Identifying biophysical assays and in silico properties that enrich for slow clearance in clinical-stage therapeutic antibodies.

ABSTRACT: Understanding the pharmacokinetic (PK) properties of a drug, such as clearance, is a crucial step for evaluating efficacy. The PK of therapeutic antibodies can be complex and is influenced by interactions with the target, Fc-receptors, anti-drug antibodies, and antibody intrinsic factors. A growing body of literature has linked biophysical properties of antibodies, particularly nonspecific-binding propensity, hydrophobicity and charged regions to rapid clearance in preclinical species and selected human PK studies. A clear understanding of the connection between biophysical properties and their impact on PK would allow for early selection and optimization of antibodies and reduce costly attrition during clinical trials due to sub-optimal human clearance. Due to the difficulty in obtaining

SUBMITTER: Grinshpun B 

PROVIDER: S-EPMC8204999 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature