[Federal Register Volume 77, Number 147 (Tuesday, July 31, 2012)]
[Notices]
[Pages 45363-45366]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-18651]


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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

[[Page 45364]]

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.

Glial Cell Line-Derived Neurotrophic Factor Opposite Strand (GDNFOS) 
for Treatment of Neurodegenerative Diseases

    Description of Technology: Glial cell line-derived neurotrophic 
factor (GDNF) is a small human protein encoded by the GDNF gene. GDNF 
has been effective therapy in laboratory animal models of Parkinson's 
disease and protects several types of neurons in the brain and 
peripheral nervous system. The NIDA inventors have discovered primate-
specific GDNFOS, encoded by the opposite strand of glial cell derived 
neurotrophic factor (GDNF) gene. The GDNFOS gene encodes for novel 
peptides that was found to be reduced in human middle temporal gyrus of 
Alzheimer's disease brains. These secreted growth proteins have 
potential neurotrophic activity and they might play a synergistic role 
in neuroprotective effects of GDNF in human brain. The NIDA inventors 
have also developed antibody against GDNFOS3 and generated compounds 
that have potential pharmaceutical use. The compounds consist of GDNFOS 
nucleic acid transcripts, GDNFOS protein or a functional fragment for 
treatment of human neurodegenerative diseases.

Potential Commercial Applications

     Synergistic role in neuroprotective effects of GDNF.
     Alzheimer's disease, Parkinson's disease, Amyotrophic 
lateral sclerosis, multiple sclerosis and diseases of peripheral organs 
such as diabetes mellitus type 1.

Competitive Advantages

     Secreted novel growth peptides.
     An antibody against GDNFOS3 was developed.

Development Stage

     Early-stage.
     Pre-clinical.
     In vitro data available.
    Inventors: Qing-Rong Liu, Mikko Airavaara, Barry Hoffer, Brandon K 
Harvey (all of NIDA).
    Publication: Airavaara M, et al. Identification of novel GDNF 
isoforms and cis-antisense GDNFOS gene and their regulation in human 
middle temporal gyrus of Alzheimer disease. J Biol Chem. 2011 Dec 
30;286(52):45093-102. [PMID 22081608]
    Intellectual Property: HHS Reference No. E-044-2012/0--U.S. 
Provisional Application No. 61/619, 296 filed 02 Apr 2012.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The National Institute on Drug 
Abuse is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate or 
commercialize GDNFOS peptide and non-coding RNAs as therapeutic agents 
for neurodegenerative diseases. For collaboration opportunities, please 
contact Vio Conley at [email protected].

Increased Therapeutic Effectiveness of Immunotoxins That Use Toxin 
Domains Lacking Human B-cell Epitopes

    Description of Technology: Immunotoxins kill cancer cells while 
allowing healthy, essential cells to survive. As a result, patients 
receiving an immunotoxin are less likely to experience the deleterious 
side-effects associated with non-discriminate therapies such as 
chemotherapy or radiation therapy. Unfortunately, the continued 
administration of immunotoxins often leads to a reduced patient 
response due to the formation of neutralizing antibodies against 
immunogenic epitopes contained within Pseudomonas exotoxin A (PE). To 
improve the therapeutic effectiveness of PE-based immunotoxins through 
multiple rounds of drug administration, NIH inventors have sought to 
identify and remove the human B-cell epitopes within PE. Previous work 
demonstrated that the removal of the murine B-cell and T-cell epitopes 
from PE reduced the immunogenicity of PE and resulted in immunotoxins 
with improved therapeutic activity. This technology involves the 
identification and removal of major human B-cell epitopes on PE by 
mutation or deletion. Considering these immunotoxins will be 
administered to humans, the removal of human immunogenic epitopes is 
important. The resulting PE-based immunotoxins have increased 
resistance to the formation of neutralizing antibodies, and are 
expected to have improved therapeutic efficacy.

Potential Commercial Applications

     Essential component of immunotoxins.
     Treatment of any disease associated with increased or 
preferential expression a specific cell surface receptor.
     Specific diseases include hematological cancers, lung 
cancer, ovarian cancer, breast cancer, and head and neck cancers.

Competitive Advantages

     PE variants now include the removal of human B-cell 
epitopes, further reducing the formation of neutralizing antibodies 
against immunotoxins which contain the PE variants.
     Less immunogenic immunotoxins result in improved 
therapeutic efficacy by permitting multiple rounds of administration in 
humans.
     Targeted therapy decreases non-specific killing of 
healthy, essential cells, resulting in fewer non-specific side-effects 
and healthier patients.
    Development Stage: Pre-clinical.
    Inventors: Ira H. Pastan et al. (NCI).
    Publication: Liu W, et al. Recombinant immunotoxin engineered for 
low immunogenicity and antigenicity by identifying and silencing human 
B-cell epitopes. Proc Natl Acad Sci USA. 2012 Jul 17;109(29):11782-7. 
[PMID 22753489]
    Intellectual Property: HHS Reference No. E-263-2011/0--U.S. 
Provisional Application No. 61/535,668 filed 16 Sep 2011.

Related Technologies

     PCT Patent Publication WO 2011/032022 (HHS Reference No. 
E-269-2009/0-PCT-02).
     US Patent Publication US 20100215656 A1 (HHS Reference No. 
E-292-2007/0-US-06).
     US Patent Publication US 20090142341 A1 (HHS Reference No. 
E-262-2005/0-US-06).
     Multiple additional patent families.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
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 John 
Hewes, Ph.D. at [email protected].

Novel Nitroxyl (HNO) Releasing Compounds and Their Use in Treating 
Diseases

    Description of Technology: Nitroxyl (HNO) is a chemical species 
that exhibits distinct biological properties in comparison to its 
oxidized product, nitric oxide (NO). Previous investigations have 
revealed that the

[[Page 45365]]

distinct properties of HNO make it a tempting species for wide 
therapeutic application as it has shown potential in the treatment of 
heart failure, cancer, and other diseases in various animal and in 
vitro models. Non-steroidal anti-inflammatory drugs (NSAIDs), such as 
aspirin and ibuprofen, are compounds that inhibit cycloxygenase (COX)-
mediated conversion of arachidonic acids to prostagladins. NSAIDs are 
known for their analgesic properties and are therapeutically involved 
in many physiological functions, including the inhibition of chronic 
pain and inflammation inhibition, prevention of heart disease, renal 
function, and cancer. Prolonged use of NSAIDs can lead to serious 
gastrointestinal and renal side effects, including ulcer perforation, 
upper gastrointestinal bleeding, and death, which has limited NSAID 
therapies.
    The instant invention described HNO-releasing NSAIDs, which combine 
the potential therapeutic benefits of HNO and NSAIDs without the 
toxicities associated with chronic NSAID use. These HNO-releasing 
NSAIDs provide a reliable controlled release of HNO making them 
desirable HNO prodrugs. The instant invention disclosed various HNO-
releasing NSAIDs and methods of treating or preventing various 
disorders with these compositions, such as cardiovascular disorders, 
cancers, pain, inflammation, and alcoholism.

Potential Commercial Applications

     Treatment of cancer.
     Treatment of cardiovascular disease.
     Aversion therapy for alcoholism.

Competitive Advantages

     Combination of therapeutic benefits of HNO and NSAIDs.
     Alleviated toxicity associated with chronic NSAID use.
     Controlled release of HNO.

Development Stage

     Early-stage.
     Pre-clinical.
    Inventors: David A. Wink and Larry K. Keefer (NCI).

Publication

    Miranda KM, et al. Comparison of the NO and HNO donating 
properties of diazeniumdiolates: primary amine adducts release HNO 
in vivo. J Med Chem. 2005 Dec 29;48(26):8220-8. [PMID 16366603]

    Intellectual Property: HHS Reference No. E-019-2010/2--
International Patent Application PCT/US2011/029072 filed 18 Mar 2011.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].

Polyclonal Antibodies for the Specialized Signaling G Protein, Gbeta5

    Description of Technology: Researchers at NIDDK have developed 
polyclonal antibodies against the G protein, Gbeta5. Gbeta5 is a unique 
and highly specialized G protein that exhibits much less homology than 
other Gbeta isoforms (~50%) and is preferentially expressed in brain 
and neuroendocrine tissue. It is expressed prominently in the neuronal 
cell membrane, as well as in the cytosol and nucleus. Although this 
distribution pattern suggests that Gbeta5 may shuttle information 
between classical G protein-signaling elements at the plasma membrane 
and the cell interior, its function in the brain is largely unknown.
    The antibodies were separately generated in rabbits to KLH-
conjugates of peptides from the N-terminus of Gbeta5 (antibody ATDG) 
and the C-terminus of Gbeta5 (antibody SGS). The antibodies can be used 
for immunoblotting (ATDG, SGS), and immunoprecipitation (ATDG). They 
can be used to facilitate our understanding of the unique biology and 
function of Gbeta5 in brain and neurons.
    Potential Commercial Applications: These antibodies can be used for 
research purposes (immunoblotting, immunoprecipitation) by those 
studying the biology and function of Gbeta5.
    Competitive Advantages: Very specific antibodies to study Gbeta5 
and G protein signaling.
    Development Stage: In vitro data available.
    Inventors: William Simonds and Jianhua Zhang (NIDDK).

Publications

    1. Zhang JH and Simonds WF. Copurification of brain G-protein 
beta5 with RGS6 and RGS7. J Neurosci. 2000 Feb 1;20(3):RC59. [PMID 
10648734]
    2. Zhang JH, et al. Nuclear localization of G protein beta 5 and 
regulator of G protein signaling 7 in neurons and brain. J Biol 
Chem. 2001 Mar 30;276(13):10284-9. [PMID 11152459]
    3. Zhang S, et al. Selective activation of effector pathways by 
brain-specific G protein beta5. J Biol Chem. 1996 Dec 
27;271(52):33575-9. [PMID 8969224]
    4. Zachariou V, et al. An essential role for DeltaFosB in the 
nucleus accumbens in morphine action. Nat Neurosci. 2006 
Feb;9(2):205-11. [PMID 16415864]

    Intellectual Property: HHS Reference No. E-192-2006/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Jaime Greene, M.S.; 301-435-5559; 
[email protected].

Polyclonal Antibodies for the Gbeta5-Associated Regulator of G Protein 
Signaling Protein, RGS7

    Description of Technology: Researchers at NIDDK have developed 
polyclonal antibodies against the Regulator of G Protein Signalling 
(RGS) protein, RGS7. RGS7 binds tightly to Gbeta5, a unique and highly 
specialized G protein that exhibits much less homology than other Gbeta 
isoforms (~50%). RGS7 is preferentially expressed in brain and 
neuroendocrine tissue. Like Gbeta5, RGS7 is expressed prominently in 
the cell membrane, as well as in the cytosol. Although this 
distribution pattern suggests that complexes containing Gbeta5 and RGS7 
may shuttle information between classical G protein-signaling elements 
at the plasma membrane and the cell interior, the function of the 
complex in the brain is largely unknown.
    The antibodies were generated in rabbits to a glutathione S-
transferase (GST) fusion protein with residues 312-469 of bovine RGS7 
(antibody 7RC-1) and react with human and rodent RGS7. The antibodies 
(7RC-1) can be used for immunoblotting and immunoprecipitation. They 
can be used to facilitate our understanding of the function of Gbeta5/
RGS7 complexes in brain and neurons.
    Potential Commercial Applications: These antibodies can be used for 
research purposes (immunoblotting, immunoprecipitation) by those 
studying the biology and function of RGS7.
    Competitive Advantages: High-titer, multi-epitope antibodies to 
study RGS7 and RGS7/Gbeta5 complexes and G protein signaling.
    Development Stage: In vitro data available.
    Inventors: William Simonds and Jianhua Zhang (NIDDK).

Publications

    1. Rojkova AM, et al. Ggamma subunit selective G protein beta 5 
mutant defines regulators of G protein signaling binding requirement 
for nuclear localization. J Biol Chem. 2003 Apr 4;278(14):12507-12. 
[PMID 12551930]
    2. Cao Y, et al. Retina Specific GTPase Accelerator RGS11/
Gbeta5S/R9AP is a Constitutive Heterotrimer Selectively Targeted to 
mGluR6 in ON-Bipolar Neurons. J Neurosci 2009 July 22; 29 (29): 
9301-13. [PMID 19625520]
    3. Anderson GR, et al. Changes in striatal signaling induce 
remodeling of RGS complexes containing Gbeta5 and R7BP subunits. Mol 
Cell Biol. 2009 Jun;29(11): 3033-44. [PMID 19332565]
    4. Panicker LM, et al. Nuclear localization of the G protein 
beta5/R7-regulator of G protein signaling protein complex is 
dependent on R7 binding protein. J

[[Page 45366]]

Neurochem. 2010 Jun;113(5):1101-12. [PMID 20100282]

    Intellectual Property: HHS Reference No. E-077-2011/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Jaime Greene, M.S.; 301-435-5559; 
[email protected].

    Dated: July 24, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-18651 Filed 7-30-12; 8:45 am]
BILLING CODE 4140-01-P