Anti-c-Met/anti-Ang2 bispecific antibody
An anti-c-Met/anti-Ang2 bispecific antibody including (a) an anti-c-Met antibody or antigen-binding fragment thereof and (b) an anti-Ang2 antibody or antigen-binding fragment thereof, a pharmaceutical composition including the anti-c-Met/anti-Ang2 bispecific antibody, and a method using the anti-c-Met/anti-Ang2 bispecific antibody.
1. An anti-c-Met/anti-Ang2 bispecific antibody comprising (a) an anti-c-Met antibody or antigen-binding fragment thereof and (b) an anti-Ang2 antibody or antigen-binding fragment thereof, wherein
the anti-c-Met antibody or antigen-binding fragment thereof comprises (i) a heavy chain variable region comprising (a) a CDR-H1 comprising SEQ ID NO: 1, 22, 23, or 24, (b) a CDR-H2 comprising SEQ ID NO: 2, 25, or 26, and (c) a CDR-H3 comprising SEQ ID NO: 3, 27, 28, or 85, and (ii) a light chain variable region comprising (a) a CDR-L1 comprising an SEQ ID NO: 10, 29, 30, 31, 32, 33 or 106, (b) a CDR-L2 comprising SEQ ID NO: 11, 34, 35, or 36, and (c) a CDR-L3 comprising SEQ ID NO: 12, 13, 14, 15, 16, 37, 86, or 89;
and the anti-Ang-2 antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region comprising (a) a CDR-H1 comprising SEQ ID NO: 109, (b) a CDR-H2 comprising SEQ ID NO: 128, and (c) a CDR-H3 comprising SEQ ID NO: 111, and (ii) a light chain variable region comprising a CDR-L1 comprising SEQ ID NO: 129, a CDR-L2 comprising SEQ ID NO: 130, and a CDR-L3 comprising SEQ ID NO: 131.
2. The anti-c-Met/anti-Ang2 bispecific antibody of claim 1 , wherein the anti-Ang2 antibody or antigen-binding fragment thereof comprises:
a heavy chain variable region comprising a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 110, and a CDR-H3 comprising SEQ ID NO: 111; and
a light chain variable region comprising a CDR-L1 comprising SEQ ID NO: 112, a CDR-L2 comprising SEQ ID NO: 113, and a CDR-L3 comprising SEQ ID NO: 114.
3. The anti-c-Met/anti-Ang2 bispecific antibody of claim 2 , wherein the anti-Ang2 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising SEQ ID NO: 115 and a light chain variable region comprising SEQ ID NO: 117.
4. The anti-c-Met/anti-Ang2 bispecific antibody of claim 1 , wherein the anti-Ang2 antibody or antigen-binding fragment thereof comprises:
a heavy chain variable region comprising a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 128, and a CDR-H3 comprising SEQ ID NO: 111; and
a light chain variable region comprising a CDR-L1 comprising SEQ ID NO: 129, a CDR-L2 comprising SEQ ID NO: 130, and a CDR-L3 comprising SEQ ID NO: 131,
with the proviso that an anti-Ang2 antibody or an antigen-binding fragment thereof does not comprise a heavy chain variable region comprising a CDR-H1 of SEQ ID NO: 109, a CDR-H2 of SEQ ID NO: 110, and a CDR-H3 of SEQ ID NO: 111, and a light chain variable region comprising a CDR-L1 of SEQ ID NO: 112, a CDR-L2 of SEQ ID NO: 113, and a CDR-L3 of SEQ ID NO: 114.
5. The anti-c-Met/anti-Ang2 bispecific antibody of claim 4 , wherein the anti-Ang2 antibody or antigen-binding fragment thereof comprises:
a heavy chain variable region comprising a CDR-H1 comprising SEQ ID NO: 109, a CDR-H2 comprising SEQ ID NO: 122 or 123, and a CDR-H3 comprising SEQ ID NO: 111; and
a light chain variable region comprising a CDR-L1 comprising SEQ ID NO: 112, 124, or 125, a CDR-L2 comprising SEQ ID NO: 113 or 126, and a CDR-L3 comprising SEQ ID NO: 114 or 127,
with the proviso that an anti-Ang2 antibody or an antigen-binding fragment thereof does not comprise a heavy chain variable region comprising a CDR-H1 of SEQ ID NO: 109, a CDR-H2 of SEQ ID NO: 110, and a CDR-H3 of SEQ ID NO: 111, and a light chain variable region comprising a CDR-L1 of SEQ ID NO: 112, a CDR-L2 of SEQ ID NO: 113, and a CDR-L3 of SEQ ID NO: 114.
6. The anti-c-Met/anti-Ang2 bispecific antibody of claim 5 , wherein the anti-Ang2 antibody or antigen-binding fragment thereof comprises:
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 160, 161, 162, 163, or 164, and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165, 166, 167, 168, 169, 170, or 171.
7. The anti-c-Met/anti-Ang2 bispecific antibody of claim 1 , wherein the anti-c-Met antibody or antigen-binding fragment thereof comprises:
a heavy chain variable region comprising SEQ ID NO: 17, 74, 87, 90, 91, 92, 93, or 94; and
a light chain variable region comprising SEQ ID NO: 196, 18, 19, 20, 21, 75, 88, 95, 96, 97, 98, 99, or 107.
8. A recombinant nucleic acid encoding the anti-c-Met/anti-Ang2 bispecific antibody of claim 1 .
9. The recombinant nucleic acid of claim 8 , wherein the recombinant nucleic acid is in an isolated vector.
10. The recombinant nucleic acid of claim 8 , wherein the recombinant nucleic acid is in an isolated cell.
11. A method of preparing an anti-c-Met/anti-Ang2 bispecific antibody of claim 1 by expressing a nucleic acid encoding the anti-c-Met/anti-Ang2 bispecific antibody in a cell and isolating the bispecific antibody from the cell.
12. A method of treating a disease associated with overexpression of c-Met or Ang2 in a subject, comprising administering the anti-c-Met/anti-Ang2 bispecific antibody of claim 1 to the subject, wherein the disease associated with overexpression of c-Met or Ang2 is lung cancer, gastric cancer, or ovarian cancer.
13. The method of claim 12 , further comprising administering Ang2 to the subject.