Patent ID: 7767207
Filing Date: 2010-08-03
Classification: A61K,A61P,C07K

Abstract:
1. An isolated antibody, or an antigen-binding portion thereof, capable of binding human IL-18, wherein said antibody or antigen-binding portion thereof comprises a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 domain selected from the group consisting of: a heavy chain CDR1 domain of SEQ ID NO: 9 or modified from SEQ ID NO: 9 by at least one amino acid substitution at a position selected from the group consisting of H30, H31, H32, H33, and H35, wherein the amino acid substitution at H30 is selected from the group consisting of A, R, N, D, C, G, H, I, F, P, S, and V; wherein the amino acid substitution at H31 is selected from the group consisting of A, C, H, S, T, and Y; wherein the amino acid substitution at H32 is selected from the group consisting of R, N, C, H, P, S, and T; wherein the amino acid substitution at H33 is selected from the group consisting of N, D, C, Q, H, L, M, F, S, and V; and wherein the amino acid substitution at H34 is selected from the group consisting of N, D, L, and F; a heavy chain CDR2 domain of SEQ ID NO: 10 or modified from SEQ ID NO: 10 by at least one amino acid substitution at a position selected from the group consisting of H52, H52a, H53, H54, H56, and H58, wherein the amino acid substitution at H52 is T; wherein the amino acid substitution at H52a is selected from the group consisting of R, Q, L, S, T and W; wherein the amino acid substitution at H53 is selected from the group consisting of A, R, N, L, P, S, and Y; wherein the amino acid substitution at H54 is selected from the group consisting of A, R, N, D, Q, L, K, M, P, S, and Y; wherein the amino acid substitution at H56 is selected from the group consisting of A, R, N, C, G, H, I, L, and F; and wherein the amino acid substitution at H58 is selected from the group consisting of A, R, Q, E, H, I, L, K, M, F, S, T, Y, P, S, T, W, Y, and V; and a heavy chain CDR3 domain of SEQ ID NO: 11 or modified from SEQ ID NO: 11 by at least one amino acid substitution at a position selected from the group consisting of H95, H96, H97, and H98, wherein the amino acid substitution at H95 is A, R, E, Q, S, Y, V, H, P, W, and C; wherein the amino acid substitution at H96 is selected from the group consisting of A, R, Q, S, Y, V, H, P, W and C; wherein the amino acid substitution at H97 is selected from the group consisting of A, R, E, Q, S, Y, V, H, P, W, and C; and wherein the amino acid substitution at H98 is selected from the group consisting of R, E, Q, S, Y, V, H, P, W, and C; and wherein said antibody or antigen-binding portion thereof comprises a light chain variable region comprising a CDR1, a CDR2, and a CDR3 domain selected from the group consisting of: a light chain CDR1 domain of SEQ ID NO: 12 or modified from SEQ ID NO: 12 by at least one amino acid substitution at a position selected from the group consisting of L30, L31, L32, and L34, wherein the amino acid substitution at L30 is selected from the group consisting of N, D, C, G, I, L, S, W, and Y; wherein the amino acid substitution at L31 is selected from the group consisting of R, N, D, C, G, H, I, L, P, S, T, and Y; wherein the amino acid substitution at L32 is selected from the group consisting of R, N, D, E, G, I, L, P, S, T, and V; and wherein the amino acid substitution at L34 is selected from the group consisting of A, R, N, D, E, H, I, L, K, M, F, P, S, T, Y and V; a light chain CDR2 domain of SEQ ID NO: 13 or modified from SEQ ID NO: 13 by at least one amino acid substitution at a position selected from the group consisting of L50, L52, L53, and L55, wherein the amino acid substitution at L50 is A, N, I, L, F, P, S, W, Y and V; wherein the amino acid substitution at L52 is selected from the group consisting of A, R, D, E, H, I, L, M, F, P, S, T, and V; wherein the amino acid substitution at L53 is selected from the group consisting of A, R, C, I, L, K, M, P, S and T; wherein the amino acid substitution at L55 is selected from the group consisting of A, R, N, D, C, G, H, I, L, S, T, and Y; and a light chain CDR3 domain of SEQ ID NO: 14 or modified from SEQ ID NO: 14 by at least one amino acid substitution at a position selected from the group consisting of L89, L90, L91, L92, L93, L94, L95, L95a, L95b, L96, and L97, wherein the amino acid substitution at L89 is A, R, E, Q, S, Y, V, H, P, W, and C; wherein the amino acid substitution at L90 is selected from the group consisting of A, R, E, Q, Y, V, H, P, W and C; wherein the amino acid substitution at L91 is selected from the group consisting of R, E, Q, S, Y, V, H, P, W, and C; and wherein the amino acid substitution at L92 is selected from the group consisting of A, R, E, Q, S, Y, V, H, P, W, and C; wherein the amino acid substitution at L93 is A, R, E, Q, Y, V, H, P, W, and C; wherein the amino acid substitution at L94 is selected from the group consisting of A, R, E, Q, Y, V, H, P, W and C; wherein the amino acid substitution at L95 is selected from the group consisting of A, R, E, Q, S, Y, V, H, P, W, and C; and wherein the amino acid substitution at L95a is selected from the group consisting of A, R, E, Q, S, Y, V, H, P, W, and C; wherein the amino acid substitution at L95b is A, R, E, Q, S, Y, V, P, W, and C; wherein the amino acid substitution at L96 is selected from the group consisting of A, R, E, Q, S, Y, H, P, W and C; and wherein the amino acid substitution at L97 is selected from the group consisting of A, R, E, Q, S, Y, H, P, W, and C; wherein the at least one amino acid substitution does not inhibit IL-18 binding to the epitope comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 3 and SEQ ID NO: 36.