Development of the SupersonicIEF Method for High-Throughput Charge Variant Analysis.

The analysis of biopharmaceuticals for charge variants occurs from early-stage samples through formulation and process-development optimization. Higher throughput methods allow increased analysis of these samples to facilitate greater understanding of the samples and to better optimize their production and formulation. To enable higher throughput charge variant analysis, a new, rapid platform imaged capillary isoelectric focusing (icIEF) method was optimized to be two to three times faster than standard methods.

Global intercompany assessment of ICIEF platform comparability for the characterization of therapeutic proteins.

An international team spanning 19 sites across 18 biopharmaceutical and in vitro diagnostics companies in the United States, Europe, and China, along with one regulatory agency, was formed to compare the precision and robustness of imaged CIEF (ICIEF) for the charge heterogeneity analysis of the National Institute of Standards and Technology (NIST) mAb and a rhPD-L1-Fc fusion protein on the iCE3 and the Maurice instruments. This information has been requested to help companies better understand how these instruments compare and how to transition ICIEF methods from iCE3 to the Maurice instrument. The different laboratories performed ICIEF on the NIST mAb and rhPD-L1-Fc with both the iCE3 and Maurice using analytical methods specifically developed for each of the molecules.

High-Throughput Screening to Identify Small Molecules That Selectively Inhibit APOL1 Protein Level in Podocytes.

High-throughput phenotypic screening is a key driver for the identification of novel chemical matter in drug discovery for challenging targets, especially for those with an unclear mechanism of pathology. For toxic or gain-of-function proteins, small-molecule suppressors are a targeting/therapeutic strategy that has been successfully applied. As with other high-throughput screens, the screening strategy and proper assays are critical for successfully identifying selective suppressors of the target of interest.

Platform Methods to Characterize the Charge Heterogeneity of Three Common Protein Therapeutics by Imaged Capillary Isoelectric Focusing.

Imaged capillary isoelectric focusing (icIEF) is a gold standard method for characterizing the charge heterogeneity of protein therapeutics. A broad range of protein therapeutics such as monoclonal antibodies, antibody-drug conjugates (ADCs), and fusion proteins are routinely analyzed by icIEF due to its high resolution and high reproducibility. Platform methods, which can be applied without modification to the analysis of different protein therapeutics, save valuable time and resources in method development and quality control.

Live Cell Membranome cDNA Screen: A Novel Homogenous Live Cell Binding Assay to Study Membrane Protein-Ligand Interaction.

Interactions between transmembrane receptors and their ligands play important roles in normal biological processes and pathological conditions. However, the binding partners for many transmembrane-like proteins remain elusive. To identify potential ligands of these orphan receptors, we developed a screening platform using a homogenous nonwash binding assay in live cells.