[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]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

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