[Federal Register Volume 81, Number 214 (Friday, November 4, 2016)]
[Notices]
[Pages 76949-76950]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-26628]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Aging (NIA), National Institute of Mental
Health (NIMH), and National Center for Advancing Translational Sciences
(NCATS): Cooperative Research and Development Agreement (CRADA) and
Licensing Opportunity for Ketamine for the Treatment of Depression and
Other Anxiety-Related Disorders
AGENCY: National Institutes of Health, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The National Institute of Aging (NIA), National Institute of
Mental Health (NIMH), and National Center for Advancing Translational
Sciences (NCATS) of the National Institutes of Health (NIH), University
of Maryland at Baltimore (UMB) and their collaborators are seeking
Cooperative Research and Development Agreement (CRADA) partners to
collaborate in the preclinical and clinical development of ketamine
metabolite (2R, 6R-HNK) for the treatment of depression and other
anxiety-related disorders.
DATES: Interested candidate partners must submit a statement of
interest and capability, no more than five pages long, to the NCATS
point of contact before January 3, 2017 for consideration.
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: As per the Anxiety and Depression
Association of America, Major depressive disorder affects 14.8 million
people in America, including children, adults, and the elderly. A
number of therapies currently exist to treat depression, although they
suffer drawbacks such as requiring weeks to take action. One particular
therapy includes the approved drug, ketamine, which has demonstrated
robust and acute antidepressant activity. However, its efficacy is
bridled with significant disadvantages including its addictive
potential and its dissociative activities. This is the case even when
administered at low doses, which limits the potential widespread use of
ketamine as an antidepressant medication.
In order to improve the treatment of depression, it is important to
explore the mechanism by which ketamine exerts its antidepressant
effects. That is precisely what the NIH and UMB scientists and
collaborators are investigating, and have found that the metabolism of
ketamine is critical to its antidepressant effects, and that the
(2R,6R)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexanone ((2R,6R)-
hydroxynorketamine (HNK)) metabolite, reversed depression-like
behaviors in mice without triggering anesthetic, dissociative, or
addictive side effects associated with ketamine. Specifically, the
researchers found that the
[[Page 76950]]
metabolite does not inhibit the non-competitive glutamatergic N-methyl-
D-aspartate (NMDA) receptor, and it exerts rapid actions that activate
the [alpha]-amino 3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
receptors. Results indicate a non-NMDA receptor dependent mechanism
underlying ketamine's antidepressant properties, which involve
bioactivity of a specific metabolite (2R, 6R-HNK) could be exploited
for drug development. Additionally, the researchers have established
appropriate salt, crystal and polymorph forms of the agent and multiple
methods of synthesis. Full ADME and polypharmacology assessment is
complete as well as pre-formulations studies.
To expedite the research, development and commercialization of
2R,6R-hydroxynorketamine (a metabolite of ketamine), the National
Institutes of Health, UMB and their collaborators are seeking one or
more CRADA and/or license agreements with appropriate pharmaceutical or
biotechnology companies in accordance with the regulations governing
the transfer of Government-developed technology and its public sector
objectives, as outlined below. The purpose of a CRADA is to find a
partner to collaborate in the development and commercialization of a
technology that is in early phases of clinical development. Under the
CRADA, key activities related to the clinical development of 2R,6R-HNK
as a therapeutic to treat a variety of mental health conditions
including depressive disorders will be performed. Collaborators should
have proven experience in drug development with specialized expertise
within depression and/or related mental health disorders. Owing to
NIH's commitment to public dissemination of data, a key criterion will
be that all outcomes from the collaborative effort will be published
including the outcomes of all clinical trials. Further, it is the goal
of NIH, UMB and other collaborators to develop the technology to the
fullest extent (as therapeutic for multiple clinical indications
including, but not limited to, anxiety, suicidal ideation, anhedonia,
PTSD, addiction, neuropathic pain, among others).
How to Apply: Interested potential CRADA collaborators will receive
detailed information on the current status of the project after signing
a confidentiality disclosure agreement (CDA) with NIH, UMB and other
collaborators. Interested candidate partners must submit a statement of
interest and capability, no more than five pages long, to the NCATS
point of contact before January 3, 2017 for consideration. Guidelines
for the preparation of a full CRADA proposal will be communicated by
the NIH to respondents that have demonstrated sufficient mutual
interests and capabilities that indicate the partnering entity will
appropriately and substantially contribute to the proposed
collaboration. Capability statements submitted after the due date may
be considered if a suitable CRADA collaborator has not been identified
by NIH and UMB among the initial pool of respondents.
Respondents interested in submitting a CRADA proposal should be
aware that it may be necessary for them to secure a patent license to
the background-patent applications in order to commercialize products
arising from a CRADA. Licensing of background technology patent rights
related to this CRADA opportunity and claimed in the pending patent
applications are available for either exclusive or non-exclusive
licensing and licensing by NIH is subject to 35 U.S.C. 207 and 37 CFR
part 404. CRADA partners are afforded an option to negotiate an
exclusive license from the NIH for inventions arising from the
performance of the CRADA research plan.
The full CRADA proposal should include a capability statement with
a detailed description of: (1) Collaborator's Expertise with mental
health disorders such as depression, (2) Collaborators' expertise in
preclinical development efforts including toxicology and chemistry,
manufacturing and controls (CMC), (3) Expertise in regulatory affairs,
particularly at the IND filing and early stage clinical trials stages,
(4) Collaborator's ability to support, directly or through contract
mechanisms, and upon the successful completion of relevant milestones,
the ongoing pharmacokinetics and biological studies, long term toxicity
studies, process chemistry and other pre-clinical development studies
needed to obtain regulatory approval of a given therapy so as to ensure
a high probability of eventual successful commercialization and; (5)
Collaborator's ability to provide adequate funding to support some pre-
clinical studies of the project as well as clinical trials.
Publications
Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI,
Manickavasagom A, Yuan P, Pribut HJ, Singh NS, Dossou KSS, Fang Y,
Huang X-P, Mayo CL, Wainer IW, Albuquerque EX, Thompson SM, Thomas
CJ, Zarate CA, Gould TD. NMDA receptor inhibition-independent
antidepressant actions of a ketamine metabolite. Nature, May 4,
2016, doi: 10:1038/nature17998.
Patent Status
(1) ``Use Of (2R,6R)-HNK, (S)-Dehydronorketamine and (R,S)-ketamine
metabolites in the treatment of depression and neuropathic pain'';
Irving W. Wainer, Ruin Moaddel, Michel Bernier, Carlos A. Zarate, Mary
Tanga, Marc C. Torjman, Michael Goldberg; Assignees: National Institute
of Aging (NIA), National Institute of Mental Health (NIMH), SRI
International, University of Medicine and Dentistry of New Jersey
(UMDNJ); U.S. Provisional Patent Application # 61/547,336; Filed:
October 14, 2011; NIH Reference # E-092-2011.
(2) ``Methods of using (2S,6S)-HNK and (2R,6R)-HNK to treat various
depressive disorders and anxiety disorders''; Craig Thomas, Todd D.
Gould, Irving W. Wainer, Carlos A. Zarate, Ruin Moaddel, Patrick
Morris, Panos Zanos; Assignees: National Institute of Aging (NIA),
National Institute of Mental Health (NIMH), National Center for
Advancing Translational Sciences (NCATS), University of Maryland at
Baltimore (UMB); U.S. Provisional Patent Application # 62/313317;
Filed: March 25, 2016; NIH Reference #E-036-2016.
(3) ``Crystal forms and methods of synthesis of (2R, 6R)-HNK and
(2S,6S)-HNK''; Craig Thomas, Patrick Morris, Carlos A. Zarate, Ruin
Moaddel, Todd D. Gould, Panos Zanos; Assignees: National Center for
Advancing Translational Sciences (NCATS), National Institute of Mental
Health (NIMH), National Institute of Aging (NIA), University of
Maryland at Baltimore (UMB); U.S. Provisional Patent Application #62/
313309; Filed: March 25, 2016; NIH Reference #E-116-2016.
Dated: October 31, 2016.
Pamela McInnes,
Deputy Director, Office of the Director, National Center for Advancing
Translational Sciences.
[FR Doc. 2016-26628 Filed 11-3-16; 8:45 am]
BILLING CODE 4140-01-P