Antibody-drug conjugate produced by binding through linker having hydrophilic structure

An antibody-drug conjugate comprising an antitumor compound represented by the following formula:

• wherein the antitumor compound is conjugated to an antibody via a linker having a structure represented by the following formula:
• -L1-L2-LP-NH—(CH2)n1-La-Lb-Lc- or -L1-L2-LP-
• wherein the antibody is connected to the terminal of L1, the antitumor compound is connected to the terminal of Lc or LP,
• wherein
• n1 represents an integer of 0 to 6,
• L1 represents -(Succinimid-3-yl-N)—(CH2)n2-C(═O)—, -(Succinimid-3-yl-N)—CH[—(CH2)n3-COOH]—C(═O)—, —CH2—C(═O)—NH—(CH2)n4-C(═O)—,
• —C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-, or —C(═O)—(CH2)n5-C(═O)—,
• wherein n2 represents an integer of 2 to 8, n3 represents an integer of 1 to 8, n4 represents an integer of 1 to 8, n5 represents an integer of 1 to 8,
• L2 represents —NH—(CH2—CH2—O)n6-CH2—CH2—C(═O)—, —N[—(CH2CH2—O)n7-CH2CH2—OH]—CH2—C(═O)—, —S—(CH2)n8-C(═O)—, or a single bond,
• wherein n6 represents an integer of 0 to 6, n7 represents an integer of 1 to 4, n8 represents an integer of 1 to 6,
• LP represents:
• (i) a peptide residue consisting of 3 to 8 amino acids wherein the peptide residue has a hydrophilic amino acid other than glycine at the N terminal, or (ii) a peptide residue comprising GGFGG (SEQ ID NO:
• 40) or GGFGGG (SEQ ID NO:
• 41),
• La represents —C(═O)—NH—, —NR1—(CH2)n9-, —O—, or a single bond,
• wherein n9 represents an integer of 1 to 6, R1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, —(CH2)na-COOH, or —(CH2)nb-OH, na represents an integer of 1 to 4, nb represents an integer of 1 to 6,
• Lb represents —CR2(—R3)—, —O—, —NR4—, or a single bond,
• wherein R2 and R3 each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, —(CH2)nc-NH2, —(CH2)nd-COOH, or —(CH2)ne-OH, R4 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, nc represents an integer of 0 to 6, nd represents an integer of 1 to 4, ne represents an integer of 1 to 4, provided that when nc is 0, R2 and R3 are not the same as each other,
• Lc represents —CH2— or —C(═O)—,
• -(Succinimid-3-yl-N)— has a structure represented by the following formula:
• which is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1,
• —(N-ly-3-Succinimid)- has a structure represented by the following formula:
• which is connected to L2 at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1,
• cyc.Hex(1,4) represents a 1,4-cyclohexylene group,
• when L2 is —S—(CH2)n8-C(═O)—, L1 is —C(═O)-cyc.Hex(1,4)-CH2—(N-ly-3-Succinimid)-.