Antibody Discovery 

 

Speed and success through our focus on synthetic antibodies.

 

Isogenica is developing LlamdA™ (single domain VHH) and Alexandria™ (human Fab) therapeutic antibodies based on our proprietary fully synthetic antibody libraries and leveraging our CIS Display and Colibra™ technologies to accelerate the discovery.

 

Synthetic Antibody Libraries

 

Constructed de novo using our Colibra™ precision fabrication system – a proprietary synthetic biology platform – and building on designs informed by computational immunology, Isogenica’s fully synthetic antibody libraries are more than 1 million times larger than libraries generated from natural sources, increasing our opportunity to source multiple novel candidates with high specificity and affinity.

The combination of superior design and Colibra™ precision fabrication has reduced by 50% the number of liability motifs compared to non-Colibra™ libraries meaning that hits directly from our libraries are more candidate-like than other approaches.

Our immunologically naïve synthetic libraries also offer the possibility to discover therapeutic antibodies against a greater range of targets and target epitopes, overcoming issues of self-tolerance and the dominant epitope bias of natural repertoires.

 

Where discovery begins: Selections using CIS Display

 

Isogenica’s massive synthetic libraries are most optimally screened for antibody binders against soluble proteins or membrane targets (cell-based selections) using the company’s proprietary CIS Display platform.

 

Based around the DNA-binding properties of the RepA protein, CIS display allows the panning of polypeptide libraries via the faithful link between each displayed library member and the dsDNA template encoding it.

 

CIS display exploits the benefits of cell-free systems in allowing routine access to around 1013 library members, whilst the use of a dsDNA template ensures a robust system suited to simple PCR-based product recovery and library construction.

 

The Advantages of CIS display

  • No transformation, unlike phage display
  • DNA-based system, not RNA
  • CIS-activity of DNA-binding protein RepA creates stable genotype-phenotype linkage
  • >1013 expressed in vitro and panned by affinity selection
  • Eluted complexes regenerated by simple PCR
  • Optimal ligands after 3-5 successive rounds
  • Robust methodology and easy technology transfer

 

Turning Hits into Leads: Lead Optimisation with Colibra and antibody engineering

 

Isogenica’s experienced team are skilled in reformatting single domain VH and Fab library hits to a wide range of formats including multi-specifics and fusion proteins to optimise affinity and develop novel modes of action.