[Federal Register Volume 67, Number 15 (Wednesday, January 23, 2002)]
[Notices]
[Pages 3219-3220]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-1613]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing: Methods 
for Preparing Bacillus Anthracis Protective Antigen for Use in Vaccines

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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SUMMARY: The invention described below is owned by an agency of the 
U.S. Government and is 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 contacting Peter A. 
Soukas, J.D., at the Office of Technology Transfer, National Institutes 
of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 
20852-3804; telephone: 301/496-7056 ext. 268; fax: 301/402-0220; e-
mail: [email protected]. A signed Confidential Disclosure Agreement 
will be required to receive a copy of the patent application.

Methods for Preparing Bacillus Anthracis Protective Antigen for Use 
in Vaccines

Joseph Shiloach (NIDDK), Stephen Leppla (NIDCR), Delia Ramirez (NIDDK), 
Rachel Schneerson (NICHD), John Robbins (NICHD)
DHHS Reference No. E-023-02/0 filed 09 Nov 2001

    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

[[Page 3220]]

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 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.

    Dated: January 15, 2002.
Jack Spiegel,
Director, Division of Technology, Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-1613 Filed 1-22-02; 8:45 am]
BILLING CODE 4140-01-P