[Federal Register Volume 78, Number 113 (Wednesday, June 12, 2013)]
[Notices]
[Pages 35290-35291]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-13895]


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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. 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.

Live Attenuated RSV Vaccines Based on Codon-Pair Deoptimization

    Description of Technology: The technology includes patent rights 
and related materials for live attenuated viruses that can be used as a 
prophylactic vaccine against respiratory syncytial virus. The viruses 
are generated using codon-pair deoptimization techniques of the RSV 
polymerase ORF alone or together with the NS1, NS2, N, P, M, SH, G, and 
F ORFs, rendering the virus temperature sensitive. Experimental growth 
data for one such virus in mice and in African Green Monkeys 
demonstrates in vivo growth attenuation.
    Potential Commercial Applications:
     Prophylactic vaccine
     Childhood and elder vaccine
    Competitive Advantages:
     Live attenuated
     Codon deoptimized
    Development Stage:
     Pre-clinical
     In vivo data available (animal)
    Inventors: Peter Collins, Cyril Le Nouen, Linda Brock, Ursula 
Buchholz (NIAID)
    Publications:
    1. Collins PL, Melero JA. Progress in understanding and controlling 
respiratory syncytial virus: still crazy after all these years. Virus 
Res. 2011 Dec;162(1-2):80-99. [PMID 21963675]
    2. Buchan JR, et al. tRNA properties help shape codon pair 
preferences in open reading frames. Nucleic Acids Res. 2006 Feb 
9;34(3):1015-27. [PMID 16473853]
    Intellectual Property:
     HHS Reference No. E-080-2013/0--US Provisional Patent 
Application No. 61/762,768 filed 08 Apr 2013
     HHS Reference No. E-080-2013/1--US Provisional Patent 
Application No. 61/794,155 filed 15 Mar 2013
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].

Improved Personalized Cancer Immunotherapy: Rapid Selection of Tumor-
Reactive T Cells Based on Expression of Specific Cell Surface Markers

    Description of Technology: Scientists at NIH have identified a 
process to select highly tumor-reactive T cells from a patient tumor 
sample based on the expression of four specific T cell surface markers: 
programmed cell death protein 1 (PD-1; CD279), 4-1BB (CD137), T cell 
Ig- and mucin-domain-containing molecule-3 (TIM-3), and/or lymphocyte 
activation gene 3 (LAG-3). After this enriched population of tumor 
fighting T cells, primarily tumor infiltrating lymphocytes (TIL), is 
selected and expanded to large quantities, it gets re-infused into the 
patient via an adoptive cell transfer (ACT) regimen. The key finding 
for this process is that the most tumor-reactive TIL found in a bulk 
population of cells obtained from a patient tumor sample reliably 
exhibit high expression of one or more of these four markers. By 
selecting cancer attacking TIL from a patient's tumor based on these 
markers prior to re-infusion, in vitro culture time is reduced to grow 
up the desired T cells and a more effective anti-cancer T cell product 
can be produced in comparison to previous TIL immunotherapy approaches.
    This new method for selecting tumor-reactive T cells/TIL from tumor 
samples should help TIL immunotherapy become more GMP compliant and 
allow greater standardized of the TIL production process to enable more 
widespread utilization of this personalized cancer treatment approach 
outside of NIH.
    Potential Commercial Applications:
     Personalized ACT immunotherapy to treat human cancers 
using T cells obtained from a tumor sample
     Possible integration into a standard procedure for 
obtaining tumor-reactive T cells/TIL from a tumor as part of a GMP-
compliant TIL manufacturing process that gains regulatory approval as a 
personalized cancer treatment option
     The immunotherapy component of a combination cancer 
therapy regimen targeting specific tumor antigens in individual 
patients
     More rapid tumor-reactive T cell culturing process for 
laboratory testing
    Competitive Advantages:
     Simpler: Tumor-reactive T cells/TIL can be selected for 
ACT from a bulk population derived from a tumor sample using common 
laboratory techniques
     More rapid: Selection of T cells/TIL based on expression 
of specific cell surface markers will reduce the culture time for these 
T cells before re-infusion into the patient to fight the tumor
     Less screening: This selection method eliminates the need 
to screen T cells/TIL for autologous tumor recognition before re-
infusion into the patient
    Development Stage:
     Early-stage
     Pre-clinical
     In vitro data available
    Inventors: Alena Gros and Steven A. Rosenberg (NCI)
    Intellectual Property: HHS Reference No. E-059-2013/0--US Patent 
Application No. 61/771,247 filed 01 March 2013; PCT Patent Application 
No. PCT/US2013/038799 filed 30 April 2013
    Related Technologies:
     HHS Reference No. E-085-2013/0--US Patent Application No. 
61/771,251; PCT Patent Application No. PCT/US2013/038813
     HHS Reference No. E-273-2009/0--US Patent No. 8,383,099; 
US Patent Application No. 13/742,541
     HHS Reference No. E-275-2002/1--US Patent No. 8,034,334; 
US Patent No. 8,287,857; Foreign counterparts in Europe, Canada, and 
Australia
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[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 
adoptive transfer of tumor infiltrating lymphocytes (TIL) for cancers 
other than melanoma. For collaboration opportunities, please

[[Page 35291]]

contact Steven A. Rosenberg, M.D., Ph.D., at [email protected] or 301-496-
4164.

Diagnostic Assays for the Detection of Thyroid Cancer

    Description of Technology: NIH scientists have developed two novel 
methods for distinguishing malignant from benign thyroid biopsy 
samples. Midkine and pleiotrophin, both low molecular weight growth 
factors, are over-expressed in many cancerous tissues. NIH researchers 
have developed ELISA assays to quantify the amount of midkine and 
pleiotrophin present in thyroid tissue samples. Levels of both growth 
factors are substantially higher in fine needle aspirates from thyroid 
cancers than from benign thyroid nodules. Application of this technique 
for the identification of thyroid cancer represents a first-in-class 
diagnostic for this disease.
    Thyroid cancer represents a disease particularly amenable to 
improved methods of diagnosis. Thyroid nodules are very common in the 
adult population. To determine whether nodules are malignant, current 
practice involves obtaining a needle biopsy which is inspected 
microscopically. The resulting findings are subjective and often 
inconclusive, leading to unnecessary surgery. Therefore, there is a 
need for methods such as the present invention to improve diagnostic 
accuracy.
    Potential Commercial Applications: A diagnostic kit for the 
detection of thyroid cancer.
    Competitive Advantages:
     High assay sensitivity permits the use of small tissue 
samples (e.g., fine needle aspirates of nodules)
     Assay can incorporate commercially-available midkine or 
pleiotrophin antibodies.
     Assay relies on proven ELISA detection technology.
    Development Stage:
     In vivo data available (animal)
     Clinical
    Inventors: Jeffrey Baron and Youn Hee Jee (NICHD)
    Intellectual Property:
     HHS Reference No. E-016-2013/0--US Application No. 61/
728,624 filed 20 Nov 2012
     HHS Reference No. E-016-2013/1--US Application No. 61/
815,342 filed 24 Apr 2013
    Licensing Contact: Sabarni Chatterjee, Ph.D., MBA; 301-435-5587; 
[email protected]
    Collaborative Research Opportunity: The National Institute of Child 
Health and Human Development, Section on Growth and Development, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
assays of biomarkers midkine, pleiotrophin in biopsy samples for cancer 
detection. For collaboration opportunities, please contact Charlotte 
McGuinness at [email protected].

Novel and Improved Methods for Constructing and Analyzing Synallele 
Libraries

    Description of Technology: Methods of constructing and analyzing 
improved synallele libraries of nucleic acid molecules is disclosed. 
Each nucleic acid molecule in these libraries (i) comprises a different 
nucleic acid sequence and (ii) encodes a mammalian secreted protein 
comprising the same amino acid sequence. Synalleles are variants of a 
gene that have the same amino acid sequence but different DNA 
sequences. It has been shown that the redundancies in the genetic code 
can result in dramatically different protein expression levels. 
Currently available synallele libraries are too limited in their size, 
diversity, and fidelity to provide a clinical use (e.g., drug 
development). Also, one of the difficulties in producing therapeutic 
proteins is the lack of suitable methods for screening hundreds, or 
even thousands, of cells expressing such proteins in order to identify 
and isolate cells which express the desired proteins in high amounts. 
This invention provides the first synallele library assembled using 
type IIS restriction enzymes and comprises more than 100,000 individual 
clones. Several novel enhancements for constructing libraries with 
increased diversity of synalleles using segment shuffling techniques 
and synallele shuffling within segments using nicking and 
polymerization are also described. Additionally, the inventors also 
disclose an efficient cell sorting method using tethered beads to 
screen for clones producing/secreting high levels of target protein.
    Potential Commercial Applications:
     Production of therapeutic proteins
     Screening of cells and clones for high expressors
    Competitive Advantages: This technology provides for increased 
chances of finding a synallele for a biopharmaceutical protein that 
increases its expression, decreases the time it takes to make clinical 
grade material, and reduces its cost of production.
    Development Stage:
     Early-stage
     Pre-clinical
     In vitro data available
    Inventors: James L. Hartley and Andrew Waters (NCI)
    Intellectual Property: HHS Reference Nos. E-218-2012/0, E-219-2012/
0, E-220-2012/0, E-221-2012/0, and E-017-2013/0--US Application No. 61/
725,807 filed 13 Nov 2012
    Licensing Contact: Suryanarayana (Sury) Vepa, Ph.D., JD; 301-435-
5020; [email protected]

Super-Resolution Fluorescence Enhanced Imaging Using Bleaching/Blinking 
Assisted Localization Microscopy (BALM)

    Description of Technology: The invention relates to systems and 
methods for localization microscopy for superresolution imaging of 
fluorescent molecules. The method utilizes intrinsic bleaching/blinking 
properties of fluorophores in which superresolution is achieved by 
capturing successive images and subtracting from each either the 
subsequent image. The location of a single fluorescent molecule can be 
identified when the molecules either photobleach, blink off, or blink 
between successive images using a higher magnification lens to achieve 
a smaller pixel size.
    Potential Commercial Applications:
     Tissue imaging
     Cell structure imaging
    Competitive Advantages: Higher magnification at lower pixel size
    Development Stage:
     Prototype
     In vitro data available
    Inventor: Bechara Kachar (NIDCD)
    Publication: Burnette DT, et al. Bleaching/blinking assisted 
localization microscopy for superresolution imaging using standard 
fluorescent molecules. Proc Natl Acad Sci U S A. 2011 Dec 
27;108(52):21081-6. [PMID 22167805]
    Intellectual Property: HHS Reference No. E-247-2011/0--US 
Provisional Patent Application No. 61/784,266 filed 14 Mar 2013
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected]

     Dated: June 6, 2013.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2013-13895 Filed 6-11-13; 8:45 am]
BILLING CODE 4140-01-P