[Federal Register Volume 80, Number 149 (Tuesday, August 4, 2015)]
[Notices]
[Pages 46309-46311]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-19082]


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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, 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. 209 and 37 CFR part 404 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.

SUPPLEMENTARY INFORMATION: Technology descriptions follow.

Interferon Alpha Hybrids

    Description of Technology: Available for licensing are hybrid 
interferon alpha (INF-alpha) polypeptides constructed by combinations 
of INFalpha21b and INFalpha2c, and mutants of these hybrids. These 
hybrid constructs have resulted in novel IFNs that either combine 
different biological properties from the parent proteins or have 
significantly different biological activity from both the parents in 
anti-proliferative, anti-viral, or competitive binding properties. For 
instance, the hybrid designated HY-3 has higher anti-proliferative 
activity in Daudi, WISH, and primary human lymphocyte cells exhibiting 
approximately 6 times higher anti-proliferative activity than either 
parent IFN. These IFN hybrids provide a powerful tool for studying the 
structure-function relationship of these molecules. The engineered IFN-
alpha proteins may have important new therapeutic applications and may 
provide greater insights into understanding of the clinical activities 
of existing IFN-alphas.
    Also available for licensing are hybrid INF-alpha nucleic acids 
encoding the hybrid polypeptides as well as cells, vectors, 
pharmaceutical compositions with these nucleic acid sequences.

Potential Commercial Applications

 Anti-viral and cancer therapeutics
 Research tool to study IFN-alpha functions

Competitive Advantages

 Ease of manufacture
 Strong anti-viral activity

    Development Stage: In vitro data available.
    Inventors: Kathryn C. Zoon (NIAID), Joseph B. Bekisz (NIAID), Mark 
P. Hayes (FDA), Renqiu Hu (FDA).

Publications

1. Hu R, et al. Protein engineering of interferon alphas. Methods 
Mol Med. 2005;116:69-80. [PMID 16000855]
2. Hu R, et al. Human IFN-alpha protein engineering: the amino acid 
residues at positions 86 and 90 are important for antiproliferative 
activity. J Immunol. 2001 Aug 1;167(3):1482-9. [PMID 11466368]
3. Hu R, et al. Divergence of binding, signaling, and biological 
responses to recombinant human hybrid IFN. J Immunol. 1999 Jul 
15;163(2):854-60. [PMID 10395679]

    Intellectual Property: HHS Reference No. E-068-1998/0--

 US Patent No. 6,685,933 issued 03 Feb 2004
 US Patent No. 7,235,232 issued 26 Jun 2007

    Licensing Contact: Peter Soukas; 301-435-4646; [email protected].

Novel Treatment for Anemia and Polycythemia: AVPR1B Molecules 
Modulating Erythropoiesis

    Description of Technology: Anemia can be caused by chronic 
diseases, chemotherapy, or radiation. Erythropoietin is commonly used 
to stimulate red blood cell production for anemia treatment, but it 
takes about a week to manifest its clinical effect. The

[[Page 46310]]

subject invention describes the arginine vasopressin receptor 1B 
(AVPR1B) stimulatory molecules that can be used to stimulate 
hematopoietic stem cell proliferation. Preliminary results from animal 
studies suggest that the number of red blood cells and their precursors 
significantly increased on day 2 following AVP administration, an onset 
time much faster than erythropoietin. The AVPR1B stimulatory molecules 
can be used to jumpstart the system and erythropoietin can be used to 
sustain the effect. In addition, the AVPR1B inhibitory molecules can be 
used to suppress hematopoietic stem cell proliferation to treat 
polycythemia (overproduction of red blood cells).

Potential Commercial Applications

     Treatment of anemia caused by chronic diseases, 
chemotherapy, or radiation.
     Anemia patients who do not respond to erythropoietin.
     Polycythemia treatment.
    Competitive Advantages: AVPR1B stimulatory molecules act faster 
than the commonly used erythropoietin for anemia treatment.

Development Stage

 Early-stage
 In vivo data available (animal)

    Inventors: Eva Mezey and Miklos Krepuska (NIDCR); Balazs Mayer and 
Krisztian Nemeth (Semmelweis University Medical School)
    Intellectual Property: HHS Reference No. E-619-2013/0--

 US Application No. 61/885,258 filed October 01, 2013 (E-619-
2013/0-US-01)
 PCT Application No. PCT/US2014/058613 filed October 01, 2014 
(E-619-2013/0-PCT-02)

    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301-435-5605; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize treatment for anemia and 
polycythemia. For collaboration opportunities, please contact David 
Bradley, Ph.D. at [email protected].

Modified AAV5 Vectors for Enhanced Transduction and Reduced Antibody 
Neutralization

    Description of Technology: Adeno-associated viruses (AAVs) are 
small nonpathogenic viruses and can integrate into the cellular genome. 
AAV vectors are among the most frequently used viral vectors for gene 
therapy because AAV vectors can infect both dividing and non-dividing 
cells, and can establish long-term transgene expression. Two major 
issues in gene therapy are the ability to efficiently transduce the 
target cells and to evade the immune response to vectors. The subject 
invention describes a mutated AAV serotype 5 by modifying sialic acid 
binding regions which mediate viral entry into host cells. Preliminary 
results from animal studies suggest that this modification can increase 
transduction by 3-4 folds in salivary glands and muscle, and can 
significantly decrease the potential of being neutralized by 
preexisting antibodies compared to the wild type. Thus, the modified 
AAV5 vectors seem to be optimal for gene therapy.
    Potential Commercial Applications: Genetically engineered AAV5 
vectors for gene therapy.

Competitive Advantages

     Enhanced transduction activity.
     Reduced the potential for being neutralized by preexisting 
antibodies.

Development Stage

 Early-stage
 In vivo data available (animal)

    Inventors: John Chiorini and Sandra Afione-Wainer (NIDCR); Mavis 
Agbandje-Mckenna and Sujata Halder (University of Florida).

Publications

1. Afione S, et al. Identification and mutagenesis of the adeno-
associated virus 5 sialic acid binding region. J Virol. 2015 Feb; 
89(3): 1660-72. [PMID 25410855]
2. Chiorini J, et al. AAV4 Vector and the uses thereof. U.S. Patent 
6,468,524, issued on October 22, 2002.
3. Chiorini J, et al. AAV5 Vector and the uses thereof. U.S. Patent 
7,479,554, issued January 20, 2009, and U.S. Patent 6.984,517, 
issued on January 10, 2006.
4. Chiorini J, et al. AAV5 Vector for transducing brain cells and 
lung cells. U.S. Patent 6,855,314, issued on February 15, 2005.

    Intellectual Property: HHS Reference No. E-097-2015/0--US 
Application No. 62/143,524 filed April 6, 2015.

Related Technologies

     E-175-2015: US 62/160,552.
     E-736-2013: PCT/US14/59825.
     E-142-2011 family: PCT/US12/34268, CA, EP and US.
     E-087-2011 family: PCT/US12/33556, EP and US.
     E-232-2011: US 14/428,929.
     E-194-2010: US 8,808,684.
     E-179-2005: US 8,283,151.
     E-227-2004: US 7,407,801.
     E-329-2003 family: US 8,137,960, US 8,685,722.
     E-105-2003: US 8,927,269.
     E-308-2001: US 7,419,817.
     E-071-2000: US 6,468,524.
     E-127-1998 family: US 6,984,517, AU, CA, EP, and JP.
    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301-435-5606; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize modified AAV5 vector for gene 
therapy. For collaboration opportunities, please contact David Bradley, 
Ph.D. at [email protected].

A Novel Adeno-Associated Virus for Gene Therapy

    Description of Technology: Adeno-associated viruses (AAVs) are 
small nonpathogenic viruses and can integrate into the cellular genome. 
AAV vectors are among the most frequently used viral vectors for gene 
therapy because AAV vectors can infect both dividing and non-dividing 
cells, and can establish long-term transgene expression. The subject 
invention describes a novel AAV termed ``44-9.'' AAV44-9 based vectors 
have high gene transfer activity in a number of cell types, including 
salivary gland cells, liver cells, and different types of neurons 
(e.g., cells of the cortex, olfactory bulb, and brain stem, and 
Purkinje cells of the cerebellum). These vectors can deliver 
heterologous genes to particular target cells through site-specific 
administration. Preliminary results from animal studies suggest that 
AAV44-9 vectors can efficiently deliver genes of interest, and the 
protein products of the delivered genes can be detected in bloodstream 
and at the local tissues. Therefore, these vectors are suitable for 
gene therapy for cells/tissues that are not efficiently targeted by 
other vectors.
    Potential Commercial Applications: AAV44-9 can be used as a 
delivery vector in gene therapy.

Competitive Advantages

     High gene transfer activity in a number of cell types 
including salivary gland cells, liver cells, and different types of 
neurons (e.g., cells of the cortex, olfactory bulb, and brain stem, and 
Purkinje cells of the cerebellum).
     As a gene transfer vector for cells that are not 
efficiently targeted by other vector.

[[Page 46311]]

Development Stage

 In vitro data available
 In vivo data available (animal)

    Inventors: John Chiorini and Giovanni Pasquale (NIDCR).
    Publication: Schmidt M, et al. Identification and characterization 
of novel adeno-associated virus isolates in ATCC virus stocks. J Virol. 
2006 May; 80 (10): 5082-5098. [PMID 16641301]
    Intellectual Property: HHS Reference No. E-175-2015/0--US 
Application No. 62/160,552 filed May 12, 2015.

Related Technologies

     E-097-2015: US 62/143,524.
     E-736-2013: PCT/US14/59825.
     E-142-2011 family: PCT/US12/34268, CA, EP and US.
     E-087-2011 family: PCT/US12/33556, EP and US.
     E-232-2011: US 14/428,929.
     E-194-2010: US 8,808,684.
     E-179-2005: US 8,283,151.
     E-227-2004: US 7,407,801.
     E-329-2003 family: US 8,137,960, US 8,685,722.
     E-105-2003: US 8,927,269.
     E-308-2001: US 7,419,817.
     E-071-2000: US 6,468,524.
     E-127-1998 family: US 6,984,517, AU, CA, EP, and JP.
    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301-435-5606; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize AAV44-9 vector for gene therapy. For 
collaboration opportunities, please contact David Bradley, Ph.D. at 
[email protected].

WNT1-Induced Secreted Protein-1 Knockout Mouse Model

    Description of Technology: WNT1-induced secreted protein-1 (WISP1) 
is expressed at high levels in osteoblasts and their precursors. WIPS1 
plays an important role in various aspects of bone formation. 
Scientists at the NIH generated Wisp1-deficient (Wisp1-/-) mice. 
Deletion of Wisp1 resulted in a decrease in bone mineral density, total 
bone volume, bone thickness, and biomechanical strength. Wisp1 knockout 
mouse model can be used to study the molecular mechanisms of bone 
turnover and patho/physiology of tissues that express WISP1.

Potential Commercial Applications

     To study the molecular mechanisms of bone formation and 
osteodifferentiation.
     To study the patho/physiology of tissues that express 
WISP1, including cartilage during osteoarthritis, healing skin, and 
other soft tissues including lung, pancreas, and heart.
    Development Stage: In vivo data available (animal).
    Inventors: Marian F. Young, Mitsuaki Ono, Azusa Maeda (all of 
NIDCR).
    Publication: Maeda A, et al. WNT1-induced secreted protein-1 
(WISP1), a novel regulator of bone turnover and Wnt signaling. J Bio 
Chem. 2015 May 29;290(22):14004-18. [PMID 25864198]
    Intellectual Property: HHS Reference No. E-234-2015/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Sally Hu, Ph.D., M.B.A.; 301-435-5606; 
[email protected]
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize WNT1-Induced Secreted Protein-1 
Knockout Mouse Model. For collaboration opportunities, please contact 
David Bradley, Ph.D. at [email protected].

    Dated: July 30, 2015.
Richard U. Rodriguez,
Acting Director, Office of Technology Transfer, National Institutes of 
Health.
[FR Doc. 2015-19082 Filed 8-3-15; 8:45 am]
BILLING CODE 4140-01-P