Ultradilute Measurements of Self-Association for the Identification of Antibodies with Favorable High-Concentration Solution Properties

• Published in: Molecular pharmaceutics 2021-07, Vol.18 (7), p.2744-2753
• Main Authors: Starr, Charles G, Makowski, Emily K, Wu, Lina, Berg, Brendan, Kingsbury, Jonathan S, Gokarn, Yatin R, Tessier, Peter M
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - metabolism; Gold - chemistry; High-Throughput Screening Assays; Humans; Metal Nanoparticles - chemistry; Protein Multimerization; Solubility; Viscosity
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.1c00280

There is significant interest in formulating antibody therapeutics as concentrated liquid solutions, but early identification of developable antibodies with optimal manufacturability, stability, and delivery attributes remains challenging. Traditional methods of identifying developable mAbs with low self-association in common antibody formulations require relatively concentrated protein solutions (>1 mg/mL), and this single challenge has frustrated early-stage and large-scale identification of antibody candidates with drug-like colloidal properties. Here, we describe charge-stabilized self-interaction nanoparticle spectroscopy (CS-SINS), an affinity-capture nanoparticle assay that measures colloidal self-interactions at ultradilute antibody concentrations (0.01 mg/mL), and is predictive of antibody developability issues of high viscosity and opalescence that manifest at four orders of magnitude higher concentrations (>100 mg/mL). CS-SINS enables large-scale, high-throughput selection of developable antibodies during early discovery.