Patent ID: 8124082
Filing Date: 2012-02-28
Classification: A61K,A61P,C07K

Abstract:
1. A method of inhibiting the interaction of a human beta7 integrin subunit with a second integrin subunit and/or a ligand by contacting a humanized antibody with the beta7 integrin, wherein said antibody is a humanized anti-integrin beta 7 antibody comprising three heavy chain hypervariable region (HVR-H1-H3) sequences and three light chain hypervariable region (HVR-L1-L3) sequences, wherein at least one HVR is a variant of SEQ ID NO. 1, 2, 3, 5, or 6, wherein: (a)(i) HVR-L1 comprises sequence A1-A11, wherein A1-A11 is RASESVDTYLH (SEQ ID NO:1), or a variant thereof, wherein (1) in SEQ ID NO:1 at position A8 T is substituted by S, D or T and at position A9 Y is substituted by L, or wherein said variant comprises (2) 1-10 (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) substitutions in SEQ ID NO:1 in any combination of the following positions: A2 (A, G, S, T, or V); A3 (S, G, I, K, N, P, Q, R, or T), A4 (E, A, D, G, H, I, K, L, N, Q, R, or V), A5 (S, A, D, G, H, I, K, N, P, R, T, V, or Y), A6 (V, A, G, I, K, L, M, Q, or R), A7 (D, A, E, G, H, I, K, L, N, P, S, T, or V), A8 (S, D, E, G, P, T or N), A9 (L, Y, I, or M), A10 (L, A, I, M, or V), and A11 (H, F, S, or Y), or wherein (3) HVR-L1 comprises a sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9; and wherein the additional hypervariable sequences are: (ii) HVR-L2 comprising sequence B1-B8, wherein B1-B8 is KYASQSIS (SEQ ID NO: 2), or a variant thereof, wherein said variant comprises 1-4 (1, 2, 3, or 4) substitutions in SEQ ID NO: 2 in any combination of the following positions: B1 (K, R, N, V, A, F, Q, H, P, I, L, Y, T, H S, E, C, D, G, or M), B5 (Q or S), B6 (S, R or L), and B7 (I, T, E, K, or V); (iii) HVR-L3 comprising sequence C1-C9, wherein C1-C9 is QQGNSLPNT (SEQ ID NO: 3), or a variant thereof, wherein said variant comprises at least one of the following substitutions in SEQ ID NO: 3 at position C8 (W, Y, R, S, A, F, H, I, L, M, N, T, or V); (iv) HVR-H1 comprising sequence D1-D10, wherein D1-D10 is GFFITNNYWG (SEQ ID NO: 4); (v) HVR-H2 comprising sequence E1-E17, wherein E1-E17 is GYISYSGSTSYNPSLKS (SEQ ID NO: 5), or a variant thereof, wherein said variant comprises 1-7 (1, 2, 3, 4, 5, 6, or 7) substitutions in SEQ ID NO: 5 in any combination of the following positions: E2 (Y, V, D, or F), E6 (S or G), E10 (S or Y), E12 (N, A, D, or T), E13 (P, D, A, or H), E15 (L or V), E17 (S or G); and (vi) HVR-H3 comprising sequence F1-F11, wherein F1-F11 is MTGSSGYFDF (SEQ ID NO: 6), or a variant thereof, wherein said variant comprises at 1 or 2 substitutions in SEQ ID NO: 6 in any combination of the following positions: F2 (R, M, A, E, G, Q, R, or S), and F11 (F or Y); or (b)(i) HVR-L1 comprises a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO:9, (ii) HVR-L2 comprises a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 67, and SEQ ID NO: 68, (iii) HVR-L3 comprises SEQ ID NO:3, (iv) HVR-H1 comprises SEQ ID NO:4, (v) HVR-H2 comprises SEQ ID NO:5, and (vi) HVR-H3 comprises SEQ ID NO:6 or 66 for relative positions F2-F11 or comprises SEQ ID NO:63 or 64 or 65 for relative positions F1-F11, wherein said humanized antibody binds integrin beta 7.