[Federal Register Volume 72, Number 200 (Wednesday, October 17, 2007)]
[Notices]
[Pages 58858-58860]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-20513]


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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.

HIV-1 Integrase Inhibitors for the Treatment of Retroviral Infections

    Description of Technology: This technology describes the structure 
and activity of N-benzyl derivatives of 2,3-dihydro-6,7-dihydroxy-1H-
isoindol-1-ones and 2,3-dihydro-6,7-dihydroxy-1H-isoindole-1,3(2H)-
diones as new HIV-1 integrase inhibitors. HIV, as well as other 
retroviruses, requires three key viral enzymes for replication: Reverse 
transcriptase, protease and integrase (IN). A significant number of 
patients fail to respond to combination therapies consisting of reverse 
transcriptase and protease inhibitors, due to the development of viral 
resistance. IN functions by initial processing of viral cDNA in a 
cleavage step termed 3'-processing (3'-P). This is followed by 
insertion of the cleaved cDNA into the host genome in a reaction known 
as ``strand transfer'' (ST). Certain agents covered under the subject 
technology have been shown to exhibit selective inhibition of ST 
reactions relative to 3'-P reactions. These compounds inhibit purified 
IN in vitro and are also active against HIV-1 derived vectors in cell-
based assay. These inhibitors may have a potential therapeutic value 
for retroviral infections, including AIDS, especially for patients 
exhibiting drug resistance to current therapy regimes.
    Applications: The treatment and prevention of HIV infections.
    Development Status: In vitro data available.
    Inventors: Terrence R. Burke Jr., Xue Zhi Zhao, Yves Pommier, and 
Elena Semenova (NCI).
    Related Publication: WG Verschueren et al. Design and optimization 
of tricyclic phtalimide analogue as novel inhibitors of HIV-1 
integrase. J Med Chem 2005 Mar 24;48(6):1930-1940.

[[Page 58859]]

    Patent Status: U.S. Provisional Application No. 60/956,636 filed 17 
Aug 2007 (HHS Reference No. E-237-2007/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301/435-5606; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Laboratory of Medicinal Chemistry and Laboratory of Molecular 
Pharmacology are seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize the HIV-1 integrase inhibitors described. 
Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Thiazepine Inhibitors of HIV-1 Integrase

    Description of Technology: The human immunodeficiency virus (HIV) 
is the causative agent of acquired immunodeficiency syndrome (AIDS). 
Drug-resistance is a critical factor contributing to the gradual loss 
of clinical benefit to treatments for HIV infection. Accordingly, 
combination therapies have further evolved to address the mutating 
resistance of HIV. However, there has been great concern regarding the 
apparent growing resistance of HIV strains to current therapies.
    It has been found that a certain class of compounds including 
thiazepines and analogs and derivatives thereof are effective and 
selective anti-integrase inhibitors. These compounds have been found to 
inhibit both viral replication and the activity of purified HIV-1 
integrase. The subject invention provides for such compounds and for 
methods of inhibiting HIV integrase.
    Inventors: Yves Pommier et al. (NCI).
    Patent Status: U.S. Patent No. 7,015,212 issued 21 Mar 2006 (HHS 
Reference No. E-036-1999/0-US-03).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301/435-5606; 
[email protected].
    Collaborative Research Opportunity: The Laboratory of Molecular 
Pharmacology of the National Cancer Institute is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize anti-integrase 
inhibitors. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Quinoline Inhibitors of Retroviral Integrase

    Description of Technology: The subject invention describes certain 
diketo quinolin-4-1 derivatives and their use as integrase inhibitors 
in the treatment of HIV infection. The results of in vitro integrase 
inhibition studies show that these derivatives have significant anti-
integrase activity (e.g., an IC50 for strand transfer inhibition of not 
greater than 2 [mu]M). Thus, these derivatives might be potentially 
important lead compounds for the development of integrase inhibitors. 
Since HIV integrase is an essential enzyme for effective viral 
replication, the development of such inhibitors of HIV integrase would 
thus potentially be useful and effective in the treatment of HIV 
infection.
    Inventors: Yves Pommier et al. (NCI).
    Patent Status: U.S. Patent Application No. 10/591,679 filed 01 Sep 
2006, claiming priority to 10 Mar 2004 (HHS Reference No. E-187-2003/0-
US-01).
    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301/435-5606; 
[email protected].

Discovery of Tropolone Inhibitors of HIV-1 Integrase that can be Used 
for the Treatment of Retroviral Infection, Including AIDS

    Description of Technology: This invention provides pharmaceutical 
compositions comprising one or more HIV-1 integrase inhibitor 
compounds, as well as methods for treatment or prevention of HIV 
infection. These compounds are alpha-hydroxytropolone or its salt, 
solvate or hydrate, and they have been shown to inhibit the integrase 
by interfering with the enzyme catalytic site by chelating magnesium 
ions, and have been shown to inhibit the strand transfer reaction. 
Integrase is an important target for AIDS therapy since it is critical 
for viral replication, and does not have cellular counterparts, which 
can potentially reduce toxic side effects. Thus, the compounds of this 
invention can be developed as novel anti-viral agents that can be used 
in combinational therapy, especially since they might be less toxic 
than other anti-viral agents.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.
    Inventors: Yves Pommier et al. (NCI).
    Patent Status: PCT Application No. PCT/US2006/046259 filed 01 Dec 
2006, which published as WO 2007/065007 on 06 Jul 2007 (HHS Reference 
No. E-308-2005/0-PCT-02).
    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301/435-5606; 
[email protected].

Integrase Inhibitors for the Treatment of Retroviral Infection 
Including Human Immunodeficiency Virus-1

    Description of Technology: Available for licensing and commercial 
development are stilbenedisulfonic acid derivatives for treatment of 
human immunodeficiency virus-1 (HIV-1) and other retroviral infections. 
Current HIV-1 therapeutic treatments target the viral protease and 
reverse transcriptase enzymes, which are essential for retroviral 
infection. However, these drugs often have limitations due to drug 
resistant variants, which render drugs ineffective. Additionally, such 
drugs are often toxic when administered in combination therapies. Thus, 
efficacious inhibitors of retroviral infection that are devoid of 
toxicity are presently needed.
    The subject invention describes stilbenedisulfonic acid 
derivatives, which target the integrase enzyme of retroviruses. Similar 
to protease and reverse transcriptase activity, integrase function is 
essential for retroviral infection. Integrase catalyzes integration of 
reverse transcribed viral DNA into a host cell's genome. For this 
reason, integrase is considered a rational therapeutic target for HIV-1 
infection. Further, integrase is a favorable target because the enzyme 
has no human cellular counterpart, which could interact with a 
potential integrase inhibitor and cause harmful side effects. Recent 
clinical data with an integrase inhibitor from Merck shows impressive 
clinical activity. The Merck compound is different from the current 
invention and is projected for FDA approval mid 2007. Thus, the subject 
invention is valuable for safe and effective treatment of HIV-1 and 
other retroviral infections.
    Application: Treatment of HIV infection.
    Development Status: The technology is ready for use in drug 
discovery and development.
    Inventors: Yves Pommier (NCI), Elena Semenova (NCI), Christophe 
Marchand (NCI).
    Patent Status: U.S. Provisional Application No. 60/849,718 filed 04 
Oct 2006 (HHS Reference No. E-264-2006/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301/435-5606; 
[email protected].


[[Page 58860]]


    Dated: October 10, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-20513 Filed 10-16-07; 8:45 am]
BILLING CODE 4140-01-P