Florian Cymer1, Tilman Schlothauer2, Alexander Knaupp2, Hermann Beck1. 1. Pharma Technical Development Analytics Biologics, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland. 2. Biochemical & Analytical Research, Large Molecule Research, Roche Pharma Research & Early Development (pRED), Roche Innovation Center, 82377 Penzberg, Germany.
Abstract
AIM: The neonatal Fc-receptor (FcRn) mediates long serum half-life of therapeutic IgG-type antibodies. This interaction represents a critical quality attribute in terms of pharmacokinetics and should be covered by respective quality control strategies. Antibodies are taken up by cells unspecifically and can bind to FcRn in early endosomes preventing lysosomal degradation and allowing release back into circulation. Reflecting this complex cycle in an in vitro assay strategy represents a challenging task. METHODOLOGY: We report the qualification of an FcRn affinity chromatographic method and, for the first time, establish a noncriticality window. We analyzed different IgG-type antibodies, subtypes, glycoforms as well as mutants. CONCLUSION: The FcRn affinity chromatographic method allows the assessment of mAb samples with respect to their pH-dependent FcRn interaction. Furthermore, the method's capabilities and current limitations are discussed.
AIM: The neonatal Fc-receptor (FcRn) mediates long serum half-life of therapeutic IgG-type antibodies. This interaction represents a critical quality attribute in terms of pharmacokinetics and should be covered by respective quality control strategies. Antibodies are taken up by cells unspecifically and can bind to FcRn in early endosomes preventing lysosomal degradation and allowing release back into circulation. Reflecting this complex cycle in an in vitro assay strategy represents a challenging task. METHODOLOGY: We report the qualification of an FcRn affinity chromatographic method and, for the first time, establish a noncriticality window. We analyzed different IgG-type antibodies, subtypes, glycoforms as well as mutants. CONCLUSION: The FcRn affinity chromatographic method allows the assessment of mAb samples with respect to their pH-dependent FcRn interaction. Furthermore, the method's capabilities and current limitations are discussed.
Authors: Nicole A Kratochwil; Stephen R Dueker; Dieter Muri; Claudia Senn; HyeJin Yoon; Byung-Yong Yu; Gwan-Ho Lee; Feng Dong; Michael B Otteneder Journal: PLoS One Date: 2018-10-17 Impact factor: 3.240