[Federal Register Volume 74, Number 147 (Monday, August 3, 2009)]
[Notices]
[Pages 38440-38442]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-18504]
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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.
Treatment of Cancer Using Metal Coordinating Compounds That Kill Multi-
Drug Resistant Cancer Cells
Description of Invention: 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. Research has generally been directed to
overcoming MDR by inhibiting the activity of ABC transporters. However,
compounds that inhibit ABC transporter activity often elicit strong and
undesirable side-effects, restricting their usefulness as therapeutics.
In an alternative approach to reducing the debilitating effects of
MDR during cancer therapy, scientists at the NIH have identified a
family of compounds
[[Page 38441]]
whose activities are enhanced, rather than decreased, in MDR cancer
cells. Particular embodiments of these ``MDR-selective compounds''
include certain metal coordinating compounds. Recent evidence suggests
that these MDR-selective compounds can be used to kill cancer cells
that overexpress ABC transporters or to re-sensitize multi-drug
resistant cancer cells to chemotherapeutics. Furthermore, the
effectiveness of these compositions in killing MDR cancer cells
correlates directly with the level of ABC transporter expression.
Importantly, MDR-selective compounds are not inhibitors of ABC
transporters, thereby reducing the likelihood of undesirable side-
effects during treatment. Thus, MDR-selective compounds represent a
powerful strategy for treating multi-drug resistant cancers as a direct
chemotherapeutic and as agents that can re-sensitize MDR cancer cells
for treatment with additional chemotherapeutic agents.
Applications
Treatment of cancers associated with multi-drug
resistance, either alone or in combination with other therapeutics.
Re-sensitization of multi-drug resistant cancer cells to
chemotherapeutic agents.
Advantages
MDR-selective compounds capitalize on one of the most
common drawbacks to cancer therapies (MDR) by using it as an advantage
for treating cancer.
The compositions do not inhibit the function of ABC
transporters, reducing the chance of side-effects during treatment.
The effects of MDR-selective compounds correlate with the
level of ABC transporter expression, allowing healthy cells which do
not express high levels of ABC transporters to better survive
treatment.
Development Status: Preclinical stage of development.
Patent Status: U.S. Provisional Application No. 61/182,511 (HHS
Reference No. E-157-2009/0-US-01).
Inventors: Gergely Szakacs et al. (NCI).
For More Information, See
C Hegedus et al. Interaction of ABC multidrug transporters
with anticancer protein kinase inhibitors: substrates and/or
inhibitors? Curr Cancer Drug Targets. 2009 May;9(3):252-272.
MD Hall et al. Synthesis, activity, and pharmacophore
development for isatin-beta-thiosemicarbazones with selective activity
toward multidrug-resistant cells. J Med Chem. 2009 May 28;52(10):3191-
3204.
U.S. Patent Application Publication 20080214606 A1 (U.S.
Patent Application 11/629,233).
Licensing Status: Available for licensing.
Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity: The Institute of Enzymology is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
MDR-selective compounds. Please contact John D. Hewes, Ph.D. at 301-
435-3121 or hewesj@mail.nih.gov for more information.
Non Toxic Peptide Treatment for Dyslipidemic and Vascular Disorders
Description of Invention: Dyslipidemia and vascular disorders such
as hyperlipidemia, hypercholesterolemia, HDL deficiency, coronary heart
disease, atherosclerosis, or thrombic stroke, have become major health
concerns in recent years. Various approaches to treating these diseases
have led to mixed success with some undesirable side effects. Long term
administration of some regimens aimed at reducing cholesterol levels in
cells can lead to persistent hypertriglyceridemia; a condition that is
characterized by chronically high triglycerides in the blood. Other
approaches, such as using peptides to stimulate the efflux of lipids
from cells, are also associated with high toxicity, which has limited
their use.
This technology uses peptide and peptide analogues with multiple
amphipathic alpha helical domains that have the dual ability to promote
lipid efflux from cells and stimulate lipoprotein lipase activity,
without inducing toxicity. It consists of motifs that mimick
apolipoprotein A-I (apoA-I), the most abundant protein constituent of
high density lipoproteins (HDLs) that is capable of inducing cellular
lipid efflux, and motif resembling apolipoprotein C-II (apoC-II), a
known activator of lipoprotein lipase. Peptides constructed with these
structural domains are capable of stimulating lipid efflux and
activating lipoprotein lipase, leading to a reduced incidence of
hypertriglyceridemia. Unlike previous methods, some amphipathic
peptides cause transient hypertriglyceridema in mice that lasts for
less than 8 hours. Mice treated with these modified peptides have shown
preserved liver function as they have failed to express increased
levels of biomarkers for liver damage and prevent hypertriglyceridemia.
Furthermore, treated mice show a reduced level of pro-atherogenic
lipoproteins. This technology demonstrates specific control of lipid
efflux and transport; a desirable property that gives it a significant
advantage for treating or preventing a vast range of vascular diseases
and their dyslipidemic precursors.
This technology also encompasses a method for identifying non-
cytotoxic peptides that promote lipid efflux from cells and activates
lipoprotein lipase.
Applications and Advantages
Peptide treatment of dyslipidemic and vascular disorders.
Transient hypertriglyceridemia with no reported toxicity.
Method of identifying therapeutic non-cytotoxic peptides.
Development Status: Pre-clinical.
Inventor: Alan T. Remaley and Marcelo Amar (NHLBI).
Publication: AT Remaley, F Thomas, JA Stonik, SJ Demosky, SE Bark,
EB Neufeld, AV Bocharov, TG Vishnyakova, AP Patterson, TL Eggerman, S
Santamarina-Fojo, HB Brewer. Synthetic amphipathic helical peptides
promote lipid efflux from cells by an ABCA1-dependent and an ABCA1-
independent pathway. J Lipid Res. 2003 Apr;44(4):828-836.
Patent Status: U.S. Provisional Application No. 60/045,213 filed 15
Apr 2008 (HHS Reference No. E-138-2008/0-US-01); PCT Application No.
PCT/US2009/040560 filed 14 Apr 2009 (HHS Reference No. E-138-2008/0-
PCT-02).
Licensing Status: Available for licensing.
Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521;
sayyidf@mail.nih.gov.
Methods for Treating or Ameliorating Fibrosis by Inhibiting the
Interaction Between IL-21 Receptor (IL-21R) and IL-21
Description of Invention: This invention includes methods for
treating or ameliorating fibrosis by inhibiting the interaction between
IL-21 Receptor (IL-21R) and IL-21 using either anti-IL21R monoclonal
antibodies (or binding fragments of anti-IL-21R mAbs), anti-IL21
monoclonal antibodies (or binding fragments of anti-IL-21 mAbs) or
soluble IL-21R (or binding fragments of IL-21R). It is believed that
the TH2 immune response, induced by IL-21, plays a major role in the
pathogenesis of tissue fibrosis. Antagonism of IL-21R by anti-IL-21R
monoclonal antibodies or the sequestration of IL-21 by soluble IL-
[[Page 38442]]
21R or anti-IL-21 monoclonal antibodies has been demonstrated to reduce
TH2 immune responses associated with fibrosis in animal models.
The causes of chronic tissue fibrosis are diverse and the market
for a therapeutic that targets fibrosis is large. Fibrosis is
associated with diverse causes which include: genetic diseases (such as
cystic fibrosis); autoimmune diseases (such as scleroderma); chronic
viral infections (such as hepatitis), parasitic infections (such as
schistosomiasis); and occupational exposures to causative agents (such
as asbestosis). Additionally, many cases of tissue fibrosis are
idiopathic.
Application: The treatment or amelioration of tissue fibrosis.
Inventors: Thomas A. Wynn (NIAID); Deborah A Young; Mary Collins;
and Michael J. Grusby.
Relevant Publication: J Pesce et al. The IL-21 receptor augments
Th2 effector function and alternative macrophage activation. J Clin
Invest 2006 Jul;116(7):2044-2055.
Patent Status: U.S. patent application no. 11/402,885 (priority
date April 14, 2005) and international patent applications including
European patent application No. EP06/0750009 (HHS Reference No. E-250-
2005).
Licensing Status: Available for non-exclusive licensing.
Licensing Contact: Surekha Vathyam, Ph.D.; 301-435-4076;
vathyams@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Allergy and Infectious Diseases is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize this invention. Please contact
Nicole Mahoney at 301-435-9017 or mahoneyn@niaid.nih.gov for more
information.
Use of Discoidin Domain Receptor 1 (DDR1) and Agents That Affect the
DDR1/Collagen Pathway
Description of Invention: Dendritic cells (DCs) are pivotal
antigen-presenting cells for initiation of an immune response. Indeed,
dendritic cells provide the basis for the production of an effective
immune response to a vaccine, particularly for antigens wherein
conventional vaccination is inadequate. DCs are also important in the
production on an immune response to tumor antigens.
The present invention discloses methods of using the receptor
tyrosine kinase discoidin domain receptor 1 (DDR1) to facilitate the
maturation/differentiation of DCs or macrophages. Activating agents of
DDR1 may be useful in the induction of highly potent, mature DCs or
highly differentiated macrophages from DC precursors, such as
monocytes. Use of this method may enhance the antigen presenting
capabilities of the immune system, leading to a more effective overall
immune response.
Inventor: Teizo Yoshimura (NCI).
Relevant Publications
1. H Kamohara et al. Discoidin domain receptor 1 isoform-a (DDR1a)
promotes migration of leukocytes in three-dimensional collagen
lattices. FASEB J. 2001 Dec;15(14):2724-2726.
2. W Matsuyama et al. Interaction of discoidin domain receptor 1
isoform b (DDR1b) with collagen activates p38 mitogen-activated protein
kinase and promotes differentiation of macrophages. FASEB J. 2003
Jul;17(10):1286-1288.
Patent Status: U.S. Application No. 10/507,385 filed 09 Sep 2004
(HHS Reference No. E-083-2002/2-US-02).
Licensing Status: Available for licensing.
Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565;
tongb@mail.nih.gov.
Dated: July 28, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-18504 Filed 7-31-09; 8:45 am]
BILLING CODE 4140-01-P