High-throughput Service for Mutational Activity Maps of Therapeutic Proteins Introduced

ProImmune have announced the introduction of MutaMap™, a new high-throughput assay service for understanding the impact of point mutations on protein therapeutic activity, including monoclonal antibodies. MutaMap provides a high-throughput service, with high-quality output data, to help decide which individual point mutations to pursue and enable better protein engineering decisions to be made, prior to committing a drug candidate to a clinical program.

MutaMap is an in vitro assay system that explores the effect of deliberate point mutations on protein activity by substituting each of the 19 possible amino acid alternatives in each position in a protein sequence, one by one. Each position of a protein of interest is altered by site-directed mutagenesis, expressed and changes in affinity or activity measured using cell-free in vitro translation of proteins and solution titration assays. These methods avoid the use of surrogate measurements for affinity or activity and have been optimised for high-throughput processing of samples without compromising on readout accuracy. The technology is particularly suited for investigating a range of the ligand-binding interactions, from high-affinity monoclonal antibodies down to the high-femtomolar range where other approaches, such as surface plasmon resonance (SPR), struggle to deliver results in high throughput.

MutaMap can deliver a high-throughput mutagenesis project for exploring 500-2000 mutations in approximately 8-12 weeks and deliver a heat map for the protein sequence of interest, showing which point mutations lead to an increase, decrease, or no change in affinity (or other activity), or non-function of the protein of interest when interacting with one, or more, of its binding partners. This effectively reveals which mutations are likely permissible or favourable for protein engineering and provides a novel tool for making informed decisions across a range of key developability objectives. These can include cherry picking mutations to improve activity, de-immunisation, altering cross-species reactivity, improved humanisation or provision of other engineered features, stability and manufacturability, prolonging half-life and developing unique new composition of matter IP.

MutaMap is the first service ProImmune is offering in the area of protein engineering. The technology is complementary to the company’s existing technologies for assessing the antigenicity of therapeutic proteins and can be readily combined with ProImmune’s leading ProMap® and ProScern® T cell assays, ProPresent® Antigen Presentation Assays and ProImmune REVEAL® MHC-peptide binding assays.