[Federal Register Volume 76, Number 147 (Monday, August 1, 2011)]
[Notices]
[Pages 45839-45841]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-19377]


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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.

ADDRESSES: 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.

Methods and Software for the Quantitative Assessment of Vasculature in 
Allantois and Retina Explants

    Description of Technology: The invention relates to methods and 
software that can facilitate and improve quantification, accuracy and 
standardization in the assessment of vasculature in angiogenesis assays 
such as in the allantois explants and the retina explants assays. The 
software of this invention can aid in the analysis of images resulting 
from these assays and thus enhance the accuracy and effectiveness of 
research in the area of angiogenesis. This in turn will lead to 
enhanced progress in the development of medical methods and drugs to 
treat diseases related to angiogenesis such as cancer, macular 
degeneration, and some pregnancy disorders.
    Applications: The software can be integrated with a variety of 
imaging systems used in conjunction with angiogenesis assays to enhance 
the assessment and the quality of research in the area of angiogenesis.
    Advantages:
     The method and software of the invention will make 
analysis of angiogenesis assays more accurate, better standardized, and 
less

[[Page 45840]]

cumbersome than existing analysis systems.
     This method and software will eliminate the user-dependent 
bias which is characteristic of existing methods.
     This method and software will generally improve the 
quality of analysis of angiogenesis assays.
     The software is suitable for integration in a variety of 
existing imaging systems and software as well as readily usable as an 
independent complementary technology in the research and biomedical 
fields.
    Development Status: The software is fully developed.
    Inventor: Enrique Zudaire (NCI).
    Relevant Publications:
    1. Pitulescu ME, Schmidt I, Benedito R, Adams RH. Inducible gene 
targeting in the neonatal vasculature and analysis of retinal 
angiogenesis in mice. Nat Protoc. 2010 Sep;5(9):1518-1534. [PMID: 
20725067].
    2. Gambardella L, et al. PI3K signaling through the dual GTPase-
activating protein ARAP3 is essential for developmental angiogenesis. 
Sci Signal 2010 Oct 26;3(145):ra76. [PMID: 20978237].
    3. Zudaire E, Gambardella L, Kurcz C, Vermeren S. A computational 
tool for quantitative analysis of vascular networks. PLoS One 
(Submitted).
    Patent Status: HHS Reference No. E-176-2011/0--Software/Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Status: The software is available for licensing.
    Licensing Contacts:
     Uri Reichman, Ph.D., MBA; 301-435-4616; [email protected].
     Michael Shmilovich, Esq.; 301-435-5019; 
[email protected].

Pyruvate as a Transient Hypoxia Inducer for Anti-cancer Therapies

    Description of Technology: Human solid tumors, such as breast 
cancer, lung cancer, ovarian cancer, pancreatic cancer and prostate 
cancer, etc. frequently have substantial volumes with low oxygen 
concentration, i.e. hypoxic. These hypoxic tumors show resistance to 
radiation and chemotherapies. To overcome such resistance, novel 
classes of agents have been designed and developed that are 
specifically active or activated under hypoxic conditions, in hypoxic 
tumors. The instant invention describes a novel idea to improve anti-
cancer effect of hypoxia-sensitive therapeutics by using a rapidly 
oxidized reducing agent such as pyruvate or succinate. In the instant 
invention, the NIH investigators found that pyruvate, an endogenous 
substrate for energy production by mitochondria, induced severe hypoxia 
in tumors within 30 minutes of intravenous injection, and the tumor 
oxygen level reversibly returned to basal level within a few hours. 
Since pyruvate seems to induce only transient hypoxia, and its safety 
profiles are known, it may have significant advantages over other 
hypoxia inducers reported to date for improving the efficacy of 
hypoxia-sensitive anti-cancer therapies.
    Applications:
     Provide a novel way to target various cancers, especially 
solid tumors for treatment;
     Improve the efficacy of using hypoxic toxins for cancer 
treatment;
     In vivo screening of oxygen-status dependent drugs.
    Market: Cancer is the second leading cause of death in the U.S. The 
National Cancer Institute estimates the overall annual costs for cancer 
in the U.S. at $107 billion; $37 billion for direct medical costs, $11 
billion for morbidity costs (cost of lost productivity), and $59 
billion for mortality costs. There is an ongoing need for innovative 
approaches to anticancer therapy.
    Development Status: Pre-clinical stage of development.
    Inventors: Drs. Shingo Matsumoto (NCI), James B. Mitchell (NCI), 
and Robert J. Gillies (H. Lee Moffitt Cancer Center and Research 
Institute) et al.
    Publication: Poster presentation in the International Society for 
Magnetic Resonance in Medicine (ISMRM) meeting in May 2011. Manuscript 
is in press.
    Patent Status: U.S. Provisional Application No. 61/478,465 filed 
April 22, 2011 (HHS Reference No. E-144-2011/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Betty B. Tong, PhD; 301-594-6565; 
[email protected].

Multivalent Vaccines for Rabies Virus and Filoviruses

    Description of Technology: No vaccine candidates against Ebola 
virus (EBOV) or Marburg virus (MARV) are nearing licensure and the need 
to develop a safe and efficacious vaccine against filoviruses 
continues. Whereas several preclinical vaccine candidates against EBOV 
or MARV exist, their further development is a major challenge based on 
safety concerns, pre-existing vector immunity, and issues such as 
manufacturing, dosage, and marketability. The inventors have developed 
a new platform based on live or chemically inactivated (killed) rabies 
virus (RABV) virions containing EBOV glycoprotein (GP) in their 
envelope. In preclinical trials, immunization with such recombinant 
RABV virions provided excellent protection in mice against lethal 
challenge with the mouse adapted EBOV and RABV. More specifically, the 
inventors have developed a trivalent filovirus vaccine based on killed 
rabies virus virions for use in humans to confer protection from all 
medically relevant filoviruses and RABV. Two additional vectors 
containing EBOV Sudan GP or MARV GP are planned to be constructed in 
addition to the previously developed EBOV Zaire GP containing vaccine. 
The efficiency of these vaccines against challenge with EBOV, MARV and 
RABV will be studied in multiple preclinical studies. Live attenuated 
vaccines are being developed for use in at risk nonhuman primate 
populations in Africa and inactivated vaccines are being developed for 
use in humans.
    Potential Commercial Applications:
     Biodefense vaccine.
     Developing country vaccine.
     Multivalent prophylactic Ebola/Marburg/rabies vaccine.
    Competitive Advantages:
     Vaccines are replication deficient and/or inactivated.
     Protection against rabies and Ebola.
     Reliable and cost-effective manufacture.
     No preexisting immunity to vectors.
     No potential vaccine reactogenicity.
    Development Stage:
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Joseph Blaney, Jason Paragas, Peter Jahrling, Reed 
Johnson (NIAID).
    Intellectual Property: HHS Reference No. E-032-2011/0 -- U.S. 
Patent Application No. 61/439,046 filed 03 Feb 2011.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].

Layered Electrophoretic Transfer for Analysis of Low or Medium Abundant 
Proteins in Tissue Samples

    Description of Technology: The subject invention is a method to 
selectively process the protein content from a two dimensional sample, 
such as a tissue section, for more detailed analysis. It is 
particularly useful for analysis of a subset of proteins from a complex 
protein mixture. The method employs a layer of polyacrylamide gels and 
an electric field. Proteins from the sample are transferred and sieved 
through a stack of polyacrylamide gels of varying concentrations. Thus, 
it is possible to analyze specific subsets of

[[Page 45841]]

proteins in the different gel layers and maintain the two dimensional 
location of the proteins within the original sample. One of the 
advantages of this technology is that it allows for isolation and 
subsequent analysis of low abundant or medium abundant proteins by a 
number of different methodologies such as imaging mass spectrometry.
    Applications:
     Protein Analysis of Tissue Samples.
     Histology and Pathology.
    Advantages:
     Isolation of low or moderately-abundant proteins in tissue 
sections.
     Method maintains 2-dimensional location of proteins in 
tissue samples.
    Development Status: In vitro data can be provided upon request.
    Market:
     Diagnostic.
     Pathology.
     Basic Research.
    Inventors: Michael Emmert-Buck, Liang Zhu, and Michael Tangrea 
(NCI).
    Publication: Zhu L, Tangrea MA, Mukherjee S, Emmert-Buck MR. 
Layered electrophoretic transfer--A method for pre-analytic processing 
of histological sections. Proteomics. 2011 Mar;11(5):883-889. [PMID: 
21280224].
    Patent Status: U.S. Provisional Application No. 61/420,258 filed 
December 6, 2010 (HHS Reference No. E-020-2011/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Kevin W. Chang, PhD; 301-435-5018; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Pathology, Pathogenetics Unit, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize layered 
electrophoretic transfer (LET). Please contact John Hewes, PhD at 301-
435-3121 or [email protected] for more information.

Pertussis Vaccine

    Description of Technology: Despite mass vaccination, reported 
pertussis cases have increased in the United States and other parts of 
the world, probably because of increased awareness, improved diagnostic 
means, and waning vaccine-induced immunity among adolescents and 
adults. Licensed vaccines do not kill the organism directly; the 
addition of a component inducing bactericidal antibodies would improve 
vaccine efficacy. This application claims Bordetella pertussis and 
Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein 
conjugates. B. pertussis and B. bronchiseptica core OS were bound to 
aminooxylated BSA via their terminal Kdo residues. The two conjugates 
induced similar anti-B. pertussis LPS IgG levels in mice. Conjugate-
induced antisera were bactericidal against B. pertussis.
    Potential Commercial Applications:
     Pertussis prophylactic conjugate vaccine.
     Use of vaccine to generate neutralizing antibodies.
    Competitive Advantages: Conjugates are easy to prepare and 
standardize; added to a recombinant pertussis toxoid, they may induce 
antibacterial and antitoxin immunity.
    Development Stage:
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Joanna Kubler-Kielb (NICHD), Rachel Schneerson (NICHD), 
John B. Robbins (NICHD), Ariel Ginzberg (NICHD), Teresa Lagergard 
(NICHD), et al.
    Publication: Kubler-Kielb J, Vinogradov E, Lagerg[aring]rd T, 
Ginzberg A, King JD, Preston A, Maskell DJ, Pozsgay V, Keith JM, 
Robbins JB, Schneerson R. Oligosaccharide conjugates of Bordetella 
pertussis and bronchiseptica induce bactericidal antibodies, an 
addition to pertussis vaccine. Proc Natl Acad Sci U S A. 2011 Mar 
8;108(10):4087-4092. [PMID: 21367691].
    Intellectual Property: HHS Reference No. E-006-2011/0--U.S. 
Application No. 61/438,190 filed 31 Jan 2011.
    Related Technology: HHS Reference No. E-183-2005/0 --U.S. 
Application No. 12/309,428 filed 16 Jan 2009.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].
    Collaborative Research Opportunity: The NICHD is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize vaccines 
against pertussis. For collaboration opportunities, please contact 
Joseph Conrad, III, PhD at [email protected].

Novel Methods for the Reversible Incorporation of Functional Groups 
Into RNA and DNA: Synthesis and Uses for 2'-O-aminooxymethyl Nucleoside 
Derivatives

    Description of Technology: The delivery of DNA/RNA therapeutic 
drugs is still a major hurdle for the clinical application of DNA/RNA-
based drugs. Also, developments in silencing the expression of specific 
genes, through RNA interference pathways, have led to an increased 
demand for synthetic RNA sequences and have created a pressing need for 
rapid and efficient methods for RNA synthesis. Recently, FDA scientists 
have developed a novel phosphoramidite, 2'-O-aminooxymethyl 
ribonucleoside (2'-O-protected compounds). The 2'-O-aminooxymethyl 
ribonucleoside can be modified with any type of functional group using 
an oximation reaction as long as the functional group contains an 
aldehyde, ketone, or acetal group. Modification of the 2'-O-
aminooxymethyl with an aldehyde results in a conjugated 2'-
phosphoramidite that could be readily converted back to the native 
ribonucleoside and its corresponding by-product. On the other hand, the 
oximation of 2'-O-aminooxymethy with a ketone results in an 
irreversible conjugated form of the phosphoramidite.
    The 2'-O-protected compounds of the present technology have several 
advantages, for example, the 2'-O-protected compound is stable during 
the various reaction steps involved in oligonucleotide synthesis; and 
the protecting group can be easily removed after the synthesis of the 
oligonucleotide, for example, by reaction with tetrabutylammonium 
fluoride; and the O-protected groups do not generate DNA/RNA alkylating 
side products, which have been reported during removal of 2'-O-(2-
cyanoethyl)oxymethyl or 2'-O-[2-(4-tolylsulfonyl)ethoxymethyl groups 
under similar conditions.
    Applications:
     Incorporation of a potentially large array of functional 
groups into RNA and DNA oligonucleotides for diagnostic and/or 
therapeutic applications.
     Conjugation of a variety of sugars or complex 
carbohydrates to DNA/RNA therapeutic oligonucleotides.
     Attachment of cell membrane-penetrating peptides to 
therapeutic DNA/RNA oligonucleotides.
    Inventors: Serge L. Beaucage and Jacek Cieslak (FDA).
    Patent Status: U.S. Provisional Application No. 61/471,451 filed 04 
April 2011 (HHS Reference No. E-262-2010/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Suryanarayana Vepa, PhD, J.D.; 301-435-5020; 
[email protected].

    Dated: July 26, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-19377 Filed 7-29-11; 8:45 am]
BILLING CODE 4140-01-P