Antibodies Against Protective Antigen

Abstract

The present invention relates to antibodies and related molecules that specifically bind to protective antigen of Bacillus anthracis (PA). Such antibodies have uses, for example, in the prevention and treatment of anthrax and anthrax toxin poisoning. The invention also relates to nucleic acid molecules encoding anti-PA antibodies, vectors and host cells containing these nucleic acids, and methods for producing the same.

1 . An isolated antibody or fragment thereof comprising:
 (a) an amino acid sequence that is at least 80% identical to a VH domain of any one of the scFvs of SEQ ID NOS:48-56;   (b) an amino acid sequence that is at least 80% identical to a VL domain of any one of the scFvs of SEQ ID NOS:48-56; or   (c) both (a) and (b);   wherein said antibody or fragment thereof specifically binds protective antigen (PA).   
     
     
         2 . The antibody or fragment thereof of  claim 1  wherein the antibody or fragment thereof is a monoclonal antibody. 
     
     
         3 . The antibody or fragment thereof of  claim 1  wherein the antibody or fragment thereof is a human antibody. 
     
     
         4 . The antibody or fragment thereof of  claim 1  wherein the antibody or fragment thereof is selected from the group consisting of:
 (a) a whole immunoglobulin molecule; 
 (b) an scFv; 
 (c) a chimeric antibody; 
 (d) a Fab fragment; 
 (e) an F(ab′)2; and 
 (f) a disulfide linked Fv. 
 
     
     
         5 . The antibody or fragment thereof of  claim 1  which comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:
 (a) a human IgM constant domain; 
 (b) a human IgG1 constant domain; 
 (c) a human IgG2 constant domain; 
 (d) a human IgG3 constant domain; 
 (e) a human IgG4 constant domain; and 
 (f) a human IgA constant domain. 
 
     
     
         6 . An isolated cell that produces the antibody or fragment thereof of  claim 1 . 
     
     
         7 . A method of treatment of anthrax infection or anthrax toxin poisoning comprising administering to an animal the antibody or fragment thereof of  claim 1 . 
     
     
         8 . The method of  claim 7  wherein the animal is a human. 
     
     
         9 . The method of  claim 7  wherein the treatment is prophylactic. 
     
     
         10 . The method of  claim 7  wherein the antibody or fragment thereof is administered in combination with a second antibody or fragment thereof that specifically binds PA. 
     
     
         11 . The method of  claim 7  wherein the antibody or fragment thereof is administered in combination with an anti-anthrax agent. 
     
     
         12 . The method of  claim 11  wherein the anti-anthrax agent is selected from the group consisting of:
 (a) a soluble form of the ATR receptor; 
 (b) a soluble form of the CMG2 receptor; 
 (c) an anti-ATR antibody; 
 (d) an anti-EF antibody; 
 (e) an anti-LF antibody; 
 (f) an anthrax vaccine; and 
 (g) a polyvalent form of the P1 peptide. 
 
     
     
         13 . The method of  claim 7  wherein the antibody or fragment thereof is administered in combination with an antibiotic. 
     
     
         14 . The method of  claim 13  wherein the antibiotic is ciprofloxacin hydrochloride. 
     
     
         15 . The method of  claim 13  wherein the antibiotic is doxycycline. 
     
     
         16 . The method of  claim 13  wherein the antibiotic is selected from the group consisting of:
 (a) penicillin G procaine; 
 (b) amoxicillan; 
 (c) ofloxacin; and 
 (d) levofloxacin. 
 
     
     
         17 . The method of  claim 7  wherein the antibody or fragment thereof is administered in combination with a member selected from the group consisting of:
 (a) a protease inhibitor; 
 (b) an anti-TNF-alpha antibody; and 
 (c) an anti-IL-1beta antibody. 
 
     
     
         18 . A kit comprising the antibody or fragment thereof of  claim 1  and a means for administering said antibody to an animal. 
     
     
         19 . The kit of  claim 18  wherein the animal is a human. 
     
     
         20 . An isolated antibody or fragment thereof comprising:
 (a) the amino acid sequence of aVH domain of any one of the scFvs of SEQ ID NOS:48-56;   (b) the amino acid sequence of the VL domain of any one of the scFvs of SEQ ID NOS:48-56; or   (c) both (a) and (b);   wherein said antibody or fragment thereof specifically binds PA.