On September 23–24, 2025, the 4th BIONNOVA Beijing Innovation Forum was successfully held in Beijing. The forum focused on full‑chain innovation collaboration and alignment with clinical needs, bringing together more than 3,000 innovation decision‑makers to discuss technological breakthroughs and industrialization pathways in cutting‑edge fields such as antibody drugs, cell and gene therapy.

Zhang Yu, Director of Process Development at Canton Biologics, was invited to attend and delivered a keynote speech titled “From Molecule to Drug Product: Challenges and Solutions in CMC Development of Bispecific Antibodies and Complex Recombinant Proteins,” sharing Canton Biologics’ technical expertise and practical experience in the development of complex biologics.

01 Market Value and Technical Challenges of Complex Protein Drugs

Zhang Yu noted in her speech that bispecific antibodies and complex recombinant proteins play an important role in the treatment of tumors, autoimmune diseases, and metabolic disorders. However, due to their multi‑domain and multi‑functional nature, they face core challenges in CMC development, including low expression levels, complex impurity profiles, and poor molecular stability. Through an integrated development strategy, Canton Biologics provides customized solutions for various difficult‑to‑express molecules.

02 Five Major Technological Breakthroughs

1. Cell Line and Upstream Process Development

By employing strategies such as molecular sequence engineering, chain expression ratio adjustment, host cell optimization, and proprietary expression vectors, protein expression levels have been significantly increased:

• Expression of a monoclonal antibody increased 6.6‑fold after sequence engineering.

• Expression of a GPCR protein increased up to 14‑fold through sequence engineering.

• Expression of a G‑protein coupled receptor increased 9.7‑fold using the GlycoExpress® cell line.

2. Proprietary Vector Technology Breakthroughs

• DTEasy vector: Designed for difficult‑to‑express proteins, increasing expression levels by 100%–400%.

• IgMax® vector system: IgM expression increased from less than 1 g/L to up to 8 g/L, with pentamer purity approaching 100%.

3. Enhanced Process Platform

The CBoost™ enhanced process platform has demonstrated outstanding results:

• 1.2‑fold increase in expression of conventional antibodies.

• Nearly 1‑fold increase in expression of difficult‑to‑express antibodies.

• Compared to conventional fed‑batch culture, the enhanced fed‑batch culture achieves nearly double the protein expression level.

4. Downstream Purification Technology Innovation

Tailored purification strategies have been developed for the characteristics of bispecific antibody molecules:

• Use of S/D inactivation instead of low‑pH inactivation to protect pH‑sensitive molecules.

• Effective removal of aggregates and mispaired impurities through two‑step chromatography (HIC and AEX).

• Successful scale‑up to 500 L with high batch‑to‑batch quality consistency.

5. Formulation Development and Analytical Methods

• Successfully developed a room‑temperature stable recombinant protein nasal spray formulation, maintaining good stability under accelerated conditions.

• Solved high‑concentration formulation challenges through viscosity reducer screening.

• Established multi‑dimensional analytical methods to confirm the structural characteristics of complex proteins.

03 One‑Stop Service Capabilities

Zhang Yu summarized that Canton Biologics adheres to the QbD philosophy, considering CMC development feasibility from the molecular design stage. Through a combination of forward‑looking assessment, integrated development, and platform‑based plus customized strategies, the company provides end‑to‑end services from gene sequence to commercial production.

Core advantages include:

• Access to high‑quality host cell platforms such as CHOzen®, CHOFlow®, and GlycoExpress®.

• High‑expression plasmid systems with proprietary IP.

• Proprietary media formulations that increase yield and modulate quality.

• Average mAb expression >8 g/L, reaching industry‑leading levels.

• Completed dozens of audits and obtained CNAS certification, with a robust quality system.

04 Conclusion

The 4th BIONNOVA Beijing Innovation Forum provided a high‑level technical exchange platform for the biopharmaceutical industry. Through this presentation, Canton Biologics fully demonstrated its technical strength and innovative achievements in the CMC development of bispecific antibodies and complex recombinant proteins.

Looking ahead, Canton Biologics will continue to deepen its work in the development of complex biologics. Through continuous technological innovation and platform optimization, we aim to provide clients with more efficient and reliable CDMO services, helping to bring innovative drugs to patients as soon as possible.