Immunoconjugates with an intracellularly-cleavable linkage

A conjugate having a structural formula selected from the group consisting of MAb-CL2A-SN-38, MAb-CL6-SN-38, MAb-CL7-SN-38 and MAb-CLX-SN-38, with a structure represented by:

• where R is hydrogen or C1 to C10 alkyl group and AA is selected from any one of the following L-amino acids:
• alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine,
• wherein the 10-hydroxy position of SN-38 in MAb-CL2A-SN-38 or MAb-CL6-SN-38 or MAb-CL7-SN-38 or MAb-CLX-SN-38 is a 10-O-ester or 10-O-carbonate derivative using a ‘COR’ moiety where the R group is a substituted alkyl residue “N(CH3)2—(CH2)n—”, where n is 2-10 and wherein the terminal amino group is optionally in the form of a quaternary salt for enhanced aqueous solubility, or an alkyl residue “CH3—(CH2)n—” where n is 0-10, or an alkoxy residue “CH3—(CH2)n—O—” where n is 0-10, or “N(CH3)2—(CH2)n—O—” where n is 2-10, or “R1O—(CH2—CH2—O)n—CH2—CH2—O—” where R1 is ethyl or methyl and n is an integer with values of 0-10.

A conjugate having a structural formula of MAb-CLY-SN-38;

• with a structure represented by:
• where R and R′ are independently hydrogen or methyl;
• and when R=R′=methyl, the structure is referred to as MAb-CL2E-SN-38.