[Federal Register Volume 78, Number 11 (Wednesday, January 16, 2013)]
[Notices]
[Pages 3437-3440]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-00738]


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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.

Optical Microscope Software for Breast Cancer Diagnosis

    Description of Technology: The instant invention discloses a 
software to analyze optical microscopic images of human breast tissue 
sections for diagnosing cancer by using the differences in spatial 
positioning of certain genes. The software uses the inherent hierarchy 
in the data and stores all the analysis and manual interaction 
information in a highly structured XML file. It is a user-friendly 
software to discriminate normal and cancerous human breast tissue 
section images that can be used for large experiments. Additionally the 
software uses a cluster of computers in the background to reduce the 
analysis time for large image datasets. Furthermore, the software of 
instant invention provides a set of tools for performing diagnostic or 
prognostic assays on new unseen datasets.
    Potential Commercial Applications:
     The software could be an essential part of an integrated 
diagnostic or prognostic assay for breast cancer detection.
     The software could be a key tool for biomedical research 
to test new markers and their applicability for diagnostic purposes.
     The use of the software could provide important 
information for understanding the underlying causes of gene 
repositioning.
    Competitive Advantages:
     The software of instant invention can be used to analyze 
relatively large datasets.
     To reduce the processing time by at least 10 fold.
     The software can be used in a broad range of quantitative 
image analysis applications.
    Development Stage:
     Prototype
     Clinical
     In vitro data available (human)
    Inventors: Kaustav Nandy (SAIC-Frederick, Inc), Stephen J. Lockett 
(SAIC-Frederick, Inc), Prabhakar R. Gudla (SAIC-Frederick, Inc), 
William Cukierski (NCI), Renee Qian (NCI), Karen J. Meaburn (NCI), Tom 
Misteli (NCI).
    Publications:
    1. Gudla PR, et al. A high-throughput system for segmenting nuclei 
using multiscale techniques. Cytometry A. 2008 May;73(5):451-66. [PMID 
18338778]
    2. Nandy K, et al. Automatic nuclei segmentation and spatial FISH 
analysis for cancer detection. Conf Proc IEEE Eng Med Biol Soc. 
2009;2009:6718-21. [PMID 19963931].
    3. Meaburn KJ, et al. Disease-specific gene repositioning in breast 
cancer. J Cell Biol. 2009 Dec 14;187(6):801-12. [PMID 19995938].
    4. Cukierski WJ, et al. Ranked retrieval of segmented nuclei for 
objective assessment of cancer gene repositioning. BMC Bioinformatics. 
2012 Sep 12;13:232. [PMID: 22971117].
    5. Nandy K, et al. Supervised learning framework for screening 
nuclei in tissue

[[Page 3438]]

sections. Conf Proc IEEE Eng Med Biol Soc. 2011;2011:5989-92. [PMID 
22255704]
    Intellectual Property: HHS Reference No. E-286-2012/0--Software. 
Patent protection is not being pursued for this technology.
    Licensing Contact: Susan Ano, Ph.D.; 301-435-5515; 
anos@mail.nih.gov.
    Collaborative Research Opportunity: The SAIC-Frederick Optical 
Microscopy and Analysis Laboratory 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 
hewesj@mail.nih.gov.

Simple Direct Zirconium-89 Cell PET Label, \89\Zr-Labeled Cells, and 
Methods for Real-Time In Vivo Pet Imaging

    Description of Technology: The capability to image cells and 
cellular processes in real time over a scale of days could dramatically 
improve research insights and the effectiveness of cell-based 
therapies. Zirconium-89 (\89\Zr) has a half-life of over three days 
(78.4 hours) over 44 times longer compared to Fluorine (\18\F) the most 
commonly used PET isotope (half-life of 1 hour and 50 minutes). \89\Zr 
is also advantageous compared to other long half-life isotopes because 
it is not limited by high background activity and cell toxicity. 
Labeling cells with \89\Zr, is currently accomplished by indirect 
methods using secondary cell-type specific reagents such as antibodies. 
This technology is a PET imaging complex of \89\Zr and polycation that 
is internalized by the cells. This complex has been able to directly 
label a wide range of cells, without the use of secondary reagents. 
\89\Zr-labeled cells of lymphocytic lineage, including T cells, natural 
killer T-cells, macrophages, dendritic cells, and stem cells, have been 
produced and imaged in vivo with minimal damage to the cells. This PET 
imaging agent can be readily combined with an MR imaging agent for 
combined PET/MR imaging of cells. The imaging capabilities enabled by 
this technology may significantly improve cell therapies, cell level 
diagnostics and aid research for non-cell based therapies.
    Potential Commercial Applications:
     Imaging
     Diagnostic
     Cell therapies
     Transplantation and transfusion
    Competitive Advantages:
     Direct labeled cells (versus indirect techniques)
     Longer half-life
     Not limited by high background activity and cell toxicity
    Development Stage:
     Early-stage
     Pre-clinical
     In vivo data available (animal)
    Inventors: Omer Aras (CC), Peter Choyke (NCI), Joseph Frank (CC), 
Noriko Sato (CC), Jeremy Pantin (NHLBI).
    Intellectual Property: HHS Reference No. E-056-2012/0--US 
Provisional Application No. 61/611964 filed 16 Mar 2012.
    Licensing Contact: Tedd Fenn; 301-435-5031; Tedd.Fenn@nih.gov
    Collaborative Research Opportunity: The NCI 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 
hewesj@mail.nih.gov.

Small, Stable, Functional, Soluble, Monomeric IgG1 Fc Molecules 
Engineered Therapies

    Description of Technology: This technology relates to small (~27 
kDa) antibody fragments that are potentially useful for therapeutic 
development. These are monomeric IgG fragment crystalizable (mFc) 
compositions; they are long half-lived, functional (pH dependent 
binders of neonatal Fc receptor--FcRn); and they are soluble and 
express efficiently in E. coli. These molecules may serve as a platform 
for development of engineered mFc-based antibodies and fusion proteins 
with therapeutic applications. Efforts to engineer antibody-based 
therapeutics, to date, have encountered technical limitations due to 
the relatively large fragment size and short fragment half-life. The 
IgG fragment crystalizable (Fc) is a dimer of two constant domains 
(CH2-CH3 chains). Fc has a long half-life, which makes it promising as 
a candidate for engineering antibody therapeutics. Fusion proteins 
based on Fc dimer molecules demonstrate extended half-life, due to the 
ability to bind FcRn at acidic pH. However, the relatively large size 
of the Fc domains (~50 kD) is not optimal. This technology uses smaller 
(~27 kDa) mFc compositions that retain efficient binding to human FcRn 
and demonstrate long half-life. These mFc compositions are promising 
for the development of novel therapeutics because the smaller size may 
allow for superior access to targets and tissues compared to full sized 
mAbs and larger fragment-based therapeutics, while also retaining 
important function characteristics.
    Potential Commercial Applications: Therapeutics--human and 
veterinary, engineered antibody and fusion proteins.
    Competitive Advantages: Smaller size results better tissue 
penetration, reduced steric hindrance, increased therapeutic efficiency 
and lower cost.
    Development Stage:
     Early-stage
     Pre-clinical
    Inventors: Dimiter S. Dimitrov and Tianlei Ying (NCI).
    Publication: Ying T, et al. Soluble monomeric IgG1 Fc. J Biol Chem. 
2012 Jun 1; 287(23):19399-408. [PMID 22518843].
    Intellectual Property: HHS Reference No. E-019-2012/0--U.S. Patent 
Application No. 61/612,138 filed 16 Mar 2012.
    Related Technologies: HHS Reference No. E-003-2007/0--
     U.S. Patent Application No. 61/063,245 filed 31 Jan 2008
     PCT Application No. PCT/US2009/0326 and related 
international applications filed on 30 Jan 2009 in Australia, Canada, 
China, Europe, Japan, and India
     U.S. Patent Application No. 12/864,758 filed 27 Jul 2010
    Licensing Contact: Tedd Fenn; 301-435-5031; Tedd.Fenn@nih.gov
    Collaborative Research Opportunity: The NCI/CCR/NP is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
Small, Stable, Functional, Soluble, Monomeric IgG1 Fc Molecules 
Engineered Therapies. For collaboration opportunities, please contact 
John Hewes, Ph.D., at hewesj@mail.nih.gov">#hewesj@mail.nih.gov.

Virus-Like Particles Mediated Protein and RNA Delivery

    Description of Technology: The invention is directed to novel 
virus-like particles (VLPs) that are capable of binding to and 
replicating within a target mammalian cell, including human cells. The 
claimed VLPs are safer than viral delivery because they are incapable 
of re-infecting target cells. The present VLPs can optionally comprise 
inhibitory recombinant polynucleotides, such as microRNA, antisense RNA 
or small hairpin RNA, to down regulate or turn off expression of a 
particular gene within the target cell. Alternatively, recombinant 
polynucleotides packaged within VLPs can comprise a gene encoding a 
therapeutic protein so as to enable expression of that protein within 
the

[[Page 3439]]

target cell. Specifically, VLPs of the invention are composed of an 
alphavirus replicon that contains a recombinant polynucleotide, a 
retroviral gag protein, and a fusogenic envelope glycoprotein.
    While the claimed VLPs have a variety of applications, therapeutic 
uses of the VLPs include directing antibody synthesis and converting 
cancer cells into antigen presenting cells. Additional applications 
include using VLPs to induce fast (approx. 3-4 hrs) and high levels of 
protein production in mammalian cells.
    Potential Commercial Applications:
     Delivery of microRNA and small hairpin RNA to reduce 
express of targeted genes in a human cell
     Delivery of coding RNA for robust expression in mammalian 
systems
     Direct antibody production by in vivo injection of 
replicons (no antigen purification)
     Therapeutic applications
    Competitive Advantages:
     High level (~million copies per cell) of RNA production/
synthesis within target cell
     Fast expression (approx. 3-4 hrs compared to 1-2 days) 
following VLP introduction into target cells
     Obviates need to use expensive antigen purification for 
proteins or antigens produced inside target cells
    Development Stage:
     Pilot
     Pre-clinical
     In vitro data available
     In vivo data available (animal)
    Inventors: Stanislaw J. Kaczmarczyk and Deb K. Chatterjee (NCI).
    Intellectual Property: HHS Reference No. E-264-2011/0--US 
Application No. 61/615,687 filed 26 Mar 2012.
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; lauren.nguyen-antczak@nih.gov.
    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 
Novel Delivery of Packaged RNA to Mammalian Cells. For collaboration 
opportunities, please contact Kevin Brand at brandk@mail.nih.gov.

A Combinatorial Cloning Platform for Construction of Expression Vectors 
for Protein Production

    Description of Technology: The Combinatorial Cloning Platform (CCP) 
of this invention is a collection of vectors for use with the Gateway 
Multisite Recombination System (Life Technologies). The CCP that is 
currently available includes plates of 192 glycerol stocks of E. coli 
each containing one of the library plasmids, and a collection of 24 
DNAs that are the downstream vectors for expression in different hosts. 
Uses of this CCP include construction of protein expression constructs 
with various fusion tags, generation of expression constructs with 
different promoters for in vivo expression, and production of clones 
with fluorescent tags for localization experiments. The advantage of 
the CCP is based on the exquisite specificity of the Multisite Gateway 
reactions, which permit linkage of multiple elements in a directional 
fashion and involve no additional DNA amplification. There is also no 
need for restriction-based cloning processes, which have a high rate of 
failure and may require optimization depending on the sites available 
in a given clone. The CCP library includes clones for fluorescent and 
luminescent reporters, epitope and solubility fusion tags, bimolecular 
fluorescence complementation (BiFC) fusions, 18 different eukaryotic 
promoters, and many other useful clones. In addition, the destination 
vector collection contains two flavors of Gateway destination vectors 
for E. coli, baculovirus, mammalian, and lentiviral expression.
    Potential Commercial Applications:
     Construction of protein expression constructs with various 
fusion tags
     Generation of expression constructs with different 
promoters for in vivo expression
     Production of clones with fluorescent tags for 
localization experiments
     Generation of constructs for making mutant cell lines or 
transgenic animals
     Production of vectors for shRNA or miRNA delivery
    Competitive Advantages: The CCP is considerably more flexible than 
currently available commercial systems for construction of protein 
expression constructs.
    Development Stage:
     Prototype
     Pre-clinical
     In vitro data available
    Inventor: Dominic Esposito (NCI).
    Publication: Hopkins RF, et al. Optimizing transient recombinant 
protein expression in mammalian cells. Methods Mol Biol. 2012;801:251-
68. [PMID 21987258].
    Intellectual Property: HHS Reference No. E-164-2011/0--Research 
Tools. Patent protection is not being pursued for these technologies.
    Licensing Contact: Suryanarayana Vepa, Ph.D., J.D.; 301-435-5020; 
vepas@mail.nih.gov.

Therapeutic Peptide Treatment for Dyslipidemic and Vascular Disorders

    Description of Technology: This invention is directed to use of 
certain peptide analogs comprising multiple amphipathic helical domains 
that are able to promote cellular lipid efflux and stimulate 
lipoprotein lipase activity. As a result, administration of invention 
peptides lead to reduced incidences of hypertriglyceridemia without 
inducing toxicity. Existing peptides that stimulate efflux of lipids 
from cells exhibit unacceptably high toxicity. Invention peptides are 
superior to existing peptides and can also be used to treat or prevent 
a vast range of vascular diseases, and their dyslipidemic precursors. 
Exemplary vascular diseases and conditions that could benefit from 
treatment with the invention peptides include: dyslipidemia, 
hyperlipidemia, hypercholesterolemia, HDL deficiency, coronary heart 
disease, atherosclerosis, and thrombic stroke.
    Potential Commercial Applications:
     Treatment of dyslipidemic and vascular disorders
     Method of identifying therapeutic non-cytotoxic peptides
    Competitive Advantages:
     Specific control of lipid efflux and transport
     Transient hypertriglyceridemia with no reported toxicity
    Development Stage:
     Early-stage
     Pre-clinical
     In vitro data available
     In vivo data available (animal)
    Inventors: Alan T Remaley and Marcelo A Amar (NHLBI).
    Publications:
    1. Remaley AT, et al. Synthetic amphipathic helical peptides 
promote lipid efflux from cells by an ABCA1-dependent and an ABCA1-
independent pathway. J Lipid Res. 2003 Apr;44(4):828-36. [PMID 
12562845].
    2. Sviridov DO, et al. Helix stabilization of amphipathic peptides 
by hydrocarbon stapling increases cholesterol efflux by the ABCA1 
transporter. Biochem Biophys Res Commun. 2011 Jul 8;410(3):446-51. 
[PMID 21672528].
    3. Osei-Hwedieh DO, et al. Apolipoprotein mimetic peptides: 
Mechanisms of action as anti-atherogenic agents. Pharmacol Ther. 2011 
Apr;130(1):83-91. [PMID 21172387].
    Intellectual Property: HHS Reference No. E-138-2008/0--US Patent 
Application No. 12/937,974 filed 14 Oct 2010.
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; lauren.nguyen-antczak@nih.gov.


[[Page 3440]]


    Dated: January 10, 2013.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2013-00738 Filed 1-15-13; 8:45 am]
BILLING CODE 4140-01-P