Notice of Availability of License; Mutant IHD1 Inhibitors Useful for Treating Cancer, 72814 [2016-25468]
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[FR Doc. 2016–25472 Filed 10–20–16; 8:45 am]
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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]
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The meetings will be closed to the
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552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
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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