[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