Human Anthrax Toxin Neutralizing Monoclonal Antibodies and Methods of Use Thereof

Abstract

The invention fully humanized monoclonal antibodies that neutralize Bacillus anthracis . Also provided are methods of treating or preventing a Bacillus anthracis infection. The invention also provides methods of passive vaccination of a subject against Bacillus anthracis.

1 . An isolated fully human monoclonal antibody or an antigen-binding fragment thereof, comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain and the VL domain each comprises three complementarity determining regions 1 to 3 (CDR1-3), and wherein each CDR comprises the following amino acid sequences: 
       
         
           
                 
                 
               
                   VH CDR1: KKPGA[[;]], 
                   (SEQ ID NO: 11) 
                 
                     
                 
                   VH CDR2: SNAIQWVRQAPGQRLEW[[;]], 
                   (SEQ ID NO: 12) 
                 
                     
                 
                   VH CDR3: YMELSSLR[[;]], 
                   (SEQ ID NO: 13) 
                 
                     
                 
                   VL CDR1: LTQSPGTLSLS[[;]], 
                   (SEQ ID NO: 14) 
                 
                     
                 
                   VL CDR2: SYSSLAW[[;]], 
                   (SEQ ID NO: 15) 
                 
                   and 
                     
                 
                     
                 
                   VL CDR3: GPDFTLTIS[[;]], 
                   (SEQ ID NO: 16) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and wherein the antibody binds to an epitope on a region of the protective antigen polypeptide of  Bacillus anthracis.    
     
     
         2 . An isolated antibody comprising:
 a heavy chain comprising a polypeptide encoded by the nucleotide sequence of SEQ ID NO: 1, and   a light chain comprising a polypeptide encoded by the nucleotide sequence of SEQ ID NO: 3,   
       wherein the antibody binds protective antigen polypeptide and neutralizes  Bacillus anthracis  lethal toxin. 
     
     
         3 . An isolated antibody comprising:
 a heavy chain comprising the amino acid sequence of SEQ ID NO: 2, and   a light chain comprising the amino acid sequence SEQ ID NO: 4,   
       wherein the antibody binds protective antigen polypeptide and neutralizes  Bacillus anthracis  lethal toxin. 
     
     
         4 . The monoclonal antibody of  claim 1 , wherein said monoclonal antibody comprises the amino acid sequences encoded by the nucleotide sequences selected from SEQ ID NO: 1 and SEQ ID NO: 3. 
     
     
         5 . The monoclonal antibody of  claim 1 , wherein said monoclonal antibody comprises the amino acid sequences selected from SEQ ID NO: 2 and SEQ ID NO: 4. 
     
     
         6 . A pharmaceutical composition comprising the monoclonal antibody of any one of  claims 1 - 5 , and a pharmaceutically acceptable carrier. 
     
     
         7 . A passive vaccine against  Bacillus anthracis , comprising the pharmaceutical composition of  claim 6 . 
     
     
         8 . A kit comprising, in one or more containers, the monoclonal antibody of any one of  claims 1 - 5 . 
     
     
         9 - 10 . (canceled)