Investigation of Off-Target Conjugation Cysteine-Based ADCs
- Employ high-resolution peptide mapping with LC-MS/MS to identify and quantify conjugation sites beyond the engineered interchain cysteines, to create residue-specific map of all drug linker attachments, revealing unexpected modifications on hinge region cysteines
- Utilize advanced data analysis software to perform comparative quantitation of on-target vs. off-target conjugation levels across different process conditions and ADC batches to facilitate data-driven process optimization and establishing meaningful in-process controls (IPCs) to ensure batch-to-batch consistency in drug distribution