[Federal Register Volume 76, Number 54 (Monday, March 21, 2011)]
[Notices]
[Pages 15326-15328]
From the Federal Register Online via the Government Publishing 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;
[email protected].
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 [email protected] 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;
[email protected].
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;
[email protected].
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 [email protected] 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;
[email protected].
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;
[email protected].
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 [email protected] 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