Introduction to bYlok

Bispecific antibodies (bsAb) are emerging as an important class of therapeutics. Bispecific antibodies have increased potential for precision targeting and higher potency. Multi antigen binding can help reduce the development of subsequent clinical resistance. Different strategies have been used in the past to create bsAbs. However, key challenges remain with the developability of bispecific antibodies:

  • Highly engineered formats that least resemble native proteins could have a higher risk of unwanted immunogenicity
  • Expression of two different heavy and light chains in a single cell can create misassembled unwanted species. These impurities can be difficult to remove due to their similarity to the correct format.
Helping you redefine your bispecific design engineering

Lonza’s bYlok® platform technology was developed keeping in mind the evolving needs of antibody-drug developers. The simplicity of application is within the design itself. It provides an engineering solution for bispecific antibodies where two different light chains are needed.

By moving the disulphide bridge from constant domains (CH1/CL) to variable domains (VH/VL), the formation of HC-LC heterodimers is favored. The modifications add minimal changes to the molecule’s natural design to minimize unwanted immune responses and support excellent manufacturability.

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Heterogeneous mixture of very similar speciesPatial solution: Knobs-into-Holes Technology bYlok TechnologyHighest probability of mispairing eventsSolves heavy chain mispairing. Knobs and holes are positioned in the CH3 region of antibodies in such a way that hinders formation of homodimers.Disulfide Bridge is moved in one of the ‘half mAbs’ from constant domains (CH1/CL) to variable domains (VH/VL).Favours formation of a heterodimer.Can require two separate cell lines (one for each ‘half mAb’); followed by assembly and fther downstream processingOnly one cell line required and simpli-fied downstream processes.Specificity A12.5%Theoretical yield~25%Theoretical yield>95%**Lonza internal dataSpecificity B

Lonza in Your Lab™

Access bYlok® for your bispecific antibody design. A precision pairing technology that links partners to better possibilities

Access to our bYlok® technology is easy. The technology is available via a simple research license to see if it fits your processes.

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