[Federal Register Volume 81, Number 204 (Friday, October 21, 2016)]
[Page 72814]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-25468]



National Institutes of Health

Notice of Availability of License; Mutant IHD1 Inhibitors Useful 
for Treating Cancer

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.


SUMMARY: The invention Mutant IHD1 Inhibitors Useful for Treating 
Cancer is owned by an agency of the U.S. Government and is available 
for licensing and/or co-development in the U.S.

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: Sury 
Vepa, Ph.D., J.D., Senior Licensing and Patenting Manager, National 
Center for Advancing Translational Sciences, NIH, 9800 Medical Center 
Drive, Rockville, MD 20850, Phone: 301-217-9197, Fax: 301-217-5736, or 
email [email protected]. A signed Confidential Disclosure 
Agreement may be required to receive copies of the patent applications.

SUPPLEMENTARY INFORMATION: This notice is made 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.

Intellectual Property

    Description of Technology: Isocitrate dehydrogenase 1 (IDH1) is an 
enzyme whose normal function is to convert isocitrate to [alpha]-
ketoglutarate. Mutated forms of this enzyme (mIDH1) are common in a 
variety of cancers including acute myeloid leukemia (AML), glioma, 
cholangiocarcinoma, chondrosarcoma and melanoma. The IDH1 mutation at 
position 132 and similar IDH1 mutations result in the enzyme gaining 
the ability to catalyze the NADPH-dependent reduction of the wild type 
enzyme's product, [alpha]-ketoglutarate to R-2-hydroxyglutarate (2-HG). 
2-HG is an oncometabolite, and its elevated levels have been shown to 
lead to de-differentiation of cells. Mutant IDH1 is an attractive 
target for anti-cancer therapeutics as inhibition reduces levels of 2-
HG. It is expected that lower 2-HG levels will result in fewer 
undifferentiated cancer cells. Furthermore, inhibition of mutant IDH1 
is expected to have little effect on non-cancerous cells, as these 
cells do not express the IDH1 mutation resulting in lower toxicity than 
typical cytotoxic anticancer agents.
    In collaboration with the University of North Carolina, the 
National Center for Advancing Translational Sciences (NCATS) 
investigators have discovered a series of novel compounds that potently 
and selectively inhibit mIDH1. These compounds reduce 2-HG levels in 
cell lines in vitro as well as in human cancer cells grown in mouse 
xenografts in vivo. These compounds show greater than 250-fold 
selectivity for the mutant enzyme over the wild-type, show favorable in 
vitro stability (in mouse, rat, dog and human hepatocyte exposure 
studies), are AMES negative, and exhibit no significant metabolic CYP 
liabilities. These compounds possess very favorable in vivo rodent 
pharmacokinetics and bioavailability and are well tolerated in rodents, 
even when dosed at high levels.

Potential Commercial Applications

     Potential treatment of cancer (AML or other solid tumors 
listed above).
     Potential treatment of rare diseases including Maffucci 
Syndrome and Ollier Disease.

Value Proposition

     Novel mutant IDH1 inhibitors are effective at lowering the 
oncometabolite, 2-HG in in vivo mouse proof-of-concept studies and are 
well suited for IND enabling studies.
    Development Stage: Pre-clinical (in vivo validation).
    Inventor(s): Matt Boxer, Kyle Brimacombe, Mindy Davis, Rajan 
Pragani, Jason Rohde, Li Liu, Surendra Karavadhi, Daniel Urban, Min 
Shen, Anton Simeonov, Ajit Jadhav (NCATS) Xiaodong Wang and Andrew 
McIver (Univ. of North Carolina at Chapel Hill)
    Intellectual Property:
    1. International Application No. PCT/US15/067406 filed on 12/22/
2015 which is entitled ``Mutant IDH1 Inhibitors Useful for Treating 
Cancer'' (HHS Ref. No: E-243-2014/0-PCT-02), and
    2. U.S. Provisional Application No. 62/353298 filed on 06/22/2016 
which is entitled ``Mutant IDH1 Inhibitors Useful for Treating Cancer'' 
(HHS Ref. No. E-189-2016/0-US-01).

    Dated: October 5, 2016.
Pamela McInnes,
Deputy Director, Office of the Director, National Center for Advancing 
Translational Sciences.
[FR Doc. 2016-25468 Filed 10-20-16; 8:45 am]