Eribulin antibody-drug conjugates and methods of use

A method of treating a subject having or suspected of having a cancer, comprising administering to the subject a therapeutically effective amount of an antibody-drug conjugate of Formula (I):

• wherein
• Ab is an antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment is capable of binding to mesothelin and comprises three heavy chain complementarity determining regions comprising the amino acid sequences of SEQ ID NO:
• 1 (HCDR1), SEQ ID NO:
• 2 (HCDR2), and SEQ ID NO:
• 3 (HCDR3);
• and three light chain complementarity determining regions comprising amino acid sequences of SEQ ID NO:
• 4 (LCDR1), SEQ ID NO:
• 5 (LCDR2), and SEQ ID NO:
• 6 (LCDR3), as defined by the Kabat numbering system;
• or three heavy chain complementarity determining regions comprising amino acid sequences of SEQ ID NO:
• 7 (HCDR1), SEQ ID NO:
• 8 (HCDR2), and SEQ ID NO:
• 9 (HCDR3);
• and three light chain complementarity determining regions comprising the amino acid sequences of SEQ ID NO:
• 10 (LCDR1), SEQ ID NO:
• 11 (LCDR2), and SEQ ID NO:
• 12 (LCDR3), as defined by the IMGT numbering system;
• D is a therapeutic agent;
• L is a cleavable linker that covalently attaches Ab to D;
• and
• p is an integer from 1 to 8.

A method of reducing or slowing the growth of a cancer cell population in a subject, comprising administering to the subject a therapeutically effective amount of an antibody-drug conjugate of Formula (I):

• wherein
• Ab is an antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment is capable of binding to mesothelin and comprises three heavy chain complementarity determining regions comprising the amino acid sequences of SEQ ID NO:
• 1 (HCDR1), SEQ ID NO:
• 2 (HCDR2), and SEQ ID NO:
• 3 (HCDR3);
• and three light chain complementarity determining regions comprising amino acid sequences of SEQ ID NO:
• 4 (LCDR1), SEQ ID NO:
• 5 (LCDR2), and SEQ ID NO:
• 6 (LCDR3), as defined by the Kabat numbering system;
• or three heavy chain complementarity determining regions comprising the amino acid sequences of SEQ ID NO:
• 7 (HCDR1), SEQ ID NO:
• 8 (HCDR2), and SEQ ID NO:
• 9 (HCDR3);
• and three light chain complementarity determining regions comprising amino acid sequences of SEQ ID NO:
• 10 (LCDR1), SEQ ID NO:
• 11 (LCDR2), and SEQ ID NO:
• 12 (LCDR3), as defined by the IMGT numbering system;
• D is a therapeutic agent;
• L is a cleavable linker that covalently attaches Ab to D;
• and
• p is an integer from 1 to 8.

A method of producing an antibody-drug conjugate of Formula (I):

• wherein
• Ab is an antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment is capable of binding to mesothelin and comprises three heavy chain complementarity determining regions comprising the amino acid sequences of SEQ ID NO:
• 1 (HCDR1), SEQ ID NO:
• 2 (HCDR2), and SEQ ID NO:
• 3 (HCDR3);
• and three light chain complementarity determining regions comprising amino acid sequences of SEQ ID NO:
• 4 (LCDR1), SEQ ID NO:
• 5 (LCDR2), and SEQ ID NO:
• 6 (LCDR3), as defined by the Kabat numbering system;
• or three heavy chain complementarity determining regions comprising the amino acid sequences of SEQ ID NO:
• 7 (HCDR1), SEQ ID NO:
• 8 (HCDR2), and SEQ ID NO:
• 9 (HCDR3);
• and three light chain complementarity determining regions comprising amino acid sequences of SEQ ID NO:
• 10 (LCDR1), SEQ ID NO:
• 11 (LCDR2), and SEQ ID NO:
• 12 (LCDR3), as defined by the IMGT numbering system;
• D is a therapeutic agent;
• L is a cleavable linker that covalently attaches Ab to D;
• and
• p is an integer from 1 to 8,
• comprising reacting the antibody or antigen-binding fragment with the cleavable linker attached to D under conditions that allow conjugation.