disorders

    Description of Technology: Triggering Receptors in Myeloid Cells 
(TREM) recently were discovered to modulate innate and adaptive 
immunity. Specifically, TREM1 amplifies the response to sepsis in 
innate immunity by activating neutrophils and other leukocytes; and 
TREM2 potentiates dendritic cell maturation in adaptive immunity.
    This invention describes a novel, inhibitory platelet surface 
protein known as TREM like Transcript (TLT-1). TLT-1 is the first 
inhibitory receptor discovered to reside within the TREM gene locus. 
Structurally, TLT-1 also possesses inhibitory domains that indicate 
this regulatory function. TLT-1 is highly expressed in peripheral blood 
platelets and may modulate many other types of myeloid cells. 
Additionally, the invention describes specific, human, single chain 
antibodies (scFvs) that recognize TLT-1.
    Applications:
    1. This discovery implies the receptor has an important regulatory 
role in both innate and adaptive immunity.
    2. TLT-1 is a potential therapeutic target for thrombosis and other 
platelet-associated disorders, as well as immune disorders, cancer, 
septic shock, infectious disease, stroke, heart disease, myocardial 
infarction, vascular disorders.
    3. Detection of soluble TLT-1 in patient plasma suggests the 
protein is a marker of ongoing coagulopathies.
    4. Defective platelet aggregation in TLT-1 null mice confirms a 
role for the protein in regulation of thrombosis associated with 
inflammation.
    Advantages:
    1. In vitro proof of concept data available--Three of the anti-TLT-
1 scFvs inhibit thrombin-induced aggregation of human platelets in a 
dose-dependent manner.
    2. Complete human origin of these antibodies suggests negligible 
immunogenicity and minimizes the problem of adverse immune responses in 
human therapy.
    3. Target validation is complete. TLT-1 null mice demonstrate 
defects in platelet aggregation with no gross bleeding defect.
    Development Status: In vitro experiments completed. Target 
validation with null mice completed. In vivo animal studies with scFv 
are currently ongoing.
    Inventors: Drs. Toshiyuki Mori, et al. (NCI)
    Patent Status: U.S. Patent Application No. 11/634,331 filed 04 Dec 
2006 (HHS Reference No. E-177-2006/0-US-01).
    Licensing Contact: Mojdeh Bahar; 301/435-2950; [email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Molecular Targets Development Program is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize antibodies that 
react specifically with TLT-1. Please contact John D. Hewes, Ph.D. at 
301-435-3121 or [email protected] for more information.

    Dated: November 5, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-22302 Filed 11-14-07; 8:45 am]
BILLING CODE 4140-01-P