Government-Owned Inventions; Availability for Licensing, 45839-45841 [2011-19377]
Download as PDF
<![CDATA[
srobinson on DSK4SPTVN1PROD with NOTICES
Federal Register / Vol. 76, No. 147 / Monday, August 1, 2011 / Notices
Combination Cancer Therapy Using an
IL13-Targeted Toxin and an HDAC
Inhibitor
Description of Technology: Typical
cancer treatments such as
chemotherapy, radiation therapy and
surgical resection are non-specific
processes that kill healthy cells as well
as diseased cells, ultimately resulting in
discomfort and undesirable side-effects
for patients. In an effort to reduce the
burden on cancer patients, a
tremendous effort has been placed on
developing ways to increase the
specificity of cancer treatments. One
way to increase specificity is to identify
proteins which are present on the
surface of cancer cells but absent on
normal healthy cells, and use that
protein as a target for delivering a
therapeutic agent. Because the
therapeutic agent only reaches the
diseased cell, patients are less likely to
experience non-specific side-effects,
reducing their pain burden during
treatment.
IL13-receptor-alpha-2 (IL13–Ra2) is a
cell surface protein that is selectively
expressed on certain diseased cells,
including cancer cells. IL13–Ra2 binds
to the cytokine IL13, suggesting that a
therapeutic agent fused to IL13 can
target and kill only those cancer cells
which express IL13–Ra2. Our inventors
previously constructed fusion proteins
comprising (1) IL13 and (2) an active
fragment of the bacterial toxin
Pseudomonas exotoxin A (PE). These
IL13–PE fusion proteins demonstrated
the ability to selectively kill cancer cells
that overexpressed IL13–Ra2, as well as
other types of diseased cells (asthma,
pulmonary fibrosis) which
overexpressed IL13–Ra2. This suggested
that IL13–PE fusion proteins were
excellent candidates for new therapeutic
agents.
In an effort to increase the
effectiveness of these IL13–PE fusion
proteins, the inventors sought ways to
increase the expression of IL13–Ra2 on
cancer cells, thereby increasing the rate
at which the therapeutic agent could kill
the diseased cell. Histone deacetylase
(HDAC) inhibitors have been employed
as anti-cancer agents for several years,
and a number of HDAC inhibitors are
currently in clinical trials. Although the
exact mechanism by which HDAC
inhibitors function is unclear, it is
believed that the ability of these
molecules to increase the expression of
anti-cancer genes is behind their
therapeutic effect.
This invention concerns a means of
improving specific cancer therapy
through the combination of (a) IL13–PE
fusion proteins and (b) HDAC
VerDate Mar<15>2010
17:45 Jul 29, 2011
Jkt 223001
inhibitors. The inventors surprisingly
found that the expression of IL13–Ra2
increased in several types of pancreatic
cancer cells in response to HDAC
inhibitors, whereas normal, healthy
cells did not experience such an
increase in IL13–Ra2 expression. The
use of IL13–PE fusion proteins in
combination with HDAC inhibitors
improved specific killing of pancreatic
cancer cells relative to the use of IL13–
PE fusion proteins in the absence of the
HDAC inhibitors. This suggested that
the use of IL13–PE fusion proteins along
with HDAC inhibitors was a strong
candidate combinatorial therapeutic for
the treatment of various cancers (e.g.,
pancreatic, glioblastoma multiforme)
and other diseases characterized by
overexpression of IL13–Ra2 (e.g.,
asthma, pulmonary fibrosis).
Applications:
• Treatment of diseases associated
with the increased expression of IL13–
Ra2
• Relevant diseases include
pulmonary fibrosis, asthma and cancers
such as pancreatic cancer, glioblastoma
multiforme and other head and neck
cancers
Advantages:
• HDAC inhibitors only increased
IL13–Ra2 expression in diseased cells,
leaving normal healthy cells unaltered
• IL13–PE fusion proteins only kill
cells that overexpress IL13–Ra2,
allowing specific targeting of treatment
• Targeted treatment decreases nonspecific killing of healthy, essential
cells, resulting in fewer side-effects and
healthier patients
Development Status: Preclinical stage
of development
Inventors: Puri et al. (FDA)
Patent Status: US provisional
application 61/494,779 (HHS reference
E–107–2011/0–US–01)
For more information, see:
• US Patents 5,614,191, 5,919,456
and 6,518,061 (HHS technology
reference E–266–1994/0)
• US Patent Publication US
20040136959 A1 (HHS technology
reference E–032–2000/0)
• US Patent 7,541,040 (HHS
technology reference E–296–2001/0)
Licensing Status: Available for
licensing
Licensing Contact: David A.
Lambertson, PhD; 301–435–4632;
lambertsond@mail.nih.gov
Dated: July 26, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–19378 Filed 7–29–11; 8:45 am]
BILLING CODE 4140–01–P
PO 00000
Frm 00083
Fmt 4703
Sfmt 4703
45839
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
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
inventions to extend market coverage
for companies and may also be available
for licensing.
ADDRESSES: 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.
SUMMARY:
Methods and Software for the
Quantitative Assessment of Vasculature
in Allantois and Retina Explants
Description of Technology: The
invention relates to methods and
software that can facilitate and improve
quantification, accuracy and
standardization in the assessment of
vasculature in angiogenesis assays such
as in the allantois explants and the
retina explants assays. The software of
this invention can aid in the analysis of
images resulting from these assays and
thus enhance the accuracy and
effectiveness of research in the area of
angiogenesis. This in turn will lead to
enhanced progress in the development
of medical methods and drugs to treat
diseases related to angiogenesis such as
cancer, macular degeneration, and some
pregnancy disorders.
Applications: The software can be
integrated with a variety of imaging
systems used in conjunction with
angiogenesis assays to enhance the
assessment and the quality of research
in the area of angiogenesis.
Advantages:
• The method and software of the
invention will make analysis of
angiogenesis assays more accurate,
better standardized, and less
E:\FR\FM\01AUN1.SGM
01AUN1
45840
Federal Register / Vol. 76, No. 147 / Monday, August 1, 2011 / Notices
cumbersome than existing analysis
systems.
• This method and software will
eliminate the user-dependent bias
which is characteristic of existing
methods.
• This method and software will
generally improve the quality of
analysis of angiogenesis assays.
• The software is suitable for
integration in a variety of existing
imaging systems and software as well as
readily usable as an independent
complementary technology in the
research and biomedical fields.
Development Status: The software is
fully developed.
Inventor: Enrique Zudaire (NCI).
Relevant Publications:
1. Pitulescu ME, Schmidt I, Benedito
R, Adams RH. Inducible gene targeting
in the neonatal vasculature and analysis
of retinal angiogenesis in mice. Nat
Protoc. 2010 Sep;5(9):1518–1534.
[PMID: 20725067].
2. Gambardella L, et al. PI3K signaling
through the dual GTPase-activating
protein ARAP3 is essential for
developmental angiogenesis. Sci Signal
2010 Oct 26;3(145):ra76. [PMID:
20978237].
3. Zudaire E, Gambardella L, Kurcz C,
Vermeren S. A computational tool for
quantitative analysis of vascular
networks. PLoS One (Submitted).
Patent Status: HHS Reference No. E–
176–2011/0—Software/Research Tool.
Patent protection is not being pursued
for this technology.
Licensing Status: The software is
available for licensing.
Licensing Contacts:
• Uri Reichman, Ph.D., MBA; 301–
435–4616; UR7a@nih.gov.
• Michael Shmilovich, Esq.; 301–
435–5019; shmilovm@mail.nih.gov.
srobinson on DSK4SPTVN1PROD with NOTICES
Pyruvate as a Transient Hypoxia
Inducer for Anti-cancer Therapies
Description of Technology: Human
solid tumors, such as breast cancer, lung
cancer, ovarian cancer, pancreatic
cancer and prostate cancer, etc.
frequently have substantial volumes
with low oxygen concentration, i.e.
hypoxic. These hypoxic tumors show
resistance to radiation and
chemotherapies. To overcome such
resistance, novel classes of agents have
been designed and developed that are
specifically active or activated under
hypoxic conditions, in hypoxic tumors.
The instant invention describes a novel
idea to improve anti-cancer effect of
hypoxia-sensitive therapeutics by using
a rapidly oxidized reducing agent such
as pyruvate or succinate. In the instant
invention, the NIH investigators found
that pyruvate, an endogenous substrate
VerDate Mar<15>2010
17:45 Jul 29, 2011
Jkt 223001
for energy production by mitochondria,
induced severe hypoxia in tumors
within 30 minutes of intravenous
injection, and the tumor oxygen level
reversibly returned to basal level within
a few hours. Since pyruvate seems to
induce only transient hypoxia, and its
safety profiles are known, it may have
significant advantages over other
hypoxia inducers reported to date for
improving the efficacy of hypoxiasensitive anti-cancer therapies.
Applications:
• Provide a novel way to target
various cancers, especially solid tumors
for treatment;
• Improve the efficacy of using
hypoxic toxins for cancer treatment;
• In vivo screening of oxygen-status
dependent drugs.
Market: Cancer is the second leading
cause of death in the U.S. The National
Cancer Institute estimates the overall
annual costs for cancer in the U.S. at
$107 billion; $37 billion for direct
medical costs, $11 billion for morbidity
costs (cost of lost productivity), and $59
billion for mortality costs. There is an
ongoing need for innovative approaches
to anticancer therapy.
Development Status: Pre-clinical stage
of development.
Inventors: Drs. Shingo Matsumoto
(NCI), James B. Mitchell (NCI), and
Robert J. Gillies (H. Lee Moffitt Cancer
Center and Research Institute) et al.
Publication: Poster presentation in the
International Society for Magnetic
Resonance in Medicine (ISMRM)
meeting in May 2011. Manuscript is in
press.
Patent Status: U.S. Provisional
Application No. 61/478,465 filed April
22, 2011 (HHS Reference No. E–144–
2011/0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Betty B. Tong,
PhD; 301–594–6565;
tongb@mail.nih.gov.
Multivalent Vaccines for Rabies Virus
and Filoviruses
Description of Technology: No
vaccine candidates against Ebola virus
(EBOV) or Marburg virus (MARV) are
nearing licensure and the need to
develop a safe and efficacious vaccine
against filoviruses continues. Whereas
several preclinical vaccine candidates
against EBOV or MARV exist, their
further development is a major
challenge based on safety concerns, preexisting vector immunity, and issues
such as manufacturing, dosage, and
marketability. The inventors have
developed a new platform based on live
or chemically inactivated (killed) rabies
virus (RABV) virions containing EBOV
PO 00000
Frm 00084
Fmt 4703
Sfmt 4703
glycoprotein (GP) in their envelope. In
preclinical trials, immunization with
such recombinant RABV virions
provided excellent protection in mice
against lethal challenge with the mouse
adapted EBOV and RABV. More
specifically, the inventors have
developed a trivalent filovirus vaccine
based on killed rabies virus virions for
use in humans to confer protection from
all medically relevant filoviruses and
RABV. Two additional vectors
containing EBOV Sudan GP or MARV
GP are planned to be constructed in
addition to the previously developed
EBOV Zaire GP containing vaccine. The
efficiency of these vaccines against
challenge with EBOV, MARV and RABV
will be studied in multiple preclinical
studies. Live attenuated vaccines are
being developed for use in at risk
nonhuman primate populations in
Africa and inactivated vaccines are
being developed for use in humans.
Potential Commercial Applications:
• Biodefense vaccine.
• Developing country vaccine.
• Multivalent prophylactic Ebola/
Marburg/rabies vaccine.
Competitive Advantages:
• Vaccines are replication deficient
and/or inactivated.
• Protection against rabies and Ebola.
• Reliable and cost-effective
manufacture.
• No preexisting immunity to vectors.
• No potential vaccine reactogenicity.
Development Stage:
• Pre-clinical.
• In vitro data available.
• In vivo data available (animal).
Inventors: Joseph Blaney, Jason
Paragas, Peter Jahrling, Reed Johnson
(NIAID).
Intellectual Property: HHS Reference
No. E–032–2011/0 — U.S. Patent
Application No. 61/439,046 filed 03 Feb
2011.
Licensing Contact: Peter A. Soukas,
J.D.; 301–435–4646;
soukasp@mail.nih.gov.
Layered Electrophoretic Transfer for
Analysis of Low or Medium Abundant
Proteins in Tissue Samples
Description of Technology: The
subject invention is a method to
selectively process the protein content
from a two dimensional sample, such as
a tissue section, for more detailed
analysis. It is particularly useful for
analysis of a subset of proteins from a
complex protein mixture. The method
employs a layer of polyacrylamide gels
and an electric field. Proteins from the
sample are transferred and sieved
through a stack of polyacrylamide gels
of varying concentrations. Thus, it is
possible to analyze specific subsets of
E:\FR\FM\01AUN1.SGM
01AUN1
Federal Register / Vol. 76, No. 147 / Monday, August 1, 2011 / Notices
proteins in the different gel layers and
maintain the two dimensional location
of the proteins within the original
sample. One of the advantages of this
technology is that it allows for isolation
and subsequent analysis of low
abundant or medium abundant proteins
by a number of different methodologies
such as imaging mass spectrometry.
Applications:
• Protein Analysis of Tissue Samples.
• Histology and Pathology.
Advantages:
• Isolation of low or moderatelyabundant proteins in tissue sections.
• Method maintains 2-dimensional
location of proteins in tissue samples.
Development Status: In vitro data can
be provided upon request.
Market:
• Diagnostic.
• Pathology.
• Basic Research.
Inventors: Michael Emmert-Buck,
Liang Zhu, and Michael Tangrea (NCI).
Publication: Zhu L, Tangrea MA,
Mukherjee S, Emmert-Buck MR.
Layered electrophoretic transfer—A
method for pre-analytic processing of
histological sections. Proteomics. 2011
Mar;11(5):883–889. [PMID: 21280224].
Patent Status: U.S. Provisional
Application No. 61/420,258 filed
December 6, 2010 (HHS Reference No.
E–020–2011/0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Kevin W. Chang,
PhD; 301–435–5018;
changke@mail.nih.gov.
Collaborative Research Opportunity:
The Center for Cancer Research,
Laboratory of Pathology, Pathogenetics
Unit, is seeking statements of capability
or interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
layered electrophoretic transfer (LET).
Please contact John Hewes, PhD at 301–
435–3121 or hewesj@mail.nih.gov for
more information.
srobinson on DSK4SPTVN1PROD with NOTICES
Pertussis Vaccine
Description of Technology: Despite
mass vaccination, reported pertussis
cases have increased in the United
States and other parts of the world,
probably because of increased
awareness, improved diagnostic means,
and waning vaccine-induced immunity
among adolescents and adults. Licensed
vaccines do not kill the organism
directly; the addition of a component
inducing bactericidal antibodies would
improve vaccine efficacy. This
application claims Bordetella pertussis
and Bordetella bronchiseptica LPSderived core oligosaccharide (OS)
protein conjugates. B. pertussis and B.
VerDate Mar<15>2010
17:45 Jul 29, 2011
Jkt 223001
bronchiseptica core OS were bound to
aminooxylated BSA via their terminal
Kdo residues. The two conjugates
induced similar anti-B. pertussis LPS
IgG levels in mice. Conjugate-induced
antisera were bactericidal against B.
pertussis.
Potential Commercial Applications:
• Pertussis prophylactic conjugate
vaccine.
• Use of vaccine to generate
neutralizing antibodies.
Competitive Advantages: Conjugates
are easy to prepare and standardize;
added to a recombinant pertussis
toxoid, they may induce antibacterial
and antitoxin immunity.
Development Stage:
• Pre-clinical.
• In vitro data available.
• In vivo data available (animal).
Inventors: Joanna Kubler-Kielb
(NICHD), Rachel Schneerson (NICHD),
John B. Robbins (NICHD), Ariel
Ginzberg (NICHD), Teresa Lagergard
(NICHD), et al.
Publication: Kubler-Kielb J,
˚
Vinogradov E, Lagergard T, Ginzberg A,
King JD, Preston A, Maskell DJ, Pozsgay
V, Keith JM, Robbins JB, Schneerson R.
Oligosaccharide conjugates of Bordetella
pertussis and bronchiseptica induce
bactericidal antibodies, an addition to
pertussis vaccine. Proc Natl Acad Sci U
S A. 2011 Mar 8;108(10):4087–4092.
[PMID: 21367691].
Intellectual Property: HHS Reference
No. E–006–2011/0—U.S. Application
No. 61/438,190 filed 31 Jan 2011.
Related Technology: HHS Reference
No. E–183–2005/0 —U.S. Application
No. 12/309,428 filed 16 Jan 2009.
Licensing Contact: Peter A. Soukas,
J.D.; 301–435–4646;
soukasp@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 vaccines against
pertussis. For collaboration
opportunities, please contact Joseph
Conrad, III, PhD at
jmconrad@mail.nih.gov.
Novel Methods for the Reversible
Incorporation of Functional Groups
Into RNA and DNA: Synthesis and Uses
for 2′-O-aminooxymethyl Nucleoside
Derivatives
Description of Technology: The
delivery of DNA/RNA therapeutic drugs
is still a major hurdle for the clinical
application of DNA/RNA-based drugs.
Also, developments in silencing the
expression of specific genes, through
RNA interference pathways, have led to
an increased demand for synthetic RNA
PO 00000
Frm 00085
Fmt 4703
Sfmt 9990
45841
sequences and have created a pressing
need for rapid and efficient methods for
RNA synthesis. Recently, FDA scientists
have developed a novel
phosphoramidite, 2′-O-aminooxymethyl
ribonucleoside (2′-O-protected
compounds). The 2′-O-aminooxymethyl
ribonucleoside can be modified with
any type of functional group using an
oximation reaction as long as the
functional group contains an aldehyde,
ketone, or acetal group. Modification of
the 2′-O-aminooxymethyl with an
aldehyde results in a conjugated 2′phosphoramidite that could be readily
converted back to the native
ribonucleoside and its corresponding
by-product. On the other hand, the
oximation of 2′-O-aminooxymethy with
a ketone results in an irreversible
conjugated form of the
phosphoramidite.
The 2′-O-protected compounds of the
present technology have several
advantages, for example, the 2′-Oprotected compound is stable during the
various reaction steps involved in
oligonucleotide synthesis; and the
protecting group can be easily removed
after the synthesis of the
oligonucleotide, for example, by
reaction with tetrabutylammonium
fluoride; and the O-protected groups do
not generate DNA/RNA alkylating side
products, which have been reported
during removal of 2′-O-(2cyanoethyl)oxymethyl or 2′-O-[2-(4tolylsulfonyl)ethoxymethyl groups
under similar conditions.
Applications:
• Incorporation of a potentially large
array of functional groups into RNA and
DNA oligonucleotides for diagnostic
and/or therapeutic applications.
• Conjugation of a variety of sugars or
complex carbohydrates to DNA/RNA
therapeutic oligonucleotides.
• Attachment of cell membranepenetrating peptides to therapeutic
DNA/RNA oligonucleotides.
Inventors: Serge L. Beaucage and
Jacek Cieslak (FDA).
Patent Status: U.S. Provisional
Application No. 61/471,451 filed 04
April 2011 (HHS Reference No. E–262–
2010/0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Suryanarayana
Vepa, PhD, J.D.; 301–435–5020;
vepas@mail.nih.gov.
Dated: July 26, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–19377 Filed 7–29–11; 8:45 am]
BILLING CODE 4140–01–P
E:\FR\FM\01AUN1.SGM
01AUN1
]]>Agencies
[Federal Register Volume 76, Number 147 (Monday, August 1, 2011)]
[Notices]
[Pages 45839-45841]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-19377]
-----------------------------------------------------------------------
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.
ADDRESSES: 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.
Methods and Software for the Quantitative Assessment of Vasculature in
Allantois and Retina Explants
Description of Technology: The invention relates to methods and
software that can facilitate and improve quantification, accuracy and
standardization in the assessment of vasculature in angiogenesis assays
such as in the allantois explants and the retina explants assays. The
software of this invention can aid in the analysis of images resulting
from these assays and thus enhance the accuracy and effectiveness of
research in the area of angiogenesis. This in turn will lead to
enhanced progress in the development of medical methods and drugs to
treat diseases related to angiogenesis such as cancer, macular
degeneration, and some pregnancy disorders.
Applications: The software can be integrated with a variety of
imaging systems used in conjunction with angiogenesis assays to enhance
the assessment and the quality of research in the area of angiogenesis.
Advantages:
The method and software of the invention will make
analysis of angiogenesis assays more accurate, better standardized, and
less
[[Page 45840]]
cumbersome than existing analysis systems.
This method and software will eliminate the user-dependent
bias which is characteristic of existing methods.
This method and software will generally improve the
quality of analysis of angiogenesis assays.
The software is suitable for integration in a variety of
existing imaging systems and software as well as readily usable as an
independent complementary technology in the research and biomedical
fields.
Development Status: The software is fully developed.
Inventor: Enrique Zudaire (NCI).
Relevant Publications:
1. Pitulescu ME, Schmidt I, Benedito R, Adams RH. Inducible gene
targeting in the neonatal vasculature and analysis of retinal
angiogenesis in mice. Nat Protoc. 2010 Sep;5(9):1518-1534. [PMID:
20725067].
2. Gambardella L, et al. PI3K signaling through the dual GTPase-
activating protein ARAP3 is essential for developmental angiogenesis.
Sci Signal 2010 Oct 26;3(145):ra76. [PMID: 20978237].
3. Zudaire E, Gambardella L, Kurcz C, Vermeren S. A computational
tool for quantitative analysis of vascular networks. PLoS One
(Submitted).
Patent Status: HHS Reference No. E-176-2011/0--Software/Research
Tool. Patent protection is not being pursued for this technology.
Licensing Status: The software is available for licensing.
Licensing Contacts:
Uri Reichman, Ph.D., MBA; 301-435-4616; UR7a@nih.gov.
Michael Shmilovich, Esq.; 301-435-5019;
shmilovm@mail.nih.gov.
Pyruvate as a Transient Hypoxia Inducer for Anti-cancer Therapies
Description of Technology: Human solid tumors, such as breast
cancer, lung cancer, ovarian cancer, pancreatic cancer and prostate
cancer, etc. frequently have substantial volumes with low oxygen
concentration, i.e. hypoxic. These hypoxic tumors show resistance to
radiation and chemotherapies. To overcome such resistance, novel
classes of agents have been designed and developed that are
specifically active or activated under hypoxic conditions, in hypoxic
tumors. The instant invention describes a novel idea to improve anti-
cancer effect of hypoxia-sensitive therapeutics by using a rapidly
oxidized reducing agent such as pyruvate or succinate. In the instant
invention, the NIH investigators found that pyruvate, an endogenous
substrate for energy production by mitochondria, induced severe hypoxia
in tumors within 30 minutes of intravenous injection, and the tumor
oxygen level reversibly returned to basal level within a few hours.
Since pyruvate seems to induce only transient hypoxia, and its safety
profiles are known, it may have significant advantages over other
hypoxia inducers reported to date for improving the efficacy of
hypoxia-sensitive anti-cancer therapies.
Applications:
Provide a novel way to target various cancers, especially
solid tumors for treatment;
Improve the efficacy of using hypoxic toxins for cancer
treatment;
In vivo screening of oxygen-status dependent drugs.
Market: Cancer is the second leading cause of death in the U.S. The
National Cancer Institute estimates the overall annual costs for cancer
in the U.S. at $107 billion; $37 billion for direct medical costs, $11
billion for morbidity costs (cost of lost productivity), and $59
billion for mortality costs. There is an ongoing need for innovative
approaches to anticancer therapy.
Development Status: Pre-clinical stage of development.
Inventors: Drs. Shingo Matsumoto (NCI), James B. Mitchell (NCI),
and Robert J. Gillies (H. Lee Moffitt Cancer Center and Research
Institute) et al.
Publication: Poster presentation in the International Society for
Magnetic Resonance in Medicine (ISMRM) meeting in May 2011. Manuscript
is in press.
Patent Status: U.S. Provisional Application No. 61/478,465 filed
April 22, 2011 (HHS Reference No. E-144-2011/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Betty B. Tong, PhD; 301-594-6565;
tongb@mail.nih.gov.
Multivalent Vaccines for Rabies Virus and Filoviruses
Description of Technology: No vaccine candidates against Ebola
virus (EBOV) or Marburg virus (MARV) are nearing licensure and the need
to develop a safe and efficacious vaccine against filoviruses
continues. Whereas several preclinical vaccine candidates against EBOV
or MARV exist, their further development is a major challenge based on
safety concerns, pre-existing vector immunity, and issues such as
manufacturing, dosage, and marketability. The inventors have developed
a new platform based on live or chemically inactivated (killed) rabies
virus (RABV) virions containing EBOV glycoprotein (GP) in their
envelope. In preclinical trials, immunization with such recombinant
RABV virions provided excellent protection in mice against lethal
challenge with the mouse adapted EBOV and RABV. More specifically, the
inventors have developed a trivalent filovirus vaccine based on killed
rabies virus virions for use in humans to confer protection from all
medically relevant filoviruses and RABV. Two additional vectors
containing EBOV Sudan GP or MARV GP are planned to be constructed in
addition to the previously developed EBOV Zaire GP containing vaccine.
The efficiency of these vaccines against challenge with EBOV, MARV and
RABV will be studied in multiple preclinical studies. Live attenuated
vaccines are being developed for use in at risk nonhuman primate
populations in Africa and inactivated vaccines are being developed for
use in humans.
Potential Commercial Applications:
Biodefense vaccine.
Developing country vaccine.
Multivalent prophylactic Ebola/Marburg/rabies vaccine.
Competitive Advantages:
Vaccines are replication deficient and/or inactivated.
Protection against rabies and Ebola.
Reliable and cost-effective manufacture.
No preexisting immunity to vectors.
No potential vaccine reactogenicity.
Development Stage:
Pre-clinical.
In vitro data available.
In vivo data available (animal).
Inventors: Joseph Blaney, Jason Paragas, Peter Jahrling, Reed
Johnson (NIAID).
Intellectual Property: HHS Reference No. E-032-2011/0 -- U.S.
Patent Application No. 61/439,046 filed 03 Feb 2011.
Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646;
soukasp@mail.nih.gov.
Layered Electrophoretic Transfer for Analysis of Low or Medium Abundant
Proteins in Tissue Samples
Description of Technology: The subject invention is a method to
selectively process the protein content from a two dimensional sample,
such as a tissue section, for more detailed analysis. It is
particularly useful for analysis of a subset of proteins from a complex
protein mixture. The method employs a layer of polyacrylamide gels and
an electric field. Proteins from the sample are transferred and sieved
through a stack of polyacrylamide gels of varying concentrations. Thus,
it is possible to analyze specific subsets of
[[Page 45841]]
proteins in the different gel layers and maintain the two dimensional
location of the proteins within the original sample. One of the
advantages of this technology is that it allows for isolation and
subsequent analysis of low abundant or medium abundant proteins by a
number of different methodologies such as imaging mass spectrometry.
Applications:
Protein Analysis of Tissue Samples.
Histology and Pathology.
Advantages:
Isolation of low or moderately-abundant proteins in tissue
sections.
Method maintains 2-dimensional location of proteins in
tissue samples.
Development Status: In vitro data can be provided upon request.
Market:
Diagnostic.
Pathology.
Basic Research.
Inventors: Michael Emmert-Buck, Liang Zhu, and Michael Tangrea
(NCI).
Publication: Zhu L, Tangrea MA, Mukherjee S, Emmert-Buck MR.
Layered electrophoretic transfer--A method for pre-analytic processing
of histological sections. Proteomics. 2011 Mar;11(5):883-889. [PMID:
21280224].
Patent Status: U.S. Provisional Application No. 61/420,258 filed
December 6, 2010 (HHS Reference No. E-020-2011/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Kevin W. Chang, PhD; 301-435-5018;
changke@mail.nih.gov.
Collaborative Research Opportunity: The Center for Cancer Research,
Laboratory of Pathology, Pathogenetics Unit, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize layered
electrophoretic transfer (LET). Please contact John Hewes, PhD at 301-
435-3121 or hewesj@mail.nih.gov for more information.
Pertussis Vaccine
Description of Technology: Despite mass vaccination, reported
pertussis cases have increased in the United States and other parts of
the world, probably because of increased awareness, improved diagnostic
means, and waning vaccine-induced immunity among adolescents and
adults. Licensed vaccines do not kill the organism directly; the
addition of a component inducing bactericidal antibodies would improve
vaccine efficacy. This application claims Bordetella pertussis and
Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein
conjugates. B. pertussis and B. bronchiseptica core OS were bound to
aminooxylated BSA via their terminal Kdo residues. The two conjugates
induced similar anti-B. pertussis LPS IgG levels in mice. Conjugate-
induced antisera were bactericidal against B. pertussis.
Potential Commercial Applications:
Pertussis prophylactic conjugate vaccine.
Use of vaccine to generate neutralizing antibodies.
Competitive Advantages: Conjugates are easy to prepare and
standardize; added to a recombinant pertussis toxoid, they may induce
antibacterial and antitoxin immunity.
Development Stage:
Pre-clinical.
In vitro data available.
In vivo data available (animal).
Inventors: Joanna Kubler-Kielb (NICHD), Rachel Schneerson (NICHD),
John B. Robbins (NICHD), Ariel Ginzberg (NICHD), Teresa Lagergard
(NICHD), et al.
Publication: Kubler-Kielb J, Vinogradov E, Lagerg[aring]rd T,
Ginzberg A, King JD, Preston A, Maskell DJ, Pozsgay V, Keith JM,
Robbins JB, Schneerson R. Oligosaccharide conjugates of Bordetella
pertussis and bronchiseptica induce bactericidal antibodies, an
addition to pertussis vaccine. Proc Natl Acad Sci U S A. 2011 Mar
8;108(10):4087-4092. [PMID: 21367691].
Intellectual Property: HHS Reference No. E-006-2011/0--U.S.
Application No. 61/438,190 filed 31 Jan 2011.
Related Technology: HHS Reference No. E-183-2005/0 --U.S.
Application No. 12/309,428 filed 16 Jan 2009.
Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646;
soukasp@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 vaccines
against pertussis. For collaboration opportunities, please contact
Joseph Conrad, III, PhD at jmconrad@mail.nih.gov.
Novel Methods for the Reversible Incorporation of Functional Groups
Into RNA and DNA: Synthesis and Uses for 2'-O-aminooxymethyl Nucleoside
Derivatives
Description of Technology: The delivery of DNA/RNA therapeutic
drugs is still a major hurdle for the clinical application of DNA/RNA-
based drugs. Also, developments in silencing the expression of specific
genes, through RNA interference pathways, have led to an increased
demand for synthetic RNA sequences and have created a pressing need for
rapid and efficient methods for RNA synthesis. Recently, FDA scientists
have developed a novel phosphoramidite, 2'-O-aminooxymethyl
ribonucleoside (2'-O-protected compounds). The 2'-O-aminooxymethyl
ribonucleoside can be modified with any type of functional group using
an oximation reaction as long as the functional group contains an
aldehyde, ketone, or acetal group. Modification of the 2'-O-
aminooxymethyl with an aldehyde results in a conjugated 2'-
phosphoramidite that could be readily converted back to the native
ribonucleoside and its corresponding by-product. On the other hand, the
oximation of 2'-O-aminooxymethy with a ketone results in an
irreversible conjugated form of the phosphoramidite.
The 2'-O-protected compounds of the present technology have several
advantages, for example, the 2'-O-protected compound is stable during
the various reaction steps involved in oligonucleotide synthesis; and
the protecting group can be easily removed after the synthesis of the
oligonucleotide, for example, by reaction with tetrabutylammonium
fluoride; and the O-protected groups do not generate DNA/RNA alkylating
side products, which have been reported during removal of 2'-O-(2-
cyanoethyl)oxymethyl or 2'-O-[2-(4-tolylsulfonyl)ethoxymethyl groups
under similar conditions.
Applications:
Incorporation of a potentially large array of functional
groups into RNA and DNA oligonucleotides for diagnostic and/or
therapeutic applications.
Conjugation of a variety of sugars or complex
carbohydrates to DNA/RNA therapeutic oligonucleotides.
Attachment of cell membrane-penetrating peptides to
therapeutic DNA/RNA oligonucleotides.
Inventors: Serge L. Beaucage and Jacek Cieslak (FDA).
Patent Status: U.S. Provisional Application No. 61/471,451 filed 04
April 2011 (HHS Reference No. E-262-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Suryanarayana Vepa, PhD, J.D.; 301-435-5020;
vepas@mail.nih.gov.
Dated: July 26, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-19377 Filed 7-29-11; 8:45 am]
BILLING CODE 4140-01-P
