Anti-EGFR antibody and anti-c-Met/anti-EGFR bispecific antibodies comprising the same
An anti-EGFR scFV fragment, an anti-c-Met/anti-EGFR bispecific antibody including the same, and a method of preventing and/or treating a cancer using the same are provided.
1. An anti-EGFR antibody or an antigen-binding fragment thereof, comprising:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 111;
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 114.
2. The anti-EGFR antibody or an antigen-binding fragment thereof according to claim 1 , comprising:
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 115 or SEQ ID NO: 117,
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 116 or SEQ ID NO: 118, or
a combination thereof.
3. The anti-EGFR antibody or an antigen-binding fragment thereof according to claim 2 , wherein the anti-EGFR antibody or an antigen-binding fragment is an anti-EGFR scFv comprising:
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 115 or SEQ ID NO: 117, and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 116 or SEQ ID NO: 118.
4. An anti-c-Met/anti-EGFR bispecific antibody comprising an anti-c-Met antibody or an antigen-binding fragment thereof and an anti-EGFR antibody or an antigen-binding fragment thereof, wherein
the anti-c-Met antibody or an 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; and
the anti-EGFR antibody or an antigen-binding fragment thereof comprises:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 109, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 110, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 111;
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 112, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 114.
5. The anti-c-Met/anti-EGFR bispecific antibody according to claim 4 , wherein the antigen-binding fragment of the anti-c-Met antibody or the anti-EGFR antibody is selected from the group consisting of scFv, (scFv)2, scFvFc, Fab, Fab′, and F(ab′)2.
6. The anti-c-Met/anti-EGFR bispecific antibody according to claim 4 , wherein the anti-c-Met antibody 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, 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, SEQ ID NO: 37.
7. The anti-c-Met/anti-EGFR 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,
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 121, or
a combination of the heavy chain variable region and the light chain variable region.
8. The anti-c-Met/anti-EGFR bispecific antibody according to claim 4 , wherein the anti-c-Met antibody comprises:
a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 62, the amino acid sequence from the 18 th to 462 nd positions of SEQ ID NO: 62, SEQ ID NO: 64, the amino acid sequence from the 18 th to 461 st positions of SEQ ID NO: 64, 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 SEQ ID NO: 68, the amino acid sequence from the 20 to 240 th positions of SEQ ID NO: 68, SEQ ID NO: 70, the amino acid sequence from the 20 to 240 th positions of SEQ ID NO: 70, and SEQ ID NO: 108.
9. The anti-c-Met/anti-EGFR bispecific antibody according to claim 4 , wherein the anti-EGFR antibody or the antigen-binding fragment thereof comprises:
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 115 or SEQ ID NO: 117,
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 116 or SEQ ID NO: 118, or
a combination thereof.
10. The anti-c-Met/anti-EGFR bispecific antibody according to claim 4 , wherein the anti-EGFR antibody or the antigen-binding fragment thereof is linked to C-terminus of the anti-c-Met antibody.
11. A pharmaceutical composition comprising the anti-EGFR antibody or the antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
12. A pharmaceutical composition comprising the anti-c-Met/anti-EGFR bispecific antibody of claim 4 and a pharmaceutically acceptable carrier.
13. The anti-c-Met/anti-EGFR 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 121;
and the anti-EGFR antibody or the antigen-binding fragment thereof comprises:
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 115 or SEQ ID NO: 117, and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 116 or SEQ ID NO: 118.