Antibodies directed to
This disclosure generally relates to therapeutic antibodies for treating Bacillus anthracis ( B. anthracis ) infection, to specific variants thereof, pharmaceutical composition comprising them and to methods for their use.
1. An isolated monoclonal antibody or any antigen-binding fragment thereof which binds to Bacillus anthracis protective antigen, wherein the antibody comprises a heavy chain variable region comprising:
a) the complementarity determining region CDRH1 comprising the amino acid sequence of IFTNYNMH denoted by SEQ ID NO. 3;
b) the complementarity determining region CDRH2 comprising the amino acid sequence AIYPRTGDTSYNQKFKG denoted by SEQ ID NO. 4; and
c) the complementarity determining region CDRH3 comprising the amino acid sequence ARDGFAY denoted by SEQ ID NO. 5; and
a light chain variable region comprising:
d) the complementarity determining region CDRL1 comprising the amino acid sequence RASQDISNYLN denoted by SEQ ID NO. 8;
e) the complementarity determining region CDRL2 comprising the amino acid sequence YTSRLHS denoted by SEQ ID NO. 9; and
f) the complementarity determining region CDRL3 comprising the amino acid sequence QQGKTLPWT denoted by SEQ ID NO. 10.
2. The isolated monoclonal antibody according to claim 1 , wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 1 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 6.
3. The isolated monoclonal antibody according to claim 1 , wherein said heavy chain variable region is of the amino acid sequence denoted by SEQ ID NO. 2 or a variant thereof in which at least one position selected from the group consisting of position 1 and position 16 of SEQ ID NO. 2 is substituted.
4. The isolated monoclonal antibody according to claim 1 , wherein said light chain variable region is of the amino acid sequence denoted by SEQ ID NO. 7 or a variant thereof in which at least one position selected from the group consisting of positions 3, 9, 21, 57 and 87 of SEQ ID NO. 7 is substituted.
5. The isolated monoclonal antibody according to claim 1 , wherein said heavy chain variable region is of the amino acid sequence denoted by SEQ ID NO. 2 and wherein said light chain variable region is of the amino acid sequence denoted by SEQ ID NO. 7.
6. The isolated monoclonal antibody according to claim 1 , wherein said antibody is a chimeric, a humanized or a human antibody.
7. The isolated monoclonal antibody according to claim 1 , wherein said antibody is an antibody fragment selected from the group consisting of Fv, single chain Fv (scFv), heavy chain variable region, light chain variable region, Fab, F(ab) 2 ′ and any combination thereof.
8. A pharmaceutical composition comprising as an active ingredient the isolated monoclonal antibody or any antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.
9. The pharmaceutical composition according to claim 8 , wherein said composition further comprises at least one additional anti-anthrax agent.
10. A kit comprising:
(i) an isolated monoclonal antibody or any antigen-binding fragment thereof which binds to Bacillus anthracis protective antigen, wherein the antibody comprises a heavy chain variable region comprising:
a) the complementarity determining region CDRH1 comprising the amino acid sequence of IFTNYNMH denoted by SEQ ID NO. 3;
b) the complementarity determining region CDRH2 comprising the amino acid sequence AIYPRTGDTSYNQKFKG denoted by SEQ ID NO. 4; and
c) the complementarity determining region CDRH3 comprising the amino acid sequence ARDGFAY denoted by SEQ ID NO. 5; and
a light chain variable region comprising:
d) the complementarity determining region CDRL1 comprising the amino acid sequence RASQDISNYLN denoted by SEQ ID NO. 8;
e) the complementarity determining region CDRL2 comprising the amino acid sequence YTSRLHS denoted by SEQ ID NO. 9; and
f) the complementarity determining region CDRL3 comprising the amino acid sequence QQGKTLPWT denoted by SEQ ID NO. 10; and
(ii) instructions for use.
11. An isolated chimeric antibody, or any antigen-binding fragment thereof which binds to Bacillus anthracis protective antigen, wherein the antibody comprises a heavy chain variable region comprising:
a) the complementarity determining region CDRH1 comprising the amino acid sequence of IFTNYNMH denoted by SEQ ID NO. 3;
b) the complementarity determining region CDRH2 comprising the amino acid sequence AIYPRTGDTSYNQKFKG denoted by SEQ ID NO. 4; and
c) the complementarity determining region CDRH3 comprising the amino acid sequence ARDGFAY denoted by SEQ ID NO. 5; and
a light chain variable region comprising:
d) the complementarity determining region CDRL1 comprising the amino acid sequence RASQDISNYLN denoted by SEQ ID NO. 8;
e) the complementarity determining region CDRL2 comprising the amino acid sequence YTSRLHS denoted by SEQ ID NO. 9; and
f) the complementarity determining region CDRL3 comprising the amino acid sequence QQGKTLPWT denoted by SEQ ID NO. 10.
12. The isolated chimeric antibody according to claim 11 , wherein the antibody comprises a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 2, or a variant thereof in which at least one position selected from the group consisting of position 1 and position 16 of SEQ ID NO. 2 is substituted, and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 7, or a variant thereof in which at least one position selected from the group consisting of positions 3, 9, 21, 57 and 87 of SEQ ID NO. 7 is substituted.