Government-Owned Inventions; Availability for Licensing, 67381-67385 [2012-27426]
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Federal Register / Vol. 77, No. 218 / Friday, November 9, 2012 / Notices
request from the American Association
of Medical Colleges (AAMC) that was
interested in knowing what items were
in the survey instrument. The purpose
of this notice is to allow an additional
30 days for public comment. The
National Institutes of Health may not
conduct or sponsor, and the respondent
is not required to respond to, an
information collection that has been
extended, revised, or implemented on or
after October 1, 1995, unless it displays
a currently valid OMB control number.
Proposed Collection: Title: Ethical
Dilemmas in Surgery and Utilization of
Hospital Ethics Consultation Service: A
Survey. Type of Information Collection
Request: NEW. Need and Use of
Information Collection: This survey is
intended to collect information about
the ethical dilemmas that surgeons have
faced in their practices over the past
year, and assess their experiences, if
any, with their hospital consultation
services. Specifically, the information
gathered in this study will be valuable
in understanding the ethical dilemmas
that surgeons face, the utility of
institution ethics consultations services
for surgeons, and to identify what
barriers, if any, discourage surgeons
from utilizing these services. The results
of this study can be used by medical
professionals, hospitals, and bioethicists
in several important ways. First, they
will provide a better understanding the
ethical dilemmas that surgeons face in
Estimated
number of
respondents
Type of respondents
their practices. Second, they will
provide understanding of factors that
determine the current utilization of
hospital consultation services by
surgeons. Third, information collected
on the barriers to surgeons’ use of ethics
consultation services will provide better
insight into the perspective and culture
of surgery as it relates to ethical
dilemmas in their practices and how
ethics consultation services could better
support surgeons when faced with these
dilemmas. Frequency of Response:
Once. Affected Public: Individuals;
Businesses or other for-profit. Type of
Respondents: Individuals.
The annual reporting burden is as
follows:
Estimated
number of
responses per
respondent
Average
burden per
response
(in hours)
Estimated total
annual burden
hours
requested
598
1
15/60
150
Total ..........................................................................................................
tkelley on DSK3SPTVN1PROD with NOTICES
Surgeons ..........................................................................................................
598
........................
........................
150
There are no capital, operating, or
maintenance costs to report.
Request for Comments: Written
comments and/or suggestions from the
public and affected agencies are invited
on one or more of the following points:
(1) Whether the proposed collection of
information is necessary for the proper
performance of the function of the
agency, including whether the
information will have practical utility;
(2) The accuracy of the agency’s
estimate of the burden of the proposed
collection of information, including the
validity of the methodology and
assumptions used; (3) Ways to enhance
the quality, utility, and clarity of the
information to be collected; and (4)
Ways to minimize the burden of the
collection of information on those who
are to respond, including the use of
appropriate automated, electronic,
mechanical, or other technological
collection techniques or other forms of
information technology.
Direct Comments to OMB: Written
comments and/or suggestions regarding
the item(s) contained in this notice,
especially regarding the estimated
public burden and associated response
time, should be directed to the: Office
of Management and Budget, Office of
Regulatory Affairs,
OIRA_submission@omb.eop.gov or by
fax to 202–395–6974, Attention: Desk
Officer for NIH. To request more
information on the proposed project or
to obtain a copy of the data collection
plans and instruments, contact: Marion
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Danis, MD, Department of Clinical
Bioethics, National Institutes of Health,
Building 10, Room 1C118, Bethesda,
MD 20892–1156; Telephone: 301–435–
8727; Facsimile: 301–496–0760; Email:
mdanis@cc.nih.gov.
Comments Due Date: Comments
regarding this information collection are
best assured of having their full effect if
received within 30-days of the date of
this publication.
Dated: August 28, 2012.
Laura Lee,
Project Clearance Liason, CC, National
Institutes of Health.
[FR Doc. 2012–27445 Filed 11–8–12; 8:45 am]
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.
BILLING CODE 4140–01–P
Cell Lines Expressing Nuclear and/or
Mitochondrial RNase H1
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
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
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
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
SUMMARY:
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Federal Register / Vol. 77, No. 218 / Friday, November 9, 2012 / Notices
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;
tongb@mail.nih.gov.
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
jmconrad@mail.nih.gov.
tkelley on DSK3SPTVN1PROD with NOTICES
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
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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°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 NguyenAntczak, Ph.D., J.D.; 301–435–4074;
nguyenantczakla@mail.nih.gov.
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.
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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 NguyenAntczak, Ph.D., J.D.; 301–435–4074;
nguyenantczakla@mail.nih.gov.
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 mcguinnc@mail.nih.gov.
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
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small molecules have been tested for the
ability to activate GCase in vitro and
show chaperone activity in a patientderived 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; tarak@mail.nih.gov.
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
maruganj@mail.nih.gov.
tkelley on DSK3SPTVN1PROD with NOTICES
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
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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;
vepas@mail.nih.gov.
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
maruganj@mail.nih.gov.
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.
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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 selfassembly 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.
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tkelley on DSK3SPTVN1PROD with NOTICES
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 CaseBased 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;
stansbej@mail.nih.gov.
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 hewesj@mail.nih.gov.
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
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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 (SAICFrederick, 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
PO 00000
Frm 00056
Fmt 4703
Sfmt 4703
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 selfassembly 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 CaseBased 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;
stansbej@mail.nih.gov.
Collaborative Research Opportunity:
The NCI Center for Cancer Research
E:\FR\FM\09NON1.SGM
09NON1
Federal Register / Vol. 77, No. 218 / Friday, November 9, 2012 / Notices
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 hewesj@mail.nih.gov.
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Human Genome Research
Institute; Amended Notice of Meeting
Notice is hereby given of a change in
the meeting of the National Human
Genome Research Institute Special
Emphasis Panel, October 29, 2012, 8:00
a.m. to October 30, 2012, 5:00 p.m.,
Residence Inn Bethesda Downtown,
7335 Wisconsin Avenue, Montgomery I
& II, Bethesda, MD 20814 which was
published in the Federal Register on
October 4, 2012, 77 FR 60706.
Due to Hurricane Sandy, this meeting
has been moved from October 29–30,
2012 to January 7, 2013. The meeting is
closed to the public.
Dated: November 5, 2012.
David Clary,
Program Analyst, Office of Federal Advisory
Committee Policy.
[FR Doc. 2012–27429 Filed 11–8–12; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
tkelley on DSK3SPTVN1PROD with NOTICES
Center for Scientific Review; Notice of
Closed Meetings
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amended (5 U.S.C. App.), notice is
hereby given of the following meetings.
The meetings will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
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property such as patentable material,
and personal information concerning
individuals associated with the grant
VerDate Mar<15>2010
17:34 Nov 08, 2012
Jkt 229001
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: Center for Scientific
Review Special Emphasis Panel Neuronal
Plasticity and Regeneration.
Date: November 28–29, 2012.
Time: 9:30 a.m. to 4:00 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health, 6701
Rockledge Drive, Bethesda, MD 20892,
(Virtual Meeting).
Contact Person: Laurent Taupenot, Ph.D.,
Scientific Review Officer, Center for
Scientific Review, National Institutes of
Health, 6701 Rockledge Drive, Room 4811,
MSC 7850, Bethesda, MD 20892, 301–435–
1203, taupenol@csr.nih.gov.
This notice is being published less than 15
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Name of Committee: Center for Scientific
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Date: December 6–7, 2012.
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Place: National Institutes of Health, 6701
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Health, 6701 Rockledge Drive, Room 4192,
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9887, hamelinc@csr.nih.gov.
Name of Committee: Center for Scientific
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Conflicts: Asthma, Allergy, and
Environmental Exposure Applications.
Date: December 10, 2012.
Time: 1:30 p.m. to 4:30 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health, 6701
Rockledge Drive, Bethesda, MD 20892
(Telephone Conference Call).
Contact Person: Everett E. Sinnett, Ph.D.,
Scientific Review Officer, Center for
Scientific Review, National Institutes of
Health, 6701 Rockledge Drive, Room 2178,
MSC 7818, Bethesda, MD 20892, 301–435–
1016, sinnett@nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.306, Comparative Medicine;
93.333, Clinical Research, 93.306, 93.333,
93.337, 93.393–93.396, 93.837–93.844,
93.846–93.878, 93.892, 93.893, National
Institutes of Health, HHS)
Dated: November 5, 2012.
Melanie J. Gray,
Program Analyst, Office of Federal Advisory
Committee Policy.
[FR Doc. 2012–27430 Filed 11–8–12; 8:45 am]
BILLING CODE 4140–01–P
PO 00000
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute of General Medical
Sciences; Notice of Closed Meeting
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amended (5 U.S.C. App.), notice is
hereby given of the following meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
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Name of Committee: National Institute of
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Contact Person: John J. Laffan, Ph.D.,
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Review, National Institute of General Medical
Sciences, National Institutes of Health, 45
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(Catalogue of Federal Domestic Assistance
Program Nos. 93.375, Minority Biomedical
Research Support; 93.821, Cell Biology and
Biophysics Research; 93.859, Pharmacology,
Physiology, and Biological Chemistry
Research; 93.862, Genetics and
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Minority Access to Research Careers; 93.96,
Special Minority Initiatives, National
Institutes of Health, HHS)
Dated: November 5, 2012.
Melanie J. Gray,
Program Analyst, Office of Federal Advisory
Committee Policy.
[FR Doc. 2012–27427 Filed 11–8–12; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute of Allergy and
Infectious Diseases; Notice of Closed
Meeting
Pursuant to section 10(d) of the
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E:\FR\FM\09NON1.SGM
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]]>Agencies
[Federal Register Volume 77, Number 218 (Friday, November 9, 2012)]
[Notices]
[Pages 67381-67385]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-27426]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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;
tongb@mail.nih.gov.
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
jmconrad@mail.nih.gov.
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; nguyenantczakla@mail.nih.gov.
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; nguyenantczakla@mail.nih.gov.
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 mcguinnc@mail.nih.gov.
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;
tarak@mail.nih.gov.
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
maruganj@mail.nih.gov.
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;
vepas@mail.nih.gov.
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
maruganj@mail.nih.gov.
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;
stansbej@mail.nih.gov.
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
hewesj@mail.nih.gov.
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;
stansbej@mail.nih.gov.
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
hewesj@mail.nih.gov.
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
