Hydrophilic antibody-drug conjugates

A Compound having the formula:

• (a) (LH)p′-LA
• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• LH is an optionally branched hydrophilic linker, each branch of LH having the formula:
• -AA1—RL1—RL2—RL3—;
• LA is a Ligand Attachment component;
• and
• p′ is an integer from 1 to 4;
• and
• wherein the left and right lines of LH indicate attachment sites for a DE unit and LA, respectively;
• or
• (b) ([LH]p′-LA)p-L
• or a pharmaceutically acceptable salt or solvate thereof;
• wherein:
• L is a Ligand that specifically binds to a target;
• LH is an optionally branched hydrophilic linker, each branch of LH having the formula:
• -AA1—RL1—RL2—RL3—;
• LA is a Ligand Attachment component;
• the subscript p is an integer from about 4 to 20;
• and
• the subscript p′ is an integer from 1 to 4;
• wherein the left and right lines of LH indicate attachment sites to the DE Unit and LA, respectively;
• wherein in (a) or (b):
• AA1 is a hydrophilic amino acid that can form a cleavable bond with a DE unit when it is attached;
• RL1 is a hydrophilic amino acid or an optionally substituted alkylene, which may share an atom with LA when RL2 and RL3 are not present;
• RL2 is optional and is selected from a hydrophilic amino acid and an optionally substituted alkylene, which may share an atom with LA when RL2 is present and RL3 is not present;
• and
• RL3 is optional and is selected from a hydrophilic amino acid and an optionally substituted alkylene, which may share an atom with LA when RL3 is present,
• wherein at least one of RL1, RL2, and RL3 is an amino acid that is covalently linked by a reactive group in its side chain to an adjacent group.