# High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice

## TL;DR

This study shows that early screening of antibody interactions can predict their behavior in mice, helping reduce drug development risks.

## Contribution

The study introduces high throughput assays for cross-interaction measures that correlate with antibody clearance rates in mice.

## Key findings

- Clearance rates in mice correlated with two cross-interaction assays, especially a yeast-based non-specificity assay.
- Self-association assays correlated with each other but not with mouse clearance rates.
- Early screening of antibody interactions can help reduce late-stage development risks.

## Abstract

Although improvements in technology for the isolation of potential therapeutic antibodies have made the process increasingly predictable, the development of biologically active monoclonal antibodies (mAbs) into drugs can often be impeded by developability issues such as poor expression, solubility, and promiscuous cross-reactivity. Establishing early stage developability screening assays capable of predicting late stage behavior is therefore of high value to minimize development risks. Toward this goal, we selected a panel of 16 monoclonal antibodies (mAbs) representing different developability profiles, in terms of self- and cross-interaction propensity, and examined their downstream behavior from expression titer to accelerated stability and pharmacokinetics in mice. Clearance rates showed significant rank-order correlations to 2 cross-interaction related assays, with the closest correlation to a non-specificity assay on the surface of yeast. Additionally, 2 self-association assays correlated with each other but not to mouse clearance rate. This case study suggests that combining assays capable of high throughput screening of self- and cross-interaction early in the discovery stage could significantly lower downstream development risks.