Improving Multispecific Antibody Bioprocesses Through Coculture and Column-Based Redox Reactions: Part II

Area of Science:

• Biotechnology
• Protein Engineering
• Pharmaceutical Manufacturing

Background:

• Multispecific antibodies offer unique therapeutic mechanisms but present production challenges.
• Existing electrostatic-steering methods require separate bioreactors, complicating manufacturing campaigns.

Purpose of the Study:

• To develop a novel, streamlined bioprocess for producing electrostatic-steering-based multispecific antibodies.
• To improve manufacturing efficiency and reduce complexity compared to traditional methods.

Main Methods:

• Co-culturing two separate cell lines for simultaneous production of parental homodimers in a single bioreactor.
• Implementing a column-based redox reaction for controlled heterodimerization and disulfide bond formation.
• Utilizing protein A resin for capture, reduction, and elution of homodimers.

Main Results:

• Achieved high conversion rates (>90%) from homodimers to heterodimers.
• Maintained multispecific percentages above 95% in drug substance pools.
• Demonstrated robust and efficient performance from lab to manufacturing scale with controlled impurity profiles.

Conclusions:

• The novel bioprocess simplifies manufacturing by combining simultaneous homodimer production and column-based redox reactions.
• This approach is scalable, efficient, and yields high-purity multispecific antibodies.
• The method aligns multispecific production with antibody-like processes, optimizing resource utilization.