[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