[Federal Register Volume 77, Number 94 (Tuesday, May 15, 2012)]
[Notices]
[Pages 28608-28610]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-11691]


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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.

Therapeutic RNA Switches and Auto-Recognizing Therapeutic R/DNA 
Chimeric Nanoparticles (NP) for HIV Treatment

    Description of Technology: RNA interference (RNAi) as a therapeutic 
agent is routinely used to knock down the expression of target genes in 
diseased cells. Using siRNAs it is possible to knock down target mRNA 
expression. It is possible, for example, to induce cell death through 
co-RNAi by simultaneously targeting several human anti-apoptotic genes 
with different siRNAs. NIH inventors computationally and experimentally 
developed a new technology that utilizes two (or more) cognate RNA/DNA 
NPs that, when recombined within the cell, trigger the RNAi pathway as 
well as other functionalities that exist inside diseased cells. This 
new methodology therefore opens a new route in the development of auto-
recognizing ``smart'' nucleic acids based nanoparticles for a wide 
range of applications in biomedical RNA nanotechnology. This new 
approach may overcome several issues commonly associated with the 
clinical delivery of siRNA, such as intravascular degradation, the 
potential for immune-mediated toxicities, tissue specificity and 
pharmacodynamics.
    Potential Commercial Applications:
     Therapeutics that control gene expression (e.g., anti-
apoptotic genes).
     Combinations with other therapeutics to treat cancer, RNA 
viruses (e.g., HIV) and other RNA related diseases.
     Triggered release of siRNAs within cells.
     Research on targeting cells.
     Labeling of targeted cells.
     Research on cancer cells harboring cancer and other RNA 
related diseases in patients.
     Research on treatment of RNA related viruses.
    Competitive Advantages:
     Size overcomes problems with traditional siRNA 
pharmacokinetics.
     Chemical stability improves half-life.
     Incorporation of multiple functionalities split and 
otherwise.
     Multi-stage delivery controls activation.
    Development Stage:
     Prototype.
     In vitro data available.
    Inventors: Bruce A. Shapiro (NCI), Eckart HU Bindewald (NCI), 
Kirill A. Afonin (NCI), Arti Santhanam (NCI), Mathias Viard (SAIC), Luc 
Jaeger (UCSB).
    Intellectual Property: HHS Reference No. E-038-2012/0--Research 
Material.

[[Page 28609]]

Patent protection is not being pursued for this technology.
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].
    Collaborative Research Opportunity: The NCI Center for Cancer 
Research Nanobiology Program is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize this technology to advance antiviral 
therapy concepts. For collaboration opportunities, please contact John 
Hewes, Ph.D. at [email protected].

Multilayer X-Ray Transmission Grating Array for Phase-Contrast Imaging 
and Tomography

    Description of Technology: Classical X-ray Computed Tomography (CT) 
and radiography are based on X-ray absorption and cannot show soft 
tissue structures as well as Magnetic Resonance Imaging (MRI). 
Detecting the phase delay/advance of X-rays that travel through the 
body could enhance soft tissue contrast 10-100 times. Submicron-period 
X-ray transmission gratings for medical x-ray energies can 
substantially enhance the phase detection sensitivity, but fabrication 
is a great challenge. This invention includes a method to fabricate 
multilayer transmission gratings of large areas. The design uses 
multilayer deposition of alternating materials on a staircase substrate 
to form micro grating arrays of extremely small periods and high aspect 
ratio in large areas. This invention should substantially improve the 
visibility of soft tissue structures and reduce radiation dose to 
patients.
    Potential Commercial Applications:
     X-ray diagnostic imaging.
     X-ray non-destructive materials testing.
     X-ray security screening.
     X-ray lithography of nanostructures.
     Also applies to neutron beam or proton beam imaging.
    Competitive Advantages:
     Gratings of ultra-high aspect ratio and small period allow 
phase-contrast imaging at high x-ray energies which are suitable for 
human body CT, and provide better soft tissue contrast in radiography 
and CT.
     Reduces radiation exposure to patient.
     Large area gratings enable full field imaging without 
raster or line scanning.
    Development Stage:
     Pre-clinical.
     Early-stage.
    Inventor: Han Wen (NHLBI).
    Publication: Lynch SK, et al. Multilayer-coated micro-grating array 
for x-ray phase-contrast imaging. Proc. SPIE 8076, 80760F (2011); 
http://dx.doi.org/10.1117/12.888939.
    Intellectual Property: HHS Reference No. E-207-2011/0--U.S. 
Provisional Application No. 61/578,719 filed 21 Dec 2011.
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].
    Collaborative Research Opportunity: The Imaging Physics Lab, 
Biophysics and Biochemistry Center, NHLBI/NIH, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize multilayer-
coated gratings for phase-contrast CT. For collaboration opportunities, 
please contact Dr. Han Wen at [email protected].

Human DNA Polymerase Gamma for Testing the Effect of Drugs on 
Mitochondrial Function

    Description of Technology: One of the primary means for treating 
HIV infection is the use of antiviral nucleotide or nucleoside analogs. 
These analogs work by inhibiting the activity of reverse transcriptase, 
the enzyme responsible for preparing the HIV genome for integration 
into the DNA of the host cell. Although these analogs do not have an 
effect on the polymerases responsible for replicating the human genome, 
the polymerase responsible for replicating the mitochondrial genome is 
sensitive to these analogs. When patients are exposed to nucleotide or 
nucleoside analogs through long-term treatment regimens, the 
replication of the mitochondrial genome can be adversely affected. 
Since mitochondrial functionality is necessary for cell activity, the 
nucleotide and nucleoside analogs can cause serious and unwanted side-
effects.
    This invention concerns the cloning and purification of human DNA 
polymerase gamma, the polymerase responsible for replicating the 
mitochondrial genome. The enzymes that have been purified include the 
wild-type version, a version which lacks exonuclease (proofreading) 
activity, and several versions with modified activity due to the 
mutation of the enzyme. These purified enzymes can be used to directly 
test the effects of new drugs that affect the activity of polymerases, 
such as nucleotide and nucleoside analogs.
    Potential Commercial Applications:
     Research reagent to screen the effects of antiviral drugs 
(nucleotide and nucleoside analogs) on mitochondrial function.
     Research reagent to test the mitochondrial toxicity of 
other drugs that can affect polymerase activity.
    Competitive Advantages:
     Purified polymerase allows for direct analysis of the 
effect of nucleotide analogs on DNA polymerase gamma.
     Different formats of the enzyme such as the exonuclease-
deficient version, allows comprehensive testing of drug candidates.
    Development Stage: In vitro data available.
    Inventors: William Copeland et al. (NIEHS).
    Publication: Longley MJ, et al. Characterization of the native and 
recombinant catalytic subunit of human DNA polymerase gamma: 
identification of residues critical for exonuclease activity and 
dideoxynucleotide sensitivity. Biochemistry. 1998 Jul 21;37(29):10529-
39. [PMID 9671525]
    Intellectual Property: HHS Reference Nos. E-191-2011/0, B-035-1998/
0, and B-035-1998/1--Research Materials. Patent protection is not being 
pursued for these technologies.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The NIEHS is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize the antibodies. 
For collaboration opportunities, please contact Elizabeth Denholm at 
[email protected].

Biomarker To Predict High-Risk Clinical Outcomes for Colon, Lung, and 
Ovarian Cancers

    Description of Technology: It has long been known that general 
genomic instability is associated with cancer. NIH scientists Drs. 
Habermann and Reid at the National Cancer Institute, along with West 
Virginia University scientists Drs. Mettu and Guo, have recently 
identified specific genes whose instability is strongly associated with 
poor outcomes for colon, small-cell lung, and ovarian cancers. Using 
this 12-gene genomic instability signature as a biomarker could be a 
diagnostic tool for identifying high-risk patients that would benefit 
from more aggressive forms of treatment.
    Potential Commercial Applications: Diagnostic tool for identifying 
patients at high-risk for developing colon, small-cell lung, and 
ovarian cancers that are recurring and/or aggressive.
    Competitive Advantages:
     Allows more accurate prognoses by separating high-risk 
from low-risk cancer patient populations.

[[Page 28610]]

     Allows doctors to choose more individualized therapies for 
patients based on whether the cancer is at high or low risk for 
aggressiveness or recurrence.
    Development Stage: Clinical.
    Inventors: Thomas K. Ried (NCI) et al.
    Intellectual Property: HHS Reference No. E-119-2011/0--PCT 
Application No. PCT/US2011/061871 filed 22 Nov 2011.
    Licensing Contact: Surekha Vathyam, Ph.D.; 301-435-4076; 
[email protected].

Isolation of Hybridomas Producing Monoclonal Antibodies (MAbs) 
Inhibitory to Human CYP2J2

    Description of Technology: The National Institutes of Health 
announces three specific monoclonal antibodies that strongly inhibit 
and/or immunoblot the human cytochrome P450 2J2 (CYP2J2).
    Cytochrome P450s catalyze the NADPH-dependent oxidation of 
arachidonic acid to various eicosanoids found in several species. The 
eicosanoids are biosynthesized in numerous tissues including pancreas, 
intestine, kidney, heart and lung where they are involved in many 
different biological activities.
    MAb 6-5-20-8 selectively inhibits CYP2J2-mediated arachidonic acid 
metabolism by more than 80% and also immunoblots the enzyme. MAb 6-2-
16-1 also selectively inhibits arachidonic acid metabolism by more than 
80% but does not immunoblot the enzyme. MAb 5-3-2-2 is not inhibitory 
but selectively immunoblots the enzyme. These antibodies can be used to 
identify and quantify inter-individual variation in physiological 
functions and to study pharmacological drug metabolism in various 
tissues.
    Potential Commercial Applications:
     These antibodies can be used to identify and quantify 
inter-individual variation in physiological functions.
     These antibodies can be used to study pharmacological drug 
metabolism in various tissues.
    Competitive Advantages: These antibodies strongly inhibit and/or 
immunoblot the human cytochrome P450 2J2 (CYP2J2).
    Development Stage: In vitro data available.
    Inventors: Darryl C. Zeldin (NIEHS) et al.
    Publications:
    1. Wu S, et al. Molecular cloning and expression of CYP2J2, a human 
cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. 
J Biol Chem. 1996 Feb 16;271(7):3460-8. [PMID 8631948]
    2. Node K, et al. Anti-inflammatory properties of cytochrome P450 
epoxygenase-derived eicosanoids. Science 1999 Aug 20;285(5431):1276-9. 
[PMID 10455056]
    3. Node K, et al. Activation of Galpha s mediates induction of 
tissue-type plasminogen activator gene transcription by 
epoxyeicosatrienoic acids. J Biol Chem. 2001 May 11;276(19):15983-9. 
[PMID 11279071]
    4. Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. 
J Biol Chem. 2001 Sep 28;276(39):36059-62. [PMID 11451964]
    5. Yang B, et al. Overexpression of cytochrome P450 CYP2J2 protects 
against hypoxia-reoxygenation injury in cultured bovine aortic 
endothelial cells. Mol Pharmacol. 2001 Aug;60(2):310-20. [PMID 
11455018]
    6. King LM, et al. Cloning of CYP2J2 gene and identification of 
functional polymorphisms. Mol Pharmacol. 2002 Apr;61(4):840-52. [PMID 
11901223]
    7. Sun J, et al. Inhibition of vascular smooth muscle cell 
migration by cytochrome p450 epoxygenase-derived eicosanoids. Circ Res. 
2002 May 17;90(9):1020-7. [PMID 12016269]
    Intellectual Property: HHS Reference No. E-337-2003/0--Research 
Material. Patent protection has not been pursued for this technology.
    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
[email protected]
    Collaborative Research Opportunity: The NIEHS is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize this antibody. 
For collaboration opportunities, please contact Elizabeth Denholm at 
[email protected].

    Dated: May 9, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-11691 Filed 5-14-12; 8:45 am]
BILLING CODE 4140-01-P