Custom Ligand Design

In addition to selectivity and affinity (which are key features of the technology) the screening process also allows incorporation of important attributes that relate to the final purification process, for example binding and elution conditions, contamination in the source material, and ligand stability. This unique combination of selectivity and process functionality has proven to be highly effective in identifying ligands that meet customer requirements regarding defined purification processes. Our ligand discovery process has led to the successful development of purification products for specific clients, resulting in:

• decreased clean-room time and increased yield through significantly reducing the amount of purification steps required
• increased purity by highly specific capturing and removal of host cell proteins
• the ability to elute at pHs that leave the target biotherapeutic completely intact and active
  

A standard custom ligand project can be divided into three phases and typically takes 8 months to complete. The structuring of the project allows for intermediary review and decision points at selected time intervals during the project.

Phase 1

Construction of expression libraries that represent the single domain antibody repertoire of a llama previously immunized with a target molecule of interest from which target specific ligands are isolated.

Phase 2

The resulting immune libraries are screened, at monoclonal level, for ligands that specifically bind to the target molecule. The robustness of our screening process allows the incorporation of specific requirements that closely relate to the final chromatography process, e.g. binding and elution conditions, contamination in the source material, and ligand stability.

Phase 3

In phase 3 the selected ligands are purified and immobilized onto a suitable matrix, followed by small scale affinity chromatography testing of the matrix under defined process conditions. Identified leads can be further evaluated by the customer at small scale.

In many cases BAC may already have an antigen library available, in which case phase I of the study does not need to be performed. Moreover, if a library exists BAC can easily probe that library for potential binders, increasing the chance of success.

For examples of our custom ligand design capabilities please have a look at our case studies.

After selection of the lead ligands BAC will work together with the customer and a media vendor of the customer’s choice to produce a cGMP compatible resin, including a Regulatory Support File. BAC has successfully completed this for more than 5 affinity resins, currently in clinical design-in.