Affinity Maturation

Affinity Maturation

We go further than Affinity Improvement. 

We’ve adopted a novel approach to affinity maturation. Experience helps us to deliver an antibody optimization service for you that increases the binding, but also considers manufacturing, stability or immunogenicity.

Using our Rational Affinity Maturation Platform (RAMP™), we can help those who want to develop the best possible antibody sequence by exploring the natural somatic hypermutation space of their antibody and introducing diversity both in the frameworks and the CDRs.

We don’t use phage display in our approach. We do something different.

Rational Library Design

RAMP™ offers a novel, proprietary, method for library design, which explores the natural somatic hypermutation space of your antibody sequence. Using this approach, substitutions are incorporated into both the framework and CDR regions. Restrictions ensure that safety or manufacturing liabilities will not be introduced. This unique approach can allow for natural mutations that may unexpectedly improve the profile of your antibody.

In Silico Selection

Using in silico modelling and molecular docking we interrogate the antibody library, selecting those with predicted improvements in both binding potential and stability. Balance of function and developability is a key principle of RAMP™.

This rapid selection approach enables us to focus a library of >1015 variants down to a micro-library of approx. 100 sequences, for in vitro expression and characterization.

Micro Library Expression and Characterisation

An important benefit of our approach to Affinity Maturation is that there is no need to express a large physical library of variants. With RAMP™, we express a micro-library of selected variants in CHO cells in the IgG format. There is no bias for scFv or Fab format and no bias for stability in bacterial expression. Binding kinetics and biophysical attributes of all variants are characterized in vitro.

A high proportion of expressed mAbs display improved affinity compared to the parental mAb; offering a rich pool for selection of your lead candidate antibody or start point for repeated rounds of RAMP™.

Highlights from our approach to Affinity Maturation

  • Natural approach to library design
  • No need to generate a large physical library of variants
  • No bias for scFv format or bacterial expression (required for phage display)
  • Characterisation of mAbs in full IgG format
  • Rapid timelines (under 3 months)
  • High proportion of expressed mAbs display improved affinity
  • >10-fold affinity improvement per round

 

We use a totally novel approach to generating diversity, therefore exploring new sequence space that other approaches will not do. Diversity is key! Our studies and experience teach that the framework regions, not only impact stability, but also binding. Our approach allows new sequences to be found that have unpredictable and beneficial consequences.

Proving the results with Cathepsin S – Click  the  image  below  to download the PDF

Novel approach to affinity maturation

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