title: Effects of arginine on photostability and thermal stability of IgG1 monoclonal antibodies.
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 (T(m)) of IMC-1A as determined by differential scanning calorimetry (DSC) was significantly decreased ( approximately 3.3 degrees 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.
authors: Formulation Development, ImClone Systems, A Wholly-Owned Subsidiary of Eli Lilly and Company, 59-61 ImClone Drive, Branchburg, NJ 08876, USA. haripada.maity@imclone.com
authors: Haripada
authors: H
authors: Maity
authors: Courtney
authors: C
authors: O'Dell
authors: Arvind
authors: A
authors: Srivastava
authors: Joel
authors: J
authors: Goldstein
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001120:Arginine / Q000494:pharmacology*; D002021:Buffers; D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007074:Immunoglobulin G / Q000737:chemistry*; D008027:Light; D055668:Photochemical Processes; D017510:Protein Folding; D055550:Protein Stability; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal; D002021:Buffers; D007074:Immunoglobulin G; D001120:Arginine