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Charge Pair BsAb Generation Service

Creative Biolabs is an undisputed global leader in the bispecific antibodies (BsAbs) market. With our professional scientists hammering at Creative Biolabs, we can offer high quality charge pair BsAb generation service. With the unique charge pair platform, our talented scientists can develop best-in-class BsAbs for diverse therapeutic applications.

Heterodimeric IgG is formed by the incorporation of two different IgG molecules in the Fc region. It is a potential BsAb format and holds the overall size and natural structure of the regular IgG with good bioavailability and pharmacokinetics profile. As co-expressing two different HCs and two different LCs in the same cell to produce a functional IgG BsAb, only 1 in 10 combinations has the correct configuration. There are several methods to enhance HC heterodimerization and decrease the combinations to four, such as engineering the CH3 domain of antibody by knob-into-hole, or SEED, or charge pair residues. However, the LC-HC mispairing problem still exists. One approach to solve this problem is to use a common LC, whereas it is time consuming to measure and engineer a promiscuous LC which enables to accommodate two different HCs while keeping the desirable functional properties. Other approaches have been explored to produce monovalent BsAbs.

This figure shows the chain association problem. Representation of the antibody combinations enable to be generated by a quadroma cell line.

Figure 1. This figure shows the chain association problem. Representation of the antibody combinations enable to be generated by a quadroma cell line. In total 16 formats are possible, of which six are identical. Six tetramers, containing the desired BsAb, occur twice (each with a yield of 12.5%).

Charge Pair Technique

To overcome the LC-HC mispairing issue, the method of producing BsAbs from two different pre-existent antibodies by electrostatic steering mechanism has been widely used. This format of BsAb is named as hetero-IgG, which is formed by engineering the HC and LC of the two different antibodies in such a way that they enable to assemble exclusively into a BsAb without other contaminating species. This takes advantage of the charge pair strategy for CH3 engineering in order that two different HCs form a heterodimer exclusively. Besides, by using an electrostatic steering effect to engineer interface residues between LC and HC, the possible mispairing of LCs to noncognate HCs are able to be prevented. In this way, a full-length BsAb from two pre-existent antibodies in mammalian cells without using any artificial linkers can be performed. Moreover, the resulting BsAbs are stable and amenable to commercial manufacturing without excessive aggregation or loss of yield. According to the features of targeting two different antigens or two different epitopes on the same antigen, this new format BsAb showed great potential for treating serious diseases with unmet needs.

Residues at VH-VL and CH1-CL interfaces for substitutions are buried, conserved, and spatially close. (Liu, Z., 2015)

Figure 2. Residues at VH-VL and CH1-CL interfaces for substitutions are buried, conserved, and spatially close. (Liu, Z., 2015)

Charge pair bispecific antibody provided by Creative Biolabs possesses comparable high affinity against antigens as its parental antibodies. It would be an ideal tool for your academic or clinical studies. We offer customers pure and functional BsAbs through charge pair platform for variant therapeutic applications. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.

References

1. Liu, Z.; et al. A novel antibody engineering strategy for making monovalent bispecific heterodimeric IgG antibodies by electrostatic steering mechanism. Journal of Biological Chemistry. 2015, 290(12): 7535-7562.
2. Gunasekaran, K.; et al. Enhancing Antibody Fc Heterodimer Formation through Electrostatic Steering Effects applications to bispecific molecules and monovalent IgG. Journal of Biological Chemistry. 2010, 285(25): 19637-19646.

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