Radiolabeled MET binding proteins for immuno-PET imaging and methods of use thereof
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsMarcus Kelly, Dangshe Ma, William Olson
Life of this patent
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Abstract
Radiolabeled anti-MET antibodies and MET×MET bispecific antibodies and their use in immuno-PET imaging are provided herein. Included are methods of detecting the presence of MET proteins in a subject or sample and methods of monitoring efficacy of treatment of a Met expressing tumor.
Claims47
A radiolabeled antibody conjugate comprising:
- (a) an antibody or antigen-binding fragment thereof that binds MET, wherein the antibody or antigen-binding fragment thereof comprises:
- (i) three heavy chain complementarity determining regions (HCDRs) in a heavy chain variable region (HCVR) having an amino acid sequence selected from the group consisting of SEQ ID NO:
- 2, 10, 18, 26, 34, 42, 50, 58, 66, 74, 82, 90, 98, 106, 114, 122, and 130;
- and (ii) three light chain complementarity determining regions (LCDRs) in a light chain variable region (LCVR) having an amino acid sequence of SEQ ID NO:
- 138,
- (b) a chelating moiety, and
- (c) a positron emitter.
A radiolabeled antibody conjugate comprising:
- (a) an antibody or antigen-binding fragment thereof that binds MET, wherein the antibody comprises three heavy chain complementarity determining regions (HCDRs) in a heavy chain variable region (HCVR), wherein the HCVR has an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2, 10, 18, 26, 34, 42, 50, 58, 66, 74, 82, 90, 98, 106, 114, 122, and 130;
- and three light chain complementarity determining regions (LCDRs) in a light chain variable region (LCVR), wherein the LCVR has an amino acid sequence of SEQ ID NO:
- 138,
- (b) a chelating moiety, and
- (c) a positron emitter.
A method for treating a subject having a solid tumor comprising:
- (a) determining that the solid tumor is MET-positive, comprising:
- (i) administering a radiolabeled antibody conjugate to the subject in need thereof, wherein the conjugate comprises:
- an antibody or antigen-binding fragment thereof that binds MET, wherein the antibody or antigen-binding fragment thereof comprises three HCDRs in an HCVR having an amino acid sequence selected from the group consisting of SEQ ID NO:
- 2, 10, 18, 26, 34, 42, 50, 58, 66, 74, 82, 90, 98, 106, 114, 122, and 130;
- and three LCDRs in an LCVR having an amino acid sequence of SEQ ID NO:
- 138;
- and
- (ii) imaging localization of the radiolabeled antibody conjugate in the tumor by positron emission tomography (PET) imaging, wherein presence of the radiolabeled antibody conjugate in the tumor indicates that the tumor is MET-positive;
- and
- (b) administering one or more doses of an inhibitor of the HGF/MET signaling pathway to the subject in need thereof.
A compound of Formula (III):
- wherein A is an antibody or antigen binding fragment thereof that binds MET and k is an integer from 1-30;
- wherein the antibody or antigen-binding fragment thereof comprises three HCDRs in an HCVR having an amino acid sequence selected from the group consisting of SEQ ID NO:
- 2, 10, 18, 26, 34, 42, 50, 58, 66, 74, 82, 90, 98, 106, 114, 122, and 130;
- and three LCDRs in an LCVR having an amino acid sequence of SEQ ID NO:
- 138.
An antibody conjugate comprising (i) an antibody or antigen-binding fragment thereof that binds MET, wherein the antibody or antigen-binding fragment thereof comprises three HCDRs in an HCVR having an amino acid sequence selected from the group consisting of SEQ ID NO:
- 2, 10, 18, 26, 34, 42, 50, 58, 66, 74, 82, 90, 98, 106, 114, 122, and 130;
- and three LCDRs in an LCVR having an amino acid sequence of SEQ ID NO:
- 138;
- and (ii) one or more chelating moieties.
Dependencies are inferred from the claim text.