Anti-c-Met Antibodies
AssigneeEli Lilly and Company
InventorsJulian Davies, Ling Liu, Jirong Lu
Life of this patent
Estimating the term…
Abstract
Provided is a monoclonal antibody, or antigen-binding fragment thereof that binds to c-Met. Such antibodies, or antigen-binding fragments thereof, are useful in in vivo, ex vivo or in vitro immunochemical and other imaging methods for detecting cell surface c-Met receptor levels for diagnostic, prognostic and predictive purposes, and for optimizing therapeutic regimens in patients harboring tumors in which c-Met is implicated in pathogenesis.
Claims22
1-40. (canceled)
An antibody, or an antigen-binding Fab fragment thereof, that specifically binds to the extracellular domain (ECD) of mature human c-Met consisting of amino acids 25-932 of SEQ ID NO:
- 19, the antibody or the Fab fragment comprising:
- i. light chain complementarity determining regions LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences SVSSSISSTNLH (SEQ ID NO:
- 1), GTSNLAS (SEQ ID NO:
- 2), and QQWSSYPYT (SEQ ID NO:
- 3), respectively;
- and
- ii. heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3 consisting of the amino acid sequences GYTFTSRYIH (SEQ ID NO:
- 4), WIYPVTGDTYYNEKFKG (SEQ ID NO:
- 5), and GGGMFYY (SEQ ID NO:
- 6), respectively.
A composition comprising:
- a. an antibody, or an antigen-binding Fab fragment thereof, that specifically binds to the extracellular domain (ECD) of mature human c-Met consisting of amino acids 25-932 of SEQ ID NO:
- 19, the antibody or the Fab fragment comprising:
- i. light chain complementarity determining regions LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences SVSSSISSTNLH (SEQ ID NO:
- 1), GTSNLAS (SEQ ID NO:
- 2), and QQWSSYPYT (SEQ ID NO:
- 3), respectively;
- and
- ii. heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3 consisting of the amino acid sequences GYTFTSRYIH (SEQ ID NO:
- 4), WIYPVTGDTYYNEKFKG (SEQ ID NO:
- 5), and GGGMFYY (SEQ ID NO:
- 6), respectively, and
- b. a diagnostically acceptable carrier, diluent, or excipient.
A method of detecting c-Met expressed by a human cell, the method comprising:
- (a) contacting said cell with an antibody, or an antigen-binding Fab fragment thereof, that specifically binds to the ECD of mature human c-Met consisting of amino acids 25-932 of SEQ ID NO:
- 19, the antibody or the Fab fragment comprising:
- i. light chain complementarity determining regions LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences SVSSSISSTNLH (SEQ ID NO:
- 1), GTSNLAS (SEQ ID NO:
- 2), and QQWSSYPYT (SEQ ID NO:
- 3), respectively;
- and
- ii. heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences GYTFTSRYIH (SEQ ID NO:
- 4), WIYPVTGDTYYNEKFKG (SEQ ID NO:
- 5), and GGGMFYY (SEQ ID NO:
- 6), respectively, for a time and under conditions that permit said antibody or the Fab fragment to bind to the ECD;
- (b) optionally, removing any non-specifically bound antibody or Fab fragment;
- and
- (c) detecting and/or quantifying the amount of the antibody or the Fab fragment which is specifically bound to the ECD.
A method of selecting a patient having a tumor suitable for treatment with an anti-c-Met therapeutic antibody or chemotherapeutic agent, comprising:
- (a) contacting at least one cell from said tumor with an antibody, or an antigen-binding Fab fragment thereof, that specifically binds to the ECD of mature human c-Met consisting of amino acids 25-932 of SEQ ID NO:
- 19, the antibody or the Fab fragment comprising:
- i. light chain complementarity determining regions LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences SVSSSISSTNLH (SEQ ID NO:
- 1), GTSNLAS (SEQ ID NO:
- 2), and QQWSSYPYT (SEQ ID NO:
- 3), respectively;
- and
- ii. heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences GYTFTSRYIH (SEQ ID NO:
- 4), WIYPVTGDTYYNEKFKG (SEQ ID NO:
- 5), and GGGMFYY (SEQ ID NO:
- 6), respectively, for a time and under conditions that permit said antibody, or the Fab fragment, to bind to the ECD;
- (b) optionally, removing any non-specifically bound antibody or Fab fragment;
- and
- (c) detecting and/or quantifying the amount of antibody or Fab fragment which is specifically bound to the ECD, wherein the presence of the antibody or Fab fragment specifically bound to the ECD identifies the patient as being appropriate for treatment with said anti-c-Met therapeutic antibody or chemotherapeutic agent.
Dependencies are inferred from the claim text.