[Federal Register Volume 75, Number 231 (Thursday, December 2, 2010)]
[Notices]
[Pages 75177-75179]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-30279]


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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.

Novel Compositions and Methods To Treat Glioblastoma and Other Cancers

    Description of Technology: There remains a significant unmet need 
for therapeutics to treating glioblastoma multiforme, a very aggressive 
type of brain tumor. Glioblastoma is difficult to treat with 
conventional surgery, chemical, and radiation therapies. With 
approximately 18,000 new glioblastoma cases in the U.S. each year, and 
a comparable market in Europe, the global market for such products 
forecast to be over $300 million. In light of the high unmet need in 
malignant astrocytoma and little in the way of pipeline competition, 
this indication represents a potential easy route to market for new 
drugs.

[[Page 75178]]

    Researchers at the National Cancer Institute (NCI) have identified 
two novel molecular targets, annexin 1 (Anx A1) and its receptor formyl 
peptide receptor 1 (FPR1), for new anti-glioblastoma therapies. Anx A1 
and FPR1 mediate growth, invasion, production of angiogenic factors, 
tumor formation, and are abnormally expressed by more highly malignant 
glioblastomas. Depletion of Anx A1 in glioblastoma cells resulted in 
their reduced capacity to form tumors; additional depletion of FPR1 
further reduced this capacity. Further, the NCI researchers have found 
a correlation between Anx A1 expression and the degree of malignancy of 
human gliomas.
    Novel anti-glioblastoma therapies encompassed by this invention 
include neutralizing antibodies against Anx A1 and FPR1, small compound 
agonists of Anx A1 and FPR1, small interference RNAs (siRNAs) that 
deplete Anx A1 and FPR1 from glioblastoma cells, as well as delivery 
methods to effectively administer the Anx A1 and FPR1 targeting drugs 
into brain tissues.

Applications

     Treatment of glioblastoma multiforme and other brain 
tumors.
     Treatments for inhibiting neoplastic cell growth.
     Treatments for inhibiting tumor progression and 
metastasis.
     Treatments for inhibiting angiogenesis in a tumor.

Advantages

     High specificity.
     Does not require radiation.
     A correlation between expression of the molecular target 
and the degree of tumor malignancy is known.
     Wide-range/flexibility of potential therapies and 
approaches.
    Development Status: Pre-clinical.
    Inventors: Ji Ming Wang et al. (NCI).
    Relevant Publication: Y Zhou, et al. Formylpeptide receptor FPR and 
the rapid growth of malignant human gliomas. J Natl Cancer Inst. 2005 
Jun 1;97(11):823-835. [PubMed: 15928303]
    Patent Status: U.S. Provisional Application No. 61/388,983, filed 
01 Oct 2010 (HHS Reference No. E-297-2010/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Patrick P. McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Molecular Immunoregulation, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this 
technology. Please contact John Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Synovial Sarcoma X Breakpoint-2 (SSX-2) Specific Human T Cell Receptors 
for Treating a Wide-Range of Cancers

    Description of Technology: Many current approaches for treating 
cancer also generate harsh side effects in patients. In addition, a 
sizable patient population does not respond to generalized chemotherapy 
and radiation treatments for cancer. There is an urgent need to develop 
new therapeutic strategies aimed at reducing side-effects and 
increasing specific anti-tumor activity in individual patients. 
Adoptive immunotherapy is a promising new approach to cancer treatment 
that engineers an individual's innate and adaptive immune system to 
fight against specific diseases, including cancer. As research and 
development continues in this area, scientists continue to improve cell 
transfer therapies by targeting an increasing collection of tumor 
antigens with more effective immune cell cultures.
    T cell receptors (TCRs) are proteins that recognize antigens in the 
context of infected or transformed cells and activate T cells to 
mediate an immune response and destroy abnormal cells. TCRs consist of 
two domains, one variable domain that recognizes the antigen and one 
constant region that helps the TCR anchor to the membrane and transmit 
recognition signals by interacting with other proteins. When a TCR is 
stimulated by an antigen, such as a tumor antigen, some signaling 
pathways activated in the cell lead to the production of cytokines, 
which mediate the immune response.
    Scientists at the National Institutes of Health (NIH) have 
developed T cells genetically engineered to recognize synovial sarcoma 
X breakpoint-2 (SSX-2) peptide antigens. SSX proteins, including SSX-2, 
are expressed primarily by tumor cells from a variety of cancers, 
including pancreatic cancer where very few treatment options exist. 
Other than germ cells of the testis, normal cells do not express SSX 
proteins and, thus, should not be targeted by therapies directed 
against these proteins. Therefore, SSX proteins represent a promising 
target for cancer immunotherapy. There are ten (10) known members of 
the SSX protein family designated SSX-1 through SSX-10. The T cell 
receptors (TCRs) developed by these NIH scientists have specificity for 
SSX-2 and deliver a robust immune response when they encounter SSX-2 
expressing cells. However, these TCRs also recognize five (5) other SSX 
family members, including SSX-3, SSX-4, SSX-5, SSX-9, and/or SSX-10, 
and deliver a productive, intermediate immune response in the context 
of target cells expressing these antigens. This versatile antigen 
coverage could allow these SSX-specific TCRs to be utilized in the 
treatment of multiple types of cancer in a wide array of cancer 
patients. Infusing cancer patients with SSX-2 specific T cells via 
adoptive immunotherapy could prove to be a powerful approach for 
selectively attacking tumors without generating toxicity against 
noncancerous cells.

Applications

     Immunotherapeutics to treat and/or prevent the recurrence 
of a variety of human cancers, including pancreatic cancer and 
melanoma, by adoptively transferring the gene-modified T cells into 
patients whose tumors express a SSX family member protein recognized by 
this TCR.
     A drug component of a combination immunotherapy regimen 
aimed at targeting specific tumor-associated antigens, including SSX-2, 
SSX-3, SSX-4, SSX-5, SSX-9, and/or SSX-10 expressed by cancer cells 
within individual patients.
     A research tool to investigate signaling pathways in SSX-2 
expressing cancer cells.
     An in vitro diagnostic tool to screen for cells expressing 
an SSX antigen from a recognized member of the SSX protein family.

Advantages

     Selective toxicity for tumor cells--SSX-2 and other SSX 
proteins are only expressed on testis germ cells and tumor cells. Thus, 
infused cells expressing an anti-SSX-2 TCR should target SSX-expressing 
tumor cells with little or no toxicity to normal cells. Immunotherapy 
with these cells is not anticipated to elicit harsh side effects to 
patients.
     Ability to recognize multiple SSX antigens--Since these 
SSX-2 directed TCRs can also recognize five (5) additional SSX family 
members (SSX-3, 4, 5, 9, and 10), cells expressing these TCRs are 
expected to be able to fight a larger range of tumor types. If in the 
course of attacking SSX-2 expressing tumor cells in a patient these 
cells also encounter tumor cells expressing other recognized SSX 
antigens, then these cells would still be capable of eliminating the 
non-SSX-2 expressing cell. The ability of these TCRs to recognize 
multiple SSX antigens may

[[Page 75179]]

allow it to be utilized to treat a broader population of patients.
     Versatile antigen recognition--These TCRs are CD8 and CD4 
independent meaning that cells expressing these TCRs are capable of 
eliciting an immune response in the absence of CD8 or CD4 molecule 
expression on the T cell. When utilized for immunotherapy, this 
versatility allows engineered T cells expressing this TCR to recognize 
and eliminate tumors expressing SSX-2 regardless of how the antigen is 
presented to the T cell.
    Development Status: This technology is in a preclinical stage of 
development.
    Inventors: Richard A. Morgan et al. (NCI).

Publications

    1. N Chinnasamy, et al. Development of HLA-A2 Restricted TCR 
Against Cancer Testis Antigen SSX-2 for Adoptive Immunotherapy of 
Cancer. Abstracts for the 25th Annual Meeting of the International 
Society for Biological Therapy of Cancer, J Immunother. 2010 
Oct;33(8):860, DOI 10.1097/CJI.0b013e3181f1e08d.
    2. D Valmori, et al. Expression of synovial sarcoma X (SSX) 
antigens in epithelial ovarian cancer and identification of SSX-4 
epitopes recognized by CD4+ T cells. Clin Cancer Res. 2006 Jan 
15;12(2):398-404. [PubMed: 16428478]
    3. G Bricard, et al. Naturally acquired MAGE-A10- and SSX-2-
specific CD8+ T cell responses in patients with hepatocellular 
carcinoma. J Immunol. 2005 Feb 1;174(3):1709-1716. [PubMed: 15661935]
    Patent Status: U.S. Provisional Application No. 61/384,931 filed 21 
Sept 2010 (HHS Reference No. E-269-2010/0-US-01).
    Related Technologies: T cell receptor technologies developed 
against other CTAs: E-304-2006/0 and E-312-2007/1 (anti-NY-ESO-1) and 
E-236-2010/0 (anti-MAGE-A3).
    Licensing Status: Available for licensing.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Surgery Branch, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize the use of T cell receptor gene therapy for 
the treatment of cancer. Please contact John Hewes, Ph.D. at 301-435-
3121 or [email protected] for more information.

    Dated: November 24, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-30279 Filed 12-1-10; 8:45 am]
BILLING CODE 4140-01-P