[Federal Register Volume 80, Number 57 (Wednesday, March 25, 2015)]
[Notices]
[Pages 15790-15791]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-06845]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

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.

SUPPLEMENTARY INFORMATION: Technology descriptions follow.

Engineered Antibody Domains With Increased FcRn Binding and in vivo 
Half-Life

    Description of Technology: Monoclonal antibodies (mAbs) are a fast 
growing class of new therapeutic molecules. However, their large size 
remains a significant challenge, preventing them from targeting 
sterically restricted epitopes and efficiently penetrating into 
tissues. Smaller antibody fragments and engineered variants are under 
development to address this challenge, but to date their therapeutic 
applications have been limited due to rapid clearance and short half-
life which greatly decrease their efficacy in vivo.
    This technology describes two antibody constant domains or binders 
with increased FcRn binding and in vivo half-life. In addition, these 
binders are small in size (16kDa), very stable, and can be efficiently 
expressed in E. coli. As a result, the binders are particularly well 
suited as scaffolds for the generation of antibody libraries, from 
which a desired antigen binders could be developed into therapeutic 
products with much greater potency compared to existing mAbs. They 
could also be used as fusion partners to extend the half-life of 
candidate protein therapeutics.

Potential Commercial Applications

     Antibody scaffolds for library construction, and the 
generation of therapeutics against various diseases.
     Fusion partners to extend the half-life of candidate 
protein therapeutics.

Competitive Advantages

     Small (16kD) size for better tissue penetration, and in 
the case of fusion proteins, reduced steric hindrance for therapeutic 
activity.
     Superior stability compared to isolated CH2 domains and 
stability comparable to or higher than that of an isolated Fc fragment.
     Exhibit greatly enhanced FcRn binding abilities, including 
more potent transcytosis and longer in vivo half-life.
     Can be efficiently expressed in E. coli.

Development Stage

     Early-stage
     In vitro data available
     In vivo data available (animal)

    Inventors: Dimiter Dimitrov and Tianlei Ying (NCI).
    Intellectual Property: HHS Reference No. E-136-2014/0--US 
Provisional Application No. 62/022,810 filed July 10, 2014.
    Licensing Contact: Whitney Hastings, Ph.D.; 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 
Engineered Antibody Domains. For collaboration opportunities, please 
contact John D. Hewes, Ph.D. at [email protected] or 240-276-5515.

CXCR4 Reduction Leads to Enhancement of Engraftment of Hematopoietic 
Stem Cells

    Description of Technology: Methods of enhancing engraftment of 
donor hematopoietic stem cells (HSCs) by reducing expression or 
activity of

[[Page 15791]]

CXCR4 in HSCs is described. HSC are the only cells in the bone marrow 
that are both pluripotent and long lived. Bone marrow transplantation 
(BMT) using HSC is an increasingly common medical therapy for severe 
hematologic cancers and primary hematologic immunodeficiencies. 
However, for significant HSC engraftment to occur there must usually be 
pre-transplant conditioning with either irradiation or chemotherapy or 
both. The technology described herein shows that it is possible to 
replace HSC without the need for pre-transplant conditioning regimen. 
It is known that the chemokine receptor CXCR4 plays a critical role in 
HSC homing to the bone marrow and in HSC quiescence. The inventors have 
identified a patient in which one copy of CXCR4 had been deleted in a 
somatic mutation of an HSC and this cell had clonally repopulated the 
bone marrow. This led to experiments in mice where the inventors 
clearly demonstrated in a bone marrow transplantation model, that donor 
cells with a single copy of the Cxcr4 gene repopulate recipient mice 
much faster and last much longer than donor cells having two copies of 
the Cxcr4 gene. This technology which shows that HSCs with one copy of 
the CXCR4 gene have a durable selective advantage in bone marrow 
repopulation can solve the problem frequently encountered in gene 
therapy, i.e., the short-lived nature of gene-corrected cells, by 
utilizing recently discovered gene editing methods that can be used to 
delete one copy of CXCR4 gene in gene-corrected cells.

Potential Commercial Applications

     Improvement of engraftment in gene therapy protocols and 
in HSC transplantation.
     Improved bone marrow transplantation, enhancing the 
efficiency and durability of donor cell repopulation.

Competitive Advantages

     This technology potentially facilitates HSC 
transplantation without the need of radiation or chemotherapy 
conditioning.
     This technology may uniquely overcome a major hurdle 
limiting all gene therapy applications, namely the failure to correct 
the gene defect over a long time.

Development Stage

     Early-stage
     In vitro data available
     In vivo data available (animal)

    Inventors: Jiliang Gao, Philip M. Murphy, David H. McDermott, Marie 
Siwicki, Harry L. Malech, and Joy Liu (all of NIAID).
    Publication: McDermott DH, et al. Chromothriptic cure of WHIM 
syndrome. Cell. 2015 Feb 12;160(4):686-99. [PMID 25662009].
    Intellectual Property: HHS Reference No. E-173-2014/0--US Patent 
Application No. 62/026,138 filed July 18, 2014.
    Licensing Contact: Sury Vepa, Ph.D., J.D.; 301-435-5020; 
[email protected].

Development of GPR124 Wildtype and Knockout Brain Endothelial Reporter 
Cells

    Description of Technology: There is currently no effective way to 
block beta-catenin signaling specifically in brain endothelial cells. 
There is neither an effective way to block beta-catenin signaling 
stimulated by a particular Wnt family member such as WNT7. The reporter 
cells created by the NIH investigator from GPR124 knockout mice provide 
a unique and effective tool to screen for drugs that can specifically 
interfere with the Wnt7/GPR124 signaling pathway. Such drugs have 
potential for widespread therapeutic application in the treatment of 
cerebrovascular diseases, the third leading cause of death in the 
United States, and a variety of neurodegenerative disorders such as 
Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, 
multiple sclerosis, and others.
    Potential Commercial Applications: Research tools for drug 
screening.
    Competitive Advantages: The reporter cells are ideal for screening 
for drugs that specifically interfere with the Wnt7/GPR124 signaling 
pathway as the cells have no inherent low level Gpr124 expression.
    Development Stage: Prototype.
    Inventor: Brad St. Croix (NCI).
    Publication: Posokhova E, et al. GPR124 functions as a WNT7-
specific coactivator of canonical beta-catenin signaling. Cell Rep. 
2015 Jan 13;10 (2):123-30. [PMID 25558062].
    Intellectual Property: HHS Reference No. E-079-2015/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[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 agents that antagonize or promote Gpr124 function. For 
collaboration opportunities, please contact John D. Hewes, Ph.D. at 
[email protected].

    Dated: March 20, 2015.
Richard U. Rodriguez,
Acting Director, Office of Technology Transfer, National Institutes of 
Health.
[FR Doc. 2015-06845 Filed 3-24-15; 8:45 am]
 BILLING CODE 4140-01-P