Humanized Anti-Factor D Antibodies And Uses Thereof

Abstract

The invention relates to humanized anti-human Factor D monoclonal antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

1 - 37 . (canceled) 
     
     
         38 . An antibody or an antigen-binding fragment thereof that binds to the same epitope as an anti-Factor D antibody or an anti-Factor D antibody fragment thereof comprising a variable light chain comprising a CDR-L1 having the sequence of SEQ ID NO: 16; a CDR-L2 having the sequence of SEQ ID NO: 17, 21 or 24, and a CDR-L3 having the sequence of SEQ ID NO: 18, 19 or 22. 
     
     
         39 . An antibody or an antigen-binding fragment thereof that binds to the same epitope as an anti-Factor D antibody or an anti-Factor D antibody fragment thereof comprising a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 13, 23 or 25; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 15 or 20. 
     
     
         40 . An antibody or an antigen-binding fragment thereof that binds to the same epitope as an anti-Factor D antibody or an anti-Factor D antibody fragment thereof comprising:
 (i) a variable light chain comprising a CDR-L1 having the sequence of SEQ ID NO: 16; a CDR-L2 having the sequence of SEQ ID NO: 17, 21 or 24, and a CDR-L3 having the sequence of SEQ ID NO: 18, 19 or 22; and   (ii) a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 13, 23 or 25; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 15 or 20.   
     
     
         41 . The antibody or the antigen-binding fragment thereof of  claim 38 , wherein the CDR-L1 has the sequence of SEQ ID NO: 16; the CDR-L2 has the sequence of SEQ ID NO: 21, or 24; and the CDR-L3 has the sequence of SEQ ID NO: 18, 19 or 22. 
     
     
         42 . The antibody or the antigen-binding fragment thereof of  claim 38 , wherein the CDR-L1 has the sequence of SEQ ID NO: 16; the CDR-L2 has the sequence of SEQ ID NO: 17, 21 or 24, and the CDR-L3 has the sequence of SEQ ID NO: 19 or 22. 
     
     
         43 . The antibody or the antigen-binding fragment thereof of  claim 39 , wherein the CDR-H1 has the sequence of SEQ ID NO: 23 or 25; the CDR-H2 has the sequence of SEQ ID NO: 14; and the CDR-H3 has the sequence of SEQ ID NO: 15 or 20. 
     
     
         44 . The antibody or the antigen-binding fragment thereof of  claim 39 , wherein the CDR-H1 has the sequence of SEQ ID NO: 13, 23 or 25; the CDR-H2 has the sequence of SEQ ID NO: 14; and the CDR-H3 has the sequence of SEQ ID NO: 20. 
     
     
         45 . The antibody or the antigen-binding fragment thereof of  claim 40 , wherein the CDR-L1 has the sequence of SEQ ID NO: 16, the CDR-L2 has the sequence of SEQ ID NO: 17, the CDR-L3 has the sequence of SEQ ID NO: 18, the CDR-H1 has the sequence of SEQ ID NO: 13, the CDR-H2 has the sequence of SEQ ID NO: 14, and the CDR-H3 has the sequence of SEQ ID NO: 15. 
     
     
         46 . The antibody or the antigen-binding fragment thereof of  claim 40 , wherein the CDR-L1 has the sequence of SEQ ID NO: 16, the CDR-L2 has the sequence of SEQ ID NO: 21, the CDR-L3 has the sequence of SEQ ID NO: 22, the CDR-H1 has the sequence of SEQ ID NO: 23, the CDR-H2 has the sequence of SEQ ID NO: 14, and the CDR-H3 has the sequence of SEQ ID NO: 20. 
     
     
         47 . The antibody or the antigen-binding fragment thereof of  claim 40 , wherein the CDR-L1 has the sequence of SEQ ID NO: 16, the CDR-L2 has the sequence of SEQ ID NO: 24, the CDR-L3 has the sequence of SEQ ID NO: 22, the CDR-H1 has the sequence of SEQ ID NO: 25, the CDR-H2 has the sequence of SEQ ID NO: 14, and the CDR-H3 has the sequence of SEQ ID NO: 20. 
     
     
         48 . The antibody or the antigen-binding fragment thereof of  claim 38 , wherein the variable light chain comprises the sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. 
     
     
         49 . The antibody or the antigen-binding fragment thereof of  claim 39 , wherein the variable heavy chain comprises the sequence of SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12. 
     
     
         50 . The antibody or the antigen-binding fragment thereof of  claim 45 , wherein the variable light chain comprises the sequence of SEQ ID NO: 5, and wherein the variable heavy chain comprises the sequence of SEQ ID NO: 6. 
     
     
         51 . The antibody or the antigen-binding fragment thereof of  claim 46 , wherein the variable light chain comprises the sequence of SEQ ID NO: 9, and wherein the variable heavy chain comprises the sequence of SEQ ID NO: 10. 
     
     
         52 . The antibody or the antigen-binding fragment thereof of  claim 47 , wherein the variable light chain comprises the sequence of SEQ ID NO: 11, and wherein the variable heavy chain comprises the sequence of SEQ ID NO: 12. 
     
     
         53 .   v  claim 40 , wherein the variable light chain comprises the sequence of SEQ ID NO: 7, and wherein the variable heavy chain comprises the sequence of SEQ ID NO: 8. 
     
     
         54 . The antibody or the antigen-binding fragment thereof of  claim 53 , wherein the amino acid at position 104 of SEQ ID NO: 7 is substituted with a valine.