Monoclonal Antibodies that Neutralize Anthrax Protective Antigen (PA) Toxin

Abstract

The present invention relates to monoclonal antibodies that bind or neutralize anthrax protective antigen (PA) toxin. The invention provides such antibodies, fragments of such antibodies retaining anthrax PA toxin-binding ability, fully human or humanized antibodies retaining anthrax PA toxin-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.

1 - 18 . (canceled) 
     
     
         19 . A method for the treatment of anthrax disease comprising administering to a patient a therapeutically effective amount of a pharmaceutical preparation comprising a monoclonal antibody that binds anthrax protective antigen (PA) and a pharmaceutically acceptable carrier. 
     
     
         20 . A method for prophylaxis against anthrax disease comprising administering to a patient a prophylactically effective amount of a pharmaceutical preparation comprising a monoclonal antibody that binds anthrax protective antigen (PA) and a pharmaceutically acceptable carrier. 
     
     
         21 - 24 . (canceled) 
     
     
         25 . The method of  claim 19 , wherein said monoclonal antibody comprises:
 a heavy chain CDR1 region consisting of the amino acid sequence of SEQ ID NO:3, a heavy chain CDR 2 region consisting of the amino acid sequence of SEQ ID NO:5, a heavy chain CDR3 region consisting of the amino acid sequence of SEQ ID NO:7, a light chain CDR1 region consisting of the amino acid sequence of SEQ ID NO:11, a light chain CDR2 region consisting of the amino acid sequence of SEQ ID NO:13, and a light chain CDR3 region consisting of the amino acid sequence of SEQ ID NO:15; or   a heavy chain CDR1 region consisting of the amino acid sequence of SEQ ID NO:19, a heavy chain CDR 2 region consisting of the amino acid sequence of SEQ ID NO:21, a heavy chain CDR3 region consisting of the amino acid sequence of SEQ ID NO:23, a light chain CDR1 region consisting of the amino acid sequence of SEQ ID NO:27, a light chain CDR2 region consisting of the amino acid sequence of SEQ ID NO:29, and a light chain CDR3 region consisting of the amino acid sequence of SEQ ID NO:31.   
     
     
         26 . The method of  claim 19 , wherein said monoclonal antibody comprises a heavy chain Fd region including the amino acid sequence of SEQ ID NO: 1 (when heavy chain CDR3 region is SEQ ID NO: 7) or SEQ ID NO: 17 (when heavy chain CDR3 region is SEQ ID NO: 23). 
     
     
         27 . The method of  claim 19 , wherein said monoclonal antibody comprises a light chain region having the amino acid sequence of SEQ ID NO: 9 (when heavy chain CDR3 region is SEQ ID NO: 7) or SEQ ID NO: 25 (when heavy chain CDR3 region is SEQ ID NO: 23). 
     
     
         28 . The method of  claim 20 , wherein said monoclonal antibody comprises:
 a heavy chain CDR1 region consisting of the amino acid sequence of SEQ ID NO:3, a heavy chain CDR 2 region consisting of the amino acid sequence of SEQ ID NO:5, a heavy chain CDR3 region consisting of the amino acid sequence of SEQ ID NO:7, a light chain CDR1 region consisting of the amino acid sequence of SEQ ID NO:11, a light chain CDR2 region consisting of the amino acid sequence of SEQ ID NO:13, and a light chain CDR3 region consisting of the amino acid sequence of SEQ ID NO:15; or   a heavy chain CDR1 region consisting of the amino acid sequence of SEQ ID NO:19, a heavy chain CDR 2 region consisting of the amino acid sequence of SEQ ID NO:21, a heavy chain CDR3 region consisting of the amino acid sequence of SEQ ID NO:23, a light chain CDR1 region consisting of the amino acid sequence of SEQ ID NO:27, a light chain CDR2 region consisting of the amino acid sequence of SEQ ID NO:29, and a light chain CDR3 region consisting of the amino acid sequence of SEQ ID NO:31.   
     
     
         29 . The method of  claim 20 , wherein said monoclonal antibody comprises a heavy chain Fd region including the amino acid sequence of SEQ ID NO: 1 (when heavy chain CDR3 region is SEQ ID NO: 7) or SEQ ID NO: 17 (when heavy chain CDR3 region is SEQ ID NO: 23). 
     
     
         30 . The method of  claim 20 , wherein said monoclonal antibody comprises a light chain region having the amino acid sequence of SEQ ID NO: 9 (when heavy chain CDR3 region is SEQ ID NO: 7) or SEQ ID NO: 25 (when heavy chain CDR3 region is SEQ ID NO: 23).