Government-Owned Inventions; Availability for Licensing, 69343-69346 [E9-31075]
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Federal Register / Vol. 74, No. 250 / Thursday, December 31, 2009 / Notices
69343
EXHIBIT 3—ESTIMATED COST OF THE EVALUATION
Cost component
Total cost
Annualized cost
Protocol Development .................................................................................................................................
Data Collection Activities .............................................................................................................................
Data Analysis ...............................................................................................................................................
Publication of Results ..................................................................................................................................
Travel for Site Visits ....................................................................................................................................
$40,278
91,104
45,252
24,370
8,823
$20,139
45,552
22,626
12,185
4,412
Total ......................................................................................................................................................
209,827
104,914
Request for Comments
In accordance with the above-cited
Paperwork Reduction Act legislation,
comments on AHRQ’s information
collection are requested with regard to
any of the following: (a) Whether the
proposed collection of information is
necessary for the proper performance of
AHRQ healthcare research and
healthcare information dissemination
functions, including whether the
information will have practical utility;
(b) the accuracy of AHRQ’s estimate of
burden (including hours and costs) of
the proposed collection(s) of
information; (c) ways to enhance the
quality, utility, and clarity of the
information to be collected; and (d)
ways to minimize the burden of the
collection of information upon the
respondents, including the use of
automated collection techniques or
other forms of information technology.
Comments submitted in response to
this notice will be summarized and
included in the Agency’s subsequent
request for OMB approval of the
proposed information collection. All
comments will become a matter of
public record.
Dated: December 10, 2009.
Carolyn M. Clancy,
Director.
[FR Doc. E9–30957 Filed 12–30–09; 8:45 am]
BILLING CODE 4160–90–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
erowe on DSK5CLS3C1PROD with NOTICES
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
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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 shortlived 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 antiapoptotic 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
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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 proteaseresistant 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;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity:
The Center for Cancer Research,
Laboratory of Molecular Biology, is
seeking statements of capability or
interest from parties interested in
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Federal Register / Vol. 74, No. 250 / Thursday, December 31, 2009 / Notices
collaborative research to further
develop, evaluate, or commercialize this
technology. Please contact John D.
Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
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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 lifethreatening 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;
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• 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 performanceenhancing 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;
vathyams@mail.nih.gov.
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;
pazmance@mail.nih.gov 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.
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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
(AlphaScreenTM) 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.
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Federal Register / Vol. 74, No. 250 / Thursday, December 31, 2009 / Notices
• 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 highthroughput assay. Mol Cancer Ther.
2009 Jan;8(1):240–248.
2. S Antony, et al. Novel highthroughput 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
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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;
bishse@mail.nih.gov.
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
hewesj@mail.nih.gov 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
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69345
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;
sydnorc@mail.nih.gov.
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
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Federal Register / Vol. 74, No. 250 / Thursday, December 31, 2009 / Notices
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; anos@mail.nih.gov.
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
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.
erowe on DSK5CLS3C1PROD with NOTICES
Fourier X-ray Scattering and PhaseContrast Imaging: Enhanced Contrast
and Sensitivity of X-ray Images
Description of Technology: The
invention offered for licensing is
broadly applicable to medical diagnostic
imaging, biological imaging, industrial
non-destructive testing, security
screening, and other routine x-ray
inspections. The invention provides a
method and apparatus that can
significantly improve and enhance the
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contrast and sensitivity of x-ray images.
More specifically, the method described
in the invention provides a technique to
obtain in a single shot x-ray diffraction,
differential phase-contrast, as well as
the conventional absorption images. Xray diffraction reveals information about
microscopic structures in the imaged
object from nanometer to micrometer
scales which enables detection of
specific materials and disease
pathologies that are invisible in
conventional x-ray images. The main
advantage of the invention over prior art
is the single-shot capability without the
need to scan an analyzer crystal or
grating, and without the need for any
hardware beyond standard radiography
equipment. It also offers flexibility in
hardware configuration to target specific
materials by their diffraction signature.
For this reason the invention is highly
adaptable and well suited for day-to-day
applications of x-ray radiography and
computed tomography.
In one of the embodiments of the
invention for example, a scattering
imaging method uses a transmission
grid to modulate the intensity of a beam
of an x-ray radiation source. A detector
captures a raw image from the
modulated intensity pattern. A
diffraction image can be automatically
generated from the detected modulated
intensity pattern.
In yet another embodiment, both a
diffraction image and a differential
phase-contrast image are obtained in a
single exposure. Advantageously,
commercially available x-ray grids and
radiography machines can be used for
this method, and exact positioning of
the grid is unnecessary, as the method
works for any non-zero distance
between the grid and the detector. Thus,
the speed and ease of implementation
makes it suitable for both planar
radiography and 3D computed
tomography. In addition to its medical
diagnostics significance, the invention
can be utilized in other, non-medical
applications such as non-destructive
inspections and security screening.
Applications
• Medical diagnostic radiography and
computed tomography. For example,
imaging blood vessels, imaging of bones
(i.e., osteoporosis, fractures).
• Non-invasive characterization of
material microscopic structures by
planar radiography or 3D computed
tomography implementations of the
invention.
• Detection of materials by their
diffraction signature in x-ray
inspections and security screening.
Advantages: Although x-ray
diffraction and phase-contrast imaging
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can detect materials and structures that
are invisible by conventional absorption
images, current techniques remain
difficult to implement due to
requirements for specialized x-ray
optical components and/or brilliant
sources, and lengthy scanning of
analyzer components such as perfect
crystals or high-density gratings. A
recent publication (US2007/0183563
A1) mentioned that by using a detector
with elements less than 1⁄3 of the pitch
of an analyzer grating, it is possible to
obtain differential phase-contrast images
in one measurement without the need to
scan. US2007/0183580 A1 further
elaborates on this technique and
specifies that the detector elements are
an integer fraction of the grating pitch
so that sub-groups of the detectors can
report x-ray intensities of different
portions of a grating period, from which
the phase shift of the grating pattern is
measured. Such detectors are highly
challenging to realize, and are not able
to cope with varying pitches or patterns
of x-ray beam modulation.
It is additionally known in the art to
remove the effects of scattering with the
use of grids, gratings, or other masks of
periodically arranged opaque areas.
Specifically, a mask or multiple masks
of periodically arranged opaque areas
are placed in the x-ray path, such that
periodic dark shadows are created on a
recorder surface either by direct
geometric shadowing or by waveinterference effects. The shadow areas
only receive x-ray which is scattered in
the object. The signals of these shadow
areas are subtracted from the raw image
to yield an image free of the effects of
scattering.
Nonetheless, the above variations
require exacting procedures or are
expensive, making the prior art illsuited for today’s routine x-ray imaging
applications, including non-destructive
testing (e.g., component inspection
without damage), security screening,
and medical diagnostic exams.
The present technology overcomes the
drawbacks of the prior art by allowing
the acquisition of x-ray diffraction,
differential phase-contrast and
absorption images all in a single
exposure without the need for scanning
or any hardware beyond commercial
radiography equipment.
It is particularly flexible when
compared to prior art in that the number
of transmission grids, their patterns and
their positions can all be adjusted to
selectively detect or enhance specific
materials, such as contrast agents in
medical diagnostic imaging or explosive
materials in security screening.
Development Status: The invention is
fully developed.
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]]>Agencies
[Federal Register Volume 74, Number 250 (Thursday, December 31, 2009)]
[Notices]
[Pages 69343-69346]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-31075]
-----------------------------------------------------------------------
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.
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;
lambertsond@mail.nih.gov.
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
hewesj@mail.nih.gov 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;
vathyams@mail.nih.gov.
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; pazmance@mail.nih.gov 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;
bishse@mail.nih.gov.
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 hewesj@mail.nih.gov 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;
sydnorc@mail.nih.gov.
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; anos@mail.nih.gov.
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
