Bispecific Antibody Production Service

Bispecific antibody structure and formats

Structurally, antibodies can be categorized based on the number of binding domains they possess (their valency), and how they are divided between the different targets. For instance, bispecific antibodies are often classified as “1 + 1” (two binding sites, one for each target), “2 + 2” (four binding sites, two for each target), or “2+1” (three binding sites, two for one target, one for the other). Further combinations are possible, and more targets can be engaged using multi-specific antibodies.

Additional structural characterization can be made by looking at the format of the bispecific and the sequences used to join the different domains. “Traditional” structures closely resemble regular monoclonal antibodies (mAbs) but have different binding domains on each Fab arm (Figure 2A). These can be further embellished by the addition of other binding regions, such as scFvs or Fab domains, which leads to the creation of multi-specific molecules (Figures 2B and 2C).

Non-antibody bispecifics can be created through the linkage of binding domains without Fc regions. These domains can be antibody fragments, such as individual scFvs (common with bispecific T-cell engagers), Fab domains, VHH domains, or other proteins with an affinity for the desired target(s).



Finally, additional modifications may be added to augment the function of the bispecific molecule. Most frequently, these modifications would be used to silence immune effector functions, which are typically undesirable for trans co-engagers. However, any other mutations used with traditional antibodies can theoretically be transferred into a bispecific antibody.

The choice of which bispecific antibody to use is non-trivial and should be made through a combination of application, manufacturing, and commercial considerations. Our experts are happy to assist you in this decision!

evitria has access to bYlok® bispecific pairing technology

Thanks to a non-exclusive license agreement with Lonza, we are able to implement bYlok® bispecific pairing technology in our bispecific antibody expression services. This technology addresses a major challenge in bsAb production: HC-LC mispairing.

With bYlok® bispecific pairing technology, we are able to achieve over 95% correct heavy-light chain pairings, significantly improving the effectiveness of our bsAb services. It also allows using CHO cells for the in vitro expression of bsAbs, enabling us to combine the power of this innovative technology with the strengths of our preferred antibody expression cell line.