Human Phage Display

Overview

Antibody discovery technology that incorporates human volunteer-derived antibody sequences into bacteriophage particles displaying antibody fragments on their surface; incubation with a target antigen selects binders that are sequenced, generating large initial hit sets screened by activity and biophysical assays. A human phage display library was used to discover mastacimab; the library is created by incorporating antibody sequences from human volunteers into phage particles that display antibody fragments on their surface, which are incubated with the TFPI K2 domain target and binders sequenced, generating large hit sets in the low nanomolar binding range. Hits from the TFPI phage display screen were screened for activity using an ex vivo thrombin generation assay with plasma from hemophilia patients, and a large number of crystal structures were solved to confirm binding to the correct K2 domain region — specifically the arginine that projects into the factor Xa active site. (Antibody Discovery by Phage Display (25:00-30:00))