Affinity Maturation Services

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Fusion Antibodies has developed a novel affinity maturation platform (RAMP™) for the rapid optimisation of your antibody building upon more than 17 years’ experience in antibody engineering and humanization.

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We harness the natural process

 Affinity maturation is the natural process by which immunoglobulins undergo somatic hypermutation and selection, as part of the adaptive immune response, in order to increase their binding affinity to their target antigen.

Fusion Antibodies’ RAMP™ platform adopts lessons from nature and combines a rational approach to library design, with rapid in silico selection for both improved binding potential and predicted stability. The result is that we will generate an enriched ‘micro-library’ of variants with improved stability and affinity for the target.

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Our process

Step 1: Rational Library Design

Using our proprietary library design, we explore the natural somatic hypermutation space of your antibody sequence, identifying motifs that are susceptible to mutation. Our library design incorporates mutations in both the framework and complementarity determining regions (CDRs) of the antibody. Framework diversity has been a key factor in the success of the Fusion Antibodies CDRx™ humanization platform and is critical in making this the most efficient affinity maturation platform available to the market.

Furthermore, our library design algorithms explicitly filter candidate sequences including sequence liabilities, which is important for the downstream manufacturability and cost of goods (COGs) of the selected antibodies.

Step 2: In Silico Selection

Using in silico modelling and molecular docking we interrogate the library of antibody variants, 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 approx. 100 sequences. Due to the manageable number of variants they can be expressed in a full IgG format in mammalian cells which negates any selection bias that can occur with phage display approaches that require a scFv format and bacterial expression.

Step 3: ‘Micro-Library’ Expression and Characterisation

The enriched library (of approx. 100 variants) is expressed in the full IgG format in CHO cells and purified prior to in vitro characterisation. Target binding (ELISA, BLI), expression yield and stability (DSF) are assessed for each antibody variant and parental control. Specificity, aggregation propensity and other biophysical characteristics may also be assessed at this stage.

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™.

 

RAMP™ Highlights

  • 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

 

Flexible Work Packages

We understand what is important to you. Fusion Antibodies can offer a complete range of services from antibody humanization, affinity maturation and stable expression. You may choose to include/exclude as many stages as you would like from your final package. Our goal is to develop the best possible antibodies using our custom package of services to support your development pathway.

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