主权项 |
1. A method for reducing human IL-1 activity in a human subject in need thereof, comprising administering to the human subject a binding protein, wherein the binding protein comprises an antigen binding domain, said binding protein capable of binding human IL-1β, said antigen binding domain comprising six CDRs: CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, as defined below:
CDR-H1: X1-Y-D-M-S (SEQ ID NO:190), wherein;
X1 is, K or R; CDR-H2: Y-X2-S-X4-G-G-X7-G-T-Y-Y-P-D-X14-X15-K-G (SEQ ID NO:191), wherein;
X2 is I or V;X4 is S or H;X7 is G or A;X14 is T or S; andX15 is V or A; CDR-H3: G-G-V-X4-K-G-X7-F-D-X10 (SEQ ID NO:192), wherein;
X4 is T or Y;X7 is Y or C; andX10 is V, E, L, M, Q, or Y; CDR-L1: R-A-S-G-N-I-X7-X8-X9-L-X11 (SEQ ID NO:193), wherein;
X7 is H, Y, or W;X8 is N, G, T, Q, E, H, D, or K;X9 is Y or W; andX11 is T, A, or N; CDR-L2: X1-A-K-X4-L-X6-X7 (SEQ ID NO:194), wherein;
X1 is N, Q, or D;X4 is T, N, I, E, or S;X6 is A, M, or E; andX7 is D, E, S, or A; and CDR-L3: Q-X2-F-W-X5-X6-P-X8-X9 (SEQ ID NO:195), wherein;
X2 is H or Q;X5 is S, N, T, K, R, or M;X6 is I or L;X8 is Y or A; andX9 is T, I, and N; except that CDR-H2 cannot be Y-I-S-S-G-G-G-G-T-Y-Y-P-D-T-V-K-G (SEQ ID NO:18); CDR-H3 cannot be G-G-V-T-K-G-Y-F-D-V (SEQ ID NO:19); CDR-L1 cannot be R-A-S-G-N-I-H-N-Y-L-T (SEQ ID NO:20); CDR-L2 cannot be N-A-K-T-L-A-D (SEQ ID NO:21); and CDR-L3 cannot be Q-H-F-W-S-I-P-Y-T (SEQ ID NO:22), such that the human IL-1 activity in the human subject suffering from a disorder in which IL-1 activity is detrimental is reduced. |