Bioconjugation is a chemical strategy to form a stable covalent link between two molecules, at least one of which is a biomolecule such as a protein. A very prominent type of bioconjugate is antibody-drug conjugates (ADCs), which is a powerful class of therapeutic agents in oncology and hematology that is gaining momentum in today’s market with seven FDA approved ADCs since 2019. Today`s approved ADCs are based on stochastic conjugation to either lysine or cysteine residues. Since the first approved ADCs, continued efforts have yielded new technologies with the focus now on even more new payloads with novel modes of action and new linkers with improved stability. The goal is also to include more site-specific conjugation technology and enzymatic conjugation when the linker payload is attached to the antibody by an enzyme. In addition to the growing market of ADCs, there is a healthy pipeline of other modalities, including a range of non-toxic payloads or alternative target binding formats, such as smaller antibody-like proteins. Due to the diversification of conjugation technologies, payloads, linker technologies and antibody modalities new purification challenges are emerging. While in conventional ADC processes a simple Tangential Flow Filtration (TFF) step is often sufficient to purify the product other purification methods such as chromatography are becoming increasingly important. This presentation gives an overview of Lonza`s approach for chromatography development of a bioconjugate process including several case studies.
- Navigating the diverse conjugation technology landscape
- Purification challenges with novel conjugate modalities
- Development of a robust and scalable chromatographic purification