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Government-Owned Inventions; Availability for Licensing

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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: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

A New Mouse Monoclonal Antibody Against Human Microphthalmia Transcription Factor (MITF)

Description of Technology: Micropthalmia Transcription Factor (MITF) plays an important role in melanocyte development and melanoma growth. MlTF is important for embryonic development, regulating the generation of pigment cells and formation of melanomas and other tumors. MITF is made in various isoforms that may play unique roles for different organs during different developmental periods. Additionally, tissue MITF levels can serve as a molecular marker for the diagnosis of metastatic melanoma and therapeutic response.

This technology involves the generation of several novel mouse monoclonal antibodies against a sub-domain of an MITF fragment that is cleaved during cell death. Importantly, these antibodies cross-react with human MITF. The antibody was raised by immunizing mice that are incapable of producing the MITF sub-domain used as the antigen. Three (3) different “clones” of these antibodies are currently available and their corresponding hybridoma names are 6A5 (IgG1), 1D2 (IgG2a) and 3D1 (IgG2a).

Applications: (1) Novel mouse monoclonal antibodies specific to a domain of MITF as research material; (2) Novel mouse monoclonal antibodies that cross react with human MITF.

Market: The currently commercially available MITF monoclonal antibodies recognize a particular domain of MITF. These have been made available by several companies including Neomarkers, Abcam, Biomeda Corporation, and Calbiochem.

This antibody reacts with a different sub-domain of MITF and cross reacts with human MITF.

Development Status: The technology is ready for the market.

Inventors: Dr. Heinz Arnheiter, Mr. Wenfang Liu and Dr. Hideki Murakami.

Relevant Publications Related to MITF:

1. LA Garraway, HR Widlund, MA Rubin, G Getz, AJ Berger, S Ramaswamy, R Beroukhim, DA Milner, SR Granter, J Du, C Lee, SN Wagner, C Li, TR Golub, DL Rimm, ML Meyerson, DE Fisher, WR Sellers. “Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.” Nature 2005 Jul 7;436(7047):117-122.

2. SR Granter, KN Weilbaecher, C Quigley, DE Fisher. “Role for microphthalmia transcription factor in the diagnosis of metastatic malignant melanoma.” Appl Immunohistochem Mol Morphol. 2002 Mar; 10(1):47-51.

Patent Status: HHS Reference No. E-228-2006/0—Research Material

Availability: The inventor is no longer accepting requests for the antibody; it will now be solely available via a Biological Material License (BML).

Licensing Contact: David A. Lambertson, PhD.; 301/435-4632; lambertsond@od.nih.gov.

Diamidine Inhibitors of Tdp1 as Anti-Cancer Agents

Description of Technology: Available for licensing and commercial development are methods and compositions for treating cancer, using novel compounds derived from diamidine. Diamidine and its derivatives are potent inhibitors of tyrosyl-DNA-phosphodiesterase (Tdp1), which may be useful in chemotherapy.

Camptothecins are effective Topoisomerase I (Top1) inhibitors, and two derivatives (Topotecan® and Camptosar®) are currently approved for treatment of ovarian and colorectal cancer. Camptothecins damage DNA by trapping covalent complexes between the Top1 catalytic tyrosine and the 3'-end of the broken DNA. Tdp1 repairs Top1-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. Thus, the presence and activity of Tdp1 can reduce the effectiveness of camptothecins as anti-cancer agents. In addition, Tdp1 repairs free-radical-mediated DNA breaks.

Inhibition of Tdp1 using diamidine or its derivatives, may reduce repair of DNA breaks and increase the rate of apoptosis in cancer cells. In addition, diamidine derivatives have the potential to enhance the anti-neoplastic activity of Top1 inhibitors, by reducing repair of Top1-DNA lesions through inhibition of Tdp1.

Development Status: Pre-clinical stage.

Inventors: Yves Pommier and Christophe Marchand (NCI).

Publications:

1. Z Liao et al. “Inhibition of human Tyrosyl-DNA Phosphodiesterase (Tdp1) by aminoglycoside antibiotics and ribosome inhibitors.” Mol Pharmacol. 2006 Apr 17; Epub ahead of print, doi:10.1124/mol.105.021865.

2. Y Pommier. “Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints.” Curr Med Chem Anticancer Agents. 2004 Sep; 4(5):429-34. Review.

3. Y Pommier et al. “Repair of and checkpoint response to topoisomerase I mediated DNA damage.” Mutat Res. 2003 Nov 27;532(1-2):173-203. Review.

Patent Status: U.S. Provisional Application No. 60/786,604 filed 27 Mar 2006 (HHS Reference No. E-165-2006/0-US-01).

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: David A. Lambertson, PhD.; 301/435-4632; lambertsond@od.nih.gov. Start Printed Page 37587

Collaborative Research Opportunity: The Laboratory of Molecular Pharmacology at the National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diamidine derivatives, particularly optimizing them for therapeutic use. Please contact Lisa Finkelstein at 301/451-7458 for more information.

Use of Tetracyclines as Anti-Cancer Agents

Description of Technology: The invention describes compositions of tetracycline compounds and their derivatives as having anticancer activity, as well as methods of treating cancer. Tetracyclines are commonly used as antibiotics; however, testing of these compounds in a high throughput screening system revealed certain derivatives to be potent inhibitors of tyrosyl-DNA-phosphodiesterase (Tdp1).

Camptothecins are effective Topoisomerase I (Top1) inhibitors, and two derivatives (Topotecan® and Camptosar®) are currently approved for treatment of ovarian and colorectal cancer. Camptothecins damage DNA by trapping covalent complexes between the Top1 catalytic tyrosine and the 3'-end of the broken DNA. Tdp1 repairs Top1-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. This can reduce the effectiveness of camptothecins as anti-cancer agents. In addition, Tdp1 repairs free-radical-mediated DNA breaks.

As disclosed in the instant technology, tetracyclines have the potential to enhance the anti-neoplastic activity of Top1 inhibitors by reducing repair of Top1-DNA lesions through inhibition of Tdp1. Inhibition of Tdp1 may also reduce repair of DNA breaks and increase the rate of apoptosis in cancer cells, making them potential anti-cancer agents on their own.

Development Status: Pre-clinical stage.

Inventors: Yves Pommier (NCI), Christophe Marchand (NCI), Laurent Thibaut (NCI).

Publications:

1. Z Liao et al. “Inhibition of human Tyrosyl-DNA Phosphodiesterase (Tdp1) by aminoglycoside antibiotics and ribosome inhibitors.” Mol Pharmacol. 2006 Apr 17; Epub ahead of print, doi:10.1124/mol.105.021865.

2. Y Pommier. “Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints.” Curr Med Chem Anticancer Agents. 2004 Sep; 4(5):429-34. Review.

3. Y Pommier et al. “Repair of and checkpoint response to topoisomerase I mediated DNA damage.” Mutat Res. 2003 Nov 27;532(1-2):173-203. Review.

Patent Status: U.S. Provisional Application No. 60/786,746 filed 27 Mar 2006 (HHS Reference No. E-097-2006/0-US-01).

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: David A. Lambertson, PhD.; 301/435-4632; lambertsond@od.nih.gov.

Collaborative Research Opportunity: The Laboratory of Molecular Pharmacology at the National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize tetracycline derivatives, particularly optimizing them for therapeutic use. Please contact Lisa Finkelstein at 301/451-7458 for more information.

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Dated: June 23, 2006.

David R. Sadowski,

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

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[FR Doc. 06-5882 Filed 6-29-06; 8:45 am]

BILLING CODE 4140-01-P