[Federal Register Volume 77, Number 218 (Friday, November 9, 2012)]
[Notices]
[Pages 67381-67385]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-27426]


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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, Public Health Service, 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. 207 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.

Cell Lines Expressing Nuclear and/or Mitochondrial RNase H1

    Description of Technology: RNase H1 has been shown to remove RNA/
DNA hybrids and either too much or too little enzyme can lead to 
undesirable effects such as deletions of DNA. The gene encoding RNase 
H1 in mammalian cells produces two forms of the protein. One is 
targeted to the nucleus of the cell and the other to the mitochondrial 
organelle. To study the effects of expression as well as to understand 
the regulation of the frequency with which each form is made, NIH 
investigators constructed cells derived from HEK293 cells where 
expression of each or both forms is/are expressed only after addition 
of doxycycline as a small molecule inducer compound. The set of cell 
lines could be important in the process of analysis of RNA/DNA hybrids 
as each

[[Page 67382]]

cell line expresses different amounts of each form.
    Potential Commercial Applications: Research materials to study RNA/
DNA hybrids
    Competitive Advantages: Not available elsewhere
    Development Stage:
     Prototype
     Pre-clinical
     In vitro data available
    Inventors: Robert J. Crouch and Yutaka Suzuki (NICHD).
    Publication: Suzuki Y, et al. An upstream open reading frame and 
the context of the two AUG codons affect the abundance of mitochondrial 
and nuclear RNase H1. Mol Cell Biol. 2010 Nov;30(21):5123-34. [PMID 
20823270]
    Intellectual Property: HHS Reference No. E-273-2012/0--Research 
Material. 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 Program in Genomics of 
Differentiation, NICHD, is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate or commercialize small molecule inhibitors of RNase H1, genome 
instability, or transcription and translation. For collaboration 
opportunities, please contact Joseph Conrad III, Ph.D. at 
[email protected].

Improved Transposase Compositions for Whole Genome Sequencing

    Description of Technology: The invention provides improved 
transposase enzymes engineered to exhibit reduced sequence biases, and 
to operate more efficiently than wildtype transposases.
    Scientists at NIDDK and John Hopkins University jointly developed 
mutant transposases that are superior to wildtype transposases in whole 
genome sequencing applications. Transposases facilitate the cleavage of 
certain DNA segments, called transposons, at specific sites within a 
genome and their subsequent insertions at random sites. Addition of 
transposases and labeled transposons to whole genome preparations allow 
for one-pot, simultaneous fragmentation and identification of targeted 
DNA sequences.
    Mutations introduced by the inventors facilitate formation of 
dimeric enzyme complexes with enhanced activity and stability. These 
modifications result in more efficient fragmentation and tagging of 
genomic DNA.
    Potential Commercial Applications: Kits for whole genome 
sequencing.
    Competitive Advantages:
     Can easily be expressed in the bacterium, E. coli, and 
purified in large quantities.
     Are soluble, stable and exist as smaller active complexes 
compared to native enzymes.
     Are fully active at room temperature (23-30[deg]C).
     Have a higher transposition activity and show minimal 
insertional sequence bias in-vitro compared to the wild type.
    Development Stage:
     Prototype
     Pilot
     In vitro data available
    Inventors: Fred Dyda (NIDDK), Alison Hickman (NIDDK), Nancy Craig 
(Johns Hopkins School of Medicine), Sunil Gangadharan (Johns Hopkins 
School of Medicine).
    Intellectual Property: HHS Reference No. E-194-2012/0--U.S. 
Provisional Application No. 61/652,560 filed 29 May 2012.
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; [email protected].

Improved Monoclonal Antibodies Against Neuregulin 2

    Description of Technology: The invention provides highly selective 
monoclonal antibodies against the extracellular domain (ECD) or 
intracellular domain (ICD) of neuregulin-2, a ligand for the ErbB 
receptors in adult human brain. Neuregulins regulate a diverse array of 
neurological process in the central nervous system and are implicated 
in schizophrenia and other psychiatric disorders. However, an 
understanding of the specific role of neuregulin 2 has been hindered by 
a lack of specific antibodies useful in immunoblotting and 
immunohistology studies. Commercially available antibodies do not 
perform as well in these applications when compared to the invention 
antibodies. A mouse monoclonal antibody directed to the ECD is 
available for licensing (clone 8D11, HHS Ref. No. E-192-2012), and 
rabbit antibodies directed to the ICD are also available (clone 11-11, 
HHS Ref. No. E-193-2012; clone 15-10, HHS Ref. No. E-189-2012; and 
clone 9-2, HHS Ref. No. E-188-2012). Antibodies from clones 8D11 and 
11-11 have been validated for immunohistology and antibodies from 
clones 15-10 and 9-2 have been validated for Western blotting using 
brain tissue from wild-type and neuregulin 2 deficient mice.
    Potential Commercial Applications: Superior monoclonal antibody for 
Western blotting or immunohistology analysis of tissue sections
    Competitive Advantages:
     Superior binding specificity in comparison to commercially 
available antibodies
     Developed antibodies bind specific, characterized regions 
on neuregulin 2
    Development Stage:
     Prototype
     In vitro data available
    Inventors: Detlef Vullhorst, Andres Buonanno, Irina Karavanov (all 
of NICHD).
    Intellectual Property: HHS Reference Nos. E-188-2012/0, E-189-2012/
0, E-190-2012/0, E-191-2012/0, E-192-2012/0, E-193-2012/0. This is a 
Research Tool--patent protection is not being pursued for this 
technology.
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; [email protected].
    Collaborative Research Opportunity: The NICHD is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize neuregulin-2 
monoclonal antibodies. For collaboration opportunities, please contact 
Charlotte McGuinness at [email protected].

Glucocerebrosidase Activators for the Treatment of Gaucher Disease, 
Parkinson's Disease, and Other Proteinopathies

    Description of Technology: Gaucher disease is a rare lysosomal 
storage disease that is characterized by a loss of function of the 
glucocerebrosidase (GCase) enzyme, which results in a decreased ability 
to degrade its lipid substrate, glucocerebroside. The intracellular 
build up of this lipid causes a broad range of clinical manifestations, 
ranging from enlarged spleen/liver and anemia to neurodegeneration. In 
Gaucher disease, the loss of GCase function has been attributed to low 
levels of the protein in the lysosomal compartment, resulting from 
improper GCase folding and transport. Also, mutations in the GCase gene 
have been linked to some forms of Parkinson's disease, and may also be 
involved in other proteinopathies.
    This technology describes a collection of salicylic acid-derived 
small molecules that act as chaperones to activate proper GCase folding 
and subsequent transport from the endoplasmic reticulum into the 
lysosome. Unlike many other small molecule chaperones, these salicylic 
acid derivatives do not inhibit the activity of the GCase enzyme. These

[[Page 67383]]

small molecules have been tested for the ability to activate GCase in 
vitro and show chaperone activity in a patient-derived fibroblast 
translocation assay.
    Potential Commercial Applications:
     Treatment of Gaucher disease
     Treatment of Parkinson's disease
     Treatment of other lysosomal storage diseases
    Competitive Advantages: The compounds are novel small molecules 
that enhance proper GCase folding and transport without inhibiting 
enzyme activity in the lysosome.
    Development Stage:
     Early-stage
     In vitro data available
    Inventors: Juan Marugan (NCATS), Wei Zheng (NCATS), Samarjit 
Patnaik (NCATS), Noel Southall (NCATS), Ellen Sidransky (NHGRI), Ehud 
Goldin (NHGRI), Wendy Westbroek (NHGRI).
    Publication: Related publication is currently in preparation.
    Intellectual Property:
     HHS Reference No. E-144-2012/0--U.S. Provisional 
Application No. 61/616,758 filed 28 Mar 2012
     HHS Reference No. E-144-2012/1--U.S Provisional 
Application No. 61/616,773 filed 28 Mar 2012
    Licensing Contact: Tara Kirby, Ph.D.; 301-402-0220; 
[email protected].
    Collaborative Research Opportunity: The National Center for 
Advancing Translational Sciences is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize this technology. For collaboration 
opportunities, please contact Dr. Juan Marugan at 
[email protected].

Cyclodextrins as Therapeutics for Lysosomal Storage Disorders

    Description of Technology: Cyclodextrins (CD), alone or in 
combination with other agents (e.g., vitamin E), as therapeutics for 
the treatment of lysosomal storage disorders (LSDs) caused by the 
accumulation of non-cholesterol lipids.
    CDs are sugar molecules in a ring form. The alpha-CD (6 sugars), 
beta-CD (7 sugars) and gamma-CD (8 sugars) are commonly used 
cyclodextrins. The hydroxypropyl-beta cyclodextrin (HPbCD) has been 
approved for pharmaceutical use. Recent reports show that beta-
cyclodextrin including HPbCD and beta-methyl-cyclodextrin reduced 
cholesterol accumulation and neuronal cell loss in the mouse model of 
NPC1 disease.
    NCATS investigators found that CD (alpha-, beta- and gamma-CDs) 
increased intracellular Ca2+ and lysosomal exocytosis in both wild type 
cells and cells with Wolman disease, and reduced the size of enlarged 
lysosomes in six patient cell lines with LSDs. Further, CD in 
combination with tocopherol synergistically/additively reduced 
cholesterol accumulation in cells of NPC and Wolman diseases. Based on 
these results, they propose treatment of LSDs with cyclodextrins (such 
as alpha and gamma forms) alone or in combination with Vitamin E and 
its analogues for better efficacy and less side effects.
    Potential Commercial Applications:
     Treatment of lysosomal storage diseases
     Treatment of disorders caused by accumulation of non-
cholesterol lipids
    Competitive Advantages:
     Use of cyclodextrins in combination with vitamin-E (e.g., 
delta-tocopherol) provides additive therapeutic effect
     Less side effects than cyclodextrin only or vitamin E only 
for LSDs because of reduced doses for both compounds in combination
    Development Stage:
     Early-stage
     Pre-clinical
     In vitro data available
    Inventors: John McKew, Wei Zheng, Miao Xu, Manju Swaroop, Juan 
Marugan (all of NCATS).
    Intellectual Property: HHS Reference No. E-050-2012/0--US 
Provisional Application No. 61/679,668 filed 12 Aug 2012.
    Related Technology: HHS Reference No. E-294-2009/0--PCT Patent 
Application No. PCT/US2011/044590 filed 19 Jul 2011, entitled'' ``Use 
of Delta Tocopherol for the Treatment of Lysosomal Storage Disorders'' 
(Wei Zheng et al., NCATS).
    Licensing Contact: Suryanarayana Vepa, Ph.D., J.D.; 301-435-5020; 
[email protected].
    Collaborative Research Opportunity: The National Center for 
Advancing Translational Sciences is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize this technology. For collaboration 
opportunities, please contact Dr. Juan Marugan at 
[email protected].

Selective Treatment of Cancer, HIV, Other RNA Viruses and Genetically 
Related Diseases Using Therapeutic RNA Switches

    Description of Technology: Targeted therapy in cancer or viral 
infections is a challenge because the disease state manifests itself 
mainly through differences in the cell interior, for example in the 
form of the presence of a certain RNAs or proteins in the cytoplasm.
    The technology consists of designed RNA switches that activate the 
RNA interference pathway only in the presence of a trigger RNA or DNA 
to which they bind, in order to knock down a chosen gene that is not 
necessarily related to the initial trigger.
    This new approach can lead to a new type of drug that has the 
unique feature of selectively causing a biochemical effect (such as 
apoptosis) in cells that are infected by RNA viruses (such as HIV), as 
well as cancer cells. The RNA switch concept can be expanded to 
selectively treat other genetically related diseases.
    Potential Commercial Applications:
     Targeted therapeutic for viral infections, cancer stem 
cells, and genetically related diseases
     Research tool to study cancer or viral infection
    Competitive Advantages:
     Fewer side effects because the therapeutic RNA-
interference pathway is only activated by the RNA switch when it is 
intact and in its active conformation
     Selectively kills cells infected by RNA viruses
     Contains a minimal number of single stranded nucleotides, 
thus minimizing the effects of nucleases
    Development Stage: In vitro data available
    Inventors: Bruce A. Shapiro (NCI), Eckart Bindewald (SAIC-
Frederick, Inc.), Kirill Afonin (NCI), Arti Santhanam (NCI).
    Publications:
    1. Afonin KA, et al. Co-transcriptional Assembly of Chemically 
Modified RNA Nanoparticles Functionalized with siRNAs. Nano Lett. 2012 
Oct 10;12(10):5192-5. [PMID 23016824]
    2. Grabow WW, et al. ``RNA Nanotechnology in Nanomedicine,'' in 
Nanomedicine and Drug Delivery (Recent Advances in Nanoscience and 
Nanotechnology), ed. M Sebastian, et al. (New Jersey: Apple Academic 
Press, 2012), 208-220. [Book Chapter]
    3. Shukla GC, et al. A boost for the emerging field of RNA 
nanotechnology. ACS Nano. 2011 May 24;5(5):3405-18. [PMID 21604810]
    4. Afonin KA, et al. Design and self-assembly of siRNA-
functionalized RNA nanoparticles for use in automated nanomedicine. Nat 
Protoc. 2011 Dec 1;6(12):2022-34. [PMID 22134126]
    5. Bindewald E, et al. Multistrand RNA secondary structure 
prediction and nanostructure design including pseudoknots. ACS Nano. 
2011 Dec 27;5(12):9542-51. [PMID 22067111]
    6. Grabow WW, et al. Self-assembling RNA nanorings based on RNAI/II 
inverse kissing complexes. Nano Lett.

[[Page 67384]]

2011 Feb9;11(2):878-87. [PMID 21229999]
    7. Kasprzak W, et al. Use of RNA structure flexibility data in 
nanostructure modeling. Methods. 2011 Jun;54:239-50. [PMID 21163354]
    8. Afonin KA, et al. In vitro assembly of cubic RNA-based scaffolds 
designed in silico. Nat Nanotechnol. 2010 Sep;5:676-82. [PMID 20802494]
    9. Severcan I, et al. ``Computational and Experimental RNA 
Nanoparticle Design,'' in Automation in Genomics and Proteomics: An 
Engineering Case-Based Approach, ed. G Alterovitz, et al. (Hoboken: 
Wiley Publishing, 2009), 193-220. [Book Chapter]
    10. Shapiro B, et al. ``Protocols for the In silico Design of RNA 
Nanostructures,'' in Nanostructure Design Methods and Protocols, ed. E 
Gazit, R Nussinov. (Totowa, NJ: Humana Press, 2008), 93-115. [Book 
Chapter]
    11. Bindewald E, et al. Computational strategies for the automated 
design of RNA nanoscale structures from building blocks using 
NanoTiler. J Mol Graph Model. 2008 Oct;27(3):299-308. [PMID 18838281]
    12. Yingling YG, Shapiro BA. Computational design of an RNA 
hexagonal nanoring and an RNA nanotube. Nano Lett. 2007 Aug;7(8): 2328-
34. [PMID 17616164]
    Intellectual Property:
     HHS Reference No. E-038-2012/0 -- U.S. Provisional 
Application No. 61/561,247 filed 17 Nov 2011
     HHS Reference No. E-038-2012/1 -- U.S. Provisional 
Application No. 61/678,434 filed 01 Aug 2012
    Related Technology: HHS Reference No. E-039-2012/0--U.S. 
Provisional Application No. 61/561,257 filed 17 Nov 2011.
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].
    Collaborative Research Opportunity: The NCI Center for Cancer 
Research Nanobiology Program is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize therapeutic RNA switches. For 
collaboration opportunities, please contact John Hewes, Ph.D. at 
[email protected].

Activation of Therapeutic Functionalities With Chimeric RNA/DNA 
Nanoparticles for Treatment of Cancer, Viruses and Other Diseases

    Description of Technology: A new strategy based on RNA/DNA hybrid 
nanoparticles, which can be generally used for triggering multiple 
functionalities inside diseased cells is presented. Individually, each 
of the hybrids is functionally inactive and functional representation 
can only be activated by the re-association of at least two cognate 
hybrids simultaneously present in the same cell. Overall, this novel 
approach allows (i) The triggered release of therapeutic siRNAs or 
miRNAs inside the diseased cells, (ii) activation of other split 
functionalities (e.g. FRET, different aptamers, rybozymes, split 
proteins) intracellularly, (iii) higher control over targeting 
specificity (e.g. if two hybrids are decorated with two different 
tissue specific recognition moieties), (iv) biosensing and tracking of 
the delivery and re-association of these hybrids in real-time inside 
cells, (v) increasing the number of functionalities by introducing a 
branched hybrid structure, (vi) introduction of additional 
functionalities without direct interference of siRNA processivity, 
(vii) increasing the retention time in biological fluids by fine-tuning 
chemical stability through substituting the DNA strands with chemical 
analogs (e.g. LNA, PNA, etc.), (viii) conditional release of all 
functionalities.
    Potential Commercial Applications:
     Therapeutic siRNA for cancer, viruses and other diseases
     Therapeutic for delivery of multiple functionalities
     Diagnostic to visualize cancer cells, virus infected 
cells, or diseased cells, or track the delivery and effectiveness of 
siRNA treatment or other treatments associated with the particle
     Research tool to study cancer, viral infections or other 
diseases
    Competitive Advantages:
     Novel way for multiple functionality delivery and 
activation
     Enhanced chemical stability and pharmacokinetics due to 
the average size of nanoparticles exceeding 10nm
     Increased specificity for selecting cells of interest 
using more than one target gene
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Bruce A. Shapiro (NCI), Kirill Afonin (NCI), Arti 
Santhanam (NCI), Mathias Viard (SAIC-Frederick, Inc.), Eckart Bindewald 
(SAIC-Frederick, Inc.), Luc Jaeger (U of Cal. Santa Barbara).
    Publications:
    1. Afonin KA, et al. Co-transcriptional Assembly of Chemically 
Modified RNA Nanoparticles Functionalized with siRNAs. Nano Lett. 2012 
Oct 10;12(10):5192-5. [PMID 23016824]
    2. Grabow WW, et al. ``RNA Nanotechnology in Nanomedicine,'' in 
Nanomedicine and Drug Delivery (Recent Advances in Nanoscience and 
Nanotechnology), ed. M Sebastian, et al. (New Jersey: Apple Academic 
Press, 2012), 208-220. [Book Chapter]
    3. Shukla GC, et al. A boost for the emerging field of RNA 
nanotechnology. ACS Nano. 2011 May 24;5(5):3405-18. [PMID 21604810]
    4. Afonin KA, et al. Design and self-assembly of siRNA-
functionalized RNA nanoparticles for use in automated nanomedicine. Nat 
Protoc. 2011 Dec 1;6(12):2022-34. [PMID 22134126]
    5. Bindewald E, et al. Multistrand RNA secondary structure 
prediction and nanostructure design including pseudoknots. ACS Nano. 
2011 Dec 27;5(12):9542-51. [PMID 22067111]
    6. Grabow WW, et al. Self-assembling RNA nanorings based on RNAI/II 
inverse kissing complexes. Nano Lett. 2011 Feb9;11(2):878-87. [PMID 
21229999]
    7. Kasprzak W, et al. Use of RNA structure flexibility data in 
nanostructure modeling. Methods. 2011 Jun;54:239-50. [PMID 21163354]
    8. Afonin KA, et al. In vitro assembly of cubic RNA-based scaffolds 
designed in silico. Nat Nanotechnol. 2010 Sep;5:676-82. [PMID 20802494]
    9. Severcan I, et al. ``Computational and Experimental RNA 
Nanoparticle Design,'' in Automation in Genomics and Proteomics: An 
Engineering Case-Based Approach, ed. G Alterovitz, et al. (Hoboken: 
Wiley Publishing, 2009), 193-220. [Book Chapter]
    10. Shapiro B, et al. ``Protocols for the In silico Design of RNA 
Nanostructures,'' in Nanostructure Design Methods and Protocols, ed. E 
Gazit, R Nussinov. (Totowa, NJ: Humana Press, 2008), 93-115. [Book 
Chapter]
    11. Bindewald E, et al. Computational strategies for the automated 
design of RNA nanoscale structures from building blocks using 
NanoTiler. J Mol Graph Model. 2008 Oct;27(3):299-308. [PMID 18838281]
    12. Yingling YG, Shapiro BA. Computational design of an RNA 
hexagonal nanoring and an RNA nanotube. Nano Lett. 2007 Aug;7(8): 2328-
34. [PMID 17616164]
    Intellectual Property: HHS Reference No. E-039-2012/0--U.S. 
Provisional Application No. 61/561,257 filed 17 Nov 2011
    Related Technology:
     HHS Reference No. E-038-2012/0--U.S. Provisional 
Application No. 61/561,247 filed 17 Nov 2011
     HHS Reference No. E-038-2012/1--U.S. Provisional 
Application No. 61/678,434 filed 01 Aug 2012
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].
    Collaborative Research Opportunity: The NCI Center for Cancer 
Research

[[Page 67385]]

Nanobiology Program is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate or commercialize therapeutic RNA/DNA nanoparticles. For 
collaboration opportunities, please contact John Hewes, Ph.D. at 
[email protected].

    Dated: November 5, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-27426 Filed 11-8-12; 8:45 am]
BILLING CODE 4140-01-P