Abstract

We have recently enhanced our antibody drug discovery capabilities at LifeArc with the use of the IntelliSelect® technology platforms to rapidly generate in vivo mature, fully human monoclonal antibodies. Here we describe the use of the Darwin transgenic mice, combined with a high throughput antibody screening platform to deliver candidate therapeutics with the most desirable drug-like properties. Darwin mice were immunised with target antigen(s), B cells isolated from spleen and lymph nodes and antigen positive B cells were single cell sorted into 96 well plates using Fluorescent Activated Cell Sorting. Next Generation Sequencing was then used to determine the identity of the paired antibody sequences, followed by Intelliselect Screening which enabled B cell network analysis of 10000’s of antibody sequences. Cluster analysis was then performed to select 100’s of antibody clones of interest which were representative of clusters and singletons for synthesis, high throughput transfection and expression in mammalian cells and profiling in a number of biochemical and functional assays. This led to the identification of 10 functionally active antibodies which all exhibited excellent biophysical properties suitable for further therapeutic development.