Humanized or chimeric CD3 antibodies

1 . A bispecific antibody comprising a first binding region of an antibody which binds to human CD3, and a second binding region which binds a tumor-associated antigen, wherein the first binding region comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein:

(a) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 54, 2, and 3, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(b) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 58, 2, and 3, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(c) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 106, and 3, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(d) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 176, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(e) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 184, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(f) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 220, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(g) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 236, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(h) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 244, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(i) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 284, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively;

(j) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 292, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively; or

(k) the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 298, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7, respectively.

2 . The bispecific antibody according to claim 1 , wherein the VH region of the first binding region comprises:

(a) a VH sequence as set forth in SEQ ID NO: 55;

(b) a VH sequence as set forth in SEQ ID NO: 59;

(c) a VH sequence as set forth in SEQ ID NO: 107;

(d) a VH sequence as set forth in SEQ ID NO: 177;

(e) a VH sequence as set forth in SEQ ID NO: 185;

(f) a VH sequence as set forth in SEQ ID NO: 221;

(g) a VH sequence as set forth in SEQ ID NO: 237;

(h) a VH sequence as set forth in SEQ ID NO: 245;

(i) a VH sequence as set forth in SEQ ID NO: 285;

(j) a VH sequence as set forth in SEQ ID NO: 293; or

(k) a VH sequence as set forth in SEQ ID NO: 299; and

the VL region comprises a VL sequence as set forth in SEQ ID NO: 8 or SEQ ID NO: 10.

3 . The bispecific antibody according to claim 1 , which is a full-length antibody.

4 . The bispecific antibody according to claim 1 , which is chimeric or humanized.

5 . The bispecific antibody according to claim 1 , which is of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

6 . The bispecific antibody according to claim 1 , which is monovalent, bivalent or multivalent.

7 . The bispecific antibody according to claim 1 , which comprises a first heavy chain and a second heavy chain.

8 . The bispecific antibody according to claim 7 , wherein in at least one of said first and second heavy chains,

(a) the amino acid in the position corresponding to position D265 in a human IgG1 heavy chain is not D;

(b) the amino acid in the position corresponding to position N297 in a human IgG1 heavy chain is not N;

(c) the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain are not L and L, respectively;

(d) the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain are F and E; or A and A, respectively;

(e) the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain are F and E, respectively;

(f) the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain are A and A, respectively;

(g) the amino acids in the positions corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain are not L, L, and D, respectively;

(h) the amino acids in the positions corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain are F, E, and A; or A, A, and A, respectively;

(i) the amino acids in the positions corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain are F, E, and A, respectively; or

(j) the amino acids in the positions corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain, are A, A, and A, respectively.

9 . The bispecific antibody according to claim 7 , wherein in at least one of said first and second heavy chains, the amino acids in the positions corresponding to positions L234, L235, D265, N297, and P331 in a human IgG1 heavy chain are F, E, A, Q, and S, respectively.

10 . The bispecific antibody according to claim 7 , wherein each of said first and second heavy chain comprises at least a hinge region, a CH2 region, and a CH3 region, wherein in said first heavy chain, at least one of the amino acids in the positions corresponding to a position selected from the group consisting of T366, L368, K370, D399, F405, Y407, and K409 in a human IgG1 heavy chain has been substituted, and in said second heavy chain, at least one of the amino acids in the positions corresponding to a position selected from the group consisting of T366, L368, K370, D399, F405, Y407, and K409 in a human IgG1 heavy chain has been substituted, and wherein said first and said second heavy chains are not substituted in the same positions.

11 . The bispecific antibody according to claim 1 , which comprises a first heavy chain and a second heavy chain, wherein in at least one of said first and second heavy chains, one or more amino acids in the positions corresponding to positions L234, L235, D265, N297, and P331 in a human IgG1 heavy chain according to EU numbering, are not L, L, D, N, and P, respectively.

12 . The bispecific antibody according to claim 10 , wherein (a) the amino acid in the position corresponding to F405 in a human IgG1 heavy chain is L in said first heavy chain, and the amino acid in the position corresponding to K409 in a human IgG1 heavy chain is R in said second heavy chain, or (b) the amino acid in the position corresponding to F405 in a human IgG1 heavy chain is L in said second heavy chain, and the amino acid in the position corresponding to K409 in a human IgG1 heavy chain is R in said first heavy chain.

13 . A composition comprising a bispecific antibody according to claim 1 and a carrier.

14 . A pharmaceutical composition comprising a bispecific antibody according to claim 1 and a pharmaceutically acceptable carrier.

15 . A bispecific antibody comprising a first binding region of an antibody which binds to human CD3, and a second binding region which binds a different target than said first binding region, wherein the first binding region comprises a heavy chain variable (VH) region comprising CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 176, and a light chain variable (VL) sequence comprising CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7.

16 . The bispecific antibody of claim 15 , wherein the first binding region comprises a VH region comprising the sequence set forth in SEQ ID NO: 177, and a VL region comprising the sequence set forth in SEQ ID NO: 8.

17 . A pharmaceutical composition comprising the bispecific antibody of claim 15 .

18 . A bispecific antibody comprising a first binding region of an antibody which binds to human CD3, and a second binding region which binds a different target than said first binding region, wherein the first binding region comprises a heavy chain variable (VH) region comprising CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NOs: 1, 2, and 184, and a light chain variable (VL) sequence comprising CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NO: 6, the sequence GTN, and SEQ ID NO: 7.

19 . The bispecific antibody of claim 18 , wherein the first binding region comprises a VH region comprising the sequence set forth in SEQ ID NO: 185, and a VL region comprising the sequence set forth in SEQ ID NO: 8.

20 . A pharmaceutical composition comprising the bispecific antibody of claim 18 .