Government-Owned Inventions; Availability for Licensing, 15326-15328 [2011-6569]
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15326
Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices
mstockstill on DSKH9S0YB1PROD with NOTICES
tumor progression in an oral-specific
chemical carcinogenesis model. Cancer
Prevention Res. 2009 Jan;2(1):27–36.
[PubMed: 19139015]
3. Raimondi AR, Molinolo A, Gutkind
JS. Rapamycin prevents early onset of
tumorigenesis in an oral-specific K-ras
and p53 two-hit carcinogenesis model.
Cancer Res. 2009 May 15;69(10):4159–
4166. [PubMed: 19435901]
Patent Status: U.S. Patent Application
No. 13/059,335 filed August 20, 2009
(HHS Reference No. E–302–2008/0–US–
05) and related international filings
Related Technology: International
Application No. PCT/IL2010/000694
filed August 25, 2010 (HHS Reference
No. E–282–2009/0–PCT–02), entitled
‘‘Prevention and Treatment of Oral and
Lips Diseases Using Sirolimus and
Derivatives Sustained Release Delivery
Systems for Local Application to the
Oral Cavity and Lips’’
Licensing Status: Available for
licensing.
Licensing Contact: Whitney Hastings;
301–451–7337; hastingw@mail.nih.gov
Collaborative Research Opportunity:
The National Institute of Dental and
Craniofacial Research, Oral and
Pharyngeal Cancer Branch, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize this technology. Please
contact David W. Bradley, PhD at
bradleyda@nidcr.nih.gov for more
information.
Three-Dimensional Co-Culture Assay
System for Angiogenesis and Metastasis
Description of Technology: This
technology features an assay for the
detection and measurement of
angiogenesis (formation of new blood
vessels) and metastasis (spread of
cancer). The inventors have developed a
three-dimensional co-culture system
that closely mimics the in vivo
environment in which angiogenesis and
metastatic tumors develop. The coculture system consists of cancerous
cells (tumor spheroid or biopsy),
endothelial cells, and a combination of
other mammalian cells (mast cells,
adipocytes, fibroblasts, macrophages,
etc.). The cancerous cells can be
obtained from cell lines or biopsied
tumors from various cancers, such as
melanoma, ovarian cancer,
hepatocellular cancer, or colon cancer.
Cells in the three-dimensional coculture system express a fluorescent
protein having a different emission
spectrum. Consequently, the co-culture
systems can be used to identify,
monitor, and measure changes in
morphology, migration, proliferation
and apoptosis of cells involved in
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angiogenesis and/or metastasis. The cocultures are developed in 96-well plates
to allow rapid and efficient screening
for whether a drug impacts multiple cell
types, modulates angiogenesis and/or
has a therapeutic impact on metastasis.
This technology not only represents an
important tool for angiogenesis and
cancer research, but also may be
developed into a diagnostic test that
allows the development of personalized
therapies for cancer and other
angiogenesis-mediated disease.
Applications:
• Personalized therapies for cancer
and other angiogenesis-mediated
diseases
• Screening for cytotoxic compounds,
modulators of angiogenesis, and antimetastatic compounds
• Basic research applications, such as
fluorescence-activated cell sorting
(FACS), time-lapse cinematography, and
confocal microscopy
Advantages:
• Closely mimics tumor
microenvironment
• Efficient screening method for basic
research, drug discovery and for clinical
use
Development Status: Experimental
data available; inventors have also
developed a high-throughput screening
assay based on this technology
Inventors: Changge Fang, Enrique
Zudaire, Frank Cuttitta (NCI)
Patent Status:
• U.S. Provisional Application No.
60/976,732 filed 01 Oct 2007 (HHS
Reference No. E–281–2007/0–US–01)
• U.S. Application No. 12/802,666
filed 10 Jun 2010 (HHS Reference No.
E–281–2007/1–US–01)
Licensing Status: Available for
licensing.
Licensing Contact: Tara L. Kirby, PhD;
301.435.4426; kirbyt@mail.nih.gov.
Collaborative Research Opportunity:
We are very interested in setting up
collaborations with pharmaceutical,
biomedical, or academic investigators to
use our technology in the form of a
CRADA or joint grant submission (e.g.
DOD). These studies could include
expanding the complexity of a 3D coculture by increasing the partner cell
number—paralleling the current model
of in vivo angiogenesis. Our existing coculture assay incorporates both
immortalized tumor and endothelial
cells. However, other anatomically
distinct cells could be added (e.g.
pericytes, inflammatory cells [mast cell
or macrophages], or fibroblasts) to more
accurately mimic the in vivo setting. In
addition, a more thorough analysis of
our prior xenograft biopsy studies for
assessing drug sensitivity could be done
using a variety of human tumor cell
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lines that include lung, colon, breast,
prostate, and ovarian cancer. Finally,
this collaboration would segue into
clinical studies taking biopsy material
from cancer patients (following
approved IRB protocols) to evaluate
anti-angiogenic drug sensitivities to
determine the most appropriate FDA
reviewed/certified anti-cancer drugs.
The National Cancer Institute,
Radiation Oncology Branch, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize this technology as noted
above. Please contact John Hewes, PhD
at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Dated: March 15, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–6570 Filed 3–18–11; 8:45 am]
BILLING CODE 4140–01–P
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:
Synthetic Peptide Inhibitors of the Wnt
Pathway
Description of Technology: Available
for licensing are peptide inhibitors of
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mstockstill on DSKH9S0YB1PROD with NOTICES
Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices
the Wnt signaling pathway, a pathway
that is activated in many cancer types.
To date, there are few small molecules
that target canonical Wnt/b-catenin
signaling and those that have been
discovered have low potency and do not
directly target b-catenin, the pathway’s
key signal mediator. The investigators
have developed peptide inhibitors that
selectively target a conserved region in
b-catenin essential for promoting cell
growth but not cell adhesion and
differentiation. Furthermore, these
peptides have been synthetically
modified to enhance cell penetration
and structure stability thereby
increasing their potency and efficacy.
Interestingly, these peptides inhibit the
canonical Wnt signaling pathway but
not non-canonical Wnt signaling. As a
result, these inhibitors potentially
provide effective chemotherapies for
tumors, such as colon and cervical,
which depend upon canonical Wnt
signaling. Moreover, as these inhibitors
do not disrupt non-canonical Wnt
signaling, which plays a role in kidney,
lung, and vascular development, and
they are likely to have minimal negative
side effects. Additionally, these
peptides can serve as an effective tool
for researches to elucidate the roles of
Wnt canonical and non-canonical
signaling in development and many
pathological conditions.
Applications:
• Cancer therapeutics
• Research tool to study Wnt
signaling pathways
Advantages:
• Selective inhibitors that target cell
growth but not differentiation
• Synthetic molecules with increased
stability and cell penetration that can be
manufactured in large quantities under
GMP conditions
Development Status: The technology
is currently in the pre-clinical stage of
development.
Market: Peptide drug market is
growing at a compound annual rate of
7.5% with an estimated value in excess
of $13 billion in 2010
Inventors: Nadya Tarasova, Alan
Perantoni, Shunsuke Tanigawa (NCI)
Related Publication: S Tanigawa et al.
Wnt4 induces nephronic tubules in
metanephric mesenchyme by a noncanonical mechanism. Dev Biol. 2011
Jan 20. E-pub ahead of print,
doi:10.1016/j.physletb.2003.10.071.
[PubMed: 21256838]
Patent Status: U.S. Provisional
Application No. 61/422,857 filed 14 Dec
2010 (HHS Reference No. E–021–2011/
0–US–01)
Licensing Status: Available for
licensing.
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Jkt 223001
Licensing Contact: Jennifer Wong;
301–435–4633; wongje@mail.nih.gov.
Collaborative Research Opportunity:
The Center for Cancer Research, Cancer
and Inflammation Program and Cancer
and Developmental Biology Laboratory,
are seeking statements of capability or
interest from parties interested in
collaborative research to further develop
and commercialize Wnt pathway
inhibitors. Please contact John Hewes,
PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Therapeutic Approach for Autoimmune
Diseases, Inflammatory Diseases and
Cancers by Blocking CIKS–TRAF6
Interactions
Description of Technology: CIKS (also
known as Act1 or TRAF3IP2) is an
intracellular adaptor protein involved in
the signaling pathway of IL–17
cytokines. Interaction between CIKS and
tumor necrosis factor receptorassociated factor (TRAF 6) is important
for IL–17 signaling and collectively, IL–
17, CIKS, and TRAF6 are involved in
inflammatory responses associated with
autoimmune diseases, inflammatory
diseases, and cancers. Inhibition of
CIKS activity has been shown to prevent
and alleviate pathological symptoms in
an animal model of rheumatoid arthritis
and multiple sclerosis, and it is
hypothesized that disruption of the
interaction between CIKS and TRAF6 is
a therapeutic strategy for the selective
prevention of certain IL–17-mediated
diseases.
NIAID investigators have discovered a
short sequence within CIKS that is
responsible for CIKS interaction with
TRAF6. The disclosed sequence can be
used to develop blocking peptides for
the treatment of IL–17-mediated
autoimmune diseases, inflammatory
diseases, and cancers.
Applications: Therapeutics for IL–17mediated diseases, such as
inflammatory diseases, autoimmune
diseases, and cancer.
Advantages: Selective inhibition of
CIKS–TRAF6 interactions.
Development Status: Basic research.
Inventors: Ulrich Siebenlist, Soeren U.
Soender, Sun Saret (NIAID).
Publications:
1. Pisitkun P, et al. (2010) [PubMed:
20662069]
2. Claudio E, et al. (2009) [PubMed:
19155511]
Patent Status: U.S. Provisional
Application No. 61/418,782 filed 01 Dec
2010 (HHS Reference No. E–268–2010/
0–US–01)
Licensing Status: Available for
licensing.
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15327
Licensing Contact: Tara L. Kirby, PhD;
301–435–4426; tarak@mail.nih.gov.
Tiopronin Specifically Kills and Resensitizes Multi-Drug Resistant Cells to
Chemotherapy
Description of Technology: One of the
major hindrances to successful cancer
chemotherapy is the development of
multi-drug resistance (MDR) in cancer
cells. MDR is frequently caused by the
increased expression or activity of ABC
transporter proteins in response to the
toxic agents used in chemotherapy. The
increased expression or activity of the
ABC transporter proteins causes the
toxic agents to be removed from cells
before they can kill the cell. As a result,
research has generally been directed to
overcoming MDR by inhibiting the
activity of ABC transporters, thus
causing the chemotherapeutic agents to
remain in the cell long enough to exert
their effects. However, compounds that
inhibit ABC transporter activity often
elicit strong and undesirable side-effects
due to the inhibition of ABC transporter
function in normal cells, thereby
restricting their usefulness as
therapeutics.
Investigators at the NIH have now
discovered that the amino acid analog
Tiopronin has the ability to kill multidrug resistant cancer cells while leaving
normal cells relatively unharmed. This
suggests that Tiopronin can be
developed as a therapeutic for multidrug resistant cancers. Furthermore,
Tiopronin re-sensitizes multi-drug
resistant cells to chemotherapeutic
agents over time. This may allow
cyclical administration of
chemotherapeutics without the
development of permanent resistance to
the agents, increasing the effectiveness
of chemotherapy as a cancer treatment.
Importantly, Tiopronin is not an
inhibitor of ABC transporter function
because it kills multi-drug resistant cells
without affecting the activity of ABC
transporters. As a result, the undesirable
side-effects that have prevented the use
of inhibitors of ABC transporters as
therapeutics should not affect the
therapeutic application of Tiopronin.
Applications:
• Treatment of cancers associated
with MDR, either alone or in
combination with other therapeutics
• Resensitization of multi-drug
resistant cells to chemotherapeutic
agents, allowing cyclical administration
of chemotherapy
Advantages:
• Tiopronin capitalizes on one of the
most common drawbacks to cancer
therapies (MDR) by using it as an
advantage for treating cancer
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21MRN1
15328
Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices
mstockstill on DSKH9S0YB1PROD with NOTICES
• Tiopronin does not inhibit the
activity of ABC transporters, thereby
reducing the chance of undesired sideeffects during treatment
• The effects of Tiopronin correlates
with the level of ABC transporter
expression, allowing healthy cells to
better survive treatments
• Tiopronin can also improve the
effectiveness of chemotherapy by resensitizing resistant cells that were
previously considered impervious to
treatment
• Tiopronin has already been
approved for use in humans for the
treatment of cytinuria, facilitating the
pathway for use in humans as a
treatment for cancer
Development Status: Preclinical stage
of development, in vitro data
Inventors: Andrew S. Goldsborough et
al. (NCI)
US Patent Status: US Provisional
Application 61/407,948 (E–227–2010/0–
US–01)
Licensing Status: The technology is
available for exclusive licensing.
Licensing Contact: David Lambertson,
PhD; 301–435–4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute,
Multidrug Resistance Section, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize this technology. Please
contact John Hewes, PhD at 301–435–
3121 or hewesj@mail.nih.gov for more
information.
Identification of EGFR as a Receptor for
AAV6 Transduction
Description of Technology: AAV
vectors offer unique advantages in gene
therapy applications. Studies have
shown that these replication deficient
parvovirus vectors can deliver DNA to
specific tissues and confer long-term
transgene expression in a variety of
systems. Although many studies have
looked at the tissue-specific expression
elicited by each of the AAV serotypes,
a true understanding of how AAV
transduces these tissues is still unclear.
Of the large AAV family, only a few
receptors or co-receptors have been
identified. The ability to better target
transduction to specific tissues on the
basis of the receptors that each serotype
uses for entry is essential for selecting
a serotype given the receptor expression
in specific tissue, or to exploit altered
receptor expression under disease
conditions.
AAV6 has been reported to effectively
transduce muscle, lung, brain, and
multiple types of tumors, including
gliomas and lung adenocarcinomas. By
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using a bioinformatics based screen
approach, the NIH investigators
discovered that the epidermal growth
factor receptor (EGFR) is a co-receptor
for AAV6 infection in mammalian cells,
and is necessary for efficient vector
internalization.
Applications and Market: Improved
gene therapy applications.
Development Status: Pre-clinical stage
of development.
Inventors: John A. Chiorini, Melodie
L. Weller, Michael Schmidt (NIDCR)
Publication: Weller ML,
Amornphimoltham P, Schmidt M,
Wilson PA, Gutkind JS, Chiorini JA.
Epidermal growth factor receptor is a
co-receptor for adeno-associated virus
serotype 6. Nat Med. 2010
Jun;16(6):662–664. [PubMed: 20473307]
Patent Status: U.S. Utility Patent
Application No. 12/879,142 filed 10 Sep
2010 (HHS Reference No. E–194–2010/
0–US–01)
Licensing Status: Available for
licensing.
Licensing Contact: Betty B. Tong,
PhD; 301–594–6565;
tongb@mail.nih.gov.
Therapeutic Approach to
Neurodegenerative Disorders Using a
TFP5-Peptide
Description of Technology: This
invention discloses methods for treating
neurodegenerative diseases by
administering cyclin dependent kinase
5 (Cdk5) inhibitory peptides derived
from P35, the activator of Cdk5.
Abnormally hyperactive Cdk5 has been
shown to be associated with a variety of
neurodegenerative disorders. Disclosed
in this invention are isolated peptide
fragments, pharmaceutical compositions
and methods for use of such for treating
subjects with a neurodegenerative
disease, such as Alzheimer’s disease
(AD), Amyotrophic Lateral Sclerosis
(ALS) and Parkinson’s disease (PD). An
inhibitory fragment, TFP5, disclosed in
this invention, has been shown to
ameliorate symptoms of AD in disease
animal models without any evidence of
toxicity. In particular, TFP5 treatment of
rat cortical neurons reduced
hyperactivation of Cdk5 upon neuronal
stress and insults. Following
intraperitoneal (ip) injection, TFP5 was
capable of crossing the BBB and
localizing within the brain where it was
found to rescue memory deficits and
pathology in a double transgenic mouse
(APP/PS1) AD model.
Applications: Therapeutic
developments (AD, PD, ALS)
Advantages: The products are small
peptides that pass the blood brain
barrier.
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Market: Development for AD, PD, and
ALS.
Development Status: Pre-clinical;
some animal data
Inventors: Harish C. Pant (NINDS)
Patent Status: U.S. Provisional
Application No. 61/387,839 filed 29 Sep
2010 (HHS Reference No. E–144–2010/
0–US–01)
Licensing Status: Available for
licensing.
Licensing Contact: Steven H.
Standley, PhD; 301–435–4074;
sstand@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Neurological
Disorders and Stroke, Neuronal
Cytoskeletal Protein Regulation Section,
is seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
topic of invention or related laboratory
interests. Please contact Heather Gunas,
J.D., M.P.H., at 301–451–3944 or
gunash@mail.nih.gov for more
information.
Dated: March 15, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–6569 Filed 3–18–11; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute on Drug Abuse;
Notice of Closed Meetings
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
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 contract proposals and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable materials,
and personal information concerning
individuals associated with the contract
proposals, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Institute on
Drug Abuse Special Emphasis Panel; GISTE,
the Geospatial Information Systems Tool
(5558).
Date: April 18, 2011.
Time: 1:30 p.m. to 3 p.m.
Agenda: To review and evaluate contract
proposals.
E:\FR\FM\21MRN1.SGM
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]]>Agencies
[Federal Register Volume 76, Number 54 (Monday, March 21, 2011)]
[Notices]
[Pages 15326-15328]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-6569]
-----------------------------------------------------------------------
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.
Synthetic Peptide Inhibitors of the Wnt Pathway
Description of Technology: Available for licensing are peptide
inhibitors of
[[Page 15327]]
the Wnt signaling pathway, a pathway that is activated in many cancer
types. To date, there are few small molecules that target canonical
Wnt/[beta]-catenin signaling and those that have been discovered have
low potency and do not directly target [beta]-catenin, the pathway's
key signal mediator. The investigators have developed peptide
inhibitors that selectively target a conserved region in [beta]-catenin
essential for promoting cell growth but not cell adhesion and
differentiation. Furthermore, these peptides have been synthetically
modified to enhance cell penetration and structure stability thereby
increasing their potency and efficacy. Interestingly, these peptides
inhibit the canonical Wnt signaling pathway but not non-canonical Wnt
signaling. As a result, these inhibitors potentially provide effective
chemotherapies for tumors, such as colon and cervical, which depend
upon canonical Wnt signaling. Moreover, as these inhibitors do not
disrupt non-canonical Wnt signaling, which plays a role in kidney,
lung, and vascular development, and they are likely to have minimal
negative side effects. Additionally, these peptides can serve as an
effective tool for researches to elucidate the roles of Wnt canonical
and non-canonical signaling in development and many pathological
conditions.
Applications:
Cancer therapeutics
Research tool to study Wnt signaling pathways
Advantages:
Selective inhibitors that target cell growth but not
differentiation
Synthetic molecules with increased stability and cell
penetration that can be manufactured in large quantities under GMP
conditions
Development Status: The technology is currently in the pre-clinical
stage of development.
Market: Peptide drug market is growing at a compound annual rate of
7.5% with an estimated value in excess of $13 billion in 2010
Inventors: Nadya Tarasova, Alan Perantoni, Shunsuke Tanigawa (NCI)
Related Publication: S Tanigawa et al. Wnt4 induces nephronic
tubules in metanephric mesenchyme by a non-canonical mechanism. Dev
Biol. 2011 Jan 20. E-pub ahead of print, doi:10.1016/
j.physletb.2003.10.071. [PubMed: 21256838]
Patent Status: U.S. Provisional Application No. 61/422,857 filed 14
Dec 2010 (HHS Reference No. E-021-2011/0-US-01)
Licensing Status: Available for licensing.
Licensing Contact: Jennifer Wong; 301-435-4633;
wongje@mail.nih.gov.
Collaborative Research Opportunity: The Center for Cancer Research,
Cancer and Inflammation Program and Cancer and Developmental Biology
Laboratory, are seeking statements of capability or interest from
parties interested in collaborative research to further develop and
commercialize Wnt pathway inhibitors. Please contact John Hewes, PhD at
301-435-3121 or hewesj@mail.nih.gov for more information.
Therapeutic Approach for Autoimmune Diseases, Inflammatory Diseases and
Cancers by Blocking CIKS-TRAF6 Interactions
Description of Technology: CIKS (also known as Act1 or TRAF3IP2) is
an intracellular adaptor protein involved in the signaling pathway of
IL-17 cytokines. Interaction between CIKS and tumor necrosis factor
receptor-associated factor (TRAF 6) is important for IL-17 signaling
and collectively, IL-17, CIKS, and TRAF6 are involved in inflammatory
responses associated with autoimmune diseases, inflammatory diseases,
and cancers. Inhibition of CIKS activity has been shown to prevent and
alleviate pathological symptoms in an animal model of rheumatoid
arthritis and multiple sclerosis, and it is hypothesized that
disruption of the interaction between CIKS and TRAF6 is a therapeutic
strategy for the selective prevention of certain IL-17-mediated
diseases.
NIAID investigators have discovered a short sequence within CIKS
that is responsible for CIKS interaction with TRAF6. The disclosed
sequence can be used to develop blocking peptides for the treatment of
IL-17-mediated autoimmune diseases, inflammatory diseases, and cancers.
Applications: Therapeutics for IL-17-mediated diseases, such as
inflammatory diseases, autoimmune diseases, and cancer.
Advantages: Selective inhibition of CIKS-TRAF6 interactions.
Development Status: Basic research.
Inventors: Ulrich Siebenlist, Soeren U. Soender, Sun Saret (NIAID).
Publications:
1. Pisitkun P, et al. (2010) [PubMed: 20662069]
2. Claudio E, et al. (2009) [PubMed: 19155511]
Patent Status: U.S. Provisional Application No. 61/418,782 filed 01
Dec 2010 (HHS Reference No. E-268-2010/0-US-01)
Licensing Status: Available for licensing.
Licensing Contact: Tara L. Kirby, PhD; 301-435-4426;
tarak@mail.nih.gov.
Tiopronin Specifically Kills and Re-sensitizes Multi-Drug Resistant
Cells to Chemotherapy
Description of Technology: One of the major hindrances to
successful cancer chemotherapy is the development of multi-drug
resistance (MDR) in cancer cells. MDR is frequently caused by the
increased expression or activity of ABC transporter proteins in
response to the toxic agents used in chemotherapy. The increased
expression or activity of the ABC transporter proteins causes the toxic
agents to be removed from cells before they can kill the cell. As a
result, research has generally been directed to overcoming MDR by
inhibiting the activity of ABC transporters, thus causing the
chemotherapeutic agents to remain in the cell long enough to exert
their effects. However, compounds that inhibit ABC transporter activity
often elicit strong and undesirable side-effects due to the inhibition
of ABC transporter function in normal cells, thereby restricting their
usefulness as therapeutics.
Investigators at the NIH have now discovered that the amino acid
analog Tiopronin has the ability to kill multi-drug resistant cancer
cells while leaving normal cells relatively unharmed. This suggests
that Tiopronin can be developed as a therapeutic for multi-drug
resistant cancers. Furthermore, Tiopronin re-sensitizes multi-drug
resistant cells to chemotherapeutic agents over time. This may allow
cyclical administration of chemotherapeutics without the development of
permanent resistance to the agents, increasing the effectiveness of
chemotherapy as a cancer treatment.
Importantly, Tiopronin is not an inhibitor of ABC transporter
function because it kills multi-drug resistant cells without affecting
the activity of ABC transporters. As a result, the undesirable side-
effects that have prevented the use of inhibitors of ABC transporters
as therapeutics should not affect the therapeutic application of
Tiopronin.
Applications:
Treatment of cancers associated with MDR, either alone or
in combination with other therapeutics
Resensitization of multi-drug resistant cells to
chemotherapeutic agents, allowing cyclical administration of
chemotherapy
Advantages:
Tiopronin capitalizes on one of the most common drawbacks
to cancer therapies (MDR) by using it as an advantage for treating
cancer
[[Page 15328]]
Tiopronin does not inhibit the activity of ABC
transporters, thereby reducing the chance of undesired side-effects
during treatment
The effects of Tiopronin correlates with the level of ABC
transporter expression, allowing healthy cells to better survive
treatments
Tiopronin can also improve the effectiveness of
chemotherapy by re-sensitizing resistant cells that were previously
considered impervious to treatment
Tiopronin has already been approved for use in humans for
the treatment of cytinuria, facilitating the pathway for use in humans
as a treatment for cancer
Development Status: Preclinical stage of development, in vitro data
Inventors: Andrew S. Goldsborough et al. (NCI)
US Patent Status: US Provisional Application 61/407,948 (E-227-
2010/0-US-01)
Licensing Status: The technology is available for exclusive
licensing.
Licensing Contact: David Lambertson, PhD; 301-435-4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute,
Multidrug Resistance Section, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize this technology. Please contact
John Hewes, PhD at 301-435-3121 or hewesj@mail.nih.gov for more
information.
Identification of EGFR as a Receptor for AAV6 Transduction
Description of Technology: AAV vectors offer unique advantages in
gene therapy applications. Studies have shown that these replication
deficient parvovirus vectors can deliver DNA to specific tissues and
confer long-term transgene expression in a variety of systems. Although
many studies have looked at the tissue-specific expression elicited by
each of the AAV serotypes, a true understanding of how AAV transduces
these tissues is still unclear. Of the large AAV family, only a few
receptors or co-receptors have been identified. The ability to better
target transduction to specific tissues on the basis of the receptors
that each serotype uses for entry is essential for selecting a serotype
given the receptor expression in specific tissue, or to exploit altered
receptor expression under disease conditions.
AAV6 has been reported to effectively transduce muscle, lung,
brain, and multiple types of tumors, including gliomas and lung
adenocarcinomas. By using a bioinformatics based screen approach, the
NIH investigators discovered that the epidermal growth factor receptor
(EGFR) is a co-receptor for AAV6 infection in mammalian cells, and is
necessary for efficient vector internalization.
Applications and Market: Improved gene therapy applications.
Development Status: Pre-clinical stage of development.
Inventors: John A. Chiorini, Melodie L. Weller, Michael Schmidt
(NIDCR)
Publication: Weller ML, Amornphimoltham P, Schmidt M, Wilson PA,
Gutkind JS, Chiorini JA. Epidermal growth factor receptor is a co-
receptor for adeno-associated virus serotype 6. Nat Med. 2010
Jun;16(6):662-664. [PubMed: 20473307]
Patent Status: U.S. Utility Patent Application No. 12/879,142 filed
10 Sep 2010 (HHS Reference No. E-194-2010/0-US-01)
Licensing Status: Available for licensing.
Licensing Contact: Betty B. Tong, PhD; 301-594-6565;
tongb@mail.nih.gov.
Therapeutic Approach to Neurodegenerative Disorders Using a TFP5-
Peptide
Description of Technology: This invention discloses methods for
treating neurodegenerative diseases by administering cyclin dependent
kinase 5 (Cdk5) inhibitory peptides derived from P35, the activator of
Cdk5. Abnormally hyperactive Cdk5 has been shown to be associated with
a variety of neurodegenerative disorders. Disclosed in this invention
are isolated peptide fragments, pharmaceutical compositions and methods
for use of such for treating subjects with a neurodegenerative disease,
such as Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS)
and Parkinson's disease (PD). An inhibitory fragment, TFP5, disclosed
in this invention, has been shown to ameliorate symptoms of AD in
disease animal models without any evidence of toxicity. In particular,
TFP5 treatment of rat cortical neurons reduced hyperactivation of Cdk5
upon neuronal stress and insults. Following intraperitoneal (ip)
injection, TFP5 was capable of crossing the BBB and localizing within
the brain where it was found to rescue memory deficits and pathology in
a double transgenic mouse (APP/PS1) AD model.
Applications: Therapeutic developments (AD, PD, ALS)
Advantages: The products are small peptides that pass the blood
brain barrier.
Market: Development for AD, PD, and ALS.
Development Status: Pre-clinical; some animal data
Inventors: Harish C. Pant (NINDS)
Patent Status: U.S. Provisional Application No. 61/387,839 filed 29
Sep 2010 (HHS Reference No. E-144-2010/0-US-01)
Licensing Status: Available for licensing.
Licensing Contact: Steven H. Standley, PhD; 301-435-4074;
sstand@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Neurological Disorders and Stroke, Neuronal Cytoskeletal Protein
Regulation Section, is seeking statements of capability or interest
from parties interested in collaborative research to further develop,
evaluate, or commercialize topic of invention or related laboratory
interests. Please contact Heather Gunas, J.D., M.P.H., at 301-451-3944
or gunash@mail.nih.gov for more information.
Dated: March 15, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-6569 Filed 3-18-11; 8:45 am]
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