Selection and characterisation of anti-peptide synthetic antibodies for comparison with conventional reagents

Synthetic antibodies, antibodies made without the use of animals, have a number of advantages over traditional antibodies development in animals. Firstly, they avoid the use of animals; in 2019 there was an EU directive stating that animals should not be used in the discovery, production or manufacture of antibodies. Secondly, the success rate is much higher. Standard animal derived methods suffer from genetic instability or contamination of cell lines which can lead to the loss of the antibody. Thirdly, with synthetic antibodies, screening methods can be far more rigorous and elaborate. Finally, synthetic antibodies are manufactured recombinantly which makes them suitable for engineering.

The market for antibody discovery and production is large and is continuing to grow.  The global antibody market size was valued at USD 130.9 Billion in 2020 and estimated to grow USD 223.7 Billion by end of 2025. The market is growing at a CAGR of 11.31% during the forecast period (Market Data Forecast).

The market for diagnostic and research antibodies alone is large - with Research Antibodies and Reagents Market to Reach $6.32 Billion by 2027, at a CAGR of 5.6% from 2020 (Meticulous Research® Analysis)

Challenge

Until now, phage display (PD) has mostly been reserved for use in therapeutics due to its high price; a typical traditional monoclonal antibody development project is £10-15k, by PD this would be around £30-60k. This price means that it is not currently economically viable for use in diagnostics. TAC aims to significantly reduce the cost and make PD economically viable for diagnostics and for research by creating its own cell line and vector, and by streamlining the process and reducing margins as done for diagnostics manufacturing.

The Antibody Company (TAC) wants to bring this synthetic antibody technology in-house. As a proof of concept, the company wanted to develop a synthetic antibody to a peptide found on a cell surface marker. They would then test if it is possible to generate a good quality antibody to this peptide, measure its affinity and express it recombinantly as a full IgG.

Solution

With IBioIC Feasiblity funding of just under £20k, TAC was able to work with Dr Kathryn Ball and Dr Tedd Hupp at the University of Edinburgh utilising an immortal phage display library that encompassed a wide range of heavy and light chains which was compared to a commercially available antibody.

Two antibodies were developed using a technique called biopanning – using a protein to catch binding partners - of the University of Edinburgh’s phage display library.

Successful biopanning vs antigens generated active pools of scFv-bacteriophage and a higher-throughput screening method was developed for deconvolution of pools into monoclonal active phages. A pipeline for conversion of scFv sequences into IgG expression vectors for IgG purification was developed along with methods for analysing purified IgG and comparison with purified scFv. Finally, two anti-BCMA IgG sequences, with distinct activity profiles, were developed.

Outcome

Despite technical challenges which caused the project to take longer than anticipated, the project developed two antibodies using biopanning of the phage display library and both TAC and University of Edinburgh significantly increased their knowledge.

TAC has subsequently successfully applied for further funding, enabling the project to continue. TAC has brought on new staff to pursue these projects and antibody discovery for therapeutic and diagnostic uses in Scotland has been stimulated, indicating significant potential to directly and indirectly benefit the Scottish economy.

In addition, Scottish universities and companies currently look to England and Europe for their therapeutic antibody discovery and development. By providing the first step here in Scotland with a company that has already helped develop therapeutic drugs, it will keep this work local, benefit the economy, and enhance the reputation of Scotland as a site of therapeutic development.

Finally, further market analysis is being undertaken by students at University of Strathclyde in a knowledge-exchange exercise.