Anti-Her3 scFV fragment and bispecific anti-c-Met/anti-Her3 antibodies comprising the same

1. An anti-Her3 antibody or an antigen-binding fragment thereof, comprising:

a heavy chain variable region comprising the complementarity determining regions:

CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109,

CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and

CDR-H3 comprising the amino acid sequence of SEQ ID NO: 111,

and a light chain variable region comprising the complementarity determining regions:

CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112,

CDR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and

CDR-L3 comprising the amino acid sequence of SEQ ID NO: 114.

2. The anti-Her3 antibody or an antigen-binding fragment thereof according to claim 1 wherein:

the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 115,

the light chain variable region comprises the amino acid sequence of SEQ ID NO: 116, or

a combination thereof.

3. The anti-Her3 antibody or an antigen-binding fragment thereof according to claim 2 , wherein the anti-Her3 antibody or an antigen-binding fragment thereof is a Her3 scFv wherein:

the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 115,

the light chain variable region comprises the amino acid sequence of SEQ ID NO: 116, or

a combination thereof.

4. An anti-c-Met/anti-Her3 bispecific antibody comprising an anti-c-Met antibody or an antigen-binding fragment thereof and an anti-Her3 antibody or an antigen-binding fragment thereof, wherein

the anti-c-Met antibody or an antigen-binding fragment thereof binds to an epitope comprising 5 to 19 contiguous amino acids within SEQ ID NO: 71 comprising the amino acid sequence of SEQ ID NO: 73, and

the anti-Her3 antibody or an antigen-binding fragment thereof comprises:

a heavy chain variable region comprising the complementarity determining regions:

CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109,

CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, and

CDR-H3 comprising the amino acid sequence of SEQ ID NO: 111;

and a light chain variable region comprising the complementarity determining regions:

CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112,

CDR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and

CDR-L3 comprising the amino acid sequence of SEQ ID NO: 114.

5. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein the bispecific antibody comprises an anti-c-Met antigen-binding antibody fragment selected from the group consisting of scFv, (scFv)2, scFvFc, Fab, Fab′, and F(ab′)2; an anti-Her3 antigen-binding antibody fragment selected from the group consisting of scFv, (scFv)2, scFvFc, Fab, Fab′, and F(ab)2; or both.

6. The anti-c-Met/anti-Herb bispecific antibody according to claim 4 , wherein the anti-c-Met antibody or the antigen-binding fragment thereof comprises:

a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4,

a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 2,

a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 3,

a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 7,

a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 8, and

a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 15.

7. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein the anti-c-Met antibody or the antigen-binding fragment thereof comprises

a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24,

a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 25, or SEQ ID NO: 26,

a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 27, or SEQ ID NO: 28,

a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 106,

a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and

a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 37.

8. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein the anti-c-Met antibody or the antigen-binding fragment thereof comprises:

a heavy chain variable region comprising a polypeptide (CDR-H1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 22, 23, and 24, a polypeptide (CDR-H2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 2, 25, and 26, and a polypeptide (CDR-H3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 27, and 28; and

a light chain variable region comprising a polypeptide (CDR-L1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 10, 29, 30, 31, 32, 33 and 106, a polypeptide (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 11, 34, 35, and 36, and a polypeptide (CDR-L3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 12, 13, 14, 15, 16, and 37.

9. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein the anti-c-Met antibody or the antigen-binding fragment thereof comprises:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 17, 74, 87, 90, 91, 92, 93, or 94, and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 18, 19, 20, 21, 75, 88, 95, 96, 97, 98, 99, 107, or 119.

10. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein the anti-c-Met antibody comprises:

a heavy chain comprising the amino acid sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 62, the amino acid sequence from the 18 th to 462 nd positions of SEQ ID NO: 62, the amino acid sequence of SEQ ID NO: 64, the amino acid sequence from the 18 th to 461 st positions of SEQ ID NO: 64, the amino acid sequence of SEQ ID NO: 66, and the amino acid sequence from the 18 th to 460 th positions of SEQ ID NO: 66; and

a light chain comprising the amino acid sequence selected from the group consisting of the amino acid sequence of SEQ ID NO: 68, the amino acid sequence from the 21 st to 240 th positions of SEQ ID NO: 68, the amino acid sequence of SEQ ID NO: 70, the amino acid sequence from the 21 st to 240 th positions of SEQ ID NO: 70, and the amino acid sequence of SEQ ID NO: 108.

11. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein the anti-c-Met antibody comprises a heavy chain consisting of the amino acid sequence from the 18 th to 460 th positions of SEQ ID NO: 66, and a light chain consisting of the amino acid sequence from the 21 st to 240 th positions of SEQ ID NO: 68.

12. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein:

the heavy chain variable region of the anti-Her3 antibody or the antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 115,

the light chain variable region of the anti-Her3 antibody or the antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 116, or

a combination thereof.

13. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein anti-c-Met/anti-Her3 bispecific antibody comprises the anti-c-Met antibody and the anti-Her3 antibody or the antigen-binding fragment thereof which is linked to C-terminus of the anti-c-Met antibody.

14. The anti-c-Met/anti-Her3 bispecific antibody according to claim 4 , wherein the anti-c-Met antibody and anti-Her3 antibody are humanized or human antibodies.

15. A pharmaceutical composition comprising the anti-Her3 antibody or the antigen-binding fragment thereof according to claim 1 and a carrier.

16. A pharmaceutical composition comprising the anti-c-Met/anti-Her3 bispecific antibody or the antigen-binding fragment thereof according to claim 4 and a carrier.

17. A method of treating a cancer which expresses c-Met and Her3, the method comprising administering the anti-c-Met/anti-Her3 bispecific antibody or the antigen-binding fragment thereof according to claim 4 to a subject in need of treating a cancer.

18. The anti-c-Met/anti-Her3 bispecific antibody according to claim 7 , wherein the anti-c-Met antibody or the antigen-binding fragment thereof comprises:

a heavy chain variable region comprising the amino acid sequence of the 18 th to 460 th positions of SEQ ID NO: 66 and a light chain variable region comprising the amino acid sequence of the 21 st to 240 th positions of SEQ ID NO: 68.