Targeted dendrimer conjugates

A dendrimer-targeting agent conjugate, comprising:

• a) a dendrimer comprising
• i) a core unit (C), wherein the core unit is
• and
• ii) three to five generations of building units (BU), each building unit being a lysine residue having the structure
• wherein the two amino nitrogen atoms of each building unit provide an attachment point for bonding to a subsequent generation of building units, therapeutic agent or a hydrophilic polymeric group, and the acyl group of each building unit provides an attachment point for bonding to a previous generation of building units or the core unit;
• wherein the core unit is covalently attached to two building units via amide linkages, each amide linkage being formed between a nitrogen atom present in the core unit and a carbon atom of the acyl group present in a building unit;
• b) a HER2 targeting agent which is a single domain antibody having a molecular weight of from 10 kDa to 16 kDa, and comprising an antigen-binding site,
• and wherein the HER2 targeting agent has three complementarity determining regions (CDRs) 1, 2 and 3 having the amino acid sequences GFTFDDYAMS, SINWSGTHTD, and NWRDAGTTWFEKSGS, respectively, from the amino acid sequence of SEQ ID NO. 1, the HER2 targeting agent being covalently linked to a nitrogen atom in the core unit of the dendrimer by a spacer group comprising a polyethylene glycol (PEG) chain having from 2 to 60 ethyleneoxy repeat units;
• c) a therapeutic agent which is covalently linked to a surface building unit of the dendrimer via a cleavable linker, wherein the therapeutic agent is an auristatin, a maytansinoid, an anti-microtubule agent or a topoisomerase inhibitor;
• and
• d) a hydrophilic polymeric group that is covalently linked to a surface building unit of the dendrimer, wherein the hydrophilic polymeric group is a polyethylene glycol (PEG) group having a mean molecular weight in the range of from 900 to 2300 g/mole.