Anti-HER2 antibody and anti-c-Met/anti-HER2 bispecific antibodies comprising the same
An anti-HER2 antibody, an anti-c-Met/anti-HER2 bispecific antibody including the same, method for preparing same, and a method of preventing and/or treating a cancer using the same are provided.
1. An anti-HER2 antibody or an antigen-binding fragment thereof, comprising:
(1) a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 112, and a CDR-H3 comprising SEQ ID NO: 115; and
a CDR-L1 comprising SEQ ID NO: 120, a CDR-L2 comprising SEQ ID NO: 124, and a CDR-L3 comprising SEQ ID NO: 127; or
(2) a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 112, and a CDR-H3 comprising SEQ ID NO: 116; and
a CDR-L1 comprising SEQ ID NO: 121, a CDR-L2 comprising SEQ ID NO: 124, and a CDR-L3 comprising SEQ ID NO: 128;
(3) a CDR-H1 comprising SEQ ID NO: 110, a CDR-H2 comprising SEQ ID NO: 113, and a CDR-H3 comprising SEQ ID NO: 117; and
a CDR-L1 comprising SEQ ID NO: 122, a CDR-L2 comprising SEQ ID NO: 125, and a CDR-L3 comprising SEQ ID NO: 129;
(4) a CDR-H1 comprising SEQ ID NO: 111, a CDR-H2 comprising SEQ ID NO: 114, and a CDR-H3 comprising SEQ ID NO: 118; and
a CDR-L1 comprising SEQ ID NO: 123, a CDR-L2 comprising SEQ ID NO: 126, and a CDR-L3 comprising SEQ ID NO: 130;
or
(5) a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 112, and a CDR-H3 comprising SEQ ID NO: 119; and
a CDR-L1 comprising SEQ ID NO: 120, a CDR-L2 comprising SEQ ID NO: 124, and a CDR-L3 comprising SEQ ID NO: 131.
2. The anti-HER2 antibody or the antigen-binding fragment thereof of claim 1 , comprising:
(1) a heavy chain variable region comprising SEQ ID NO: 132, and
a light chain variable region comprising SEQ ID NO: 137;
(2) a heavy chain variable region comprising SEQ ID NO: 133, and
a light chain variable region comprising SEQ ID NO: 138;
(3) a heavy chain variable region comprising SEQ ID NO: 134, and
a light chain variable region comprising SEQ ID NO: 139;
(4) a heavy chain variable region comprising SEQ ID NO: 135, and
a light chain variable region comprising SEQ ID NO: 140;
or
(5) a heavy chain variable region comprising SEQ ID NO: 136, and
a light chain variable region SEQ ID NO: 141.
3. The anti-HER2 antibody or the antigen-binding fragment thereof of claim 2 , wherein the anti-HER2 antibody or the antigen binding fragment is an anti-HER2 scFv.
4. An anti-c-Met/anti-HER2 bispecific antibody comprising
(1) an anti-c-Met antibody or an antigen-binding fragment thereof and
(2) an anti-HER2 antibody or an antigen-binding fragment thereof of claim 1 .
5. The anti-c-Met/anti-HER2 bispecific antibody of claim 4 , wherein the anti-c-Met antibody or the antigen-binding fragment thereof comprises:
(1) a CDR-H1 comprising SEQ ID NO: 1;
a CDR-H2 comprising SEQ ID NO: 2;
a CDR-H3 comprising SEQ ID NO: 3;
a CDR-L1 comprising SEQ ID NO: 10;
a CDR-L2 comprising SEQ ID NO: 11; and
a CDR-L3 comprising SEQ ID NO: 13, 14, 15, or 16;
or
(2) a CDR-H1 comprising SEQ ID NO: 1;
a CDR-H2 comprising SEQ ID NO: 2;
a CDR-H3 comprising SEQ ID NO: 3;
a CDR-L1 comprising SEQ ID NO: 106;
a CDR-L2 comprising SEQ ID NO: 11; and
a CDR-L3 comprising SEQ ID NO: 13.
6. The anti-c-Met/anti-HER2 bispecific antibody of claim 5 , 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, and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 162, 18, 19, 20, 21, or 107.
7. The anti-c-Met/anti-HER2 bispecific antibody of claim 5 , 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 an amino acid sequence selected from the group consisting of SEQ ID NO: 68, the amino acid sequence from the 21 st to 240 th positions of SEQ ID NO: 68, SEQ ID NO: 70, the amino acid sequence from the 21 st to 240 th positions of SEQ ID NO: 70, and SEQ ID NO: 108.
8. The anti-c-Met/anti-HER2 bispecific antibody of claim 4 , wherein the anti-HER2 antibody or the antigen-binding fragment thereof comprises:
(1) a heavy chain variable region comprising SEQ ID NO: 132, and
a light chain variable region comprising SEQ ID NO: 137;
(2) a heavy chain variable region SEQ ID NO: 133, and
a light chain variable region comprising SEQ ID NO: 138;
(3) a heavy chain variable region comprising SEQ ID NO: 134, and
a light chain variable region comprising SEQ ID NO: 139;
(4) a heavy chain variable region comprising SEQ ID NO: 135, and
a light chain variable region comprising SEQ ID NO: 140; or
(5) a heavy chain variable region comprising SEQ ID NO: 136, and
a light chain variable region comprising SEQ ID NO: 141.
9. The anti-c-Met/anti-HER2 bispecific antibody of claim 4 , wherein the antigen-binding fragment of the anti-HER2 antibody is an anti-HER2 scFv, and the anti-HER2 scFv is linked to C-terminus of the anti-c-Met antibody.
10. A method of treating a cancer comprising administering the anti-HER2 antibody or the antigen-binding fragment thereof of claim 1 to a subject in need of cancer treatment.
11. A method of treating a cancer comprising administering the anti-c-Met/anti-HER2 bispecific antibody of claim 4 to a subject in need of cancer treatment.
12. A pharmaceutical composition comprising the anti-HER2 antibody or the antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising the anti-c-Met/anti-HER2 bispecific antibody of claim 4 and a pharmaceutically acceptable carrier.
14. The anti-HER2 antibody or the antigen-binding fragment thereof of claim 1 , comprising:
a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 112, and a CDR-H3 comprising SEQ ID NO: 115; and
a CDR-L1 comprising SEQ ID NO: 120, a CDR-L2 comprising SEQ ID NO: 124, and a CDR-L3 comprising SEQ ID NO: 127.
15. The anti-HER2 antibody or the antigen-binding fragment thereof of claim 1 , comprising:
a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 112, and a CDR-H3 comprising SEQ ID NO: 116; and
a CDR-L1 comprising SEQ ID NO: 121, a CDR-L2 comprising SEQ ID NO: 124, and a CDR-L3 comprising SEQ ID NO: 128.
16. The anti-HER2 antibody or the antigen-binding fragment thereof of claim 1 , comprising:
a CDR-H1 comprising SEQ ID NO: 110, a CDR-H2 comprising SEQ ID NO: 113, and a CDR-H3 comprising SEQ ID NO: 117; and
a CDR-L1 comprising SEQ ID NO: 122, a CDR-L2 comprising SEQ ID NO: 125, and a CDR-L3 comprising SEQ ID NO: 129.
17. The anti-HER2 antibody or the antigen-binding fragment thereof of claim 1 , comprising:
a CDR-H1 comprising SEQ ID NO: 111, a CDR-H2 comprising SEQ ID NO: 114, and a CDR-H3 comprising SEQ ID NO: 118; and
a CDR-L1 comprising SEQ ID NO: 123, a CDR-L2 comprising SEQ ID NO: 126, and a CDR-L3 comprising SEQ ID NO: 130.
18. The anti-HER2 antibody or the antigen-binding fragment thereof of claim 1 , comprising:
a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 112, and a CDR-H3 comprising SEQ ID NO: 119; and
a CDR-L1 comprising SEQ ID NO: 120, a CDR-L2 comprising SEQ ID NO: 124, and a CDR-L3 comprising SEQ ID NO: 131.