[Federal Register Volume 71, Number 126 (Friday, June 30, 2006)]
[Notices]
[Pages 37586-37587]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-5882]


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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.

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; 
[email protected].

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[supreg] and Camptosar[supreg]) 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; 
[email protected].

[[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[supreg] and Camptosar[supreg]) 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; 
[email protected].
    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.

    Dated: June 23, 2006.
David R. Sadowski,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 06-5882 Filed 6-29-06; 8:45 am]
BILLING CODE 4140-01-P