SKY59: A Long-Lasting Engineered Anti-C5 Antibody for Subcutaneously Injectable Anti-Complement Therapy

Modulating the complement system is a promising approach in drug discovery for overcoming uncontrolled complement activation, which is known to cause various disorders. While these disorders can be effectively treated by inhibiting complement C5 with a therapeutic antibody, the high concentration of C5 in plasma requires a huge dosage and frequent intravenous administration of the antibody. We have generated SKY59, an engineered humanized anti-C5 monoclonal antibody that shows long-lasting neutralization of C5 in cynomolgus monkeys, which enables subcutaneous delivery or less frequent administration. We found that, although the effective duration of the antibody was prolonged by engineering a pH-dependent C5 binding, it was not sufficient to achieve subcutaneous delivery with less frequent administration. Here, we further improved the effectiveness of the pH-dependent anti-C5 antibody by applying a novel approach: surface charge engineering.