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 anti-Factor D antibody or an antigen-binding fragment thereof, wherein the antibody comprises:
 (1) 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, and a CDR-L3 having the sequence of SEQ ID NO: 18; and   (2) a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 13; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 15.   
     
     
         39 . An anti-Factor D antibody or an antigen-binding fragment thereof, wherein the antibody comprises:
 (1) 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, and a CDR-L3 having the sequence of SEQ ID NO: 19; and   (2) a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 13; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 20.   
     
     
         40 . An anti-Factor D antibody or an antigen-binding fragment thereof, wherein the antibody comprises:
 (1) 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: 21, and a CDR-L3 having the sequence of SEQ ID NO: 22; and   (2) a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 23; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 20.   
     
     
         41 . An anti-Factor D antibody or an antigen-binding fragment thereof, wherein the antibody comprises:
 (1) 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: 24, and a CDR-L3 having the sequence of SEQ ID NO: 22; and   (2) a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 25; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 20.   
     
     
         42 . The anti-Factor D antibody or antigen-binding fragment thereof of  claim 38 , 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. 
     
     
         43 . The anti-Factor D antibody or antigen-binding fragment thereof of  claim 39 , 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. 
     
     
         44 . The anti-Factor D antibody or antigen-binding fragment thereof of  claim 40 , 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. 
     
     
         45 . The anti-Factor D antibody or antigen-binding fragment thereof of  claim 41 , 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. 
     
     
         46 . The anti-Factor D antibody or antigen-binding fragment thereof of  claim 43 , wherein the amino acid at position 104 of SEQ ID NO: 7 is substituted with a valine. 
     
     
         47 . An anti-Factor D antibody or an antigen-binding fragment thereof, wherein the antibody comprises:
 (1) a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 13; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 15; and   (2) a variable light chain comprising the amino acid sequence of SEQ ID NO: 7, wherein the amino acid at position 104 of SEQ ID NO: 7 is substituted with a valine.   
     
     
         48 . An anti-Factor D antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises:
 (1) 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, and a CDR-L3 having the sequence of SEQ ID NO: 19; and   
       (2) a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 13; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 20;
 wherein the variable light chain comprises the sequence of SEQ ID NO: 7, and the variable heavy chain comprises the sequence of SEQ ID NO: 8, and wherein the amino acid at position 104 of SEQ ID NO: 7 is substituted with a valine. 
 
     
     
         49 . The anti-Factor D antibody or antigen-binding fragment thereof of any one of  claims 38  to  48 , wherein the antigen-binding fragment is a Fab, Fab′, F(ab′) 2  or Fv fragment. 
     
     
         50 . A composition comprising the antibody or an antigen-binding fragment thereof of any one of  claims 38  to  48 .