Economical Preclinical PK Immunoassay for Human IgG Therapeutics and IgG Fc Conjugates in Mice, Rats, and Nonhuman Primates

Economical Preclinical PK Immunoassay For Human IgG Therapeutics And IgG Fc Conjugates In Mice, Rats, And Nonhuman Primates

Background

A start-up biotechnology company developed a library of constructs having the Fc portion of human IgG and their warhead denoted as X for confidential reasons.  Fc-X fusion protein drug candidates were distinguished by amino acid substitutions in the warhead moiety, changes that were predicted to affect PK characteristics.  They needed a PK assay in mice but didn’t want to exert the time and expense of developing and validating assays for each drug candidate.  They envisioned needing an assay in other preclinical species too.

The Challenge

This was viewed as an opportunity for MicroConstants to offer a widely applicable preclinical bioanalytical method to quantitate intact human therapeutic antibodies as well as molecular constructs of human IgG Fc plus warhead.  The goal was to make available such an assay for studies in mice, rats, and non-human primates.  Further, it was desired that the assay method for each species would be as similar as possible across species to allow for ease of comparisons if necessary.  Finally, high sensitivity, selectivity, and reproducibility across species were also key goals.  Please refer to the following link of the study (https://www.microconstants.com/wp-content/uploads/AAPS-PharmSci-360-2018-Immunoglobulin.pdf).

The Solution

A highly sensitive immunoassay was developed using Meso Scale Discovery (MSD) electrochemiluminescence as the assay platform and cross-species absorbed antibodies specific for human IgG as capture and probe (see link for publication).  The assay allowed for the client to conduct an efficient PK assessment  on their Fc-X drug candidates in mice.  Furthermore, the immunoassay in now offered generally by MicroConstants for clients interested in conducting such PK assessments of their drug candidates in mice, rats, or nonhuman primates.