[Federal Register Volume 79, Number 37 (Tuesday, February 25, 2014)]
[Notices]
[Pages 10537-10539]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-03957]


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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. 209 and 37 CFR Part 404 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.

Methods for Amelioration and Treatment of Pathogen-Associated 
Inflammatory Response

    Description of Technology: This CDC invention provides methods for 
preventing or treating inflammatory response-linked, infection induced 
pathologies, which are mediated by endogenous substance P. Substance P 
is a naturally-occurring and major pro-inflammatory neuromediator or 
neuromodulator, and elevated levels of substance P have been implicated 
in numerous inflammation-associated diseases. More specifically, this 
technology entails administration of anti-substance P antibodies or 
anti-substance P antibody fragments to a subject in need, thereby 
inhibiting the activity of endogenous substance P.
    Small molecule anti-inflammatory agents currently employed to treat 
inflammation frequently cause adverse side effects, such as 
gastrointestinal discomfort and decreased blood clotting efficiency. 
Use of steroid-based anti-inflammatory drugs may result in reduced 
adrenal gland function and generalized immune system inhibition. This 
technology specifically targets and alleviates substance P-induced 
hyper-inflammatory diseases, potentially avoiding the complications 
associated with other anti-inflammatory compounds. Blocking the 
activity of endogenous substance P potentially can be employed to 
prevent or treat a wide variety of diseases or syndromes caused in 
whole or part by an inflammatory response mediated by substance P. 
These include, but are not limited to, virus-mediated bronchiolitis 
including that mediated by respiratory syncytial virus, bacterial 
colitis, inflammation associated with chlamydial diseases, lung injury 
associated with staphylococcal enterotoxin B, inflammation due to 
cytomegalovirus or hepatitis B virus, sepsis, allergic diseases such as 
asthma, autoimmune diseases such as rheumatoid arthritis, pancreatitis, 
inflammatory bowel disease, inflammation associated with multiple 
sclerosis, and rejection of allografts and other transplanted tissues 
or organs.
    Potential Commercial Applications:
     Treatment of pathogen induced inflammation, especially 
bronchiolitis
     Prevention or lessening of adverse effects associated with 
other anti-inflammatory agents
     Amelioration of pain
    Competitive Advantages:
     Useful for management of numerous inflammatory-related 
viral and/or bacterial infections
     May reduce or circumvent adverse side effects associated 
with other small-molecule and/or steroid-based anti-inflammatory 
treatments
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors:

Ralph A. Tripp, Larry J. Anderson, Deborah D. Moore (all of CDC)

    Publication:
Tripp RA, et al. Respiratory syncytial virus infection and G and/or 
SH protein expression contribute to substance P, which mediates 
inflammation and enhanced pulmonary disease in BALB/c

[[Page 10538]]

mice. J Virol. 2000 Feb;74(4):1614-22. [PMID 10644330]

    Intellectual Property: HHS Reference No. E-236-2013/0--
     PCT Application No. PCT/US2000/001032 filed 14 Jan 2000
     US Patent No. 7,101,547 issued 05 Sep 2006
     Various international patent applications pending or 
issued
    Licensing Contact: Whitney Blair, J.D., M.P.H.; 301-435-4937; 
[email protected]

Recombinant Sulfated HIV Envelope Protein and Methods for Making 
Protein

    Description of Technology: This technology comprises sulfated 
recombinant gp120 proteins and peptides. Also included are methods for 
producing sulfated recombinant gp120 proteins. The focus of this 
technology is on sulfation of two tyrosines in the V2 loop of the HIV 
major envelope glycoprotein, gp120, which increase the stability of 
gp120 and promote the synthesis of gp120 protein in its native 
``closed'' conformation. Gp120 in its native form is highly sulfated; 
however, recombinant gp120 produced for vaccines or structural analyses 
typically display low levels of V2 tyrosine sulfation. Sulfation of the 
V2 loop results in increased binding to trimer-recognizing anti-HIV 
antibodies specific to the V2 loop region of gp120 (PG9, PG16, CH01, 
PGT145) and decreased binding of CD4. The sulfation of recombinant 
gp120 is accomplished by over expression of a tyrosyl sulfotransferase 
in the producing cell line. Preliminary experiments indicate the 
recombinant sulfated gp120 proteins can be used to elicit the formation 
of HIV neutralizing antibodies in immunized animals.
    Potential Commercial Applications:
     Design of HIV vaccines
     Production of HIV vaccines
     Induction of Neutralizing Antibodies
     HIV vaccine booster protein
    Competitive Advantages:
     Consistent sulfation/production of gp120
     Gp120 vaccine component with improved stability and 
immunogenicity
     Recombinant gp120 vaccine component in native conformation
    Development Stage:
     Early-stage
     In vitro data available
     In vivo data available (animal)
     Prototype
    Inventors: Paolo Lusso and Raffaello Cimbro (NIAID)
    Publication:

Cimbro R, et al. Tyrosine sulfation in the second variable loop (V2) 
of HIV-1 gp120 stabilizes V2-V3 interaction and modulates 
neutralization sensitivity. Proc Natl Acad Sci USA. E-pub before 
print, 2014 Feb 03. [doi:10.1073/pnas.1314718111]

    Intellectual Property: HHS Reference No. E-067-2012/0--PCT 
Application No. PCT/US2013/074801, claiming priority to U.S. 
Provisional Application No. 61/736,350 filed 12 Dec 2012
    Related Technology: Unpublished modifications to recombinant GP120.
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301-
435-4507; [email protected]
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize this technology as a HIV vaccine 
component or a therapeutic for treating HIV. For collaboration 
opportunities, please contact Bill Ronnenberg at 
[email protected] or 301-451-3522.

Novel Host Target for Treatment of Hepatitis C Virus Infection

    Description of Technology: The subject technology is a newly 
discovered Interferon-lambda 4 (IFNL4) protein found through analysis 
of genomic data derived from primary human hepatocytes, molecular 
cloning and functional annotation. The IFNL4 protein is related to but 
distinct from other known IFNs and its expression is inducible in 
conditions that mimic viral infection. Preliminary studies indicate 
that this protein may play a role in impaired natural and treatment 
induced clearance of HCV. These findings suggest that the protein can 
potentially be a new target for treating HCV infection.
    Potential Commercial Applications:
     Novel target for treatment of HCV infection.
     Diagnostics can be developed for detection of IFNL4 mRNA 
or protein.
     Existing biological reagents for detection of IFNL4--
expression assays, antibodies and protein.
    Competitive Advantages: IFNL4 is created by a genetic variant 
IFNL4-deltaG, which is present only in a subset of individuals, 
suggesting that IFNL4 is not an essential protein and its functional 
inactivation may be well-tolerated.
    Development Stage:
     Early-stage
     Pre-clinical
     In vitro data available
    Inventors: Liudmila Prokunina (NCI), Thomas R. O'Brien (NCI), Brian 
P. Muchmore (NCI), Raymond P. Donnelly (FDA)
    Publication:

Prokunina-Olsson L, et al. A variant upstream of IFNL3 (IL28B) 
creating novel interferon gene IFNL4 is associated with impaired 
clearance of hepatitis C virus. Nat Genet. 2013 Feb;45(2):164-71. 
[PMID 23291588]

    Intellectual Property: HHS Reference No. E-217-2011/1--
     U.S. Provisional Patent Application No. 61/616,664 filed 
28 Mar 2012
     International PCT Application No. PCT/US13/31624 filed 14 
Mar 2013, which published as WO 2013/148272 on 03 Oct 2013
    Related Technology: HHS Reference No. E-217-2011/0--
     U.S. Provisional Patent Application No. 61/543,620 filed 
05 Oct 2011
     International PCT Application No. PCT/US2012/59048 filed 
05 Oct 2012, which published as WO 2013/052862 on 11 Apr 2013
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected]
    Collaborative Research Opportunity: The NCI Division of Cancer 
Epidemiology & Genetics, Laboratory of Translational Genomics, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
development of tools for detection of IFNL4 mRNA and protein and 
modulation of its function. For collaboration opportunities, please 
contact John Hewes, Ph.D. at [email protected].

Knockout Mouse Models for Study of Cholesterol Biosynthesis and 
Metabolic Diseases

    Description of Technology: The farnesoid X receptor (FXR), also 
known as the bile acid receptor (BAR), is expressed in high levels in 
the liver and intestine, and controls the synthesis and transport of 
bile acids, which are degradation products of cholesterol. As such, FXR 
is a potential drug target for a number of metabolic disorders, such as 
dyslipidemia, diabetes and atherosclerosis.
    Available for licensing are mouse models with a total deletion of 
the FXR gene (FXR-null mouse), as well as mice with tissue-specific 
deletions of the FXR gene in the liver or in the intestine. These mice 
may be useful for the study of cholesterol and bile acid synthesis and 
their role in metabolic disease, as well as for the development of 
drugs targeting FXR.
    Potential Commercial Applications:
     Development of FXR/BAR-based drugs for the treatment of 
cholesterol

[[Page 10539]]

disorders and metabolic diseases including dyslipidemia, diabetes and 
atherosclerosis.
     Study of the role of FXR in cholesterol biosynthesis and 
metabolic disease.
    Development Stage: Early-stage
    Inventor: Frank J. Gonzalez (NCI)
    Publications:

1. Sinal C, et al. Targeted disruption of the nuclear receptor FXR/
BAR impairs bile acid and lipid homeostasis. Cell. 2000 Sep 
15;102(6):731-44. [PMID 11030617]
2. Kim I, et al. Differential regulation of bile acid homeostasis by 
the farnesoid X receptor in liver and intestine. J Lipid Res. 2007 
Dec;48(12):2664-72. [PMID 17720959]

    Intellectual Property: Research Tools--Patent protection is not 
being pursued for this technology:
     HHS Reference No. E-323-2001/0--a mouse line lacking the 
nuclear receptor FXR/BAR
     HHS Reference No. E-323-2001/1--a mouse line lacking FXR/
BAR expression in the liver
     HHS Reference No. E-323-2001/2--a mouse line lacking FXR/
BAR expression in the intestine
    Licensing Contact: Tara L. Kirby, Ph.D.; 301-435-4426; 
[email protected]

    Dated: February 19, 2014.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2014-03957 Filed 2-24-14; 8:45 am]
BILLING CODE 4140-01-P