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 isolated nucleic acid encoding 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 isolated nucleic acid encoding 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 isolated nucleic acid encoding 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 isolated nucleic acid encoding 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 isolated nucleic acid 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 isolated nucleic acid 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 isolated nucleic acid 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 isolated nucleic acid 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 isolated nucleic acid of  claim 43 , wherein the amino acid at position 104 of SEQ ID NO: 7 is substituted with a valine. 
     
     
         47 . An isolated nucleic acid encoding 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 isolated nucleic acid encoding 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 . An isolated nucleic acid encoding an 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 vector comprising the nucleic acid of any one of  claims 38  to  48 . 
     
     
         51 . A host cell comprising the vector of  claim 50 . 
     
     
         52 . A method for producing an anti-Factor D antibody or an antigen-binding fragment thereof, comprising:
 (i) culturing the host cell of  claim 51  in a media; and   (ii) purifying the antibody or fragment expressed therein.