Anti-CD70 antibody drug conjugates

A compound comprising Formula (VIII) or (IX), wherein the compound is an αCD70 antibody conjugated to a dolastatin, wherein the conjugation occurs via a non-naturally encoded amino acid in the antibody, wherein Formula (VIII) and (IX) correspond to:

• wherein:
• A is optional, and when present is lower alkylene, substituted lower alkylene, lower cycloalkylene, substituted lower cycloalkylene, lower alkenylene, substituted lower alkenylene, alkynylene, lower heteroalkylene, substituted heteroalkylene, lower heterocycloalkylene, substituted lower heterocycloalkylene, arylene, substituted arylene, heteroarylene, substituted heteroarylene, alkarylene, substituted alkarylene, aralkylene, or substituted aralkylene;
• B is optional, and when present is a linker selected from the group consisting of lower alkylene, substituted lower alkylene, lower alkenylene, substituted lower alkenylene, lower heteroalkylene, substituted lower heteroalkylene, —O—, —O-(alkylene or substituted alkylene)-, —S—, —S-(alkylene or substituted alkylene)-, —S(O)k— where k is 1, 2, or 3, —S(O)k(alkylene or substituted alkylene)-, —C(O)—, —C(O)-(alkylene or substituted alkylene)-, —C(S)—, —C(S)-(alkylene or substituted alkylene)-, —N(R′)—, —NR′-(alkylene or substituted alkylene)-, —C(O)N(R′)—, —CON(R′)-(alkylene or substituted alkylene)-, —CSN(R′)—, —CSN(R′)-(alkylene or substituted alkylene)-, —N(R′)CO-(alkylene or substituted alkylene)-, —N(R′)C(O)O—, —S(O)kN(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(S)N(R′)—, —N(R′)S(O)kN(R′)—, —N(R′)—N═, —C(R′)═N—, —C(R′)═N—N(R′)—, —C(R′)═N—N═, —C(R′)2—N═N—, and —C(R′)2—N(R′)—N(R′)—, where each R′ is independently H, alkyl, or substituted alkyl;
• R is H, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl;
• R1 is H, or an anti-CD70 (αCD70) antibody;
• R2 is OH, or an anti-CD70 (αCD70) antibody;
• R3 and R4 are each independently H, halogen, lower alkyl, or substituted lower alkyl, or R3 and R4 or two R3 groups optionally form a cycloalkyl or a heterocycloalkyl;
• Z has the structure of:
• R5 is H, COR8, C1-C6alkyl, or thiazole;
• R8 is OH;
• R6 is OH or H;
• Ar is phenyl or pyridine;
• R7 is C1-C6alkyl or hydrogen;
• L is a linker selected from the group consisting of alkylene, -alkylene-C(O)—, -(alkylene-O)n-alkylene-, -(alkylene-O)n-alkylene-C(O)—, -(alkylene-O)n—(CH2)n′—NHC(O)—(CH2)n″—C(Me)2-S—S—(CH2)n′″—NHC(O)-(alkylene-O)n″″-alkylene-, -(alkylene-O)n-alkylene-W—, -alkylene-C(O)—W—, -(alkylene-O)n-alkylene-U-alkylene-C(O)—, and -(alkylene-O)n-alkylene-U-alkylene-;
• W has the structure of:
• U has the structure of:
• and
• each n, n′, n″, n′″ and n″″ are independently integers greater than or equal to one;
• with the proviso that one and only one of R1 or R2 is an anti-CD70 (αCD70) antibody;
• or a pharmaceutically acceptable prodrug thereof.