Government-Owned Inventions; Availability for Licensing, 27150-27152 [E9-13284]
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27150
Federal Register / Vol. 74, No. 108 / Monday, June 8, 2009 / Notices
site. Submit a single copy of electronic
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Dated: May 27, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and
Planning.
[FR Doc. E9–13261 Filed 6–5–09; 8:45 am]
BILLING CODE 4160–01–S
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.
cprice-sewell on PRODPC61 with NOTICES
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.
Interactive Venn Diagram Software
Designed for Microarray Analysis
Description of Technology: Multiple
conditions from any source, but
designed for experiments involving
microarrays, will produce (significant
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gene lists for arrays) lists from each
condition, thus multiple lists. This
Java® based software provides
investigators with a method of
displaying multiple conditions in a
single graphic along with producing a
text output of genes that are the product
of these conditional intersections along
with each conditions unique list. A
standard Venn diagram is limited to
only display three (3) comparisons; this
software can display any number of
comparisons and will automatically
create lists from all intersections even if
not able to be displayed along with each
conditions unique list.
Applications:
• Microarray analysis.
• Genomics.
• Bioinformatics.
• Any environment creating multiple
lists (Business, Accounting, Inventory
Control, etc.).
Inventor: Daniel E. Sturdevant
(NIAID).
Patent Status: HHS Reference No. E–
189–2009/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing.
Licensing Contact: Michael A.
Shmilovich, Esq.; 301–435–5019;
shmilovm@mail.nih.gov.
Axenically-Produced Coxiella
burnetii and Methods for Producing
Axenic Coxiella burnetii
Description of Technology: Coxiella
burnetii is the causative agent of Q
(Query) fever. Currently, there is a need
for a safe Q fever vaccine. It is
anticipated that axenically-produced C.
burnetii, which is free of host cell
related impurities, could provide either
the basis for a whole-cell Q fever
vaccine or advance the development of
a safe recombinant Q fever vaccine.
Currently, there are no licensed Q-fever
vaccines except for a whole-cell,
formalin inactivated, vaccine which is
available in Australia (Q–Vax).
Individuals with a previous exposure to
C. burnetii may, however, have a severe
allergic reaction to this vaccine and
other individuals may experience a
headache or flu-like symptoms after
vaccination. It is anticipated that
axenically-produced C. burnetii could
provide the basis for a less reactogenic
whole-cell vaccine or facilitate the
development of a recombinant vaccine
that does not cause an allergic reaction.
Additionally, the inability to propagate
obligate intracellular pathogens under
axenic (host cell-free) culture conditions
imposes severe experimental constraints
that have negatively impacted progress
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in understanding pathogen virulence
and disease mechanisms.
Q fever is a zoonotic disease and farm
animals, pets, and rodents are
significant reservoirs for C. burnetii. C.
burnetii persists in the soil for a long
time and typically humans are exposed
to Q fever by the inhalation of the
bacterium deposited with animal waste
such as urine, feces, and amniotic fluid.
The epidemiology of Q fever is diverse
and the disease does not discriminate
between developed and developing
countries. Additionally, urban outbreaks
have been known to occur due to
windborne C. burnetii. C. burnetii is
listed as a select agent by the
Department of Health and Human
Services (HHS) because of its potential
as an agent of bioterrorism. Deployed
military personnel are also at risk of
contracting Q fever and thousands of
cases of Q fever have been reported
among military personnel since the
disease was first reported in the 1930s.
Advantages:
• The ability to propagate, previously
unpropagatable, C. burnetii without a
hostcell.
• The ability to study C. burnetii
virulence using axenic conditions or
conditions free of host cell-related
impurities.
• This technology is ready for use in
drug/vaccine discovery, production, and
development.
• Potential licensees of this invention
include companies that are: 1) seeking
vaccine production platforms based on
host cell-free (axenic) media, 2) seeking
to develop recombinant vaccines for
obligate, intracellular, bacteria; or 3)
seeking to lower costs and ease scale-up
would be potential licensees of this
technology.
Development Status: This technology
has been demonstrated with C. burnetii.
Currently, the inventors are testing this
technology for support of axenic growth
of other obligate, intracellular, bacteria
of public health significance.
Inventors: Robert A. Heinzen, Anders
Omsland, Diane C. Cockrell, Dale Howe
(NIAID).
Publication: A Omsland et al. Host
cell-free growth of the Q fever bacterium
Coxiella burnetii. Proc Natl Acad Sci
USA. 2009 Mar 17;106(11):4430–4434.
Patent Status: U.S. Provisional
Application No. 61/154,330 filed 20 Feb
2009 (HHS Reference No. E–114–2009/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301–435–4646;
soukasp@mail.nih.gov.
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Federal Register / Vol. 74, No. 108 / Monday, June 8, 2009 / Notices
Self-Expanding Stent for Valve
Replacement
Description of Technology: Aortic
stenosis and aortic regurgitation are the
most common types of aortic valvular
diseases. Such diseased aortic valves in
the body are traditionally replaced with
valve prosthesis by an open surgical
implantation. Available for licensing
and commercial development is
intellectual property covering stents for
use with valve prostheses. One possible
embodiment of the invention includes a
self-expandable stent with an elastic
tubular latticework having radial and
longitudinal direction. The stent
geometry and mechanical parameters
provide more anatomically-correct
placement and the flexible scaffolding
of the valve (using an interconnected
four-sided polygons and longitudinal
rods comprising a self-expanding stent
with a plurality of struts connecting a
plurality of rods) allow for secure
implantation with adaptable apposition
of the prosthesis in the aorta.
Applications: Cardiac Surgery;
Cardiology; Surgery; Stent implantation.
Inventors: Keith Horvath, Dumitru
Mazilu, Ming Li (NHLBI).
Publications:
1. M Li, D Mazilu, KA Horvath.
Robotic system for transapical aortic
valve replacement with MRI guidance.
Med Image Comput Comput Assist
Interv Int Conf Med Image Comput
Comput Assist Interv. 2008;11(Pt
2):476–484.
2. KA Horvath, M Li, D Mazilu, MA
Guttman, ER McVeigh. Real-time
magnetic resonance imaging guidance
for cardiovascular procedures. Semin
Thorac Cardiovasc Surg. 2007
Winter;19(4):330–335. Review.
Patent Status: U.S. Provisional
Application No. 61/172,568 filed 24 Apr
2009 (HHS Reference No. E–337–2008/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Michael A.
Shmilovich, Esq.; 301–435–5019;
shmilovm@mail.nih.gov.
Collaborative Research Opportunity:
The National Heart, Lung, and Blood
Institute, Cardiothoracic Surgery
Research Program, is seeking statements
of capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize this technology. Please
contact Peg Koelbe at 301–594–4095 or
koelblep@nhlbi.nih.gov for more
information.
Method of Diagnosing Multidrug
Resistant Tuberculosis
Description of Technology: The
invention can be used to develop tests
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that are much more rapid than
conventional tests for determining drug
resistance. It relates to the discovery
that a putative gene of Mycobacterium
tuberculosis (MTb) with no previously
identified function is responsible for the
ability of the bacteria to activate a class
of second line thioamide drugs used for
MTb infections. The gene, termed
‘‘etaA,’’ codes for the synthesis of a
monooxygenase, the enzyme
responsible for the oxidative activation
of the drugs. Mutation in the etaA gene
leads to the expression of mutated,
inactivated enzyme, thus resulting in
thioamide drug-resistant bacteria. The
significance of this discovery is that
now, resistance to the class of thioamide
drugs in clinical isolates can be
identified in a relatively short time,
eliminating the need to perform lengthy
culturing procedures.
The invention claims test methods for
determining resistance to thioamide
drugs by detecting gene mutation. These
include (a) amplifying the etaA gene or
a portion of it containing the mutation,
with a set of primers which provide
amplified product, and sequencing the
amplified product to compare the
sequence with a known sequence of the
wild-type etaA; a difference in sequence
patterns indicates mutation; (b)
subjecting the amplified gene product to
digestion by restriction enzymes and
comparing the cleaved DNA gel pattern
to the one obtained from digestion of the
wild-type etaA gene; a difference
indicates mutation in etaA; and (c)
detecting the mutations by probe
hybridization techniques, where the
amplified product hybridizes to a
nucleic acid of known sequence under
stringent conditions, and the hybridized
product is detected. In addition to the
above, the invention proposes other
detection methods such as commonly
used for SNPs. Other methods claimed
in the invention are immunoassay (i.e.,
ELISA) for the etaA gene product or
mutated versions of it, or immunoassay
and chemical analysis of the drug
metabolites, whereby the absence of the
metabolites indicates gene mutation and
impaired activating ability.
Applications: Infectious diseases,
diagnostics (bacterial); Infectious
diseases, therapeutics (anti-bacterial).
Advantages: Novel methods for
diagnosing multidrug resistant
tuberculosis that are much more rapid
than conventional tests.
Inventors: Clifton E. Barry III (NIAID),
Andrea E. DeBarber (NIAID), Khisimuzi
Mdluli (NIAID), et al.
Publication: AE DeBarber et al.
Ethionamide activation and sensitivity
in multidrug-resistant Mycobacterium
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27151
tuberculosis. Proc Natl Acad Sci U S A.
2000 Aug 15;97(17):9677–9682.
Patent Status:
• U.S. Patent No. 6,905,822 issued 14
Jun 2005 (HHS Reference No. E–093–
2000/0–US–02).
• U.S. Patent Application No. 11/
058,484 filed 14 Feb 2005 and allowed
17 Feb 2009 (HHS Reference No. E–093–
2000/0–US–03).
Licensing Status: Available for
licensing.
Licensing Contact: RC Tang, JD, LLM;
301–435–5031; tangrc@mail.nih.gov
A Novel Chimeric Protein for
Prevention and Treatment of HIV
Infection
Description of Technology: This
invention relates to bifunctional fusion
proteins effective in HIV neutralization.
Specifically, the invention is a
genetically engineered chimeric protein
composed of a soluble extracellular
region of human CD4 (sCD4) attached
via a flexible polypeptide linker to a
single-chain construct of a human
monoclonal antibody directed against a
CD4-induced, highly conserved gp120
determinant involved in co-receptor
interaction and virus entry.
Mechanistically, the binding of the
sCD4 moiety to the HIV gp120 Env
glycoprotein induces a conformational
change that enables the antibody moiety
to bind, thereby blocking Env function
and virus entry. This novel design
provides the protein with unique
characteristics that enable its extremely
strong binding to gp120, thus rendering
it a potential effective antiviral agent
against HIV. Recent studies indicate that
this novel bispecific protein displays
extremely broad neutralizing activity
against genetically diverse primary
HIV–1 isolates, with breadth much
greater than previously described (Dey
et al. J. Virology 2003). The potency is
generally at least 10-fold greater than
the best described HIV–1 neutralizing
monoclonal antibodies, and the protein
is highly active against many HIV–1
isolates that are refractory to
neutralization by these antibodies.
Importantly, the protein is composed of
almost entirely human sequences.
The chimeric protein of this invention
has considerable potential for
prevention of HIV–1 infection, both as
a topical microbicide and as a systemic
agent to protect during and after acute
exposure (e.g. vertical transmission,
post exposure prophylaxis). It also has
potential utility for treatment of chronic
infection, including gene therapy
strategies involving hematopoietic stem
cells and/or viral vectors. Such proteins,
nucleic acid molecules encoding them,
and their production and use in
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27152
Federal Register / Vol. 74, No. 108 / Monday, June 8, 2009 / Notices
preventing or treating viral infections
are claimed in the patents issued for this
invention.
Applications:
• Prophylactic and/or therapeutic
treatment for HIV infection.
• Topical microbicide treatment to
protect against HIV infection.
• Imaging of HIV infected cells in
tissues.
Advantages:
• High neutralization efficiency due
to unique bifunctional binding
characteristics.
• Potentially minimally immunogenic
or toxic (human sequences and possibly
low treatment doses).
• Broad neutralizing activity.
• Mechanism of action less
susceptible to resistance.
Development Status:
• Reproducible production and scaleup of chimeric protein has been
demonstrated.
• Potent and broad neutralization of
genetically diverse HIV–1 clinical
isolates was demonstrated.
Market: The race to develop effective
antiviral strategies against HIV infection
is ongoing. The problems exhibited by
conventional drugs (i.e. toxicity and
resistance) have triggered the pursuit of
alternative approaches to HIV/AIDS
prevention and treatment. One of the
new approaches is the development of
neutralizing antibodies against the HIV
envelope proteins. This approach has
not yet yielded any commercially viable
treatment. It is believed that the
approach presented in the subject
invention will circumvent many of the
shortcomings of the existing drugs and
other pursued approaches. If this
approach is successful the commercial
rewards will be huge because of the
global magnitude of HIV epidemics.
Inventor: Edward A. Berger (NIAID).
Publication: B Dey, CS Del Castillo,
EA Berger. Neutralization of human
immunodeficiency virus type 1 by
sCD4–17b, a single-chain chimeric
protein, based on sequential interaction
of gp120 with CD4 and coreceptor. J
Virol. 2003 March;77(5):2859–2865.
Patent Status:
HHS Reference No. E–039–1999/0—
• U.S. Patent No. 7,115,262, issued 03
October 2006.
• U.S. Application No. 11/535,957,
filed 27 September 2006, published 18
October 2007 as 20070243208.
• Australian Patent No. 765218,
issued 30 July 2003.
• Applications pending in Canada,
France, Germany, Great Britain, Italy,
Japan, Spain.
Licensing Status: Available for
licensing.
Licensing Contacts: Uri Reichman,
Ph.D, MBA; 301–435–4616;
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ur7a@nih.gov; RC Tang, JD, LLM; 301–
435–5031; tangrc@mail.nih.gov.
Collaborative Research Opportunity:
The NIAID Office of Technology
Development is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize ‘‘A Novel Chimeric
Protein for Prevention and Treatment of
HIV Infection.’’ Please contact Rick
Williams at 301–402–0960 for more
information.
Dated: June 1, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–13284 Filed 6–5–09; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2009–D–0217]
Guidance for Industry on Medication
Guides—Adding a Toll-Free Number
for Reporting Adverse Events;
Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is announcing the
availability of a guidance for industry
entitled ‘‘Medication Guides—Adding a
Toll-Free Number for Reporting Adverse
Events.’’ Beginning July 1, 2009,
manufacturers of prescription drug
products approved under the Federal
Food, Drug, and Cosmetic Act (the act)
that are required to have a Medication
Guide must add a verbatim statement to
their Medication Guides containing
FDA’s toll-free number for reporting
side effects. These manufacturers are
also required to report to FDA that they
have complied with this requirement.
This guidance explains what statement
to add to Medication Guides, where to
add it, and how to notify the agency that
such a statement has been added.
DATES: Submit written or electronic
comments on agency guidances at any
time.
Submit written requests for
single copies of this draft guidance to
the Division of Drug Information, Center
for Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 2201,
Silver Spring, MD 20993–0002. Send
one self-addressed adhesive label to
ADDRESSES:
PO 00000
Frm 00065
Fmt 4703
Sfmt 4703
assist that office in processing your
requests. Submit written comments on
the draft guidance to the Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852.
Submit electronic comments to https://
www.regulations.gov. See the
SUPPLEMENTARY INFORMATION section for
electronic access to the guidance
document.
FOR FURTHER INFORMATION CONTACT:
Nancy Clark, Center for Drug Evaluation
and Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Silver Spring, MD 20993, 301–
796–5400, Nancy.Clark@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled
‘‘Medication Guides—Adding a TollFree Number for Reporting Adverse
Events.’’ On September 27, 2007, the
President signed into law the Food and
Drug Administration Amendments Act
(FDAAA) (Public Law 110–85). Among
other things, FDAAA reauthorized the
Best Pharmaceuticals for Children Act
(BPCA) (Public Law 107–109). When
enacted in 2001, the BPCA directed
FDA to issue a final rule requiring the
labeling of each human drug product for
which an application is approved under
section 505 of the act (21 U.S.C. 355) to
include: (1) A toll-free number
maintained by FDA for the purpose of
receiving reports of adverse events
regarding drugs and (2) a statement that
the number is to be used for reporting
purposes only, not to receive medical
advice. The BPCA stated that the final
rule must reach the broadest consumer
audience and minimize the cost to the
pharmacy profession. As required, FDA
issued a proposed rule entitled ‘‘TollFree Number for Reporting Adverse
Events on Labeling for Human Drug
Products’’ (69 FR 21778, April 22,
2004), which would require, among
other things, that a side effects
statement be included in FDA-approved
Medication Guides for drug products
approved under section 505 of the act.
FDA received 22 comments on this
proposed rule and was in the process of
analyzing the comments and conducting
research on consumer comprehension of
the side effects statement when FDAAA
was enacted. Section 502(f) of FDAAA
stated that ‘‘the proposed rule * * *
entitled ‘Toll-Free Number for Reporting
Adverse Events on Labeling for Human
Drug Products’ * * * shall take effect
on January 1, 2008,’’ unless FDA issues
a final rule before that date. FDA did not
issue a final rule by January 1, 2008, so
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Agencies
[Federal Register Volume 74, Number 108 (Monday, June 8, 2009)]
[Notices]
[Pages 27150-27152]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-13284]
-----------------------------------------------------------------------
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.
Interactive Venn Diagram Software Designed for Microarray Analysis
Description of Technology: Multiple conditions from any source, but
designed for experiments involving microarrays, will produce
(significant gene lists for arrays) lists from each condition, thus
multiple lists. This Java[reg] based software provides investigators
with a method of displaying multiple conditions in a single graphic
along with producing a text output of genes that are the product of
these conditional intersections along with each conditions unique list.
A standard Venn diagram is limited to only display three (3)
comparisons; this software can display any number of comparisons and
will automatically create lists from all intersections even if not able
to be displayed along with each conditions unique list.
Applications:
Microarray analysis.
Genomics.
Bioinformatics.
Any environment creating multiple lists (Business,
Accounting, Inventory Control, etc.).
Inventor: Daniel E. Sturdevant (NIAID).
Patent Status: HHS Reference No. E-189-2009/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019;
shmilovm@mail.nih.gov.
Axenically-Produced Coxiella burnetii and Methods for Producing Axenic
Coxiella burnetii
Description of Technology: Coxiella burnetii is the causative agent
of Q (Query) fever. Currently, there is a need for a safe Q fever
vaccine. It is anticipated that axenically-produced C. burnetii, which
is free of host cell related impurities, could provide either the basis
for a whole-cell Q fever vaccine or advance the development of a safe
recombinant Q fever vaccine. Currently, there are no licensed Q-fever
vaccines except for a whole-cell, formalin inactivated, vaccine which
is available in Australia (Q-Vax). Individuals with a previous exposure
to C. burnetii may, however, have a severe allergic reaction to this
vaccine and other individuals may experience a headache or flu-like
symptoms after vaccination. It is anticipated that axenically-produced
C. burnetii could provide the basis for a less reactogenic whole-cell
vaccine or facilitate the development of a recombinant vaccine that
does not cause an allergic reaction. Additionally, the inability to
propagate obligate intracellular pathogens under axenic (host cell-
free) culture conditions imposes severe experimental constraints that
have negatively impacted progress in understanding pathogen virulence
and disease mechanisms.
Q fever is a zoonotic disease and farm animals, pets, and rodents
are significant reservoirs for C. burnetii. C. burnetii persists in the
soil for a long time and typically humans are exposed to Q fever by the
inhalation of the bacterium deposited with animal waste such as urine,
feces, and amniotic fluid. The epidemiology of Q fever is diverse and
the disease does not discriminate between developed and developing
countries. Additionally, urban outbreaks have been known to occur due
to windborne C. burnetii. C. burnetii is listed as a select agent by
the Department of Health and Human Services (HHS) because of its
potential as an agent of bioterrorism. Deployed military personnel are
also at risk of contracting Q fever and thousands of cases of Q fever
have been reported among military personnel since the disease was first
reported in the 1930s.
Advantages:
The ability to propagate, previously unpropagatable, C.
burnetii without a hostcell.
The ability to study C. burnetii virulence using axenic
conditions or conditions free of host cell-related impurities.
This technology is ready for use in drug/vaccine
discovery, production, and development.
Potential licensees of this invention include companies
that are: 1) seeking vaccine production platforms based on host cell-
free (axenic) media, 2) seeking to develop recombinant vaccines for
obligate, intracellular, bacteria; or 3) seeking to lower costs and
ease scale-up would be potential licensees of this technology.
Development Status: This technology has been demonstrated with C.
burnetii. Currently, the inventors are testing this technology for
support of axenic growth of other obligate, intracellular, bacteria of
public health significance.
Inventors: Robert A. Heinzen, Anders Omsland, Diane C. Cockrell,
Dale Howe (NIAID).
Publication: A Omsland et al. Host cell-free growth of the Q fever
bacterium Coxiella burnetii. Proc Natl Acad Sci USA. 2009 Mar
17;106(11):4430-4434.
Patent Status: U.S. Provisional Application No. 61/154,330 filed 20
Feb 2009 (HHS Reference No. E-114-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646;
soukasp@mail.nih.gov.
[[Page 27151]]
Self-Expanding Stent for Valve Replacement
Description of Technology: Aortic stenosis and aortic regurgitation
are the most common types of aortic valvular diseases. Such diseased
aortic valves in the body are traditionally replaced with valve
prosthesis by an open surgical implantation. Available for licensing
and commercial development is intellectual property covering stents for
use with valve prostheses. One possible embodiment of the invention
includes a self-expandable stent with an elastic tubular latticework
having radial and longitudinal direction. The stent geometry and
mechanical parameters provide more anatomically-correct placement and
the flexible scaffolding of the valve (using an interconnected four-
sided polygons and longitudinal rods comprising a self-expanding stent
with a plurality of struts connecting a plurality of rods) allow for
secure implantation with adaptable apposition of the prosthesis in the
aorta.
Applications: Cardiac Surgery; Cardiology; Surgery; Stent
implantation.
Inventors: Keith Horvath, Dumitru Mazilu, Ming Li (NHLBI).
Publications:
1. M Li, D Mazilu, KA Horvath. Robotic system for transapical
aortic valve replacement with MRI guidance. Med Image Comput Comput
Assist Interv Int Conf Med Image Comput Comput Assist Interv.
2008;11(Pt 2):476-484.
2. KA Horvath, M Li, D Mazilu, MA Guttman, ER McVeigh. Real-time
magnetic resonance imaging guidance for cardiovascular procedures.
Semin Thorac Cardiovasc Surg. 2007 Winter;19(4):330-335. Review.
Patent Status: U.S. Provisional Application No. 61/172,568 filed 24
Apr 2009 (HHS Reference No. E-337-2008/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019;
shmilovm@mail.nih.gov.
Collaborative Research Opportunity: The National Heart, Lung, and
Blood Institute, Cardiothoracic Surgery Research Program, is seeking
statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
this technology. Please contact Peg Koelbe at 301-594-4095 or
koelblep@nhlbi.nih.gov for more information.
Method of Diagnosing Multidrug Resistant Tuberculosis
Description of Technology: The invention can be used to develop
tests that are much more rapid than conventional tests for determining
drug resistance. It relates to the discovery that a putative gene of
Mycobacterium tuberculosis (MTb) with no previously identified function
is responsible for the ability of the bacteria to activate a class of
second line thioamide drugs used for MTb infections. The gene, termed
``etaA,'' codes for the synthesis of a monooxygenase, the enzyme
responsible for the oxidative activation of the drugs. Mutation in the
etaA gene leads to the expression of mutated, inactivated enzyme, thus
resulting in thioamide drug-resistant bacteria. The significance of
this discovery is that now, resistance to the class of thioamide drugs
in clinical isolates can be identified in a relatively short time,
eliminating the need to perform lengthy culturing procedures.
The invention claims test methods for determining resistance to
thioamide drugs by detecting gene mutation. These include (a)
amplifying the etaA gene or a portion of it containing the mutation,
with a set of primers which provide amplified product, and sequencing
the amplified product to compare the sequence with a known sequence of
the wild-type etaA; a difference in sequence patterns indicates
mutation; (b) subjecting the amplified gene product to digestion by
restriction enzymes and comparing the cleaved DNA gel pattern to the
one obtained from digestion of the wild-type etaA gene; a difference
indicates mutation in etaA; and (c) detecting the mutations by probe
hybridization techniques, where the amplified product hybridizes to a
nucleic acid of known sequence under stringent conditions, and the
hybridized product is detected. In addition to the above, the invention
proposes other detection methods such as commonly used for SNPs. Other
methods claimed in the invention are immunoassay (i.e., ELISA) for the
etaA gene product or mutated versions of it, or immunoassay and
chemical analysis of the drug metabolites, whereby the absence of the
metabolites indicates gene mutation and impaired activating ability.
Applications: Infectious diseases, diagnostics (bacterial);
Infectious diseases, therapeutics (anti-bacterial).
Advantages: Novel methods for diagnosing multidrug resistant
tuberculosis that are much more rapid than conventional tests.
Inventors: Clifton E. Barry III (NIAID), Andrea E. DeBarber
(NIAID), Khisimuzi Mdluli (NIAID), et al.
Publication: AE DeBarber et al. Ethionamide activation and
sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc
Natl Acad Sci U S A. 2000 Aug 15;97(17):9677-9682.
Patent Status:
U.S. Patent No. 6,905,822 issued 14 Jun 2005 (HHS
Reference No. E-093-2000/0-US-02).
U.S. Patent Application No. 11/058,484 filed 14 Feb 2005
and allowed 17 Feb 2009 (HHS Reference No. E-093-2000/0-US-03).
Licensing Status: Available for licensing.
Licensing Contact: RC Tang, JD, LLM; 301-435-5031;
tangrc@mail.nih.gov
A Novel Chimeric Protein for Prevention and Treatment of HIV Infection
Description of Technology: This invention relates to bifunctional
fusion proteins effective in HIV neutralization. Specifically, the
invention is a genetically engineered chimeric protein composed of a
soluble extracellular region of human CD4 (sCD4) attached via a
flexible polypeptide linker to a single-chain construct of a human
monoclonal antibody directed against a CD4-induced, highly conserved
gp120 determinant involved in co-receptor interaction and virus entry.
Mechanistically, the binding of the sCD4 moiety to the HIV gp120 Env
glycoprotein induces a conformational change that enables the antibody
moiety to bind, thereby blocking Env function and virus entry. This
novel design provides the protein with unique characteristics that
enable its extremely strong binding to gp120, thus rendering it a
potential effective antiviral agent against HIV. Recent studies
indicate that this novel bispecific protein displays extremely broad
neutralizing activity against genetically diverse primary HIV-1
isolates, with breadth much greater than previously described (Dey et
al. J. Virology 2003). The potency is generally at least 10-fold
greater than the best described HIV-1 neutralizing monoclonal
antibodies, and the protein is highly active against many HIV-1
isolates that are refractory to neutralization by these antibodies.
Importantly, the protein is composed of almost entirely human
sequences.
The chimeric protein of this invention has considerable potential
for prevention of HIV-1 infection, both as a topical microbicide and as
a systemic agent to protect during and after acute exposure (e.g.
vertical transmission, post exposure prophylaxis). It also has
potential utility for treatment of chronic infection, including gene
therapy strategies involving hematopoietic stem cells and/or viral
vectors. Such proteins, nucleic acid molecules encoding them, and their
production and use in
[[Page 27152]]
preventing or treating viral infections are claimed in the patents
issued for this invention.
Applications:
Prophylactic and/or therapeutic treatment for HIV
infection.
Topical microbicide treatment to protect against HIV
infection.
Imaging of HIV infected cells in tissues.
Advantages:
High neutralization efficiency due to unique bifunctional
binding characteristics.
Potentially minimally immunogenic or toxic (human
sequences and possibly low treatment doses).
Broad neutralizing activity.
Mechanism of action less susceptible to resistance.
Development Status:
Reproducible production and scale-up of chimeric protein
has been demonstrated.
Potent and broad neutralization of genetically diverse
HIV-1 clinical isolates was demonstrated.
Market: The race to develop effective antiviral strategies against
HIV infection is ongoing. The problems exhibited by conventional drugs
(i.e. toxicity and resistance) have triggered the pursuit of
alternative approaches to HIV/AIDS prevention and treatment. One of the
new approaches is the development of neutralizing antibodies against
the HIV envelope proteins. This approach has not yet yielded any
commercially viable treatment. It is believed that the approach
presented in the subject invention will circumvent many of the
shortcomings of the existing drugs and other pursued approaches. If
this approach is successful the commercial rewards will be huge because
of the global magnitude of HIV epidemics.
Inventor: Edward A. Berger (NIAID).
Publication: B Dey, CS Del Castillo, EA Berger. Neutralization of
human immunodeficiency virus type 1 by sCD4-17b, a single-chain
chimeric protein, based on sequential interaction of gp120 with CD4 and
coreceptor. J Virol. 2003 March;77(5):2859-2865.
Patent Status:
HHS Reference No. E-039-1999/0--
U.S. Patent No. 7,115,262, issued 03 October 2006.
U.S. Application No. 11/535,957, filed 27 September 2006,
published 18 October 2007 as 20070243208.
Australian Patent No. 765218, issued 30 July 2003.
Applications pending in Canada, France, Germany, Great
Britain, Italy, Japan, Spain.
Licensing Status: Available for licensing.
Licensing Contacts: Uri Reichman, Ph.D, MBA; 301-435-4616;
ur7a@nih.gov; RC Tang, JD, LLM; 301-435-5031; tangrc@mail.nih.gov.
Collaborative Research Opportunity: The NIAID Office of Technology
Development is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize ``A Novel Chimeric Protein for Prevention
and Treatment of HIV Infection.'' Please contact Rick Williams at 301-
402-0960 for more information.
Dated: June 1, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-13284 Filed 6-5-09; 8:45 am]
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