E7-20909. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Novel Micro-RNA Sequence Transforms Non-Functional T-Lymphocytes to Highly Functional: Key to Improved Immunotherapy for the Treatment of Cancers

Description of Technology: This technology is directed to the therapeutic use of microRNA-181a in the adoptive immunotherapy of cancer.

The adoptive transfer of anti-tumor T cells after a lymphodepleting regimen can result in the regression of metastatic cancer both in mouse and human, but the production of highly-reactive, tumor-specific T cells still represents a barrier to broad implementation of T cell-based immunotherapies. This technology enables the use of microRNA (miR)-181a, a recently identified intrinsic modulator of T-cell receptor (TCR) signaling, to improve anti-tumor T cell responsiveness. Micro-RNAs are short RNA molecules that regulate the activity of genes and appear to control biological processes.

We found that genetic engineering of T lymphocytes with miR-181a dramatically augmented the function of poorly responsive human tumor-infiltrating lymphocytes and TCR-engineered peripheral blood lymphocytes, resulting in potent anti-tumor reactivity. Furthermore, in a mouse model, miR-181a increased the function of self/tumor-specific CD8⁺ T cells enabling effective tumor destruction in the absence of vaccination or exogenous cytokines that were otherwise essential requirements. This technology is the first reported use of a miRNA gene as tool in the treatment of disease.

Applications: The microRNA sequence (“miR-181a”) can be used to enhance the tumor recognizing capacity of T-lymphocytes against several tumors.

This technology can be used for selective treatment of several cancers more effectively.

Advantages: Proof-of concept pre-clinical data are available and clinical trials are currently being planned.

This technology is based on adoptive immunotherapy, which is now an accepted and effective form of cancer treatment.

Benefits: The microRNA identified has the potential to broaden and enhance the scope of adoptive immunotherapy.

Development Status: Pre-clinical work has been completed and clinical studies are forthcoming.

Inventors: Dr. Nicholas P. Restifo et al. (NCI).

Relevant Publication: Q Li et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell. 2007 Apr 6;129(1):147-161.

Patent Status: U.S. Provisional Application filed 25 May 2007 (HHS Reference No. E-224-2007/0-US-01).

Licensing Status: This technology is available for licensing under an exclusive or non-exclusive patent license.

Licensing Contact: Michelle A. Booden, PhD; 301/451-7337; [e-mail].

Collaborative Research Opportunity: The Surgery 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 the therapeutic use of microRNA-181a in the adoptive immunotherapy of cancer. Please contact John D. Hewes, PhD at 301-435-3121 or [e-mail] for more information.

Use of HDAC Inhibitors for the Prevention and Cure for Brain Metastases of Cancers

Description of Technology: The increased survival of primary and metastatic cancers consequential of improved therapies has resulted in increased brain metastases. Few treatment options are available for cancer patients with central nervous system (CNS) metastasis. There is a need for new treatment options for CNS metastases especially brain metastases originating outside the CNS.

The present invention provides a method of treating a localized carcinoma CNS metastasis of extra-CNS origin. More specifically, the method comprises of treating a localized carcinoma CNS metastasis of extra-CNS origin with a histone deacetylase (HDAC) inhibitor (HDACI) originating in one or more organs such as lung, breast, liver, colon, and prostate. The HDACI can be any HDACI that is capable of crossing the blood-brain barrier (BBB) such as vorinostat.

Advantages: Vorinostat has been approved by the FDA for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies, and as such, has efficacy and tolerability data.

Benefits: More than 40,000 breast cancer deaths are estimated to occur in 2007. Majority of these deaths are due to metastases of the breast cancer. Approximately, 10%-20% of women with metastatic breast cancer are estimated to develop brain metastasis and the median survival after brain cancer metastasis is only one year. This technology may effectively treat breast cancer brain metastases and thus improve overall survival and quality of life of patients suffering from cancer. The current cancer chemotherapeutic market is valued at $42 billion and expected to grow.

Inventors: Patricia S. Steeg et al. (NCI).

Development Status: In vivo animal model data available with vorinostat.

Patent Status: U.S. Provisional Application No. 60/891,856 filed 02 Feb 2007 (HHS Reference No. E-084-2007/0-US-01).

Licensing Contact: John Stansberry; 301/435-5236; [e-mail].

Dated: October 11, 2007.

Steven M. Ferguson,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.