[Federal Register Volume 79, Number 75 (Friday, April 18, 2014)]
[Notices]
[Pages 21936-21938]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-08881]
-----------------------------------------------------------------------
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
[[Page 21937]]
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.
Compositions for Modification of Genomic DNA and Exogenous Gene
Expression
Description of Technology: A novel method of targeted insertion of
transgenes at CLYBL locus directly in human cells is disclosed. Also,
methods and compositions for increasing targeted insertion of a
transgene into a specific location within the cell or increasing the
frequency of gene modification in a targeted locus are disclosed.
Genome modification by precise gene targeting at specific sequence/
locus has great advantages over conventional transient expression or
random integration methodologies and, therefore, has tremendous
therapeutic potential. NIH investigators identified CLYBL gene in
Chromosome 13 as a potential safe harbor locus. To directly target
CLYBL safe-harbor in human cells without pre-engineering, they
identified a unique transcription activator-like effector nuclease
(TALEN) target sequence at CLYBL locus. The CLYBL TALENs (also termed
as C13 TALENs) constructed using pZT backbone showed high gene editing
efficiency in human 293T cells measured by both T7E1 mismatch assay and
targeted sequencing. The inventors have used TALENs to simultaneously
knock-in multiple reporter genes at up to four alleles of PPP1R12C/
AAVS1 and new CLYBL safe-harbors in human induced pluripotent stem
cells (iPSCs) and neural stem cells (NSCs). The engineered safe-harbor
knock-in cell lines maintain robust transgene expression during iPSC/
NSC self-renewal and differentiation, and CLYBL locus allowed 10-fold
stronger transgene expression than other loci. NSC lines engineered by
this methodology as well as constructs and protocols for evaluation are
also available.
Potential Commercial Applications:
Human stem cell-based gene therapy.
Drug screening.
Competitive Advantages: CLYBL safe harbor on Chromosome 13 allows
5~10-fold stronger transgene expression than AAVS1 safe harbor,
providing an alternative and potentially better solution for targeted
gene transfer/knock-in and drug-screening, especially for weak
promoter-driven transgenes.
Development Stage:
Early-stage.
In vitro data available.
Inventors: Jizhong Zou and Mahendra S. Rao (NIAMS).
Intellectual Property: HHS Reference No. E-763-2013/0-US-01--US.
Application No. 61/905,002 filed 15 Nov 2013.
Related Technology: HHS Reference No. E-762-2013/0-US-01--US.
Application No. 61/904,999 filed 15 Nov 2013.
Licensing Contact: Sury Vepa, Ph.D., J.D.; 301-435-5020;
[email protected].
Engineering Neural Stem Cells Using Homologous Recombination
Description of Technology: Methods for modifying the genome of a
Neural Stem Cell (NSC) are disclosed. Also, methods for differentiating
NSCs into neurons and glia are described. NSCs are multipotent, self-
renewing cells found in the central nervous system, capable of
differentiating into neurons and glia. NSCs can be generated
efficiently from pluripotent stem cells (PSCs) and have the capacity to
differentiate into any neuronal or glial cell type of the central
nervous system. Improvements in genome engineering of NSCs can
potentially facilitate cellular replacement therapies for the treatment
of neurodegenerative disorders. Recently, NIH investigators have
developed a procedure to efficiently engineer NSCs through homologous
recombination by introducing TAL effector nucleases (TALENs) and donor
vectors. They have designed TALENs that efficiently generate double
stranded breaks at two safe harbor loci (AAVS1 and CLYBL). These TALENs
facilitate homologous recombination without silencing at these loci.
The TALENs were delivered along with a DNA donor vector with a
ubiquitous promoter driving expression of a cDNA using a nucleofector
to get high transfection efficiencies. NSCs modified in this manner
have therapeutic potential in treating neurodegenerative diseases. NSC
lines engineered by this methodology as well as constructs and
protocols for evaluation are also available.
Potential Commercial Applications: Cellular replacement therapies
for neurodegenerative disorders.
Competitive Advantages:
The novel methods provide highly pure engineered NSC
populations which maintain the capacity to self-renew and differentiate
to neurons and astrocytes suitable for cell replacement therapies.
Safe harbor TALEN-mediated homologous recombination is a
high-efficiency method to generate targeted mini-gene transfer or
reporter knock-in cell lines in both human iPSCs and NSCs.
Development Stage:
Early-stage.
In vitro data available.
Inventors: Nasir S. Malik, Mahendra S. Rao, Jizhong Zou, Raymond
Funahashi (all of NIAMS).
Intellectual Property: HHS Reference No. E-762-2013/0-US-01--US.
Application No. 61/904,999 filed 15 Nov 2013.
Related Technology: HHS Reference No. E-763-2013/0-US-01--US.
Application No. 61/905,002 filed 15 Nov 2013.
Licensing Contact: Sury Vepa, Ph.D., J.D.; 301-435-5020;
[email protected].
Role of Novel Hepatitis Delta Virus Variant in Sj[ouml]gren's Syndrome
Description of Technology: Sj[ouml]gren's is a chronic autoimmune
disease characterized by dry mouth and eyes, fatigue, and
musculoskeletal pain resulting from the attack of the moisture-
producing glands by the body's own white blood cells. The subject
invention is based on the discovery of an association between infection
by a novel clade 1 variant of hepatitis delta virus (HDV) and primary
Sj[ouml]gren's syndrome. The association was made after detection of
the HDV nucleic acid in the salivary glands of patients diagnosed with
Sj[ouml]gren's syndrome and in vivo studies in mice that developed
Sj[ouml]gren's syndrome-like pathogenesis after expression of HDV
antigen. The discovery of this link opens the possibilities for
developing diagnostics against HDV to determine who are at risk for
developing Sj[ouml]gren's syndrome. The novel HDV variant can also
serve as a potential therapeutic target for preventing or treating
Sj[ouml]gren's.
Potential Commercial Applications:
Diagnostic for novel HDV clade 1 variant as a risk factor
for developing Sj[ouml]gren's.
Therapeutics against this newly discovered HDV clade 1
variant for prevention and/or treatment of Sj[ouml]gren's syndrome.
Competitive Advantages:
Novel diagnostic for a potentially significant risk factor
in developing Sj[ouml]gren's syndrome.
Newly discovered potential targets for treatment of
Sj[ouml]gren's.
Development Stage:
Early-stage.
In vitro data available.
In vivo data available (animal).
Inventors: Melodie L. Weller and John Chiorini (NIDCR).
[[Page 21938]]
Intellectual Property: HHS Reference No. E-736-2013/0--US
Provisional. Application No. 61/888,706 filed 09 Oct 2013.
Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018;
[email protected].
Collaborative Research Opportunity: The National Institute of
Dental and Craniofacial Research is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate or commercialize Role of Novel Hepatitis Delta Virus
Variant. For collaboration opportunities, please contact David W.
Bradley, Ph.D. at [email protected].
Treating or Inhibiting JC Polyomavirus Infection and JC Polyomavirus-
Associated Progressive Multifocal Leukoencephalopathy
Description of Technology: Available for licensing are novel
findings to generate immune response to JC polyomavirus (JCV). An
immunogenic composition with a single JCV subtype VP1 polypeptide
generates neutralizing antibodies to all JCV subtypes, including JCV
with variant VP1 polypeptides. The invention is useful for the
prevention, treatment, or inhibition of JCV infection and JCV-
associated pathologies, such as progressive multifocal
leukoencephalopathy (PML).
Also available for licensing are techniques for identifying a
subject at risk for developing PML, based on detecting the absence of
JCV neutralizing antibodies in the subject.
Potential Commercial Applications:
Pharmaceutical treatments of JC virus infection.
Pharmaceutical treatments or prevention of PML.
Prediction or early diagnosis of the development of PML.
Competitive Advantages:
Generating an immune response to all JC virus subtypes
utilizing a JC virus capsid polypeptide from a single subtype.
No known methods for identifying a subject at risk for
developing PML by detecting the absence of JC virus neutralizing
antibodies in the subject.
Development Stage:
Early-stage.
In vitro data available.
In vivo data available (animal).
In vivo data available (human).
Inventors: Christopher B. Buck (NCI), Upasana Ray (NCI), and Diana
V. Pastrana.
Publication: Buck CB. Developing vaccines against BKV and JCV.
Presentation, 5th International Conference on Polyomaviruses and Human
Diseases: Basic and Clinical Perspectives, Stresa, Italy, May 9-11,
2013. Abstract published online in June 2013 in J Neurovirol.
2013;19:307. [DOI 10.1007/s13365-013-0171-0].
Intellectual Property: HHS Reference No. E-549-2013/0--US
Provisional. Application No. 61/919,043 filed 20 Dec 2013.
Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute,
Laboratory of Cellular Oncology, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate or commercialize methods of treating JC polyomavirus-
related disorders. For collaboration opportunities, please contact John
D. Hewes, Ph.D. at [email protected].
Therapeutic for Sickle Cell Disease and Beta Thalassemias
Description of Technology: Sickle-cell disease and beta thalassemia
are among the most common hereditary blood disorders in the world. It
has been shown that patients exhibit less severe symptoms of these
disorders when they produce unusually high levels of fetal hemoglobin
(HbF). HbF production, which normally shuts off after birth, has been
considered as a viable treatment because of inability to form
hemoglobin aggregates within red blood cells responsible for painful
episodes in patients. Researchers at the National Institute of Diabetes
and Digestive and Kidney Diseases have identified a method of
regulating the expression of fetal hemoglobin in adult red blood cells.
The lead inventor and colleagues have developed novel expression
vectors designed to reactivate production of HbF proteins through
increased erythroid-specific expression of Lin28 or decreased
expression of Let-7 micro-RNAs. This technology could lead to
development of multiple types of therapeutics that ameliorate or
eliminate the pathologies associated with human sickle-cell anemia and
beta thalassemia.
Potential Commercial Applications: Ex vivo and in vivo therapeutics
for treatment of sickle-cell anemia and beta thalassemias.
Competitive Advantages:
Amplification of HbF expression 10-fold higher than
existing methods.
Reduced production of symptom-associated adult hemoglobin.
Regulation of Lin28 and Let-7 expression with no
immunogenic effects.
Potential for viral and non-viral gene delivery.
Potential for Genome Editing Therapy.
Development Stage:
Early-stage.
In vitro data available.
In vivo data available (animal).
Inventors: Jeffery L. Miller (NIDDK), Yuanwei T. Lee (NIDDK),
Colleen Byrnes (NIDDK), Jaira Vasconcellos (NIDDK), Stefan A. Muljo
(NIAID).
Publication: Lee YT, et al. LIN28B-mediated expression of fetal
hemoglobin and production of fetal-like erythrocytes from adult human
erythroblasts ex vivo. Blood. 2013 Aug 8;122(6):1034-41. [PMID
23798711].
Intellectual Property: HHS Reference No. E-456-2013/2--
International. Application No. PCT/US2013/067811 filed 31 Oct 2013.
Licensing Contact: Vince Contreras, Ph.D.; 301-435-4711;
[email protected].
Dated: April 14, 2014.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2014-08881 Filed 4-17-14; 8:45 am]
BILLING CODE 4140-01-P