[Federal Register Volume 74, Number 250 (Thursday, December 31, 2009)]
[Notices]
[Pages 69343-69346]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-31075]
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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.
Synergy of ABT-737 With an Immunotoxin To Kill Cancer Cells
Description of Technology: Programmed cell death (i.e., apoptosis)
represents an attractive approach for treating cancer. However, anti-
apoptotic proteins that are frequently active in cancer cells can allow
the cells to survive induction of apoptosis. While inhibiting anti-
apoptotic proteins has shown promise in combination with apoptosis-
inducing treatments, current inhibitors only show incomplete
effectiveness in promoting the induction of apoptosis.
ABT-737 is one such inhibitor; it can only inhibit the function of
three of the four major anti-apoptosis proteins. The fourth member,
known as a MCL1, is a short-lived protein that can still prevent
apoptosis in the presence of ABT-737. Importantly, because MCL1 is a
short-lived protein, it requires protein synthesis to maintain levels
that are sufficient to continue blocking apoptosis.
This technology uses a combination approach in the treatment of
cancer. The inventors considered that combining ABT-737 with a protein
synthesis inhibitor might completely inhibit anti-apoptotic proteins,
leading to efficient induction of apoptosis. Specifically, NIH
inventors found that combining ABT-737 and immunotoxins did result in
enhanced killing of cancer cells. Because immunotoxins function by
inhibiting protein synthesis, the two agents in combination are able to
inhibit all of the anti-apoptotic proteins simultaneously. Furthermore,
immunotoxins can be specifically targeted to cancer cells, thereby
increasing their effectiveness over a non-specific protein synthesis
inhibitor. The results suggest that the combination could represent an
effective approach to enhancing the induction of apoptosis as an anti-
cancer therapy.
Application: Combination anti-cancer therapy.
Advantages:
Overcomes the anti-apoptotic proteins frequently
associated with inducing apoptosis, thereby leading to an effective
therapeutic approach.
Synergistic effect improves toxicity of both the
apoptosis-inducing agents and immunotoxins.
Selective inhibition of protein synthesis by immunotoxins
increases effectiveness versus using non-specific inhibitors.
Development Status: Preclinical stage of development.
Inventors: David J. FitzGerald (NCI) et al.
Patent Status: U.S. Provisional Application No. 61/238,032 (HHS
Reference No. E-279-2009/0-US-01).
For more information, see:
Pastan et al., US Patent 4,892,827.
Pastan et al., US Patent 5,705,163.
Pastan et al., PCT Application PCT/US2008/075296 (WO 2009/
032954).
JE Weldon et al. A protease-resistant immunotoxin against
CD22 with greatly increased activity against CLL and diminished animal
toxicity. Blood 2009 Apr 16;113(16):3792-3800.
DJ FitzGerald et al. Recombinant immunotoxins for treating
cancer. Int J Med Microbiol. 2004 Apr;293(7-8):577-582.
Licensing Status: Available for licensing.
Licensing Contact: David A. Lambertson, PhD; 301-435-4632;
[email protected].
Collaborative Research Opportunity: The Center for Cancer Research,
Laboratory of Molecular Biology, is seeking statements of capability or
interest from parties interested in
[[Page 69344]]
collaborative research to further develop, evaluate, or commercialize
this technology. Please contact John D. Hewes, PhD at 301-435-3121 or
[email protected] for more information.
A Device for Sterile Removal of a Biological Sample From a
Cryopreserved Bag
Description of Technology: Cryopreservation through freezing in
liquid nitrogen allows the storage of biological materials for extended
periods while maintaining their activity and viability. It is commonly
used in the clinic to store blood cells, semen, and umbilical cord
blood (UCB) for future use. These materials are typically only
obtainable in limited quantities and may be of great therapeutic value,
as is the case of hematopoietic stem cells from UCB which can be used
to treat and cure a number of different life-threatening illnesses. It
is common practice to cryopreserve viably in bags a variety of
different cells obtained from the blood. Currently, even if only a
small portion of the cryopreserved sample is needed the whole bag must
be thawed, wasting much of the sample since it cannot be effectively
refrozen. There is a need for a method of retrieving a small sample
from a frozen sample of cells in a bag while preserving the
cryopreserved state and integrity of the rest of the cellular material.
Researchers at the National Heart, Lung, and Blood Institute in
collaboration with the American Fluoroseal Corporation (AFC) have
invented an apparatus that separates a small portion of a cryopreserved
biological material stored in a collection bag while maintaining the
cryopreserved integrity, sterility, and viability of the original
cryopreserved material. This device could be used to retrieve small
aliquots samples of various cryopreserved cellular products and
biological materials such as UCB, blood mononuclear cells, stem cells,
semen, and plasma while maintaining the viability and sterility of both
the retrieved sample and the original cryopreserved material.
Applications: The apparatus can be used for:
Retrieving hematopoietic stem cells from cryopreserved UCB
unit to reconstitute the bone marrow of cancer patients undergoing
radiotherapy and chemotherapy;
retrieving portions of cryopreserved blood cells for
expansion of antigen reactive T-cells, NK cells, and hematopoietic stem
cells in the laboratory;
retrieving portions of cryopreserved semen for assisted
reproductive technology;
sampling of cryopreserved blood plasma for detection of
cytokines, chemokines, or other proteins, infectious agents or
performance-enhancing drugs.
Advantages:
Ability to isolate portions or cryopreserved biological
materials while retaining viability, sterility, and cryopreserved
integrity of remaining material.
Compatibility with thousands of blood bags presently
stored in commercial and public blood banks.
Development Status: A prototype of the device has been built and
successfully tested.
Market: This novel apparatus has commercial potential in diverse
markets such as: Blood banking and blood products, human reproductive
technologies, hematopoietic stem cell and tissue transplantation,
medical devices, stem cells, and cancer therapy.
Inventors: Richard W. Childs (NHLBI), Herbert Cullis (AFC), Sumi
Vasu (NHLBI).
Patent Status: U.S. Provisional Application No. 61/175,131 filed 04
May 2009 (HHS Reference No. E-173-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Surekha Vathyam, PhD; 301-435-4076;
[email protected].
Collaborative Research Opportunity: The National Heart, Lung, and
Blood Institute, Hematology Branch, is seeking statements of capability
or interest from parties interested in collaborative research to
further develop, evaluate, or commercialize the Device for Sterile
Removal of a Biological Sample from a Cryopreserved Bag. Please contact
Cecilia Pazman, PhD, 301-402-5579; [email protected] for more
information.
Optimizing Chemotherapeutic Performance: Three Newly-Identified Classes
of Tyrosyl-DNA Phosphodiesterase (Tdp1) Inhibitors
Description of Technology: During replication, DNA is structurally
modified and cleaved by a host of enzymes, including topoisomerases.
Some chemotherapeutic agents generate their anti-cancer activity by
inducing DNA damage in rapidly replicating tumor cells, resulting in
cell death. Topoisomerase I (top1) inhibitors, such as camptothecins,
are common chemotherapeutics that prevent the religation of DNA after
cleavage during replication.
Tyrosyl-DNA phosphodiesterase (Tdp1) counteracts the action of
these chemotherapeutic agents and can reduce their effectiveness in
eliminating tumor cells. Tdp1 is an enzyme that repairs DNA lesions and
chemotherapeutic-mediated DNA damage, such as the DNA breaks induced by
top1 inhibitors. Therefore, Tdp1 is a rational anticancer target whose
inhibition should enhance the activity of common cancer
chemotherapeutics by permitting greater DNA damage in tumor cells.
Scientists at the National Institutes of Health (NIH) have
discovered three classes of compounds that specifically inhibit Tdp1,
including cephalosporin derivatives like beta-lactam antibiotics,
ellagic acid derivatives such as polyphenol antioxidants, and
verteporfin derivatives including protoporphyrins. The compounds were
identified as specific Tdp1 inhibitors via a high-throughput screening
assay (AlphaScreen\TM\) of the NIH Roadmap Molecular Libraries Small
Molecule Repository (MLSMR). One current goal of the scientists is to
identify the compounds with the greatest Tdp1 specificity and highest
inhibitory activity against cancer cell proliferation. Some of the
compounds identified are widely used to treat a variety of other
diseases, including bacterial infections (beta-lactam antibiotics) and
neurodegenerative and cardiovascular disorders (polyphenol
antioxidants).
Now, through studies at the NIH, these compounds identified as Tdp1
inhibitors could be utilized to potentiate the pharmacological action
of top1 inhibitors in the treatment of cancer with combination drug
therapies. Top1 inhibitor/Tdp1 inhibitor combination chemotherapies are
anticipated to be more selective against tumor tissues than top1
inhibitors alone. In addition, since Tdp1 is involved in repairing DNA
damage caused by oxygen radicals and tumors are known to contain excess
free radicals, Tdp1 inhibitors may also prove useful as anticancer
agents independent of their use in conjunction with top1 inhibitors.
Applications:
Cancer therapeutics administered in combination with known
cancer drugs, such as topoisomerase I inhibitors, to enhance the
activity and selectivity of these chemotherapeutics. Various types of
cancer could be treated with this combination therapy, including lung
cancer, colon cancer, breast cancer, prostate cancer, melanoma,
lymphomas, ovarian cancer, and pancreatic cancer to name a few.
[[Page 69345]]
Compounds utilized as a strategy to overcome chemotherapy
resistance in cancer patients.
Cancer drug administered alone as a sole chemotherapeutic
regimen for patients.
Advantages:
Positive S&E History with the FDA: Some compounds found
within each of these three newly-identified classes of Tdp1 inhibitors
are used to treat other health problems like bacterial infections and
cardiovascular disease. The FDA approval process for these inhibitors
in a combination therapy may be shortened given their proven track
record in other indications.
Different Approach to Combination Chemotherapy:
Combination chemotherapy is a widely accepted treatment strategy for
cancer patients, but many combinations lead to more side effects and
toxicities due to multiple drug activities. These Tdp1 inhibitors aim
to enhance the activity and selectivity of the other drug used in
combination, which could lead to greater anticancer activity without an
increase in side effects.
Development Status: This technology is in the pre-clinical stage of
development.
Market: Cancer continues to be a medical and financial burden on
U.S. public health. According to U.S. estimates, cancer is the second
leading cause of death with over 565,000 deaths reported in 2008 and
almost 1.5 million new cases were reported (excluding some skin
cancers) in 2008. In 2007, the NIH estimated that the overall cost of
cancer was $219.2 billion dollars and $89 billion went to direct
medical costs. Despite our increasing knowledge of cancer treatment and
diagnosis methods, the fight against cancer will continue to benefit
from the development of new technologies aimed at treating individuals
with disease and diagnosing susceptible patients.
Inventors: Yves Pommier (NCI) et al.
Selected Publications:
1. C Marchand, et al. Identification of phosphotyrosine mimetic
inhibitors of human tyrosyl-DNA phosphodiesterase I by a novel
AlphaScreen high-throughput assay. Mol Cancer Ther. 2009 Jan;8(1):240-
248.
2. S Antony, et al. Novel high-throughput electrochemiluminescent
assay for identification of human tyrosyl-DNA phosphodiesterase (Tdp1)
inhibitors and characterization of furamidine (NSC 305831) as an
inhibitor of Tdp1. Nucleic Acids Res. 2007;35(13):4474-4484.
3. Z Liao, et al. Inhibition of human tyrosyl-DNA phosphodiesterase
I by aminoglycoside antibiotics and ribosome inhibitors. Mol Pharmacol.
2006 Jul;70(1):366-372.
4. TS Dexheimer, et al. Tyrosyl-DNA phosphodiesterase as a target
for anticancer therapy. Anticancer Agents Med Chem. 2008 May;8(4):381-
389.
Patent Status: U.S. Provisional Application No. 61/268,130 filed 08
Jun 2009 (HHS Reference No. E-093-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Samuel E. Bish, PhD; 301-435-5282;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute,
Laboratory of Molecular Pharmacology 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 John D.
Hewes, PhD at 301-435-3121 or [email protected] for more information.
Biomarkers for Osteoarthritis
Description of Technology: Osteoarthritis is chronic, often
progressive and substantially disabling condition that becomes more
common with advanced age. Osteoarthritis commonly involves the knees,
hands, hips, neck and back resulting in pain and limitations of
movement.
Unfortunately clinically available tests are neither capable of
detecting osteoarthritis early in its development, nor sensitive enough
to adequately assess disease progression. A better means of diagnosing
early osteoarthritis and its progression that can be used to assess the
response to therapeutic treatments is needed. The currently available
laboratory techniques are highly sensitive but either lack specificity
or require large volumes of sample. Rolling Circle Amplification (RCA)
is new technology that precisely localizes unique signals arising from
single reporter molecules. RCA has been incorporated into antibody-
based microarray system protein chips that enable testing with high
sensitivity and specificity for hundreds of proteins simultaneously,
using small sample volumes.
This invention describes a method of using RCA technology for
detecting the expression of serum proteins that are perturbed in
osteoarthritis patients. The results of this testing can be used to
identify proteins associated with osteoarthritis presence, prediction
of osteoarthritis development and prognosis, predict response to
osteoarthritis treatment and potentially also identify future anti-
osteoarthritic drugs.
Inventors: Shari M. Ling et al. (NIA).
Patent Status: U.S. Patent Application No. 11/573,711 filed 14 Feb
2007 (HHS Reference No. E-354-2004/0-US-07) and related international
applications.
Licensing Status: Available for licensing.
Licensing Contact: Charlene A. Sydnor, PhD; 301-435-4689;
[email protected].
VAC-BAC Shuttle Vector System for Generating Recombinant Poxviruses
Description of Technology: This invention relates to a VAC-BAC
shuttle vector system for the creation of recombinant poxviruses from
DNA cloned in a bacterial artificial chromosome. A VAC-BAC is a
bacterial artificial chromosome (BAC) containing a vaccinia virus
genome (VAC) that can replicate in bacteria and produce infectious
virus in mammalian cells.
Applications:
VAC-BACs can be used to modify vaccinia virus DNA by
deletion, insertion or point mutation or add new DNA to the VAC genome
with methods developed for bacterial plasmids, rather than by
recombination in mammalian cells.
It can be used to produce recombinant vaccinia viruses for
gene expression.
It can be used for the production of modified vaccinia
viruses that have improved safety or immunogenicity.
Advantages:
VAC-BACs are clonally purified from bacterial colonies
before virus reconstitution in mammalian cells.
Manipulation of DNA is much simpler and faster in bacteria
than in mammalian cells.
Modified genomes can be characterized prior to virus
reconstitution.
Only virus with modified genomes will be produced so that
virus plaque isolations are not needed.
Generation of a stock of virus from a VAC-BAC is
accomplished within a week rather than many weeks.
Multiple viruses can be generated at the same time since
plaque purification is unnecessary.
Inventors: Bernard Moss and Arban Domi (NIAID).
Related Publications:
1. A Domi and B Moss. Cloning the vaccinia virus genome as a
bacterial artificial chromosome in Escherichia coli and recovery of
infectious virus in mammalian cells. Proc Natl Acad Sci USA. 2002 Sep
17;99(19):12415-12420.
2. A Domi and B Moss. Engineering of a vaccinia virus bacterial
artificial
[[Page 69346]]
chromosome in Escherichia coli by bacteriophage lambda-based
recombination. Nat Methods. 2005 Feb;2(2):95-97.
Patent Status: U.S. Patent No. 7,494,813 issued 24 Feb 2009 (HHS
Reference No. E-355-2001/2-US-02).
Licensing Status: Available for licensing.
Licensing Contact: Sue Ano, PhD; 301-435-5515; [email protected].
Dated: December 23, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-31075 Filed 12-30-09; 8:45 am]
BILLING CODE 4140-01-P