IMPROVED ANTIBODY-PAYLOAD CONJUGATES (APCS) PREPARED BY SITE-SPECIFIC CONJUGATION UTILIZING GENETIC CODE EXPANSION

The present invention relates to novel, site-specifically modified immunoglobulin molecules having the ability to bind to human epidermal growth factor receptor 2 (HER2) carrying in predetermined positions non-canonical amino acid residues (ncAAs); respective nucleic acid sequences encoding such modified immunoglobulin molecules; recombinant organisms useful for preparing such modified immunoglobulin molecules and adapted to express respective coding nucleic acid sequences; methods of preparing said site-specifically modified immunoglobulin molecules; conjugates formed between said site-specifically modified immunoglobulin molecules and a conjugation partner carrying a functional group reactive with said ncAA residues of the immunoglobulin molecule, and more particularly antibody-drug conjugates (ADCs). The invention also relates to specific conjugation partners and their preparation. The invention also relates to pharmaceutical compositions comprising such conjugates; as well as the use of such conjugates in medicine, in particular in the treatment of cancers overexpressing HER2.