[Federal Register Volume 78, Number 19 (Tuesday, January 29, 2013)]
[Notices]
[Pages 6120-6121]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-01789]


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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, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 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.

FOR FURTHER INFORMATION CONTACT: Licensing information and copies of 
the U.S. patent applications listed below may be obtained by writing to 
the indicated licensing contact at the Office of Technology Transfer, 
National Institutes of Health, 6011 Executive Boulevard, Suite 325, 
Rockville, Maryland 20852-3804; telephone: 301-496-7057; fax: 301-402-
0220. A signed Confidential Disclosure Agreement will be required to 
receive copies of the patent applications.

Novel Derivatives of Docosahexaenoylethanolamide as Therapeutics for 
Neuronal Disorders

    Description of Technology: This technology provides derivatives of 
Docosahexaenoylethanolamide (synaptamide or DEA) which have increased 
potency and hydrolysis resistance as compared to DEA (structures of 
these derivatives are available upon request), as well as methods of 
using these derivatives to promote neurogenesis, neurite growth, and/or 
synaptogenesis. Docosahexaenoic acid (DHA), an n-3 polyunsaturated 
fatty acid that accumulates in the brain during development, has been 
shown to play a key role in learning and memory development. Studies 
have also shown that DEA, a metabolite derived from DHA is very potent 
in accelerating neuronal growth and development. The inventors have 
discovered that the novel DEA derivatives they have designed are even 
more potent than DEA or DHA in accelerating neuronal growth, 
synaptogenesis and development. The inventors have shown that treatment 
of progenitor neural cells with some of these novel DEA derivatives 
leads to an increase in the amount of somatic neurons produced after 
differentiation. These novel compounds can be developed as therapeutics 
for conditions such as trauma, stroke, multiple sclerosis, Alzheimer's 
disease, brain and spinal cord injuries, and peripheral nerve injuries 
for rehabilitation.
    Potential Commercial Applications:
     Agents to promote neurogenesis, neurite growth, and 
synaptogenesis.
     Therapeutics for neurological conditions, such as 
traumatic brain injury, spinal cord injury, peripheral nerve injury, 
stroke, multiple sclerosis, autism, Alzheimer's disease, Huntington's 
disease, Parkinson's disease, and amyotrophic lateral sclerosis.
    Competitive Advantages: These derivatives of DEA provide increased 
potency and hydrolysis resistance compared to DEA.
    Development Stage:
     Prototype.
     Early-stage.
     Pre-clinical.
     In vitro data available.
    Inventors: Erika Englund (NCATS), Juan Marugan (NCATS), Samarjit 
Patnaik (NCATS), Hee-Yong Kim (NIAAA)
    Publications:
    1. Kim HY, et al. N-Docosahexaenoylethanolamide promotes 
development of hippocampal neurons. Biochem J. 2011 Apr 15;435(2):327-
36. [PMID 21281269].
    2. Kim HY, et al. A synaptogenic amide N-
docosahexaenoylethanolamide promotes hippocampal development. 
Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):114-20. [PMID 
21810478].
    3. Cao D, et al. Docosahexaenoic acid promotes hippocampal neuronal 
development and synaptic function. J Neurochem. 2009 Oct;111(2):510-21. 
[PMID 19682204].
    Intellectual Property: HHS Reference No. E-070-2012/0 -- U.S. 
Provisional Application No. 61/624,741 filed 16 Apr 2012.
    Licensing Contact: Suryanarayana (Sury) Vepa, Ph.D., J.D.; 301-435-
5020; [email protected].
    Collaborative Research Opportunity: The National Center for 
Advancing Translational Sciences is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize this technology. For collaboration 
opportunities, please contact Dr. Juan Marugan at [email protected] 
or Dr. Krishna Balakrishnan at [email protected].

High-Affinity Rabbit Monoclonal Antibodies to Mesothelin for Treatment 
of Cancer

    Description of Technology: Mesothelin is a cell surface protein 
that is highly expressed in aggressive cancers, such as malignant 
mesothelioma, ovarian cancer and pancreatic cancer. Because of this 
selective expression, mesothelin is an

[[Page 6121]]

excellent candidate for targeted therapeutics, such as monoclonal 
antibodies (mAbs) and chimeric molecules. Current anti-mesothelin 
therapeutic mAb candidates bind to an epitope in Region I of 
mesothelin. Unfortunately, Region I contains the interaction site 
MUC16/CA125, a mesothelin-interacting protein that is present in the 
serum of patients with mesothelin-related cancers. Because the current 
therapeutic mAb candidates must compete with MUC16/CA125 for binding to 
mesothelin, they may not reach their full therapeutic potential due to 
interference.
    In order to address this concern, NIH inventors generated several 
rabbit mAbs that recognize unique epitopes of mesothelin: (1) YP223, 
which recognizes region II; (2) YYP218, which recognizes region III; 
and (3) YP3 which recognizes a native conformation epitope of 
mesothelin. These mAbs bind to mesothelin with sub-nanomolar affinity 
and are not out-competed for binding by the current anti-mesothelin 
therapeutic mAb candidates or MUC16/CA125. This strong binding affinity 
for an alternative binding site on mesothelin suggests that these mAbs 
are excellent therapeutic candidates.
    Potential Commercial Applications:
     Therapeutic use, such as treatment of mesothelin-
expressing cancers as a stand-alone mAbs or as a mAb-drug conjugate 
(e.g., an immunotoxin).
     Diagnosis of mesothelin-expressing cancers.
     Antibody-related research use, including 
immunoprecipitation, western blot analysis, immunohistochemistry, 
ELISA, etc.
    Competitive Advantages:
     Binding of new epitope on mesothelin may improve 
therapeutic applications due to non-competition from serum proteins.
     High binding affinity (sub-nanomolar levels) also 
increases chances of binding and subsequent therapeutic activity.
    Development Stage:
     Early-stage.
     In vitro data available.
    Inventors: Mitchell Ho et al. (NCI).
    Publication: Ho M. Advances in liver cancer antibody therapies: A 
focus on glypican-3 and mesothelin. BioDrugs. 2011 Oct 1;25(5):275-84. 
doi: 10.2165/11595360-000000000-00000. [PMID 21942912].
    Intellectual Property: HHS Reference No. E-198-2012/0--U.S. 
Provisional Patent Application No. 61/691,719 filed 21 Aug 2012.
    Related Technologies:
     HHS Reference No. E-021-1998/0--U.S. Patent 6,809,184 
issued 26 Oct 2004.
     HHS Reference No. E-139-1999/0--U.S. Patent 7,081,518 
issued 25 Jul 2006.
     HHS Reference No. E-091-2009/0--U.S. Patent Publication US 
20120107933.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The NCI Laboratory of Molecular 
Biology is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate or 
commercialize new monoclonal antibodies to unique domains of mesothelin 
for cancer therapy or diagnostics. For collaboration opportunities, 
please contact John Hewes, Ph.D. at [email protected].

Single Domain Human Monoclonal Antibodies to Mesothelin for Treatment 
of Cancer

    Description of Technology: Mesothelin is a cell surface protein 
that is highly expressed in aggressive cancers such as malignant 
mesothelioma, ovarian cancer and pancreatic cancer. This selective 
expression makes mesothelin an excellent candidate for targeted 
therapeutics such as monoclonal antibodies (mAbs) and corresponding 
chimeric molecules. Unfortunately, current anti-mesothelin mAb 
candidates have drawbacks, such as competition with a serum protein 
(MUC16/CA125) for binding to mesothelin, the formation of neutralizing 
antibodies because they are non-human antibodies, and the inability to 
trigger complement-dependent cytotoxicity (CDC).
    In order to address this concern, NIH inventors generated two 
single domain human mAbs: SD1 and SD2. SD1 recognizes a unique epitope 
in region III of mesothelin which is not out-competed for binding by 
MUC16/CA125. SD1 was also capable of triggering CDC, as well as 
antibody-dependent cellular cytotoxicity (ADCC). Due to its human 
origin, SD1 is also less likely to elicit the formation of neutralizing 
antibodies when administered to patients. Each of these characteristics 
suggests SD1 may be an effective therapeutic agent. Indeed, SD1 was 
able to inhibit tumor growth in mouse xenograft models, and 
corresponding immunotoxins were able to inhibit tumor cell growth in 
vitro, supporting the use of SD1 as a therapeutic mAb.
    Potential Commercial Applications:
     Therapeutic use, such as treatment of mesothelin-
expressing cancers as a stand-alone mAbs or as a mAb-drug conjugate 
(e.g., an immunotoxin).
     Diagnosis of mesothelin-expressing cancers.
     Antibody-related research use, including 
immunoprecipitation, western blot analysis, immunohistochemistry, 
ELISA, etc.
    Competitive Advantages:
     Binding of a new epitope on mesothelin may improve 
therapeutic applications due to non-competition from serum proteins.
     Human origin may significantly limit the formation of 
neutralizing antibodies, thereby increasing therapeutic potential of 
the mAb.
     Ability to trigger both CDC and ADCC may elicit a more 
complete therapeutic response.
    Development Stage:
     Early-stage.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Mitchell Ho et al. (NCI).
    Publication: Ho M. Advances in liver cancer antibody therapies: A 
focus on glypican-3 and mesothelin. BioDrugs. 2011 Oct 1;25(5):275-84. 
doi: 10.2165/11595360-000000000-00000. [PMID 21942912]
    Intellectual Property: HHS Reference No. E-236-2012/0--U.S. 
Provisional Patent Application No. 61/706,396 filed 27 Sep 2012
    Related Technologies:
     HHS Reference No. E-021-1998/0--U.S. Patent 6,809,184 
issued 26 Oct 2004.
     HHS Reference No. E-139-1999/0--U.S. Patent 7,081,518 
issued 25 Jul 2006.
     HHS Reference No. E-091-2009/0--U.S. Patent Publication US 
20120107933.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The NCI Laboratory of Molecular 
Biology is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate or 
commercialize single-domain human antibodies (SD1 and SD2) to 
mesothelin for cancer therapy or diagnostics. For collaboration 
opportunities, please contact John Hewes, Ph.D. at [email protected].

    Dated: January 23, 2013.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2013-01789 Filed 1-28-13; 8:45 am]
BILLING CODE 4140-01-P