[Federal Register Volume 81, Number 177 (Tuesday, September 13, 2016)]
[Notices]
[Pages 62913-62914]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-21904]


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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.

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: Analogues of Withanolide E Sensitize Cancer 
Cells to Apoptosis.
    Keywords: TRAIL, TLR3, apoptosis, immunotherapy, tumor necrosis 
factor, TNF.
    Description of Technology: The tumor necrosis factor (TNF)-related 
apoptosis-inducing ligand (TRAIL) protein has been a target of interest 
in cancer therapy because it plays a large role in inducing cell 
apoptosis in cancer cells but not in normal cells. Although TRAIL has 
been reported to successfully target certain tumor cells which are 
resistant to traditional chemotherapy or radiation, TRAIL resistance 
has also been widely observed. Similarly, Toll-like receptor (TLR) 3 
ligands such as poly I:C have also been reported to promote apoptosis 
in certain cancer cells, though the apoptotic signaling in most cancer 
cells was weak and was only significant following longer term 
incubations. Thus, there is a need to develop compounds that can 
sensitize cancer cells to apoptosis inducing ligands, such as poly I:C 
and TRAIL.
    In collaboration with the University of Arizona, NCI investigators 
have discovered a series of compounds in the withanolide family that 
synergistically enhance the response of cancer cells to treatment with 
an apoptosis-inducing ligand. The compounds each show a 4- to 10-fold 
increase in potency compared to withanolide E alone in promoting death 
ligand-mediated cancer cell death. One biotinylated analogue in 
particular is at least 15-fold more potent than withanolide E in 
promoting apoptosis in human melanoma cells when used in combination 
with either poly I:C or TRAIL. A selection of active compounds were 
tested in murine xenograft models of human melanoma and showed 
decreased tumor growth and tumor regression.

Potential Commercial Applications

     Potential therapeutic for the treatment of cancer either 
alone or in combination with an apoptosis inducing agent such as TRAIL 
receptor or TLR 3 agonists by directly promoting tumor cell apoptosis.
     Possible indirect enhancement of cancer immunotherapy due 
to release of cancer cell antigens in the presence of the powerful 
immune-adjuvant effects of TLR3 agonists.

Value Proposition

     Withanolide E derivatives enhance the anti-cancer activity 
of known apoptosis inducing ligands such as TRAIL or poly I:C and may 
be used to enhance efficacy of TRAIL receptor or poly I:C agonists that 
are currently under development.
    Development Stage: Pre-clinical (in vivo validation).
    Inventor(s): Thomas Sayers (NCI), Alan Brooks (NCI), Curtis Henrich 
(NCI), Poonam Tewary (NCI), James McMahon (NCI), Leslie Gunatilaka 
(University of Arizona), Ya-ming Xu (University of Arizona), and E.M. 
Kithsiri Wijeratne (University of Arizona).
    Intellectual Property: US Provisional Application No. 62/292,974, 
entitled ``Method of Sensitizing Cancer Cells to The Cytotoxic Effects 
of Apoptosis Inducing Ligands in Cancer Treatment,'' filed February 9, 
2016.

Publications

    1. Tewary P., Gunatilaka A.A. and Sayers T.J. (2016) Using natural 
products to promote caspase-8-

[[Page 62914]]

dependent cancer cell death. Cancer Immunol Immunother. doi:10.1007/
s00262-016-1855-0.
    Related Technologies: US Patent 9,238,069 (HHS Ref. No. E-050-2010) 
entitled ``Use of withanolides to sensitize cancer cells to the 
cytotoxic effects of Apo2L/TRAIL'' issued January 19, 2016.
    Collaboration Opportunity: Researchers at the NCI seek licensing 
and/or co-development research collaborations for development of 
withanolide E analogues for the treatment of cancer.
    Contact Information: Requests for copies of the patent application 
or inquiries about licensing, research collaborations, and co-
development opportunities should be sent to John D. Hewes, Ph.D., 
email: [email protected].

    Dated: September 6, 2016.
John D. Hewes,
Technology Transfer Specialist, Technology Transfer Center, National 
Cancer Institute.
[FR Doc. 2016-21904 Filed 9-12-16; 8:45 am]
 BILLING CODE 4140-01-P