Government-Owned Inventions; Availability for Licensing, 55853-55855 [E8-22608]
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Federal Register / Vol. 73, No. 188 / Friday, September 26, 2008 / Notices
Cosmetic Act (the act) (21 U.S.C.
360e(d)(4) and (e)(2)), notification of an
order approving, denying, or
withdrawing approval of a PMA will
continue to include a notice of
opportunity to request review of the
order under section 515(g) of the act.
The 30-day period for requesting
reconsideration of an FDA action under
§ 10.33(b) (21 CFR 10.33(b)) for notices
announcing approval of a PMA begins
on the day the notice is placed on the
Internet. Section 10.33(b) provides that
FDA may, for good cause, extend this
30-day period. Reconsideration of a
denial or withdrawal of approval of a
PMA may be sought only by the
applicant; in these cases, the 30-day
period will begin when the applicant is
notified by FDA in writing of its
decision.
The regulations provide that FDA
publish a quarterly list of available
safety and effectiveness summaries of
55853
PMA approvals and denials that were
announced during that quarter. The
following is a list of approved PMAs for
which summaries of safety and
effectiveness were placed on the
Internet from April 1, 2008, through
June 30, 2008. There were no denial
actions during this period. The list
provides the manufacturer’s name, the
product’s generic name or the trade
name, and the approval date.
TABLE 1—LIST OF SAFETY AND EFFECTIVENESS SUMMARIES FOR APPROVED PMAS MADE AVAILABLE FROM APRIL 1,
2008, THROUGH JUNE 30, 2008
PMA No./Docket No.
Applicant
TRADE NAME
Approval Date
P050020
FDA–2008–M–0207
Abbott Diabetes Care, Inc.
FREESTYLE NAVIGATOR CONTINUOUS GLUCOSE
MONITORING SYSTEM
March 12, 2008
P010012 (S037)
FDA–2008–M–0243
Guidant Corp.
Contak Renewal 3 AVT system & contak reviewal 3AVT
HE System
March 13, 2008
P070027
FDA–2008–M–0244
Medtronic Vascular
The talent abdominal stent graft system
April 15, 2008
P060040
FDA–2008–M–0283
Thoratec Corp.
Thoratec Heartmate II Left ventricular assist
April 21, 2008
P070008
FDA–2008–M–0335
Biotronik, Inc.
Stratos LV CRT–P & stratos LV–T CRT–P, corox OTW
BP lead & corox OTW-s bp lead
May 12, 2008
P070016
FDA–2008–M–0311
Cook, Inc.
Zenith TX2 Thoracic TAA endovascular graft with the
H&LB One-shot introduction system
May 21, 2008
P070007
FDA–2008–M–0342
Medtronic Vascular
Talent Thoracic Stent Graft System
June 5, 2008
H070003
FDA–2008–M–0378
Synapse Biomedical, Inc.
NeuRx RA/4
June 17, 2008
II. Electronic Access
Persons with access to the Internet
may obtain the documents at https://
www.fda.gov/cdrh/pmapage.html.
Dated: September 12, 2008.
Daniel G. Schultz,
Director, Center for Devices and Radiological
Health.
[FR Doc. E8–22668 Filed 9–25–08; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
Methods for Preparing Bacillus
anthracis Protective Antigen for Use
in Vaccines
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
Description of Technology: This
invention relates to improved methods
of preparing Bacillus anthracis
protective antigen (PA) from a cell or
AGENCY:
jlentini on PROD1PC65 with NOTICES
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.
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18:07 Sep 25, 2008
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organism, particularly a recombinant
cell or microorganism, for use in
vaccines. Production and purification
methods of modified PA from a nonsporogenic strain of Bacillus anthracis
are described. Specifically, a scalable
fermentation and purification process is
claimed that is suitable for vaccine
development, and that produces almost
three times more product than earlierreported processes. This is
accomplished using a biologically
inactive protease-resistant PA variant in
a protease-deficient non-sporogenic
avirulent strain of B. anthracis (BH445).
One of the PA variants described in the
patent application lacks the furin and
chymotrypsin cleavage sites.
Advantages: Bacillus anthracis
protective antigen is a major component
of the currently licensed human vaccine
(Anthrax Vaccine Adsorbed, AVA).
Although the current human vaccine
has been shown to be effective against
cutaneous anthrax infection in animals
and humans and against inhalation
anthrax in rhesus monkeys, the licensed
vaccine has several limitations: (1) AVA
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55854
Federal Register / Vol. 73, No. 188 / Friday, September 26, 2008 / Notices
elicits a relatively high degree of local
and systemic adverse reactions,
probably mediated by variable amounts
of undefined bacterial products, making
standardization difficult; (2) the
immunization schedule requires
administration of six doses within an
eighteen (18) month period, followed by
annual boosters; (3) there is no defined
vaccine-induced protective level of
antibody to PA by which to evaluate
new lots of vaccines; and (4) AVA is
comprised of a wild-type PA. Thus a
vaccine comprising a modified purified
recombinant PA would be effective,
safe, allow precise standardization, and
require fewer injections.
The invention also relates to PA
variants, and/or compositions thereof,
which are useful for eliciting an
immunogenic response in mammals,
particularly humans, including
responses that provide protection
against, or reduce the severity of,
infections caused by B. anthracis. The
vaccines claimed in this application are
intended for active immunization for
prevention of B. anthracis infection, and
for preparation of immune antibodies.
Application: Improved B. anthracis
vaccines.
Development Status: Phase I clinical
studies are being performed.
Inventors: Joseph Shiloach (NIDDK),
Stephen Leppla (NIDCR), Delia Ramirez
(NIDDK), Rachel Schneerson (NICHD),
John Robbins (NICHD).
Publication: DM Ramirez et al.
Production, recovery and
immunogenicity of the protective
antigen from a recombinant strain of
Bacillus anthracis. J Ind Microbiol
Biotechnol. 2002 Apr;28(4):232–238.
Patent Status: U.S. Patent Application
No. 10/290,712 filed 08 Nov 2002 (HHS
Reference No. E–023–2002/0–US–02)
Licensing Status: Available for
exclusive or nonexclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity:
The National Institutes of Health is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
methods of preparing Bacillus anthracis
protective antigen (PA) from a cell or
organism, particularly a recombinant
cell or microorganism, for use in
vaccines. Please contact Rochelle S.
Blaustein, J.D., at 301/451–3636 or
Rochelle.Blaustein@nih.gov for
additional information.
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18:07 Sep 25, 2008
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Recombinant Modified Bacillus
anthracis Protective Antigen for Use
in Vaccines
Description of Technology: This
invention relates to improved methods
of preparing Bacillus anthracis
protective antigen (PA) for use in
vaccines. PA is a secreted, non-toxic
protein with a molecular weight of 83
KDa. PA is a major component of the
currently licensed human vaccine
(Anthrax Vaccine Adsorbed, AVA).
Although the licensed human vaccine
has been shown to be effective against
cutaneous anthrax infection in animals
and humans and against inhalation
anthrax in rhesus monkeys, the licensed
vaccine has several limitations: (1) AVA
elicits a relatively high degree of local
and systemic adverse reactions,
probably mediated by variable amounts
of undefined bacterial products, making
standardization difficult; (2) the
immunization schedule requires
administration of six doses within an
eighteen (18) month period, followed by
annual boosters; (3) there is no defined
vaccine-induced protective level of
antibody to PA by which to evaluate
new lots of vaccines; and (4) AVA is
comprised of a wild-type PA. It has been
suggested that a vaccine comprising a
modified purified recombinant PA
would be effective, safe, allow precise
standardization, and require fewer
injections.
This invention claims methods of
producing and recovering PA from a cell
or organism, particularly a recombinant
cell or microorganism. The invention
claims production and purification of
modified PA from a non-sporogenic
strain of Bacillus anthracis. In contrast
to other previously described methods,
greater quantities of PA are obtainable
from these cells or microorganisms.
Specifically, a scalable fermentation and
purification process is claimed that is
suitable for vaccine development, and
that produces almost three times more
product than earlier-reported processes.
This is accomplished using a
biologically inactive protease-resistant
PA variant in a protease-deficient nonsporogenic avirulent strain of B.
anthracis (BH445). One of the PA
variants described in the patent
application lacks the furin and
chymotrypsin cleavage sites.
The invention relates to improved
methods of producing and recovering
sporulation-deficient B. anthracis
mutant stains, and for producing and
recovering recombinant B. anthracis
protective antigen (PA), especially
modified PA which is protease resistant,
and to methods of using of these PAs or
nucleic acids encoding these PAs for
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Sfmt 4703
eliciting an immunogenic response in
humans, including responses which
provide protection against, or reduce the
severity of, B. anthracis bacterial
infections and which are useful to
prevent and/or treat illnesses caused by
B. anthracis, such as inhalation anthrax,
cutaneous anthrax and gastrointestinal
anthrax.
Application: Improved B. anthracis
vaccines.
Development Status: Phase I clinical
studies are being performed.
Inventors: Stephen Leppla (NIDCR),
M. J. Rosovitz (NIDCR), John Robbins
(NICHD), Rachel Schneerson (NICHD).
Patent Status: U.S. Patent No.
7,261,900 issued 28 Aug 2007 (HHS
Reference No. E–268–2002/0–US–02);
U.S. Patent Application No. 11/831,860
filed 31 Jul 2007 (HHS Reference No. E–
268–2002/0–US–03).
Licensing Status: Available for
exclusive or nonexclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
gPGA Conjugates for Eliciting Immune
Responses Directed Against Bacillus
anthracis and Other Bacilli
Description of Technology: This
invention claims immunogenic
conjugates of a poly-g-glutamic acid
(gPGA) of B. anthracis, or of another
bacillus that expresses a gPGA that elicit
a serum antibody response against B.
anthracis, in mammalian hosts to which
the conjugates are administered. The
invention also relates methods which
are useful for eliciting an immunogenic
response in mammals, particularly
humans, including responses which
provide protection against, or reduce the
severity of, infections caused by B.
anthracis. The vaccines claimed in this
application are intended for active
immunization for prevention of B.
anthracis infection, and for preparation
of immune antibodies. The vaccines of
this invention are designed to confer
specific immunity against infection with
B. anthracis, and to induce antibodies
specific to B. anthracis gPGA. The B.
anthracis vaccine is composed of nontoxic bacterial components, suitable for
infants, children of all ages, and adults.
Inventors: Rachel Schneerson
(NICHD), Stephen Leppla (NIAID), John
Robbins (NICHD), Joseph Shiloach
(NIDDK), Joanna Kubler-Kielb (NICHD),
Darrell Liu (NIDCR), Fathy Majadly
(NICHD).
Publication: R Schneerson et al.
Poly(gamma-D-glutamic acid) protein
conjugates induce IgG antibodies in
mice to the capsule of Bacillus
anthracis: a potential addition to the
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Federal Register / Vol. 73, No. 188 / Friday, September 26, 2008 / Notices
jlentini on PROD1PC65 with NOTICES
anthrax vaccine. Proc Natl Acad Sci
USA. 2003 Jul 22;100(15):8945–8950.
Patent Status: U.S. Patent Application
No. 10/559,825 filed 02 Dec 2005,
claiming priority to 05 Jun 2003 (HHS
Reference No. E–343–2002/0–US–04).
Licensing Status: Available for
licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
and/or e-mail
apomerantsev@niaid.nih.gov for more
information.
Monoclonal Antibodies That Neutralize
B. anthracis Protective Antigen (PA),
Lethal Factor (LF) and Edema Factor
(EF)
Description of Invention: Anthrax,
whether resulting from natural or
bioterrorist-associated exposure, is a
Improved Bacterial Host for Production constant threat to human health. The
lethality of anthrax is primarily the
of Anthrax Toxin Proteins and
result of the effects of anthrax toxin,
Vaccines: Bacillus anthracis BH450
which has 3 components: a receptorDescription of Invention: Anthrax
binding protein known as ‘‘protective
toxin has previously been made from
antigen’’ (PA) and 2 catalytic proteins
various avirulent strains of Bacillus
known as ‘‘lethal factor’’ (LF) and
anthracis. The inventors have
‘‘edema factor’’ (EF). Although
genetically engineered a new strain of B. production of an efficient anthrax
anthracis with improved properties.
vaccine is an ultimate goal, the benefits
The strain, designated BH450, is totally
of vaccination can be expected only if
deficient in the ability to make spores
a large proportion of the population at
and to produce a major extracellular
risk is immunized. The low incidence of
protease designated Peptidase M4. The
anthrax suggests that large-scale
genetic lesions introduced are defined,
vaccination may not be the most
true deletions, so there is no possibility
efficient means of controlling this
of reversion. Inability to make spores
disease. In contrast, passive
assures that laboratories growing the
administration of neutralizing human or
strain will not become contaminated
chimpanzee monoclonal antibody to a
with the very stable anthrax spores.
subject at risk for anthrax or exposed to
Inability to make peptidase M4
anthrax could provide immediate
increases the stability of proteins such
efficacy for emergency prophylaxis
as anthrax toxin that are secreted to the
against or treatment of anthrax.
culture medium.
Four monoclonal antibodies (mAbs)
Applications and Modality: B.
against PA, three mAbs against LF and
anthracis vaccine/prophylactic and
four mAbs specific for EF of anthrax
therapeutic studies.
were isolated from a phage display
Market: Research tool useful for
library generated from immunized
biodefense/therapeutic studies.
chimpanzees. Two mAbs recognizing
Development Status: The technology
PA (W1 and W2), two anti-LF mAbs
is a research tool.
efficiently neutralized the cytotoxicity
Inventors: Andrei Pomerantsev, Dana
of lethal toxin in a macrophage lysis
Hsu, Ramakrishnan Sitaraman, Craig
assay. One anti-EF mAb efficiently
Galloway, Violetta Kivovich, Stephen
neutralized edema toxin in cell culture.
Leppla (NIAID).
All five neutralizing mAbs protected
Publication: AP Pomerantsev et al.
animals from anthrax toxin challenge.
Genome engineering in Bacillus
Application: Prophylactics or
anthracis using Cre recombinase. Infect
therapeutics against B. anthracis.
Immun. 2006 Jan;74(1):682–693.
Developmental Status: Preclinical
Patent Status: HHS Reference No. E–
studies have been performed.
127–2007/0—Research Tool.
Inventors: Zhaochun Chen, Robert
Licensing Status: This technology is
Purcell, Suzanne Emerson, Stephen
not patented. The strain will be
Leppla, Mahtab Moyeri (NIAID).
transferred through a Biological
Publication: Z Chen et al. Efficient
Materials License.
neutralization of anthrax toxin by
Licensing Contact: Peter A. Soukas,
chimpanzee monoclonal antibodies
J.D.; 301/435–4646;
against protective antigen. J Infect Dis.
soukasp@mail.nih.gov.
2006 Mar 1;193(5):625–633.
Collaborative Research Opportunity:
Patent Status: PCT Application No.
The National Institute of Allergy and
PCT/US2008/054609 filed 21 Feb 2008,
Infectious Diseases, Laboratory of
Bacterial Diseases, is seeking statements claiming priority to 23 Feb 2007 (HHS
Reference No. E–123–2007/0–PCT–02);
of capability or interest from parties
U.S. Patent Application No. 11/793,735
interested in collaborative research to
filed 22 Jun 2007 (HHS Reference No.
further develop, evaluate, or
commercialize Bacillus anthracis BH450 E–146–2004/0–US–03)
Licensing Status: Available for
strain. Please contact Dr. Andrei P.
exclusive or non-exclusive licensing.
Pomerantsev at phone 301/451–9817
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55855
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Allergy and
Infectious Diseases, Laboratory of
Infectious Diseases is seeking statements
of capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize Chimpanzee/human
neutralizing monoclonal antibodies
against anthrax toxins. Please contact
Dr. Robert Purcell at 301/496–5090 for
more information.
Dated: September 18, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E8–22608 Filed 9–25–08; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
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.
Inhibitors of the Plasmodial Surface
Anion Channel as Antimalarials
Description of Technology: The
inventions described herein are
antimalarial small molecule inhibitors
of the plasmodial surface anion channel
(PSAC), an essential nutrient acquisition
ion channel expressed on human
E:\FR\FM\26SEN1.SGM
26SEN1
Agencies
[Federal Register Volume 73, Number 188 (Friday, September 26, 2008)]
[Notices]
[Pages 55853-55855]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-22608]
-----------------------------------------------------------------------
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.
Methods for Preparing Bacillus anthracis Protective Antigen for Use in
Vaccines
Description of Technology: This invention relates to improved
methods of preparing Bacillus anthracis protective antigen (PA) from a
cell or organism, particularly a recombinant cell or microorganism, for
use in vaccines. Production and purification methods of modified PA
from a non-sporogenic strain of Bacillus anthracis are described.
Specifically, a scalable fermentation and purification process is
claimed that is suitable for vaccine development, and that produces
almost three times more product than earlier-reported processes. This
is accomplished using a biologically inactive protease-resistant PA
variant in a protease-deficient non-sporogenic avirulent strain of B.
anthracis (BH445). One of the PA variants described in the patent
application lacks the furin and chymotrypsin cleavage sites.
Advantages: Bacillus anthracis protective antigen is a major
component of the currently licensed human vaccine (Anthrax Vaccine
Adsorbed, AVA). Although the current human vaccine has been shown to be
effective against cutaneous anthrax infection in animals and humans and
against inhalation anthrax in rhesus monkeys, the licensed vaccine has
several limitations: (1) AVA
[[Page 55854]]
elicits a relatively high degree of local and systemic adverse
reactions, probably mediated by variable amounts of undefined bacterial
products, making standardization difficult; (2) the immunization
schedule requires administration of six doses within an eighteen (18)
month period, followed by annual boosters; (3) there is no defined
vaccine-induced protective level of antibody to PA by which to evaluate
new lots of vaccines; and (4) AVA is comprised of a wild-type PA. Thus
a vaccine comprising a modified purified recombinant PA would be
effective, safe, allow precise standardization, and require fewer
injections.
The invention also relates to PA variants, and/or compositions
thereof, which are useful for eliciting an immunogenic response in
mammals, particularly humans, including responses that provide
protection against, or reduce the severity of, infections caused by B.
anthracis. The vaccines claimed in this application are intended for
active immunization for prevention of B. anthracis infection, and for
preparation of immune antibodies.
Application: Improved B. anthracis vaccines.
Development Status: Phase I clinical studies are being performed.
Inventors: Joseph Shiloach (NIDDK), Stephen Leppla (NIDCR), Delia
Ramirez (NIDDK), Rachel Schneerson (NICHD), John Robbins (NICHD).
Publication: DM Ramirez et al. Production, recovery and
immunogenicity of the protective antigen from a recombinant strain of
Bacillus anthracis. J Ind Microbiol Biotechnol. 2002 Apr;28(4):232-238.
Patent Status: U.S. Patent Application No. 10/290,712 filed 08 Nov
2002 (HHS Reference No. E-023-2002/0-US-02)
Licensing Status: Available for exclusive or nonexclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The National Institutes of
Health is seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate, or
commercialize methods of preparing Bacillus anthracis protective
antigen (PA) from a cell or organism, particularly a recombinant cell
or microorganism, for use in vaccines. Please contact Rochelle S.
Blaustein, J.D., at 301/451-3636 or Rochelle.Blaustein@nih.gov for
additional information.
Recombinant Modified Bacillus anthracis Protective Antigen for Use in
Vaccines
Description of Technology: This invention relates to improved
methods of preparing Bacillus anthracis protective antigen (PA) for use
in vaccines. PA is a secreted, non-toxic protein with a molecular
weight of 83 KDa. PA is a major component of the currently licensed
human vaccine (Anthrax Vaccine Adsorbed, AVA). Although the licensed
human vaccine has been shown to be effective against cutaneous anthrax
infection in animals and humans and against inhalation anthrax in
rhesus monkeys, the licensed vaccine has several limitations: (1) AVA
elicits a relatively high degree of local and systemic adverse
reactions, probably mediated by variable amounts of undefined bacterial
products, making standardization difficult; (2) the immunization
schedule requires administration of six doses within an eighteen (18)
month period, followed by annual boosters; (3) there is no defined
vaccine-induced protective level of antibody to PA by which to evaluate
new lots of vaccines; and (4) AVA is comprised of a wild-type PA. It
has been suggested that a vaccine comprising a modified purified
recombinant PA would be effective, safe, allow precise standardization,
and require fewer injections.
This invention claims methods of producing and recovering PA from a
cell or organism, particularly a recombinant cell or microorganism. The
invention claims production and purification of modified PA from a non-
sporogenic strain of Bacillus anthracis. In contrast to other
previously described methods, greater quantities of PA are obtainable
from these cells or microorganisms. Specifically, a scalable
fermentation and purification process is claimed that is suitable for
vaccine development, and that produces almost three times more product
than earlier-reported processes. This is accomplished using a
biologically inactive protease-resistant PA variant in a protease-
deficient non-sporogenic avirulent strain of B. anthracis (BH445). One
of the PA variants described in the patent application lacks the furin
and chymotrypsin cleavage sites.
The invention relates to improved methods of producing and
recovering sporulation-deficient B. anthracis mutant stains, and for
producing and recovering recombinant B. anthracis protective antigen
(PA), especially modified PA which is protease resistant, and to
methods of using of these PAs or nucleic acids encoding these PAs for
eliciting an immunogenic response in humans, including responses which
provide protection against, or reduce the severity of, B. anthracis
bacterial infections and which are useful to prevent and/or treat
illnesses caused by B. anthracis, such as inhalation anthrax, cutaneous
anthrax and gastrointestinal anthrax.
Application: Improved B. anthracis vaccines.
Development Status: Phase I clinical studies are being performed.
Inventors: Stephen Leppla (NIDCR), M. J. Rosovitz (NIDCR), John
Robbins (NICHD), Rachel Schneerson (NICHD).
Patent Status: U.S. Patent No. 7,261,900 issued 28 Aug 2007 (HHS
Reference No. E-268-2002/0-US-02); U.S. Patent Application No. 11/
831,860 filed 31 Jul 2007 (HHS Reference No. E-268-2002/0-US-03).
Licensing Status: Available for exclusive or nonexclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
[gamma]PGA Conjugates for Eliciting Immune Responses Directed Against
Bacillus anthracis and Other Bacilli
Description of Technology: This invention claims immunogenic
conjugates of a poly-[gamma]-glutamic acid ([gamma]PGA) of B.
anthracis, or of another bacillus that expresses a [gamma]PGA that
elicit a serum antibody response against B. anthracis, in mammalian
hosts to which the conjugates are administered. The invention also
relates methods which are useful for eliciting an immunogenic response
in mammals, particularly humans, including responses which provide
protection against, or reduce the severity of, infections caused by B.
anthracis. The vaccines claimed in this application are intended for
active immunization for prevention of B. anthracis infection, and for
preparation of immune antibodies. The vaccines of this invention are
designed to confer specific immunity against infection with B.
anthracis, and to induce antibodies specific to B. anthracis
[gamma]PGA. The B. anthracis vaccine is composed of non-toxic bacterial
components, suitable for infants, children of all ages, and adults.
Inventors: Rachel Schneerson (NICHD), Stephen Leppla (NIAID), John
Robbins (NICHD), Joseph Shiloach (NIDDK), Joanna Kubler-Kielb (NICHD),
Darrell Liu (NIDCR), Fathy Majadly (NICHD).
Publication: R Schneerson et al. Poly(gamma-D-glutamic acid)
protein conjugates induce IgG antibodies in mice to the capsule of
Bacillus anthracis: a potential addition to the
[[Page 55855]]
anthrax vaccine. Proc Natl Acad Sci USA. 2003 Jul 22;100(15):8945-8950.
Patent Status: U.S. Patent Application No. 10/559,825 filed 02 Dec
2005, claiming priority to 05 Jun 2003 (HHS Reference No. E-343-2002/0-
US-04).
Licensing Status: Available for licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Improved Bacterial Host for Production of Anthrax Toxin Proteins and
Vaccines: Bacillus anthracis BH450
Description of Invention: Anthrax toxin has previously been made
from various avirulent strains of Bacillus anthracis. The inventors
have genetically engineered a new strain of B. anthracis with improved
properties. The strain, designated BH450, is totally deficient in the
ability to make spores and to produce a major extracellular protease
designated Peptidase M4. The genetic lesions introduced are defined,
true deletions, so there is no possibility of reversion. Inability to
make spores assures that laboratories growing the strain will not
become contaminated with the very stable anthrax spores. Inability to
make peptidase M4 increases the stability of proteins such as anthrax
toxin that are secreted to the culture medium.
Applications and Modality: B. anthracis vaccine/prophylactic and
therapeutic studies.
Market: Research tool useful for biodefense/therapeutic studies.
Development Status: The technology is a research tool.
Inventors: Andrei Pomerantsev, Dana Hsu, Ramakrishnan Sitaraman,
Craig Galloway, Violetta Kivovich, Stephen Leppla (NIAID).
Publication: AP Pomerantsev et al. Genome engineering in Bacillus
anthracis using Cre recombinase. Infect Immun. 2006 Jan;74(1):682-693.
Patent Status: HHS Reference No. E-127-2007/0--Research Tool.
Licensing Status: This technology is not patented. The strain will
be transferred through a Biological Materials License.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Allergy and Infectious Diseases, Laboratory of Bacterial Diseases, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
Bacillus anthracis BH450 strain. Please contact Dr. Andrei P.
Pomerantsev at phone 301/451-9817 and/or e-mail
apomerantsev@niaid.nih.gov for more information.
Monoclonal Antibodies That Neutralize B. anthracis Protective Antigen
(PA), Lethal Factor (LF) and Edema Factor (EF)
Description of Invention: Anthrax, whether resulting from natural
or bioterrorist-associated exposure, is a constant threat to human
health. The lethality of anthrax is primarily the result of the effects
of anthrax toxin, which has 3 components: a receptor-binding protein
known as ``protective antigen'' (PA) and 2 catalytic proteins known as
``lethal factor'' (LF) and ``edema factor'' (EF). Although production
of an efficient anthrax vaccine is an ultimate goal, the benefits of
vaccination can be expected only if a large proportion of the
population at risk is immunized. The low incidence of anthrax suggests
that large-scale vaccination may not be the most efficient means of
controlling this disease. In contrast, passive administration of
neutralizing human or chimpanzee monoclonal antibody to a subject at
risk for anthrax or exposed to anthrax could provide immediate efficacy
for emergency prophylaxis against or treatment of anthrax.
Four monoclonal antibodies (mAbs) against PA, three mAbs against LF
and four mAbs specific for EF of anthrax were isolated from a phage
display library generated from immunized chimpanzees. Two mAbs
recognizing PA (W1 and W2), two anti-LF mAbs efficiently neutralized
the cytotoxicity of lethal toxin in a macrophage lysis assay. One anti-
EF mAb efficiently neutralized edema toxin in cell culture. All five
neutralizing mAbs protected animals from anthrax toxin challenge.
Application: Prophylactics or therapeutics against B. anthracis.
Developmental Status: Preclinical studies have been performed.
Inventors: Zhaochun Chen, Robert Purcell, Suzanne Emerson, Stephen
Leppla, Mahtab Moyeri (NIAID).
Publication: Z Chen et al. Efficient neutralization of anthrax
toxin by chimpanzee monoclonal antibodies against protective antigen. J
Infect Dis. 2006 Mar 1;193(5):625-633.
Patent Status: PCT Application No. PCT/US2008/054609 filed 21 Feb
2008, claiming priority to 23 Feb 2007 (HHS Reference No. E-123-2007/0-
PCT-02); U.S. Patent Application No. 11/793,735 filed 22 Jun 2007 (HHS
Reference No. E-146-2004/0-US-03)
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Allergy and Infectious Diseases, Laboratory of Infectious Diseases is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
Chimpanzee/human neutralizing monoclonal antibodies against anthrax
toxins. Please contact Dr. Robert Purcell at 301/496-5090 for more
information.
Dated: September 18, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E8-22608 Filed 9-25-08; 8:45 am]
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