Humanized anti-factor d antibodies and uses thereof

Abstract

The invention relates to anti-Factor D antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their production 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 . An anti-Factor D antibody comprising light chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises light chain HVR-1 comprising ITSTDIDDDMN (SEQ ID NO: 30), light chain HVR-2 comprising GGNTLRP (SEQ ID NO: 35), and light chain HVR-3 comprising LQSDSLPYT (SEQ ID NO: 38), and wherein said substitution is one or more of the following:
 (a) amino acid at position 33 of the light chain is L or I;   (b) amino acid at position 34 of the light chain is A or Q;   (c) amino acid at position 52 of the light chain is S or A;   (d) amino acid at position 104 of the light chain is V;   (e) amino acid at position 1 of the heavy chain is E;   (f) amino acid at position 99 of the heavy chain is A or Q; or   (g) amino acid at position 100 of the heavy chain is A or Q.   
     
     
         2 . An anti-Factor D antibody comprising heavy chain HVRs of a reference antibody, wherein said anti-Factor D antibody further comprises a substitution at one or more positions of said reference antibody, wherein said reference antibody comprises heavy chain HVR-1 comprising GYTFTNYGMN (SEQ ID NO: 39), heavy chain HVR-2 comprising WINTYTGETTYADDFKG (SEQ ID NO: 40), and heavy chain HVR-3 comprising EGGVNN (SEQ ID NO: 41), and wherein said substitution is one or more of the following:
 (a) amino acid at position 33 of the light chain is L or I;   (b) amino acid at position 34 of the light chain is A or Q;   (c) amino acid at position 52 of the light chain is S or A;   (d) amino acid at position 104 of the light chain is V;   (e) amino acid at position 1 of the heavy chain is E;   (f) amino acid at position 99 of the heavy chain is A or Q; or   (g) amino acid at position 100 of the heavy chain is A or Q.   
     
     
         3 .- 21 . (canceled) 
     
     
         22 . A polypeptide comprising the following amino acid sequence: X 1 VQLVQSGPELKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTYTGET TYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCEREGGVX 2 X 3 WGQGTLVTVSS (SEQ ID NO: 74), wherein X 1  is Q or E; X 2  is N, A or Q; and X 3  is N, A or Q. 
     
     
         23 . A polypeptide comprising the following amino acid sequence: DIQVTQSPSSLSASVGDRVTITCITSTDIDDDX 4 X 5 WYQQKPGKVPKLLISGGX 6 TLRPGVPSRF SGSGSGTDFTLTISSLQPEDVATYYCLQSDSLPYTFGQGTKX 7 EIK (SEQ ID NO: 73), wherein X 4  is M, L or I; X 5  is N, A or Q; X 6  is N, S or A; and X 7  is L or V. 
     
     
         24 .- 25 . (canceled) 
     
     
         26 . An anti-Factor D antibody comprising the polypeptide of  claim 22 . 
     
     
         27 . An anti-Factor D antibody comprising the polypeptide of  claim 23 . 
     
     
         28 .- 46 . (canceled) 
     
     
         47 . A polypeptide comprising an amino acid selected from SEQ ID NOs: 47, 61, 54, and 63. 
     
     
         48 .- 51 . (canceled) 
     
     
         52 . A polynucleotide encoding the antibody of  claim 1 . 
     
     
         53 . (canceled) 
     
     
         54 . A vector comprising the polynucleotide of  claim 52 . 
     
     
         55 . A host cell comprising the vector of  claim 54 . 
     
     
         56 .- 57 . (canceled) 
     
     
         58 . A method of making an anti-Factor D antibody, wherein the method comprises (a) culturing the host cell of  claim 55  under conditions suitable for expression of the polynucleotide encoding the antibody, and (b) isolating the antibody. 
     
     
         59 .- 63 . (canceled) 
     
     
         64 . A pharmaceutical formulation comprising the anti-Factor D antibody of  claim 1 , and a pharmaceutically acceptable diluent, carrier or excipient. 
     
     
         65 . An article of manufacture comprising:
 (a) the pharmaceutical formulation of  claim 64 ;   (b) a container; and   (c) a package insert or label indicating that the compound can be used to treat a complemented-associated disorder.   
     
     
         66 . A kit comprising an antibody of  claim 1  and instructions for administering said antibody to treat a complement-associated disorder. 
     
     
         67 .- 69 . (canceled) 
     
     
         70 . A method of treating a complement-associated disorder, comprising administering to a patient in need thereof a therapeutically effective amount of an anti-Factor D antibody of  claim 1 , wherein the complement-associated disorder is selected from inflammatory disorders. 
     
     
         71 .- 72 . (canceled) 
     
     
         73 . A method of treating a complement-associated disorder, comprising administering to a patient in need thereof a therapeutically effective amount of an anti-Factor D antibody of  claim 1 , wherein the complement-associated disorder is selected from ocular diseases. 
     
     
         74 .- 76 . (canceled)