Generating bispecific antibodies can be hampered by low yields, chain mispairing, homodimers, half‑antibody species, and other hard‑to‑remove impurities. These issues differ among formats, so a tailored production approach is essential to obtain material suitable for downstream work. WuXi Biologics’ Premium Bispecific Antibody (BsAb) platform combines biology‑driven design, chain‑ratio optimisation, high‑titer transient CHO expression and LC‑MS‑guided purification to consistently deliver high‑purity bsAbs across a broad range of architectures.
Key features
- LC‑MS‑assisted purification that routinely achieves >98% heterodimer purity and endotoxin levels <0.1 EU/mg.
- Scalable production from milligrams to grams, enabling a seamless transition to CMC development.
- Chain‑ratio optimisation available to improve titer and purity on demand.
- More than 20,000 bsAbs have been delivered in formats such as CrossMab, ScFv‑Fab, Fc‑fusion and others.
- Materials are suitable for both in‑vitro assays and in‑vivo studies.
Key steps
- Molecule design: The service supports diverse architectures—including CrossMab, ScFv‑Fab, WuXiBody, Fc‑fusion, charged‑pairing, common LC, different LC, bispecific VHH and other complex bispecific/trispecific formats. Design is guided by mechanism of action, pharmacokinetic considerations and anticipated production challenges.
- Expression: A high‑titer transient CHO system averages 2.6 g/L for control mAbs in 7 days and 1.49 g/L across a broad panel of bsAb projects. Chain‑ratio optimisation can be applied to enhance expression, assembly and starting‑material quality when needed.
- Purification: Each BsAb receives an LC‑MS‑guided, custom purification strategy based on its molecular properties and impurity profile. After Protein A capture, intact MS identifies the target BsAb and co‑eluting by‑products. Differences in charge, hydrophobicity or mixed‑mode behaviour are exploited to remove homodimers, mispaired species and half‑antibodies. Intact MS continuously monitors heterodimer purity to inform polishing steps.
- Analytics: LC‑MS‑based analytics are integrated throughout production to differentiate the target BsAb from closely related by‑products that may escape conventional detection. Complementary methods such as SDS‑PAGE, SEC‑HPLC and endotoxin testing provide rigorous quality assessment.
By addressing complex molecular designs and difficult impurity profiles, the Premium BsAb platform leverages LC‑MS‑guided workflows to deliver high‑quality material with >98% heterodimer purity, accelerating bispecific antibody R&D.