Monoclonal Antibodies that Neutralize B. anthracis Protective Antigen (PA), Lethal Factor (LF) and Edema Factor (EF)


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.

Potential Commercial Applications: Competitive Advantages:
Prophylactics or therapeutics against B. anthracis. 


Development Stage:
Preclinical studies have been performed.

Inventors:

Zhaochun Chen (NIAID)  ➽ more inventions...

Stephen Leppla (NIAID)  ➽ more inventions...

Suzanne Emerson (NIAID)  ➽ more inventions...

Robert Purcell (NIAID)  ➽ more inventions...

Mahtab Moayeri (NIDCR)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 8,685,396 issued 2014-04-01
U.S. Pat: 8,071,100 issued 2011-12-06
U.S. Pat: 8,574,853 issued 2013-11-05
U.S. Pat: 8,961,975 issued 2015-02-24
US Application No. 11/793,735
PCT Application No. PCT/US2008/054609
US Application No. 12/528,427
US Application No. 13/310,463
US Application No. 14/031,508
US Application No. 14/181,099
US Application No. 14/595,475

Publications:
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. PubMed abs

Collaboration 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.


Licensing Contact:
Peter Soukas, J.D.
Email: peter.soukas@nih.gov
Phone: 301-496-2644

OTT Reference No: E-146-2004/0
Updated: Sep 1, 2008