[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