Crovalimab (SKY59; RO7112689) is a novel humanized monoclonal antibody designed to target complement component 5 (C5) in a pH-dependent manner. It exhibits dissociation constants (K_D) of 15.2 nM at pH 7.4 and 16.8 ??M at pH 5.8, reflecting its pH-responsive binding affinity. Additionally, Crovalimab demonstrates strong binding to human FcRn with a K_D of 17 ??M at pH 6.0. This antibody effectively blocks the cleavage of C5 by C5 convertase and inhibits the activity of a specific C5 variant characterized by the p.Arg885His mutation. Furthermore, Crovalimab significantly inhibits the formation of the terminal complement complex C5b-9 across all three complement pathways: classical, lectin, and alternative. Due to these properties, Crovalimab is of significant interest for research into paroxysmal nocturnal hemoglobinuria (PNH) and other complement-mediated diseases, offering potential insights into novel therapeutic approaches.
Crovalimab (SKY59; RO7112689) is a novel humanized monoclonal antibody designed to target complement component 5 (C5) in a pH-dependent manner. It exhibits dissociation constants (K_D) of 15.2 nM at pH 7.4 and 16.8 ??M at pH 5.8, reflecting its pH-responsive binding affinity. Additionally, Crovalimab demonstrates strong binding to human FcRn with a K_D of 17 ??M at pH 6.0. This antibody effectively blocks the cleavage of C5 by C5 convertase and inhibits the activity of a specific C5 variant characterized by the p.Arg885His mutation. Furthermore, Crovalimab significantly inhibits the formation of the terminal complement complex C5b-9 across all three complement pathways: classical, lectin, and alternative. Due to these properties, Crovalimab is of significant interest for research into paroxysmal nocturnal hemoglobinuria (PNH) and other complement-mediated diseases, offering potential insights into novel therapeutic approaches.
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