YH007 is a therapeutic antibody cocktail therapy targeting the novel coronavirus (SARS-CoV-2), which was developed in the RenMab model, a fully humanized immunoglobulin mouse model created using Biocytogen’s proprietary gene editing technologies. Cryo-EM data indicates that the two fully humanized monoclonal antibodies Ab1 and Ab5 bound to S protein of SARS-CoV-2 without competition, and both had obvious neutralizing activity. This project is in the stage of CMC development.
Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.