[Federal Register Volume 79, Number 68 (Wednesday, April 9, 2014)]
[Notices]
[Pages 19634-19637]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-07871]
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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.
Monoclonal Antibody Fragments for Targeting Therapeutics to Growth
Plate Cartilage
Description of Technology: A child's growth is dependent on the
proper functioning of the growth plate, a specialized cartilage
structure located at the ends of long bones and within the vertebrae.
The primary function of the growth plate is to generate new cartilage,
which is then converted into bone tissue and results in the lengthening
of bones. Current treatments for severe short stature and skeletal
growth disorders are limited. Recombinant human growth hormone (GH) is
typically used but the results are less than optimal and have potential
adverse effects. The instant invention discloses that monoclonal
antibodies that bind to matrilin-3, a protein specifically expressed in
cartilage tissue, could be used for treating or inhibiting growth plate
disorders, such as a skeletal dysplasia or short stature.
Potential Commercial Applications: A new treatment option for
growth plate disorders, such as skeletal dysplasia or short stature.
Competitive Advantages: Avoidance of the risks associated with
systemic treatment using growth hormone, such as increased intracranial
pressure, slipped capital femoral epiphysis, insulin resistance, and
possibly type II diabetes.
Development Stage:
Early-stage.
In vitro data available.
Inventors: Jeffrey Baron (NICHD), Sao Fong (Crystal) Cheung
(NICHD), Chun Kin Julian Lui (NICHD), Dimiter S. Dimitrov (NCI),
Zhongyu Zhu (NCI).
Intellectual Property: HHS Reference No. E-003-2014/0--US
Application No. 61/927,904 filed 15 Jan 2014.
Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565;
[email protected].
Collaborative Research Opportunity: The Eunice Kennedy Shriver
National Institute of Child Health and Human Development and the
National Cancer Institute are seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate or commercialize treatment of skeletal disorders and
short stature to increase growth using targeting antibodies. For
collaboration opportunities, please contact Joseph Conrad III, Ph.D. at
[email protected].
Human Antibodies Against Middle East Respiratory Syndrome Coronavirus
Description of Technology: No effective therapeutics or vaccines
are available against Middle East Respiratory Syndrome Coronavirus
(MERS-CoV). This technology is for human antibodies targeting MERS-CoV.
Certain of these antibodies bind with epitopes of the MERS-CoV receptor
binding domain (RBD) of MERS-CoV spike (S) protein with high affinity
and are capable of neutralized the virus in a pseudovirus assay. The
MERS-CoV-S protein is believed to be required for binding and virus
entry during MERS-CoV infection. The human to human aspect of
transmission and the high mortality rate associated with MERS-CoV
infection have raised concerns over the potential for a future MERS-CoV
pandemic and emphasized the need for development of effective
therapeutics and vaccines. The antibodies of this technology represent
candidate antibody-based therapeutics for treatment of MERS-CoV
infection.
Potential Commercial Applications: Antibody-based therapeutics for
treatment of MERS-CoV infection.
Competitive Advantages:
No vaccine or other biologic therapy is available.
High binding (sub-nanomolar) affinity.
Relative safety and long half-lives.
Development Stage:
Early-stage.
In vitro data available.
Inventors: Dimiter Dimitrov (NCI), Tianlei Ying (NCI), Tina Yu
(NCI), Kwok Yuen (University of Hong Kong).
Publications:
1. Zaki AM, et al. Isolation of a novel coronavirus from a man with
pneumonia in Saudi Arabia. N Engl J Med. 2012 Nov 8;367(19):1814-20.
[PMID 23075143]
2. Zhu Z, et al. Exceptionally potent cross-reactive neutralization of
Nipah and Hendra viruses by a human monoclonal antibody. J Infect Dis.
2008 Mar 15;197(6):846-53. [PMID 18271743]
3. Zhu Z, et al. Potent cross-reactive neutralization of SARS
coronavirus isolates by human monoclonal antibodies. Proc Natl Acad Sci
U S A. 2007 Jul 17;104(29):12123-8. [PMID 17620608]
Intellectual Property: HHS Reference No. E-002-2014/0--U.S. Patent
Application No. 61/892,750 filed 18 Oct 2013.
[[Page 19635]]
Licensing Contact: Tedd Fenn; 424-297-0336; [email protected].
Collaborative Research Opportunity: The National Cancer Institute,
Cancer and Inflammation Program, Laboratory of Experimental Immunology,
is seeking statements of capability or interest from parties interested
in collaborative research to further develop, evaluate or commercialize
animal studies, cGMP Manufacturing, clinical trials. For collaboration
opportunities, please contact John D. Hewes, Ph.D. at
[email protected].
Novel Small Molecule Antimalarials for Elimination of Malaria
Transmission
Description of Technology: The transmission of malaria begins with
injection of sporozoites into a human from the bite of a female
anopheles mosquito, which initiates the malarial life cycle in humans.
When a mosquito bites an infected human, the ingested male and female
malaria gametocytes fuse to form a zygote that eventually becomes an
oocyst. Each oocyst produces thousands of sporozoites which migrate to
the mosquito salivary glands, ready to infect a new human host.
Currently, the available therapeutics for malaria can effectively
eliminate the asexual stages of malarial parasites that cause clinical
symptoms in patients. However, their abilities to eliminate the
gametocyte (sexual stage of the parasites) as well as the liver stage
parasites are limited. The subject technology involves novel compounds,
which include Torin 2, that are potently gametocytocidal in in vitro
assays and in a mouse model of malaria, completely blocked the host-to-
mosquito transmission by suppressing oocytes formation in mosquitoes.
Potential Commercial Applications: Novel therapeutics for
elimination of malaria transmission and treatment of drug resistant
malaria patients.
Competitive Advantages:
These novel compounds are effective against gametocytes,
the sexual stage of malarial parasites, whereas currently available
antimalarials have limited effectiveness against this form of the
parasite.
The compounds provide an alternative treatment against
malaria for patients with glucose-6-phosphate dehydrogenase deficiency.
These compounds are active against drug resistant strains
of malaria.
Development Stage:
Early-stage.
In vitro data available.
In vivo data available (animal).
Inventors: Wei Sun (NCATS), Wei Zheng (NCATS), Seameen J. Dehdashti
(NCATS), Noel T. Southhall (NCATS), Takeshi Tanaka (NIAID), Wenwei
Huang (NCATS), John C. McKew (NCATS).
Publication: Sun W, et al. Chemical signatures and new drug targets
for gametocytocidal drug development. Sci Rep. 2014 Jan 17;4:3743.
[PMID 24434750].
Intellectual Property: HHS Reference No. E-751-2013/0--U.S.
Provisional Patent Application No. 61/904,884 filed 15 Nov 2013.
Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018;
[email protected].
Compositions and Methods for Improved Lyme Disease Diagnosis
Description of Technology: This CDC-developed technology entails
novel compositions and methods related to the diagnosis of Lyme
disease. Lyme disease, caused by the Borrelia burgdorferi bacterium, is
the most common tick-borne infectious disease in the US and Europe.
Diagnosis of Lyme disease is particularly challenging as symptoms often
appear long after exposure. At present, the only FDA-approved
diagnostic for Lyme disease involves patient blood tests for particular
antibodies; these include an ELISA to measure patient antibody levels
and a Western blot assay to detect antibodies specific to B.
burgdorferi. One problem with the current diagnostic approach is that
patient antibodies for the bacterium are not detectable until two to
five weeks following the initial tick bite, and there is no way to
differentiate between antibodies generated by a current infection or by
a prior exposure.
This technology hinges on a unique approach that would detect
whether a patient has a presently active B. burgdorferi infection. A
fully developed assay based on these innovations would exploit the
detection of the B. burgdorferi BbHtrA protease and/or its unique
cleavage products to carry out a timely diagnosis of infection. While
other direct detection methods, such as culturing, PCR and antigen
capture, are often used in research laboratory settings, they have not
demonstrated consistent efficacy as clinical diagnostic tools in the
first few weeks following tick bite exposure. Further, despite the lack
of a rapid and efficient readout for the aforementioned antibody-based
Lyme disease diagnostics, there are currently no FDA-approved
comparable alternatives. This technology provides a unique opportunity
for rapid and accurate identification of B. burgdorferi infection, as
well as distinguishing current bacterium exposure from prior exposure,
thereby providing critical information to better inform treatment
strategy and improve patient outcomes.
Potential Commercial Applications:
Lyme disease/B. burgdorferi diagnostics.
Zoonotic/tick-borne disease surveillance.
Informing clinician strategies and improving patient
outcomes.
Reducing diagnosis time for patients concerned about tick
bites.
Competitive Advantages:
Present Lyme disease diagnostics cannot distinguish
between current bacterium infections and prior exposures; this
technology will provide such distinctions.
Predominant antibody-based diagnostics currently available
require weeks before efficacy and may require re-testing at later dates
to avoid false negatives; this technology directly addresses this
problem.
Other alternative direct detection methods (e.g., PCR,
culturing) have shown limited efficacy as clinical diagnostics.
Development Stage: In vitro data available.
Inventors: Barbara Johnson and Theresa Russell (CDC).
Publications:
1. Stricker RB, et al. Borrelia burgdorferi aggrecanase activity: more
evidence for persistent infection in Lyme disease. Front Cell Infect
Microbiol. 2013 Aug 14;3:40. [PMID 23967405]
2. Russell TM, et al. Lyme disease spirochaetes possess an aggrecan-
binding protease with aggrecanase activity. Mol Microbiol. 2013
Oct;90(2):228-40. [PMID 23710801]
3. Russell TM, et al. Borrelia burgdorferi BbHtrA degrades host ECM
proteins and stimulates release of inflammatory cytokines in vitro. Mol
Microbiol. 2013 Oct;90(2):241-51. [PMID 23980719]
Intellectual Property: HHS Reference No. E-204-2013/0 -
U.S. Application No. 61/588,820 filed 20 Jan 2012.
PCT Application No. PCT/US2013/022379 filed 21 Jan 2013.
Related Technology: HHS Reference No. E-573-2013/0.
Licensing Contact: Whitney Blair, J.D., M.P.H.; 301-435-4937;
[email protected].
Zirconium-89 PET Imaging Agent for Cancer
Description of Technology: The technology is tetrahydroxamate
chelation technology that provides a stable Zr-89 chelated immuno-PET
imaging agent for cancer that reduces the amounts of Zr-89 that is
released
[[Page 19636]]
from the current state of the art chemistry and agent, desferrioxamine
B (DFB), that is currently in clinical use. The tetrahydroxamates in
either a linear or macrocyclic form exhibit greater stability as
chelating agents for Zr-89 as compared to the currently in use
siderophore DFB, a trihydroxamate. In imaging agents currently in
clinical development, Zr-89 leaks from the DFB chelate which results in
radioisotope accumulation in the bone 2-3 days after injection that
increases over time. Upon in vitro examination, the tetrahydroxamate
chelated Zr-89 remained kinetically inert at 7 or more days while that
formed from DFB demonstrated instability.
Potential Commercial Applications:
PET imaging.
Cancer imaging.
Immuno-PET imaging.
Competitive Advantages:
High stability.
Low toxicity.
Development Status:
Prototype.
In vitro data available.
Inventors: Francois Guerard (NCI), Yong Sok Lee (CIT), Martin
Brechbiel (NCI).
Publications:
1. Zhou Y, et al. Mapping biological behaviors by application of
longer-lived positron emitting radionuclides. 2013 Jul;65(8):1098-111.
[PMID 23123291]
2. Deri MA, et al. PET imaging with 89Zr: from radiochemistry to the
clinic. Nucl Med Biol. 2013 Jan;40(1):3-14. [PMID 22998840]
3. Vosjan MJ, et al. Conjugation and radiolabeling of monoclonal
antibodies with zirconium-89 for PET imaging using the bifunctional
chelate p-isothiocyanatobenzyl-desferrioxamine. Nat Protoc. 2010
Apr;5(4):739-43. [PMID 20360768]
4. Nayak TK, et al. PET and MRI of metastatic peritoneal and pulmonary
colorectal cancer in mice with human epidermal growth factor receptor
1-targeted 89Zr-labeled panitumumab. J Nucl Med. 2012 Jan;53(1):113-20.
[PMID 22213822]
5. Evans MJ, et al. Imaging tumor burden in the brain with 89Zr-
transferrin. J Nucl Med. 2013 Jan;54(1):90-5. [PMID 23236019]
6. Guerard F, et al. Investigation of Zr(IV) and 89Zr(IV) complexation
with hydroxamates: progress towards designing a better chelator than
desferrioxamine B for immuno-PET imaging. Chem Commun (Camb). 2013 Feb
1;49(10):1002-4. [PMID 23250287]
7. Guerard F, et al. Rational Design, Synthesis and Evaluation of
Tetrahydroxamic Acid Chelators for Stable Complexation of ZrIV. Chem
Eur J. (in press)
Intellectual Property: HHS Reference No. E-111-2013/0 -
U.S. Provisional Patent Application 61/779,016 filed 13
Mar 2013.
PCT Application PCT/US2014/24048 filed 12 Mar 2014.
Related Technologies:
HHS Reference No. E-194-2007/0.
HHS Reference No. E-226-2006/0.
HHS Reference No. E-067-1990/0.
Licensing Contact: Michael A. Shmilovich; 301-435-5019;
[email protected].
Collaborative Research Opportunity: The Radioimmune & Inorganic
Chemistry Section, ROB, CCR, NCI, is seeking statements of capability
or interest from parties interested in collaborative research to
further develop, evaluate or commercialize tetrahydroxamate chelation
technology for Zirconium-89 PET Imaging. For collaboration
opportunities, please contact John D. Hewes, Ph.D. at
[email protected].
Ex-vivo Production of Regulatory B-Cells (Breg) for Use in Auto-Immune
Indications
Description of Technology: Regulatory B-cells (Breg) play an
important role in reducing autoimmunity and reduced levels of these
cells are implicated in etiology of several auto-inflammatory diseases.
Despite their impact in many diseases, their physiological inducers are
unknown. Given that Bregs are a very rare B-cell, identifying factors
that promote their development would allow in vivo modulation of Breg
levels and ex-vivo production of large amounts of antigen-specific
Bregs to use in immunotherapy for auto-inflammatory diseases.
The invention herein, is a method of ex-vivo production of Breg.
The method of production involves treating isolated primary B cells or
B cell lines with IL-35 to induce their conversion into IL-10-producing
Breg. Using this method, B-regulatory cells can be produced in large
quantity and used in a Breg-based therapy against autoimmune diseases
including but not limited to uveitis and sarcoidosis.
Potential Commercial Applications:
In vivo modulation of Breg levels.
Supplement the low population of Breg in a patient
suffering from an autoimmune disease where it is known that B-
regulatory cell populations are severely reduced (i.e. uveitis)
Use in immunotherapy for the treatment of other autoimmune
diseases such as multiple sclerosis, sarcoidosis, colitis, and
arthritis.
Competitive Advantages:
There is no known biological or chemical agent that can
induce Bregs ex-vivo.
This method produces large quantities of Bregs and can
therefore aid in Breg-based therapy.
Pre-clinical mouse model data available that uses the
Bregs to treat experimental autoimmune uveitis (EAU).
Development Stage: In vivo data available (animal).
Inventors: Charles E. Egwuagu, Ren-Xi, Wang, Cheng-Rong Yu (all of
NEI).
Relevant Publications:
1. Shen P, et al. IL-35-producing B cells are critical regulators of
immunity during autoimmune and infectious diseases. Nature. 2014 Mar
20;507(7492):366-70. [PMID 24572363]
2. Ding Q, et al. Regulatory B cells are identified by expression of
TIM-1 and can be induced through TIM-1 ligation to promote tolerance in
mice. J Clin Invest. 2011 Sep;121(9):3645-56. [PMID 21821911]
3. Carter NA, et al. Mice lacking endogenous IL-10-producing regulatory
B cells develop exacerbated disease and present with an increased
frequency of Th1/Th17 but a decrease in regulatory T cells. J Immunol.
2011 May 15;186(10):5569-79. [PMID 21464089]
4. Collison LW, et al. IL-35-mediated induction of a potent regulatory
T cell population. Nat Immunol. 2010 Dec;11(12):1093-101. [PMID
20953201]
5. Kochetkova I, et al. IL-35 stimulation of CD39+ regulatory T cells
confers protection against collagen II-induced arthritis via the
production of IL-10. J Immunol. 2010 Jun 15;184(12):7144-53. [PMID
20483737]
Intellectual Property: HHS Reference No. E-036-2012/0--
U.S. Patent Application No. 61/637,915 filed 25 Apr 2012.
PCT Application No. PCT/US2013/036175 filed 11 Apr 2013,
which published as WO 2013/162905 on 31 Oct 2013.
Licensing Contact: Yolanda Mock-Hawkins, Ph.D., M.B.A.; 301-435-
5170; [email protected].
Collaborative Research Opportunity: The National Eye Institute,
Molecular Immunology Section, is seeking statements of capability or
interest from parties interested in collaborative
[[Page 19637]]
research to further develop, evaluate or commercialize Ex-vivo
Production of Regulatory B-Cells (Breg). For collaboration
opportunities, please contact Alan Hubbs, Ph.D. at [email protected].
SCGB3A2 for Treatment of Cancer
Description of Technology: A novel method of treating lung cancer
using uteroglobin-related protein 1 (UGRP1), also known as
secretoglobin family 3A member 2 (SCGB3A2) is disclosed. SCGB3A2 is a
member of the uteroglobin/Clara cell secretory protein or Secretoglobin
gene superfamily of secretory proteins that is predominantly expressed
in the epithelial cells of the trachea, bronchus, and bronchioles, and
is known for its anti-inflammatory activity. The inventors have
previously discovered the growth factor and anti-fibrotic activities of
SCGB3A2 and proposed the use of SCGB3A2 as a therapeutic to treat
neonatal respiratory distress and as an agent to promote lung
development, and to inhibit or reduce pulmonary fibrosis caused by an
anti-cancer agent. Recently, the inventors have made a surprising
discovery that the secretory protein SCGB3A2 also has anti-cancer
activity, in addition to its known growth factor, anti-inflammatory,
and anti-fibrotic activities. The inventors have used SCGB3A2-induced
inhibition of metastasis in the iv- and sc-injected LLC cells lung
metastasis model, Scgb3a2-null mice injected with LLC cells with and
without SCGB3A2, and Scgb3a2-lung transgenic mice subjected to tobacco
carcinogen induced mouse carcinogenesis bioassay to confirm their
discovery that SCGB3A2 has anti-cancer activity.
Potential Commercial Applications: Therapeutics for treating
cancers.
Competitive Advantages:
This technology provides, for the first time, a new mode
of treating lung cancer using SCGB3A2.
Because SCGB3A2 is predominantly expressed in lung
airways, low toxicity is anticipated by the use of SCGB3A2 as a
therapeutic.
Unique mode of action (affects both metastasis and growth
(proliferation) of cancer cells) makes SCGB3A2 more effective as a
therapeutic.
Development Stage:
Early-stage.
In vitro data available.
In vivo data available (animal).
Inventors: Kimura Shioko, Cai Yan, and Murata Miyuki (NCI).
Publication: Cai Y, et al. Preclinical evaluation of human
secretoglobin 3A2 in mouse models of lung development and fibrosis. Am
J Physiol Lung Cell Mol Physiol. 2014 Jan 1;306(1):L10-22. [PMID
24213919].
Intellectual Property: HHS Reference No. E-286-2006/3--US
Provisional Patent Application No. 61/862,429 filed 05 Aug 2013.
Related Technologies: HHS Reference Nos. E-286-2006/0, 1, 2-
US Patent No. 8,133,859 issued 13 Mar 2012.
US Patent No. 8,501,688 issued 06 Aug 2013.
US Patent Application No. 13/959,628 filed 05 Aug 2013.
Licensing Contact: Suryanarayana (Sury) Vepa; 301-435-5020;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute,
Laboratory of Metabolism, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate or commercialize SCGB3A2 as an anti-cancer reagent,
which mainly works through the JNK pathway. For collaboration
opportunities, please contact John D. Hewes, Ph.D. at
[email protected].
Dated: April 3, 2014.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2014-07871 Filed 4-8-14; 8:45 am]
BILLING CODE 4140-01-P