Bispecific anti-Cmet/anti-Her2 antibodies
There are provided an anti-c-Met/anti-Her2 bispecific antibody, and a method for preventing and/or treating cancer using the same.
1. An anti-c-Met/anti-Her2 bispecific antibody comprising (a) an anti-c-Met antibody in an IgG form comprising six complementarity determining regions (CDRs), linked to (b) an antigen-binding fragment of an anti-Her2 antibody comprising six complementarity determining regions,
wherein the anti-c-Met antibody comprises:
(i) a heavy chain variable region comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2 and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and
(ii) a light chain variable region comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16.
2. The anti-c-Met/anti-Her2 bispecific antibody according to claim 1 , wherein the antigen-binding fragment is an scFv, (scFv)2, Fab, Fab′ or F(ab′) 2 .
3. The anti-c-Met/anti-Her2 bispecific antibody according to claim 1 , wherein the anti-c-Met antibody comprises:
(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 17, and
(ii) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 114, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO: 21.
4. The anti-c-Met/anti-Her2 bispecific antibody according to claim 1 , wherein the anti-c-Met antibody comprises:
(i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 62, the amino acid sequence from positions 18 to 462 of SEQ ID NO: 62, the amino acid sequence of SEQ ID NO: 64, the amino acid sequence from positions 18 to 461 of SEQ ID NO: 64, the amino acid sequence of SEQ ID NO: 66, or the amino acid sequence from positions 18 to 460 of SEQ ID NO: 66; and
(ii) a light chain comprising the amino acid sequence of SEQ ID NO: 68, the amino acid sequence from positions 21 to 240 of SEQ ID NO: 68, the amino acid sequence of SEQ ID NO: 70, the amino acid sequence from positions 21 to 240 of SEQ ID NO: 70.
5. The anti-c-Met/anti-Her2 bispecific antibody according to claim 1 , wherein the anti-c-Met antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 66 or the amino acid sequence from positions 18 to 460 of SEQ ID NO: 66, and a light chain comprising the amino acid sequence of SEQ ID NO: 68 or the amino acid sequence from positions 21 to 240 of SEQ ID NO: 68.
6. The anti-c-Met/anti-Her2 bispecific antibody according to claim 1 , wherein the anti-Her2 antigen binding fragment is an antigen binding fragment from Trastuzumab or Pertuzumab.
7. The anti-c-Met/anti-Her2 bispecific antibody according to claim 1 , wherein the antigen-binding fragment of the anti-Her2 antibody is covalently linked to the C-terminus of the anti-c-Met antibody.
8. The anti-c-Met/anti-Her2 bispecific antibody according to claim 7 , wherein the antigen-binding fragment of the anti-Her2 antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 109 and a light chain variable region comprising the sequence of SEQ ID NO: 111.
9. A pharmaceutical composition comprising the anti-c-Met/anti-Her2 bispecific antibody according to claim 1 and a pharmaceutically acceptable carrier.
10. A method of treatment of a cancer, comprising administering the anti-c-Met/anti-Her2 bispecific antibody of claim 1 to a patient in need thereof.