Extrapolating differential scanning calorimetry data for monoclonal antibodies to low temperatures.

Publisher: Elsevier Country of Publication: United States NLM ID: 0370535 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0309 (Electronic) Linking ISSN: 00032697 NLM ISO Abbreviation: Anal Biochem Subsets: MEDLINE

Publication: <2000- > : San Diego, CA : Elsevier
Original Publication: Orlando Fl : Academic Press

Antibodies, Monoclonal*/chemistry ; Calorimetry, Differential Scanning* ; Protein Denaturation*; Cold Temperature ; Temperature ; Protein Stability ; Thermodynamics

For irreversible denaturation transitions such as those exhibited by monoclonal antibodies, differential scanning calorimetry provides the denaturation temperature, T m , the rate of denaturation at T m , and the activation energy at T m . These three quantities are essential but not sufficient for an accurate extrapolation of the rate of denaturation to temperatures of 25 °C and below. We have observed that the activation energy is not constant but temperature dependent due to the existence of an activation heat capacity, C p,a . It is shown in this paper that a model that incorporates C p,a is able to account for previous observations like, for example, that increasing the T m does not always improve the stability at low temperatures; that some antibodies exhibit lower stabilities at 5 °C than at 25 °C; or that low temperature stabilities do not follow the rank order derived from T m values. Most importantly, the activation heat capacity model is able to reproduce time dependent stabilities measured by size exclusion chromatography at low temperatures.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)

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R01 GM057144 United States GM NIGMS NIH HHS

Keywords: Differential scanning calorimetry; Protein stability; Temperature denaturation; mAb aggregation; mAb denaturation

0 (Antibodies, Monoclonal)

Date Created: 20240420 Date Completed: 20240513 Latest Revision: 20240725

20240726

PMC11268162

10.1016/j.ab.2024.115533

38642818