Abstract
This study demonstrates that arginine is a highly effective solvent additive which significantly reduces the light induced aggregation of four IgG1 type monoclonal antibodies (named as IMC-1A, IMC-1B, IMC-1C and IMC-1D) as measured by size exclusion chromatography. All experiments were performed in a phosphate buffer system containing either sodium chloride or arginine hydrochloride. The protein samples were exposed to light in a photo chamber according to ICH (International Conference on Harmonization) guidelines. Thermal unfolding transition temperature (Tm) of IMC- 1A as determined by differential scanning calorimetry (DSC) was significantly decreased (∼ 3.3°C) in the presence of arginine hydrochloride as compared to in sodium chloride. However, a noticeable increase in thermal stability was observed for IMC-1B, IMC-1C and IMC-1D in the presence of arginine hydrochloride. The photostability of all these molecules was significantly enhanced by arginine hydrochloride and both a direct and inverse correlation was observed between conformational stability and photostability. To our knowledge, this paper for the first time, demonstrates that arginine hydrochloride considerably reduces the light induced aggregation of monoclonal antibodies. Arginine hydrochloride is also known to increase protein solubility and its ability to extensively reduce light induced aggregation makes it a potential solvent additive for the formulation development of therapeutic proteins.
Keywords: Photostability, thermal stability, differential scanning calorimetry, aggregation, IgG1
Current Pharmaceutical Biotechnology
Title: Effects of Arginine on Photostability and Thermal Stability of IgG1 Monoclonal Antibodies
Volume: 10 Issue: 8
Author(s): Haripada Maity, Courtney O'Dell, Arvind Srivastava and Joel Goldstein
Affiliation:
Keywords: Photostability, thermal stability, differential scanning calorimetry, aggregation, IgG1
Abstract: This study demonstrates that arginine is a highly effective solvent additive which significantly reduces the light induced aggregation of four IgG1 type monoclonal antibodies (named as IMC-1A, IMC-1B, IMC-1C and IMC-1D) as measured by size exclusion chromatography. All experiments were performed in a phosphate buffer system containing either sodium chloride or arginine hydrochloride. The protein samples were exposed to light in a photo chamber according to ICH (International Conference on Harmonization) guidelines. Thermal unfolding transition temperature (Tm) of IMC- 1A as determined by differential scanning calorimetry (DSC) was significantly decreased (∼ 3.3°C) in the presence of arginine hydrochloride as compared to in sodium chloride. However, a noticeable increase in thermal stability was observed for IMC-1B, IMC-1C and IMC-1D in the presence of arginine hydrochloride. The photostability of all these molecules was significantly enhanced by arginine hydrochloride and both a direct and inverse correlation was observed between conformational stability and photostability. To our knowledge, this paper for the first time, demonstrates that arginine hydrochloride considerably reduces the light induced aggregation of monoclonal antibodies. Arginine hydrochloride is also known to increase protein solubility and its ability to extensively reduce light induced aggregation makes it a potential solvent additive for the formulation development of therapeutic proteins.
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Cite this article as:
Maity Haripada, O'Dell Courtney, Srivastava Arvind and Goldstein Joel, Effects of Arginine on Photostability and Thermal Stability of IgG1 Monoclonal Antibodies, Current Pharmaceutical Biotechnology 2009; 10 (8) . https://dx.doi.org/10.2174/138920109789978711
DOI https://dx.doi.org/10.2174/138920109789978711 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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