[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]
BILLING CODE 4140-01-P