2011-17227. National Institutes of Health

AGENCY:

Public Health Service, National Institutes of Health, 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.

Mouse Model and Derived Cells That Hypersecrete Leukemia Inhibitory Factor (LIF)

Description of Technology: Embryonic stem cells (ESCs) are pluripotent cells that can be cultured indefinitely, and maintain their capability to differentiate into all cell lineages. To maintain these cells as well as various types of related induced stem cells and progenitor cells in culture, Mouse Embryonic Fibroblasts (MEFs) are routinely used as feeder cells, largely to serve as a source of Leukemia Inhibitory Factor (LIF). ESCs can also be cultured without feeders if the medium is supplemented with recombinant LIF and other factors. However, these methods of culturing ESCs suffer from certain drawbacks, such as limited proliferation capacity and variability of primary MEFs. Therefore, finding improved conditions that maintain ESC pluripotency is an area of great interest.

Scientists at NIEHS have now developed a knock-in (KI) mouse model in which LIF is overproduced from its endogenous locus because of increased stability of its mRNA. MEFs and presumably other cells derived from the homozygous mice hypersecrete LIF protein; lesser degrees of overexpression would be expected from heterozygous mice. These mice can be used to study LIF function, including how LIF contributes to various physiological and pathological states. Cells derived from these mice can be used to culture ESCs, as well as other progenitor cells. Cells or genetic material derived from these mice can also be used as sources of LIF for isolation and purification.

Applications

• Maintenance of ESCs and progenitor cells.
• In vivo, cellular and cell-free sources of LIF.
• Sources of LIF for isolation and purification.
• Studies of LIF function in mice, such as contribution of LIF to tumor growth.

Inventors: Dr. Perry Blackshear (NIEHS), et al.

Patent Status: HHS Reference No. E-175-2011/0 —Research Tool. Patent protection is not being pursued for this technology.

Licensing Status: Available for licensing under a Biological Materials License Agreement.

Licensing Contact: Betty B. Tong, PhD; 301-594-6565; [e-mail].

Collaborative Research Opportunity: The NIEHS Laboratory of Signal Transduction is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these mice or other strains derived from them, or cells or other reagents derived from them. Please contact Dr. Elizabeth Denholm ([e-mail]) in the NIEHS Office of Technology Transfer, or the Inventor Dr. Perry Blackshear ([e-mail]) for more information.

Inhibitors of Human Apurinic/Apyrimidinic Endonuclease 1 (APE1), an Anticancer Drug Target

Description of Technology: APE1 is the primary mammalian enzyme responsible for the removal of abasic (AP sites) in DNA and functions as part of the base excision DNA repair pathway (BER). BER is instrumental in the repair of DNA damage caused by DNA alkylating agents (e.g. many cancer chemotherapeutics). APE1 has been shown to be overexpressed in cancer cells. It has been postulated that APE1 would be an attractive target in anti-cancer treatment paradigms; preclinical and clinical data confirm that APE1 is a valid anticancer drug target.

To date, only one APE1 small molecule inhibitor has progressed to clinical trials (methoxyamine hydrochloride), and this compound inhibits a wide range of repair processes, which could result in undesired side-effects. The NIH inventors now report the discovery of a novel APE1 small molecule inhibitor, which exhibits potent in vitro activity, potentiates the cytotoxicity of DNA damaging agents (alkylators methylmethane sulfonate and Temozolomide), results in the accumulation of AP sites, and has favorable pharmacokinetic properties. The inventors plan to carry out further studies in mouse tumor xenograft models.

Applications: Cancer therapeutics as single agent as well as in combination therapy.

Development Status: In vivo pharmacokinetics data on lead compounds available.

Inventors: David J. Maloney, et al. (NHGRI).

Publication: Manuscript submitted.

Patent Status: U.S. Provisional Patent Application No. 61/480,145 filed April 28, 2011 (HHS Reference No. E-094-2011/0-US-01).

Licensing Status: Available for licensing.

Licensing Contact: Betty B. Tong, PhD; 301-594-6565; [e-mail].

Collaborative Research Opportunity: The NIH Center for Translational Therapeutics, NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the above technology. Please contact Lili Portilla, Acting Director of Technology Transfer and Partnerships, NCTT at [e-mail] for more information.

Dated: July 1, 2011.

Richard U. Rodriguez,

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