[Federal Register Volume 81, Number 210 (Monday, October 31, 2016)]
[Notices]
[Pages 75421-75423]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-26129]


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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, HHS.

ACTION: Notice.

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SUMMARY: The invention listed below is owned by an agency of the U.S. 
Government and is available for licensing and/or co-development in the 
U.S. in accordance with 35 U.S.C. 209 and 37 CFR part 404 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 and/or co-development.

ADDRESSES: Invention Development and Marketing Unit, Technology 
Transfer Center, National Cancer Institute, 9609 Medical Center Drive, 
Mail Stop 9702, Rockville, MD 20850-9702.

[[Page 75422]]


FOR FURTHER INFORMATION CONTACT: Information on licensing and co-
development research collaborations, and copies of the U.S. patent 
applications listed below may be obtained by contacting: Attn. 
Invention Development and Marketing Unit, Technology Transfer Center, 
National Cancer Institute, 9609 Medical Center Drive, Mail Stop 9702, 
Rockville, MD 20850-9702, Tel. 240-276-5515 or email 
[email protected]. A signed Confidential Disclosure 
Agreement may be required to receive copies of the patent applications.

SUPPLEMENTARY INFORMATION: Technology description follows.

Title of Invention

    Small Molecule Inhibitors of Drug Resistant Forms of HIV-1 
Integrase

Description of Technology

    Integrase strand transfer inhibitors (``INSTIs'') are currently in 
use as a component of prophylactic antiretroviral therapy for 
preventing HIV-1 infection from progressing to AIDS. Three INSTIs are 
approved by the FDA for inclusion in antiretroviral regiments: 
Raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG). 
Clinicians have already identified several HIV-1 integrase mutations 
that confer resistance to RAL and EVG, and additional mutations that 
confer resistance to all three INSTIs has been identified in the 
laboratory.
    Researchers at the National Cancer Institute discovered small-
molecule compounds containing 1-hydroxy-2-oxo-1,8-naphthyridine 
moieties whose activity against HIV-1 integrase mutants confer 
resistance to currently approved INSTIs. These new compounds exhibit 
potent and selective activity against comprehensive and varied panels 
of INSTI-resistant mutants of HIV-1 integrase. Preliminary rodent 
efficacy, metabolic, and pharmacokinetic studies have been completed by 
the NCI researchers.
    The National Cancer Institute (NCI) seeks partners to in-license or 
co-develop this class of compounds for therapeutic use. Parties 
interested in licensing the technology should submit an Application for 
Licensing, and seek detailed information from the Licensing and 
Patenting Manager indicated below.
    Co-development partners would apply under a Cooperative Research 
and Development (CRADA) to conduct pre-clinical studies that include 
lead optimization, in vitro and in vivo evaluation and preclinical 
development of a novel series of INSTIs for the treatment of infection 
by HIV-1 strains with resistance to currently available integrase 
inhibitors, including raltegravir and elvitegravir. Under the CRADA, 
further in vitro and in vivo ADME, as well as activity studies, will be 
conducted by the partner on current and optimized lead compounds using 
rodent and non-rodent models. Efficacy studies in non-human primates of 
select compounds are needed and will be part of the CRADA program. The 
CRADA scope will also include all aspects of toxicity studies, and 
synthesis scale up under GMP of optimized lead compounds to support 
submission of a successful IND application.
    Interested potential CRADA collaborators can receive detailed 
information by contacting the Licensing and Patenting Manager (see 
below). Interested parties will receive detailed information on the 
current status of the project after signing a confidentiality 
disclosure agreement (CDA) with NCI. Interested candidate partners must 
submit a statement of interest and capability to the NCI point of 
contact for consideration by 5:00 p.m. Eastern Standard Time, December 
30, 2016.
    Guidelines for the preparation of a full CRADA proposal will be 
communicated to all respondents with whom initial confidential 
discussions have been established. Licensing of background technology 
related to this CRADA opportunity, specifically HHS Reference No.: E-
093-2013/0,1,2, entitled ``Compounds for Inhibiting Drug-Resistant 
Strains of HIV-1 Integrase'', is also available to potential 
collaborators. All proposals received by the above date will be 
considered. NCI reserves the right to consider additional proposals or 
none at all if no partner is selected from the initial response.
    Further information about the NCI Technology Transfer Center can be 
found on its Web site http://techtransfer.cancer.gov.

Potential Commercial Applications

     HIV therapeutic for drug-resistant compounds of HIV-1 
integrase

Value Proposition

     Currently, the only INSTI effective against drug resistant 
mutants of HIV-1 integrase

Development Stage

    Pre-clinical (in vivo validation)

Inventor(s)

    Terrence Burke, Stephen Hughes, Yves Pommier, Xue Zhao, Mathieu 
Metifiot, Stephen Smith, Barry Johnson, Christophe Marchand (all from 
NCI)

Intellectual Property

HHS Reference No.: E-093-2013/0,1,2; all entitled ``Compounds For 
Inhibiting Drug-Resistant Strains Of HIV-1 Integrase''
US Provisional App. No.: 61/952,928 filed May 16, 2013
US Provisional App. No.: 61/899,061 filed November 1, 2013
International App. No.: PCT/US2014/037905 filed May 13, 2014
Brazilian App. No.: BR1120150287603 filed May 13, 2014
Canadian App. No.: CA2912064 filed May 13, 2014
Chinese App. No.: 2014-80039611.5 filed May 13, 2014
European App. No.: 14728395.6 filed May 13, 2014
Indian App. No.: 3937/KOLNP/2015 filed May 13, 2014
Japanese App. No.: JP100078282 filed May 13, 2014
US Non-Provisional App. No.: 14/891,309 filed May 13, 2014
South African App. No.: ZA2015/08408 filed May 13, 2014

Publications

Zhao, X.Z. et al., ``HIV-1 Integrase Strand Transfer Inhibitors with 
Reduced Susceptibility to Drug Resistant Mutant Integrases'', ACS 
Chem Biol., Apr 15, 2016, 11(4):1074-81.
M[eacute]tifiot, M. et al., ``Selectivity for strand-transfer over 
3'-processing and susceptibility to clinical resistance of HIV-1 
integrase inhibitors are driven by key enzyme-DNA interactions in 
the active site'', Nucleic Acids Res., Aug 19, 2016, 44(14):6896-
906.
Zhao, X. Z. et al., ``4-Amino-1-hydroxy-2-oxo-1,8-naphthyridine-
containing compounds having high potency against raltegravir-
resistant integrase mutants of HIV-1'', J. Med. Chem., 57, 5190-5202 
(2014), Doi: 10.1021/jm501059k
Zhao, X. Z. et al., ``Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-
3-carboxamide-containing HIV-1 integrase inhibitors having high 
antiviral potency against cells harboring raltegravir-resistant 
integrase mutants'', J. Med. Chem., 57, 1573-1582 (2014), Doi: 
10.1021/jm401902n

Contact Information

    Requests for copies of the patent application and inquiries about 
licensing, research collaborations, and co-development opportunities 
for this invention should be sent to Lauren Nguyen-Antczak, Ph.D., 
J.D., Senior Licensing & Patenting Manager, NCI Technology Transfer 
Center, 8490 Progress Drive, Suite 400, Frederick, MD 21701, Tel: (301) 
624-8752, email: [email protected].


[[Page 75423]]


    Dated: October 25, 2016.
John D. Hewes,
Technology Transfer Specialist, Technology Transfer Center, National 
Cancer Institute.
[FR Doc. 2016-26129 Filed 10-28-16; 8:45 am]
BILLING CODE 4140-01-P