Bringing novel ADC formats into the clinic

This white paper from Lonza explains how next-generation antibody-drug conjugates (ADCs), especially antibody-oligonucleotide conjugates (AOCs), are expanding bioconjugate therapies beyond traditional cancer treatments. It focuses on the challenges of conjugation, analytical testing, purification, and scaling up AOC manufacturing, and highlights how optimized processes can support clinical and commercial development.

• Novel ADC formats: New payloads such as oligonucleotides, peptides, polymers and chelators, along with new antibody and linker technologies, are expanding bioconjugates beyond traditional ADCs.
• AOC conjugation challenges: Oligonucleotides are larger and can be negatively charged, requiring careful optimization of reaction time, stoichiometry and conjugation condition
• Purification & analytics: TFF alone may not efficiently remove unconjugated oligonucleotides, so chromatography and specialized analytical methods such as SDS-PAGE/densitometry are important.
• Scale-up to GMP: Process development is designed to create robust, reproducible and scalable manufacturing processes, supporting the transition from early development to GMP production.