Use of Cbl as biomarker for identifying subject suitable for treatment with anti-c-Met antibody

摘要

A method of identifying a cell sample or a subject suitable for treatment with an anti-c-Met antibody or antigen binding fragment thereof that specifically binds to an epitope within a SEMA domain of a c-Met protein by determining a Cbl concentration, a Cbl mutation, and/or a mutation of a site of c-Met for interaction with Cbl in a cell sample from a subject, as well as related compositions and methods.

主权项

1. A method of identifying a subject suitable for treatment with an anti-c-Met antibody or antigen binding fragment thereof that specifically binds to an epitope within a SEMA domain of a c-Met protein, the method comprising:
(1) determining a Cbl concentration, a Cbl mutation, and/or a mutation of a site of c-Met for interaction with Cbl in a cell sample from a subject; (2) determining that the subject is suitable for treatment with the anti-c-Met antibody when Cbl is present at a low level or absent in the cell sample or when Cbl or c-Met contains a mutation that inhibits interaction between Cbl and c-Met; and (3) administering the anti-c-Met antibody or antigen-binding fragment thereof to the subject determined to be suitable for treatment, wherein the anti-c-Met antibody or antigen-binding fragment thereof comprises SEQ ID NOs: 1-3, 10, 11, and 13, specifically binds to an epitope having 5 to 19 consecutive amino acids of SEQ ID NO: 71 that includes the amino sequence of SEQ ID NO: 73 (EEPSQ), and promotes LRIG1-mediated c-Met degradation.