mAbs · Available online 30 Jul 2026 · In press · DOI 10.1080/19420862.2026.2709948
Santosh Kumar Paidi, Julissa Ibrahim, Kateryna Stepurska, Jonathan Zarzar, Saeed Izadi, Erina Rude, Steven Luu, Daniel Kovner, Kelly O’Connor, Karenna Bol, Shrenik Mehta, Nisana Andersen, Nicole Stephens, Emily Makowski, Joel Heisler, Trevor Swartz, Paul J. Carter, Tomasz Baginski
Predicting high-concentration viscosity of monoclonal antibodies is crucial for their development as therapeutics for subcutaneous delivery, but traditional experimental rheometry methods for assessing viscosity are low-throughput, which limits their utility. This study evaluates self-interaction nanoparticle spectroscopy (SINS) assays – specifically charge-stabilized SINS (CS-SINS) and PEG-stabilized SINS (PS-SINS) – for high-throughput viscosity prediction. We characterized 96 IgG1 antibodies, assessing SINS against in silico descriptors and dynamic light scattering (DLS) data. CS-SINS showed strong correlation with charge, offering limited additional utility. In contrast, PS-SINS provided orthogonal information; integrating it with in silico data and DLS significantly improved random forest model accuracy for binary viscosity classification. PS-SINS measurements in multiple buffers captured complementary information, achieving comparable accuracy without DLS. Importantly, PS-SINS scores exhibited a strong logarithmic relationship with high-concentration viscosity in Fc variants of clinical antibodies (r = 0.72 and r = 0.85 for trastuzumab and omalizumab variants, respectively), suggesting a direct mechanistic link. Furthermore, PS-SINS performed reliably with one column-purified (protein A) samples, supporting its early-stage application. These findings establish PS-SINS as a high-throughput tool to accelerate the developability assessment of antibody candidates.
Abstract from DOAJ. Public domain (CC0 1.0).
Read the article at the publisher →
Paidi, S., Ibrahim, J., Stepurska, K., et al. (2026). Self-interaction nanoparticle spectroscopy predicts high-concentration viscosity of therapeutic IgG1 antibodies. mAbs. https://doi.org/10.1080/19420862.2026.2709948