Anti-c-Met/anti-EGFR bispecific antibodies
There are provided an anti-c-Met/anti-EGFR bispecific antibody, a method for treating cancer using the same, and an anti-EGFR scFv fragment.
1. An anti-c-Met/anti-EGFR bispecific antibody comprising (a) an anti-c-Met antibody or an antigen-binding fragment thereof and (b) an anti-EGFR antibody or an antigen-binding fragment thereof,
wherein the anti-c-Met antibody or the antigen-binding fragment thereof comprises:
(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3,
(d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 37.
2. The anti-c-Met/anti-EGFR bispecific antibody according to claim 1 , wherein the antigen-binding fragment is scFv, (scFv)2, scFvFc, Fab, Fab′ or F(ab′) 2 .
3. The anti-c-Met/anti-EGFR bispecific antibody according to claim 1 , wherein the anti-c-Met antibody or the antigen-binding fragment thereof comprises:
(i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 62, the amino acid sequence from the 18 th to 462 nd positions of the amino acid sequence 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 the amino acid sequence of SEQ ID NO: 64, the amino acid sequence of SEQ ID NO: 66, or the amino acid sequence from the 18 th to 460 th positions of the amino acid sequence 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 the 21 st to 240 th positions of the amino acid sequence of SEQ ID NO: 68, the amino acid sequence of SEQ ID NO: 70, or the amino acid sequence from the 21 st to 240 th positions of the amino acid sequence of SEQ ID NO: 70.
4. The anti-c-Met/anti-EGFR bispecific antibody according to claim 1 , wherein the antigen-binding fragment of the anti-EGFR antibody is:
(a) an antigen binding fragment of Cetuximab,
(b) an antigen binding fragment of Panitumumab, or
(c) an antigen binding fragment comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 109 or SEQ ID NO: 113, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 111 or SEQ ID NO: 114.
5. The anti-c-Met/anti-EGFR bispecific antibody according to claim 1 , comprising an anti-c-Met antibody and an antigen-binding fragment of an anti-EGFR antibody, wherein the antigen-binding fragment of the anti-EGFR antibody is coupled to the C terminus of the anti-c-Met antibody.
6. A method of treatment of a cancer, comprising administering the anti-c-Met/anti-EGFR bispecific antibody of claim 1 to a patient in need thereof.
7. The method according to claim 6 , wherein the antigen-binding fragment is scFv, (scFv)2, scFvFc, Fab, Fab′ or F(ab′) 2 of the antibody.
8. The method according to claim 6 , wherein the antigen-binding fragment of the anti-EGFR antibody is
(a) an antigen binding fragment of Cetuximab,
(b) an antigen binding fragment of Panitumumab, or
(c) an antigen binding fragment comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 109 or SEQ ID NO: 113, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 111 or SEQ ID NO: 114.
9. The method according to claim 6 , wherein the anti-c-Met/anti-EGFR bispecific antibody comprises an anti-c-Met antibody and an antigen-binding fragment of an anti-EGFR antibody, wherein the antigen-binding fragment of the anti-EGFR antibody is coupled to the C terminus of the anti-c-Met antibody.