LAP: Liability Antibody Profiler by sequence & structural mapping of natural and therapeutic antibodies.

ABSTRACT: Antibody-based therapeutics must not undergo chemical modifications that would impair their efficacy or hinder their developability. A commonly used technique to de-risk lead biotherapeutic candidates annotates chemical liability motifs on their sequence. By analyzing sequences from all major sources of data (therapeutics, patents, GenBank, literature, and next-generation sequencing outputs), we find that almost all antibodies contain an average of 3-4 such liability motifs in their paratopes, irrespective of the source dataset. This is in line with the common wisdom that liability motif annotation is over-predictive. Therefore, we have compiled three computational flags to prioritize liability motifs for removal from lead drug candidates: 1. germline, to reflect naturally occurring motifs

SUBMITTER: Satlawa T 

PROVIDER: S-EPMC10957075 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature