Compositions and methods related to anti-EGFR antibody drug conjugates

An antibody drug conjugate, having the structure of Formula I:

• wherein:
• G is a glucuronic acid moiety or
• wherein R3 is hydrogen or a carboxyl protecting group;
• and each R4 is independently hydrogen or a hydroxyl protecting group;
• A represents an anti-EGFR antibody;
• B represents an active agent;
• W is —C(O)—, —C(O)NR′—, —C(O)O—, —S(O)2NR′—, —P(O)R″NR′—, —S(O)NR′—, or —PO2NR′—, in each case where the C(O), S, or P is directly bound to the phenyl ring, and R′ and R″ are each independently hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, (C1-C8)alkylthio, mono- or di-(C1-C8)alkylamino, (C3-C20)heteroaryl, or (C6-C20)aryl;
• each Z independently represents hydrogen, (C1-C8)alkyl, halogen, cyano, or nitro;
• n is an integer from 1 to 3;
• L comprises an alkylene chain of 3 to 50 atoms that covalently links A to W, wherein the chain further comprises an oxime and either:
• (a) the oxygen atom of the oxime is substituted with a group that covalently links the oxime to W;
• and the carbon atom of the oxime is substituted with a group that covalently links the oxime to A;
• or
• (b) the carbon atom of the oxime is substituted with a group that covalently links the oxime to W;
• and the oxygen atom of the oxime is substituted with a group that covalently links the oxime to A;
• R1 and R2 are each independently hydrogen, (C1-C8)alkyl, or (C3-C8)cycloalkyl, or R1 and R2 taken together with the carbon atom to which they are attached form a (C3-C8)cycloalkyl ring;
• and
• the moieties connecting A and B, taken together, form the linker.