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Bispecific IgGs Generation Service

Creative Biolabs provides world class bispecific IgG engineering services based on the latest antibody engineering technology platforms. Our scientists employ the most advanced techniques to provide comprehensive bispecific antibody (BsAb) services for research and therapeutic market.

The features of bispecific IgGs

  • Bispecific IgG is a widely used BsAb format. It is monovalent for each antigen.
  • As the name indicates, Bispecific IgGs remains the general size and structure of a conventional IgG and thus such BsAbs antibodies have the most similar biophysical properties to a regular IgG including serum high stability, half-life and tissue penetration.
  • Bispecific IgGs are bispecific and bivalent molecules with Fc portion. Fc engineering can be performed to alter the Fc-mediated effector functions such as ADCC, CDC and ADCP.
  • With our experience in BsAbs manufacturing, bispecific IgGs are generated by recombinant expression or hybrid-hybridoma technology. We usually use mammalian cell lines as hosts to produce bispecific IgGs.

Schematic diagram of the Fab domain exchange resulting in the formation of a BsAb when combined with the KiH technology. (Schaefer, W., 2011)

Figure 1. Schematic diagram of the Fab domain exchange resulting in the formation of a BsAb when combined with the KiH technology. (Schaefer, W., 2011)

The developability of bispecific IgGs

In the generation of BsIgGs, to obtain heterodimers with high purity is a great challenge. Because it is low yield of desired BsIgGs in coexpression of two heavy and two light chains in a single host cell and it is difficult to remove the closely related mispaired IgG contaminants. In order to improve the developability of BsIgGs, a variety of techniques and formats have been developed to force heterodimerization and assembly of bispecific IgG-like molecules. Based on the previous studies, the strategies used to overcome the heavy chain-pairing problem of BsIgGs include Knob-into-holes (KIH), DuoBody, Azymetric, Charge pair, HA-TH, SEEDbody, differential protein A affinity, etc. Meanwhile, the technology of antibody domain crossover can avoid the light pairing problems. Take KIH technology as an example, the heterodimerization yields with correct heavy chain association can be above 97% by introducing six mutations onto the Fc domain.

Creative Biolabs uses advanced techniques to generate a wide variety of fully functional bispecific IgG antibodies. The bispecific IgG antibodies include:

Figure 2. Alternative formats for bispecific IgGs (Christoph Spiess et al. 2015)

Creative Biolabs is a trusted partner in BsAb services. With decades of experience in antibody research, our scientists can engineer BsAbs of different subtypes from various species to meet the unique requirements of every client. For more detailed information, please feel free to contact us or directly send us an online inquiry.

References

1. Schaefer, W.; et al. Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proceedings of the National academy of Sciences. 2015, 108(27): 11187-11192.
2. Dübel, S. Handbook of therapeutic antibodies (Vol. 1). John Wiley & Sons. 2014.

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