Tuning the Assembly of Bispecific Antibodies by Playing on Differential Polypeptide Chain Molar Ratios

Biotechnology and Bioprocess Engineering:
24 August 2023

https://doi.org/10.1007/s12257-023-0057-9

KBI Biopharma’s Mammalian Cell Line Development team at our Geneva, Switzerland location, together with their colleagues, recently published the results of their research in Biotechnology and Bioprocess Engineering.  

There is a growing, global need for robust bispecific antibody (bsAb) development, as bsAbs encompass one of the most promising, proven classes of therapeutics recently reaching the market. This is due to their ability to bind to two different epitopes and offer the flexibility of performing multiple mechanisms of action. With ongoing advances in protein engineering coupled with robust purification methods to remove homodimers, an increasing number of bsAbs are progressing from development to clinic at a rapid rate. These complex molecules require a special focus on engineering and specific optimization throughout the development and manufacturing process, prioritizing quality, efficiencies, and time savings in bsAb production and purification to capitalize on their incredible therapeutic potential.  

In their article Tuning the Assembly of Bispecific Antibodies by Playing on Differential Polypeptide Chain Molar Ratios, the authors evaluate the impact of manipulating different molar ratios of three polypeptide chains, concluding that by adding gene copies at specific ratios, the expression of bsAbs can be influenced beyond the initial engineering stage¹.  

Learn More about Bispecific Antibody Production at KBI Biopharma 

While many bsAbs in development fundamentally maintain the heavy and light chain structure of standard antibodies, advancements in protein engineering have allowed for developing smaller versions (BiTEs, DARTs, etc.) and for engineering more complex versions for things like extra binding domains to be appended to the heavy and/or light chains. KBI Biopharma has experience in classical formats of heavy chain/light chain bsAbs, as well as in more complex molecules like BiTEs, DARTs, and appended domains and several pairing technologies (e.g., knob-into-hole, electrostatic interaction, charge opposite, and introduction of artificial disulfide bounds).  

Our mammalian-based bispecific expression combines best-in-class cell line development with unmatched expertise and experience in mammalian-based contract development and manufacturing across a diverse portfolio of molecule formats. Learn more about KBI Biopharma’s solutions for bispecifics to jump-start your program today.  

1. De Temmerman, C., Bernard, P., Aeberli, Q. et al. Tuning the Assembly of Bispecific Antibodies by Playing on Differential Polypeptide Chain Molar Ratios. Biotechnol Bioproc E (2023). https://doi.org/10.1007/s12257-023-0057-9