Small-scale screening method for low-viscosity antibody solutions using small-angle X-ray scattering

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Abstract

In this study, we investigated the concentration range in which self-association starts to form in humanized IgG monoclonal antibody (mAb) solutions. Furthermore, on the basis of the results, we developed a practical method of screening for low-viscosity antibody solutions by using small-angle X-ray scattering (SAXS) measurements utilizing small quantities of samples. With lower-viscosity mAb3, self-association was not detected in the range of 1–80 mg/mL. With higher-viscosity mAb1, on the other hand, self-association was detected in the range of 10–20 mg/mL and was clearly enhanced by a decrease in temperature. The viscosities of mAb solutions at 160, 180, and 200 mg/mL at 25 °C quantitatively correlated very well with the particle size parameters obtained by SAXS measurements of mAb solutions at 15 mg/mL at 5 °C. The quantity of mAb sample required for the SAXS measurements was only 0.15 mg, which is about one-hundredth of that required for actual viscosity measurements at a high concentration, and such quantities could be available even at an early stage of development. In conclusion, the SAXS analysis method proposed in this study is a valuable tool for the development of concentrated mAb therapeutics with high manufacturability and high usability for subcutaneous injection.

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