کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10162636 | 1114336 | 2014 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Stability of Monoclonal Antibodies at High-Concentration: Head-to-Head Comparison of the IgG1 and IgG4 Subclass
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Few studies have so far directly compared the impact of antibody subclass on protein stability. This case study investigates two mAbs (one IgG1 and one IgG4) with identical variable region. Investigations of mAbs that recognize similar epitopes are necessary to identify possible differences between the IgG subclasses. Both physical and chemical stability were evaluated by applying a range of methods to measure formation of protein aggregates [sizeexclusion chromatography (SEC)-HPLC and UV340 nm], structural integrity (circular dichroism and FTIR), thermodynamic stability (differential scanning calorimetry), colloidal interactions (dynamic light scattering), and fragmentation and deamidation (SEC-HPLC and capillary isoelectric focusing). The impact of pH (4-9) and ionic strength (10 and 150Â mm) was investigated using highlyconcentrated (150Â mg/mL) mAb formulations. Lower conformational stability was identified for the IgG4 resulting in increased levels of soluble aggregates. The IgG1 was chemically less stable as compared with the IgG4, presumably because of the higher flexibility in the IgG1 hinge region. The thermodynamic stability of individual mAb domains was also addressed in detail. The stability of our mAb molecules is clearly affected by the IgG framework, and this study suggests that subclass switching may alter aggregation propensity and aggregation pathway and thus potentially improve the overall formulation stability while retaining antigen specificity. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:115-127, 2014
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 1, January 2014, Pages 115-127
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 1, January 2014, Pages 115-127
نویسندگان
Martin S. Neergaard, Anders D. Nielsen, Henrik Parshad, Marco Van De Weert,