[Federal Register Volume 78, Number 102 (Tuesday, May 28, 2013)]
[Notices]
[Pages 31948-31950]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-12531]


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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.

Assay for Quantifying Fragile X Mental Retardation-1 Gene Product

    Description of Technology: The invention is directed to a 
fluorescence based assay to quantify the protein product of the Fragile 
X Mental Retardation-1 (FMR1) gene in a biological sample.
    Fragile X syndrome (FXS) is an X-linked genetic disease that is 
responsible for intellectual disability and is also the most common 
single gene cause of autism. FXS is typically caused by loss of 
expression of the FMR1 gene, which codes for an RNA-binding protein 
called FMRP. FXS patients exhibit a wide spectrum of symptoms with 
varying degrees of cognitive and psychosocial impairment. The severity 
of these symptoms correlates well with the levels of FMRP present in 
the FXS patient. Because the FMR1 gene is silenced in varying degrees, 
the levels of FMRP in any particular FXS patient could vary greatly.
    Scientists at NIDDK and NCATS have developed a sensitive, time 
resolved fluorescence based assay to quantify FMRP levels in a 
biological sample. Unlike other assays, the invention assay utilizes 
two highly-specific antibodies that bind to different sites of FMRP so 
as to enable precise and reliable quantification. Currently, there is 
no approved drug to treat FXS. The invention assay can be used as a 
high throughput screen to identify and evaluate candidate drugs. In 
addition, the invention assay can be used to assess and/or predict the 
severity of a patient's condition based on the amount of FMRP present.
    Potential Commercial Applications:

 Diagnosis assay
 High throughput screen of drug libraries
 Optimization assay to further develop potential drug 
candidates

    Competitive Advantages:

 Fast, accurate, and reliable assay to quantify FMRP in easy-
to-use fluorescence based format
 Adaptable for high throughput use

    Development Stage:

 Prototype
 Pilot
 In vitro data available

    Inventors: Wei Zheng (NCATS), Karen P. Usdin (NIDDK), Manju Swaroop 
(NCATS), Daman Kumari (NIDDK)
    Intellectual Property: HHS Reference No. E-083-2013/0--US 
Application No. 61/793,577 filed 15 March 2013
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; [email protected].
    Collaborative Research Opportunity: The National Center for 
Advancing Translational Sciences (NCATS) is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize Assay for 
Quantifying Fragile X Mental Retardation-1 Gene Product. For 
collaboration opportunities, please contact the NCATS Technology 
Development Coordinator at [email protected].

[[Page 31949]]

A Novel HIV-1 Entry Inhibitor

    Description of Technology: The subject invention describes a novel 
polypeptide comprising a single human CD4 domain (mD1.22) which is 
highly soluble and stable with significantly higher neutralizing 
activity and lower non-specific binding to human blood cell lines. More 
specifically, mD1.22 is highly promising for several applications due 
to its biophysical properties: (1) For conjugating with cytotoxic 
molecules for eradication of HIV-infected cells; (2) for generating 
multi-specific multi-valent HIV inhibitors with high neutralization 
potency and breadth, and relatively small molecular size; (3) for 
generating nanobio-sensors for rapid HIV detection; and (4) for 
studying the biological functions of CD4 in immune responses and HIV 
entry.
    Potential Commercial Applications:

 HIV therapeutics
 Prophylactics
 Detection reagents
 Research reagent

    Competitive Advantages:

 Does not show measurable interaction with MHCII.
 Can be solubly expressed in E. coli with high yields leading 
to decreased production costs.

    Development Stage:

 Early-stage
 In vitro data available

    Inventors: Dimiter Dimitrov, Weizao Chen, Prabakaran Ponraj (NCI)
    Publications:

1. Chen W, et al. Engineered single human CD4 domains as potent HIV-
1 inhibitors and components of vaccine immunogens. J Virol. 
2011;85(18):9395-405. [PMID 21715496]
2. Chen W, et al. Bifunctional fusion proteins of the human 
engineered antibody domain m36 with human soluble CD4 are potent 
inhibitors of diverse HIV-1 isolates. Antiviral Res. 2010;88(1):107-
15. [PMID 20709110]
3. Chen W, et al. Human domain antibodies to conserved sterically 
restricted regions on gpl20 as exceptionally potent cross-reactive 
HIV-1 neutralizers. Proc Natl Acad Sci USA. 2008;105(44):17121-6. 
[PMID 18957538]
4. Lagenaur LA, et al. sCD4-17b bifunctional proteins: extremely 
broad and potent neutralization of HIV-1 Env pseudotyped viruses 
from genetically diverse primary isolates. Retrovirology 2010 Feb 
16;7:11. [PMID 20158904]
5. Saha P, et al. Design and characterization of stabilized 
derivatives of human CD4D12 and CD4D1. Biochemistry 2011 Sep 
20;50(37):7891-900. [PMID 21827143]

    Intellectual Property: HHS Reference No. E-033-2013/0--US 
Provisional Patent Application No. 61/791,885 filed 15 Mar 2013
    Related Technologies: HHS Reference No. E-103-2010/1--

 PCT Application No. PCT/US2011/3743961 filed on 20 May 2011
 National stage filing in EP (EP Application No. 11722270.3) 
and in USA (US Application No. 13/699,535) on 21 Nov. 2012
    Licensing Contact: Sally H. Hu, Ph.D., M.B.A.; 301-435-5606; 
[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 
A Novel HIV-1 Entry Inhibitor. For collaboration opportunities, please 
contact John D. Hewes, Ph.D. at [email protected].

Novel Fusion Proteins for HIV Vaccine

    Description of Technology: The subject invention describes novel 
fusion proteins (CD4i antibody-HIV-1 envelop glycoprotein (gp120)) 
which can be used as (1) potential vaccine immunogens that could be 
more efficient than gp120 alone; (2) candidate therapeutics; and (3) 
research reagents for exploration of HIV-1 gp120 conformational 
flexibility, elucidation of mechanisms of virus entry, and evasion of 
immune responses.
    Potential Commercial Applications:

 Develop HIV vaccine
 Research reagent
 Research tools to study the conformations flexibility of 
gp120, the mechanisms of virus entry, and evasion of immune responses

    Competitive Advantages:

 The potential vaccine immunogens that could be more efficient 
than gp120 alone
 Higher affinity with CD4 and antibodies directed against CD4-
binding site than gp120 alone

    Development Stage:

 Early-stage
 In vitro data available

    Inventors: Dimiter Dimitrov and Weizao Chen (NCI)
    Publications:

1. Dey B, et al. Characterization of human immunodeficiency virus 
type 1 monomeric and trimeric gp120 glycoproteins stabilized in the 
CD4-bound state: antigenicity, biophysics, and immunogenicity. J 
Virol. 2007 Jun;81(11):5579-93. [PMID 17360741]
2. Dey B, et al. Structure-based stabilization of HIV-1 gp120 
enhances humoral immune responses to the induced co-receptor binding 
site. PLoS Pathog. 2009 May;5(5):el000445. [PMID 19478876]
3. Xiang SH, et al. Mutagenic stabilization and/or disruption of a 
CD4-bound state reveals distinct conformations of the human 
immunodeficiency virus type 1 gp120 envelope glycoprotein. J Virol. 
2002 Oct;76(19):9888-99. [PMID 12208966]

    Intellectual Property: HHS Reference No. E-256-2012/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Sally H. Hu, Ph.D., M.B.A.; 301-435-5605; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
(NCI) is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate or 
commercialize Novel Fusion Proteins for HIV Vaccine. For collaboration 
opportunities, please contact John D. Hewes, Ph.D. at 
[email protected].

A Novel Human Antibody for Deploying CH2 Based Therapeutics

    Description of Technology: The subject invention describes a novel 
human antibody (anti-CH2 Fab m01m1) which could be used safely in vitro 
and in vivo for the detection of CH2 (Fc and IgG as well). More 
specifically, anti-CH2 Fab m01m1 recognizes a conformational epitope on 
CH2 so it can be used to monitor the conformational changes when CH2 is 
modified and mutated, as well as to select proper folded isolated CH2 
domains. Thus, anti-CH2 Fab m01m1 is a powerful research reagent for 
developing the CH2-based novel therapeutics (nanoantibodies, nAbs) and 
for identifying several binders against various antigens from CH2-based 
libraries.
    Potential Commercial Applications:

 Research reagent
 Facilitate the development of CH2-based novel therapeutics
 Can be used as a library for therapeutic candidates

    Competitive Advantages: Novel antibody.

    Development Stage:

 Early-stage
 In vitro data available
    Publications:

1. Prabakaran P, et al. Structure of an isolated unglycosylated 
antibody C(H)2 domain. Acta Crystallogr D Biol Crystallogr. 2008 
Oct; 64(Pt 10):1062-7. [PMID 18931413]
2. Dimitrov DS. Engineered CH2 domains (nanoantibodies). MAbs. 2009 
Jan-Feb;1(1):26-8. [PMID 20046570]
3. Gong R, et al. Engineered human antibody constant domains with 
increased stability. J Biol Chem. 2009 May 22;284(21):14203-10. 
[PMID 19307178]
4. Xiao X, et al. A large library based on a

[[Page 31950]]

novel (CH2) scaffold: identification of HIV-1 inhibitors. Biochem 
Biophys Res Commun. 2009 Sep 18;387(2):387-92. [PMID 19615335]
5. Wozniak-Knopp G, et al. Stabilisation of the Fc fragment of human 
IgG1 by engineered intradomain disulfide bonds. PLoS One. 
2012;7(1):e30083 [PMID 22272277]

    Inventors: Dimiter Dimitrov (NCI) and Rui Gong (formerly NCI).
    Intellectual Property: HHS Reference No. E-245-2012/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Sally H. Hu, Ph.D., M.B.A.; 301-435-5606; 
[email protected]
    Collaborative Research Opportunity: The National Cancer Institute 
(NCI) is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate or 
commercialize A Novel Human Antibody for Deploying CH2 Based 
Therapeutics. For collaboration opportunities, please contact John D. 
Hewes, Ph.D. at [email protected].

Methods for Producing Stem Cell-like Memory T cells for Use in T cell-
based Immunotherapies

    Description of Technology: T cells currently employed for T cell-
based immunotherapies are often senescent, terminally differentiated 
cells with poor proliferate and survival capacity. Recently, however, 
NIH scientists identified and characterized a new human memory T cell 
population with stem cell-like properties. Since these T cells have 
limited quantities in vivo, the scientists have developed methods by 
which high numbers of these cells can be generated ex vivo for use in T 
cell-based immunotherapies. Specifically, this technology describes a 
method for generating the stem cell-like memory T cells by stimulating 
naive T cells in the presence of inhibitors of GSK-3beta. It also 
describes a method for obtaining the stem cell-like memory T cells by 
sorting T cell lymphocytes using flow cytometry. These stem cell-like 
memory T cells display enhanced proliferation and survival upon 
transfer, have the multipotent capacity to generate all memory and 
effector T cell subsets and show increased anti-tumor activity in a 
humanized mouse tumor model. Consequently, the coupling of T cell 
receptor or chimeric receptor gene transfer with this method will 
enable the generation of a large number of memory stem cells with the 
desired specificity to effectively treat patients with cancer and 
chronic infectious diseases.
    Potential Commercial Applications:

 Ex vivo generation of stem cell-like memory T cells for T 
cell-based immunotherapy
 Treatment for patients with cancer and chronic infectious 
diseases

    Competitive Advantages:

 Enhanced proliferation and survival upon transfer
 Multipotent capacity to generate all memory and effector T 
cell subsets
 Increased anti-tumor actovity

    Development Stage:

 Pre-clinical
 In vitro data available
 In vivo data available (animal)

    Inventors: Luca Gattinoni (NCI), Enrico Lugli (NIAID), Mario 
Roederer (NIAID), Nicholas Restifo (NCI)
    Publications:

1. Gattinoni L, et al. A human T cell memory subset with stem cell-
like properties. Nat Med. 2011 Sep 18;17(10):1290-7. [PMID 21926977]
2. Gattinoni L, et al. Wnt signaling arrests effector T cell 
differentiation and generates CD8+ memory stem cells. Nat Med. 2009 
Jul;15(7):808-13. [PMID 19525962]
3. Lugli E, et al. Identification, isolation and in vitro expansion 
of human and nonhuman primate T stem cell memory cells. Nat Protoc. 
2013 Jan;8(1):33-42. [PMID 23222456]

    Intellectual Property: HHS Reference No. E-174-2012/0--PCT 
Application No. PCT/US12/053947 filed 06 Sep 2012
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[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 
the use of T memory stem cells for T cell-based immunotherapies. For 
collaboration opportunities, please contact Luca Gattinoni at 
[email protected] or 301-451-6914, or Nicholas Restifo at 
[email protected] or 301-496-4904.

    Dated: May 21, 2013.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2013-12531 Filed 5-24-13; 8:45 am]
BILLING CODE 4140-01-P