Anti-cMET antibody
The invention relates to a novel antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region. The invention also relates to a composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.
1 . A pharmaceutical composition comprising ( 1 ) a monoclonal antibody comprising:
a heavy chain comprising complementarity determining regions (CDR) CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID NOs: 1, 2, and 3, respectively;
a light chain comprising CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences SEQ ID NOs: 5, 6, and 7; and
a modified hinge region comprising the amino acid sequence SEQ ID NO: 28;
wherein the monoclonal antibody is chemically coupled to a mitotic inhibitor; and
(2) a kinase inhibitor.
2 . The pharmaceutical composition of claim 1 , wherein the monoclonal antibody comprises:
a heavy chain variable domain comprising the amino acid sequence SEQ ID NO: 4; and
a light chain variable domain comprising amino acid sequence SEQ ID NO: 10.
3 . The pharmaceutical composition of claim 1 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
4 . The pharmaceutical composition of claim 3 , wherein the human light chain constant region is of the IgG2 kappa isotype.
5 . The pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable vehicle.
6 . A method of treating non-small cell lung cancer in a subject in need thereof, the method comprising administering to the subject:
(1) a therapeutically effective amount of a monoclonal antibody comprising:
a heavy chain comprising complementarity determining regions (CDR) CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID NOs: 1, 2, and 3, respectively;
a light chain comprising CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences SEQ ID NOs: 5, 6, and 7; and
a modified hinge region comprising the amino acid sequence SEQ ID NO: 28, wherein the monoclonal antibody is chemically coupled to a mitotic inhibitor; and
(2) a kinase inhibitor.
7 . The method of claim 6 , wherein the monoclonal antibody comprises:
a heavy chain variable domain comprising the amino acid sequence SEQ ID NO: 4; and
a light chain variable domain comprising amino acid sequence SEQ ID NO: 10.