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Optimizing NBE PK/PD assays using the Gyrolab Affinity Software; conveniently within the bioanalyst's existing
Maria Myzithras1, Tammy Bigwarfe1, Erica Waltz1
1Biotherapeutics Discovery, Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA.
Bioanalysis
|February 17, 2018
Summary
This study demonstrates how Gyros affinity software on the Gyrolab platform can characterize binding affinities of therapeutic reagents. It helps optimize bioanalytical assays by investigating target coverage issues in pharmacokinetic/PD studies.
Area of Science:
- Biotechnology and Bioanalysis
- Pharmacokinetics and Pharmacodynamics (PK/PD)
Background:
- The Gyrolab platform is a widely used automated microfluidics system for bioanalysis of protein therapeutics, known for its low sample and reagent requirements.
- Gyros offers specialized affinity software for high-throughput determination of binding affinities in solution using miniaturized reactions.
Purpose of the Study:
- To characterize Connective Tissue Growth Factor (CTGF)-targeting reagents using Gyros affinity software on the Gyrolab instrument.
- To investigate the cause of sub-optimal target coverage observed in a cynomolgus monkey pharmacokinetic/pharmacodynamic (PK/PD) study involving anti-CTGF antibodies.
Main Methods:
- Utilized Gyros affinity software on the Gyrolab platform for high-throughput characterization of multiple CTGF-targeting reagents.
- Analyzed binding affinities of the dosed antibody, target, and assay reagents in the context of a PK/PD study.
Main Results:
- Identified significant differences in binding affinities between the anti-CTGF antibody, CTGF target, and the assay reagents used.
- These binding affinity differences correlated with the observed <100% target coverage in the PK/PD study.
Conclusions:
- The binding affinity data provides insights into the reduced target coverage observed in the bioanalytical assay.
- Highlights the utility of Gyros affinity software for reagent characterization and optimization of PK/PD bioanalytical assays within the Gyrolab workflow.