Il-18 binding proteins

Abstract

The present invention encompasses IL-18 binding proteins, particularly antibodies that bind human interleukin-18 (hIL-18). Specifically, the invention relates to antibodies that are entirely human antibodies. Preferred antibodies have high affinity for hIL-18 and/or that neutralize hIL-18 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-18 and for inhibiting hIL-1 activity, e.g., in a human subject suffering from a disorder in which hIL-18 activity is detrimental.

1 . A binding protein comprising an antigen binding domain capable of binding human IL-18, said antigen binding domain comprises at least one CDR comprising an amino acid sequence selected from the group consisting of:
 CDR-H1. X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7  (SEQ ID NO: 42), wherein;
 X 1  is S, N, H, R, or Y; 
 X 2  is Y, G, R, S, or C; 
 X 3  is W, G, Y, D, S, V, or I; 
 X 4  is I, H, W, Y, M, L, or D; 
 X 5  is G, Y, S, N, or H; 
 X 6  is W, or is not present; and 
 X 7  is T, S, G, or is not present; 
   CDR-H2. X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -X 15 -X 16 -X 17  (SEQ ID NO: 43), wherein;
 X 1  is F, Y, H, S, or V; 
 X 2  is I, or F; 
 X 3  is Y, S, or W; 
 X 4  is P, Y; or S; 
 X 5  is G, S, R, or D; 
 X 6  is D, or G; 
 X 7  is S, T, G, or R; 
 X 8  is E, T, I, or N; 
 X 9  is T, Y, N, I, K, or H; 
 X 10  is R, Y, or S; 
 X 11  is Y, N, or S; 
 X 12  is S, P, A, or V; 
 X 13  is P, S, or D; 
 X 14  is T, L, or S; 
 X 15  is F, K, or V; 
 X 16  is Q, S, or K; and 
 X 17  is G, or is not present; 
   CDR-H3. X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -X 15 -X 16 -X 17 -X 18  (SEQ ID NO: 44), wherein;
 X 1  is V, D, E, S, or C; 
 X 2  is G, R, D, S, K, L, Y; or A; 
 X 3  is S, G, Y, or R; 
 X 4  is G, S, Y; N, T, or D; 
 X 5  is W, S, A, G, Y; or T; 
 X 6  is Y, G, S, F, W, or N; 
 X 7  is P, S, F, Y, V, G, W, or V; 
 X 8  is Y, F, D, P, M, I, or N; 
 X 9  is T, W, D, L, Y, E, P, F, or G; 
 X 10  is F, D, Y, H, V, Y; or is not present; 
 X 11  is D, Y, F, L, or is not present; 
 X 12  is I, D, Y, or is not present; 
 X 13  is Y, or is not present; 
 X 14  is Y, or is not present; 
 X 15  is G, or is not present; 
 X 16  is M, or is not present; 
 X 17  is D, or is not present; and 
 X 18  is V, or is not present; 
   CDR-L 1 . X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -X 15 -X 16 -X 17  (SEQ ID NO: 45), wherein;
 X 1  is R, or K; 
 X 2  is A, G, or S; 
 X 3  is S; 
 X 4  is E, R, Q, or H; 
 X 5  is S, I, T, or N; 
 X 6  is I, V, L, or F; 
 X 7  is S, G, L, N, or R; 
 X 8  is S, G, Y, R, N, H, or D; 
 X 9  is N, G, Y, R, or S; 
 X 10  is L, Y, S, or D; 
 X 11  is A, L, N, V, G, or D; 
 X 12  is A, N, E, K, G, or is not present; 
 X 13  is K, T, N, or is not present; 
 X 14  is N, Y, T, or is not present; 
 X 15  is Y, L, or is not present; 
 X 16  is L, C, Y, or is not present; and 
 X 17  is A, D, or is not present; 
   CDR-L 2 . X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7  (SEQ ID NO: 46), wherein;
 X 1  is T, G, S, W, or E; 
 X 2  is A, V, T, I, or L; 
 X 3  is S, or F; 
 X 4  is T, I, N, S, R, or Y; 
 X 5  is R, or L; 
 X 6  is A, Q, E, or F; and 
 X 7  is T, or S; 
   
       and
 CDR-L 3 . X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10  (SEQ ID NO: 47), wherein;
 X 1  is Q, or M; 
 X 2  is Q, H, or Y; 
 X 3  is Y, N, G, S, or R; 
 X 4  is N, H, Y, D, G, V, L, or I; 
 X 5  is N, G, I, Y, S, Q, F, or E; 
 X 6  is W, S, T, L, I, or F; 
 X 7  is P, L, T, D, or I; 
 X 8  is S, L, P, C, W, I, or F; 
 X 9  is I, T, S, or is not present; and 
 X 10  is T, or is not present. 
 
 
     
     
         2 - 79 . (canceled)