[Federal Register Volume 71, Number 102 (Friday, May 26, 2006)]
[Notices]
[Pages 30427-30428]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-8167]


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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.

Tetrahalogenated Compounds Useful as Inhibitors

    Description of Technology: Cancer is the second leading cause of 
death in United States and it is estimated that there will be 
approximately 600,000 deaths caused by cancer in 2006. A major drawback 
of the existing chemotherapies is the cytotoxic side-effects that are 
associated with them. Thus, there is a need to develop new therapeutic 
approaches with reduced side-effects.
    Anti-angiogenic therapy is a recent approach in cancer therapeutics 
targeting the formation of blood vessels that are necessary for tumor 
growth. Recently, the anti-angiogenic molecule bevacizumab (Avastin) 
has gained approval from the FDA for the first-line treatment of 
metastatic colon cancer in combination with standard chemotherapy. 
Another promising anti-angiogenic molecule is thalidomide. Thalidomide 
has been approved as an anti-cancer agent and for other use in Europe 
and Australia. However, its use as a drug has been limited by its 
effect as a teratogen, necessitating the development of new thalidomide 
analogs with improved efficacy and reduced toxicity.
    This technology describes synthesis of several tetrahalogenated 
thalidomide derivatives that are potentially more anti-angiogenic than 
thalidomide. More specifically, two series of analogs based on two 
major common pharmacophores have been synthesized. One series preserves 
the thalidomide common structure, while the other series contains a 
different common structure (tetrafluorobenzamides). Several analogs 
from both series have shown significant anti-angiogenic properties, in 
vitro. This technology has therapeutic potential for a broad spectrum 
of cancer related diseases alone, or in combination with existing 
therapies.
    Applications: Novel tetrahalogenated thalidomide analogs containing 
the thalidomide pharmacophore with improved anti-angiogenic activity; 
Novel tetrahalogenated thalidomide analogs containing a different 
common structure (tetrafluorobenzamides) with considerable anti-
angiogenic activity; Use of the compounds for the treatment of several 
cancers; Use of the compounds for the treatment other diseases 
including autoimmune diseases.
    Market: 600,000 deaths from cancer related diseases estimated in 
2006. The technology platform involving novel anti-angiogenic small 
molecule cancer therapy technology has a potential market of more than 
2 billion U.S. dollars. The technology platform has additional market 
in treating several other clinical problems such as autoimmune 
diseases.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: William D. Figg (NCI), Erin Lepper (SAIC), et al.
    Publications:
    SS Ng et al., ``Antitumor effects of thalidomide analogs in human 
prostate cancer xenografts implanted in immunodeficient mice,'' Clin 
Cancer Res. 2004 Jun 15; 10 (12 Pt 1):4192-7.
    WL Dahut et al., ``Randomized phase II trial of docetaxel plus 
thalidomide in androgen-independent prostate cancer,'' J Clin Oncol. 
2004 Jul 1; 22 (13): 2532-9.
    S Kumar et al., ``Antimyeloma activity of two novel N-substituted 
and tetraflourinated thalidomide analogs,'' Leukemia 2005 Jul; 19 
(7):1253-61.
    Patent Status: U.S. Provisional Application filed 13 Apr 2006 (HHS 
Reference No. E-080-2006/0-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 National Cancer Institute, 
Center for Cancer Research, Medical Oncology Branch, Molecular 
Pharmacology Section is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize tetrafluorinated compounds as anti-cancer 
therapeutics.

[[Page 30428]]

Please contact Dr. W. Figg at 301-402-3623 for more information.

Anti-Notch-1 Monoclonal Antibodies for Inducing Cellular 
Differentiation and Apoptosis

    Description of Technology: As cancer cells progress towards more 
aggressive forms, they often become highly resistant to drug or 
radiation-induced apoptosis, generally through the loss of function 
p53, a gene which can trigger apoptosis in response to DNA damage. 
Thus, novel strategies to induce apoptosis in tumor cells, especially 
p53-deficient cells, is an attractive and an active area of research.
    Using a model constituted by a p53-deficient mouse leukemia cell 
line, PHS scientists found that: (1) Antisense synthetic DNA 
oligonucleotides and stable incorporation of an antisense gene (a model 
for gene therapy) targeting notch-1, when given together with a 
differentiation-inducing antitumor drug, cause the cells to respond by 
massive apoptosis rather than differentiation; (2) stable incorporation 
of an antisense notch-1 gene increases apoptosis in these cells even in 
the absence of any antitumor drugs. This suggests that antisense Notch-
1 treatment, by antisense oligonucleotides or by gene therapy, may be 
used alone or together with anti-cancer drugs to cause apoptosis in 
tumor cells.
    This invention provides compositions, pharmaceutical compositions, 
and methods for stimulating/increasing cell differentiation, and is 
particularly related to the treatment of tumors which have increased 
Notch-1 expression. A polyclonal and/or monoclonal antibody generated 
against human Notch-1 Epidermal Growth Factor (``EGF'') that recognizes 
an extracellular epitope of Notch-1 and that stimulates target cell 
differentiation in the presence of a differentiation inducing agent is 
disclosed as is the hybridoma which produces these antibodies.
    Inventors: Lucio L Miele and Chana Y. Fuchs (FDA).
    Patent Status: PCT Application No. PCT/US99/23162 filed 01 Oct 
1999, which published as WO 00/20576 on 13 Apr 2000 (HHS Reference No. 
E-176-1998/1-PCT-01); U.S. Patent Application No. 11/069,208 filed 28 
Feb 2005, claiming priority to 02 Oct 1998 (HHS Reference No. E-176-
1998/1-US-08).
    Licensing Contact: David A. Lambertson, PhD.; 301-435-4632; 
[email protected].

Novel Bis-Acridones as Anti-Tumor Agents: Potential for Treating Drug 
Resistant Tumors

    Description of Technology: Cancer is the second leading cause of 
death in United States and it is estimated that there will be 
approximately 600,000 deaths caused by cancer in 2006. Current 
chemotherapies are mostly based on the use of small molecules. A major 
drawback of these existing chemotherapies is the acquired or inherent 
resistance of certain tumors against these drugs. Treating resistant 
tumors has been a major challenge in the successful management of 
cancer, necessitating the development of new therapies to treat 
resistant tumors and thus expanding the life expectancy of cancer 
patients.
    The present invention discloses novel derivatives of Bis-acridones 
and related molecules and their pharmaceutically acceptable salts and 
their use as anti-tumor agents. Some of the derivatives have high anti-
tumor activity both in vitro and in vivo. In addition to its anti-tumor 
activity these above mentioned compounds have been shown to be potent 
irreversible inhibitors of P-glycoprotein, a member of the ABC 
transporter protein family that has a major role in conferring multi-
drug resistance. Therefore, these compounds have the potential of being 
used in combination with traditional chemotherapy to treat drug 
resistant tumors. In addition, to its anti-neoplastic property some of 
the derivatives of this family of compounds have been shown to have 
anti-HIV property.
    Inventors: Christopher J. Michejda et al. (NCI).
    Publications:
    WM Cholody et al., ``Bisimidazoacridones and related compounds: New 
antineoplastic agents with high selectivity against colon tumors,'' J 
Med Chem. 1995 Aug 4; 38 (16): 3043-52.
    JA Turpin et al., ``Inhibition of acute-, latent-, and chronic-
phase human immunodeficiency virus type 1 (HIV-1) replication by a 
bistriazoloacridone analog that selectively inhibits HIV-1 
transcription,'' Antimicrob Agents Chemother. 1998 Mar; 42 (3):487-94.
    Patent Status: U.S. Patent No. 5,508,289 issued 16 Apr 1996 (HHS 
Reference No. E-106-1994/0-US-01); European Patent No. 0750612 issued.
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Michelle A. Booden, PhD.; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize certain derivatives of Bis-
acridones and related molecules as well as their pharmaceutically 
acceptable salts as anti-tumor agents. Please contact Kathy Higinbotham 
at 301-846-5465 or [email protected] for more information.

    Dated: May 19, 2006.
David R. Sadowski,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
 [FR Doc. E6-8167 Filed 5-25-06; 8:45 am]
BILLING CODE 4140-01-P