Notice of Availability of License; Mutant IHD1 Inhibitors Useful for Treating Cancer, 72814 [2016-25468]

Download as PDF 72814 Federal Register / Vol. 81, No. 204 / Friday, October 21, 2016 / Notices and Skin Diseases Clinical Trials Review Committee. Date: October 25–26, 2016. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and evaluate grant applications. Place: Bethesda Marriott Suites, 6711 Democracy Boulevard, Bethesda, MD 20817. Contact Person: Kathy Salaita, SCD, Scientific Review Officer, Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, NIH, 6701 Democracy Blvd., Building One, Room 818, Bethesda, MD 20892, 301–594–5033, kathy.salaita@nih.gov. This notice is being published less than 15 days prior to the meeting due to the timing limitations imposed by the review and funding cycle. Name of Committee: National Institute of Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel; NIAMS Institutional Training Grants (T32) Review Meeting. Date: October 28, 2016. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and evaluate grant applications. Place: 6701 Democracy Boulevard, Building One, Conference Room 807, Bethesda, MD 20892. Contact Person: Yin Liu, Ph.D., MD, Scientific Review Officer, Scientific Review Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, NIH, 6701 Democracy Blvd., Building One, Room 824, Bethesda, MD 20892, 301–594–8919, liuy@mail.nih.gov. This notice is being published less than 15 days prior to the meeting due to the timing limitations imposed by the review and funding cycle. (Catalogue of Federal Domestic Assistance Program Nos. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research, National Institutes of Health, HHS) Dated: October 17, 2016. Sylvia L. Neal, Program Analyst, Office of Federal Advisory Committee Policy. [FR Doc. 2016–25472 Filed 10–20–16; 8:45 am] BILLING CODE 4140–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health asabaliauskas on DSK3SPTVN1PROD with NOTICES Notice of Availability of License; Mutant IHD1 Inhibitors Useful for Treating Cancer AGENCY: National Institutes of Health, HHS. ACTION: Notice. 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. SUMMARY: VerDate Sep<11>2014 19:06 Oct 20, 2016 Jkt 241001 FOR FURTHER INFORMATION CONTACT: Information on licensing and codevelopment 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 NCATSPartnerships@mail.nih.gov. 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 a-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, aketoglutarate 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 noncancerous 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 PO 00000 Frm 00045 Fmt 4703 Sfmt 4703 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] BILLING CODE 4140–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meetings. The meetings will be closed to the public in accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications and the discussions could disclose E:\FR\FM\21OCN1.SGM 21OCN1

Agencies

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


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

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 NCATSPartnerships@mail.nih.gov. 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]
BILLING CODE 4140-01-P