[Federal Register Volume 73, Number 188 (Friday, September 26, 2008)]
[Notices]
[Pages 55853-55855]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-22608]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
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SUMMARY: The inventions listed below are owned by an agency of the U.S.
Government and are available for licensing in the U.S. in accordance
with 35 U.S.C. 207 to achieve expeditious commercialization of results
of federally-funded research and development. Foreign patent
applications are filed on selected inventions to extend market coverage
for companies and may also be available for licensing.
ADDRESSES: Licensing information and copies of the U.S. patent
applications listed below may be obtained by writing to the indicated
licensing contact at the Office of Technology Transfer, National
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville,
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A
signed Confidential Disclosure Agreement will be required to receive
copies of the patent applications.
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;
[email protected].
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 [email protected] 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;
[email protected].
[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;
[email protected].
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;
[email protected].
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
[email protected] 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;
[email protected].
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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