[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]


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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

[[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