Figure 1

Schematic illustration of pro-Canakinumab selective activation by MMP-9 cleavage and specific neutralization of IL-1β at the inflamed region in autoinflammatory diseases. We engineered the human IgG1 hinge as an Ab lock (i.e. EPKSCDKTHTCPPCP) in front of the antigen-binding site of Canakinumab (fully human anti-human IL-1β mAb) by using MMP-9 substrate peptide as linker to generate pro-Canakinumab. After the Ab lock is removed by the MMP-9 expressed in the disease region, the cleaved pro-Canakinumab is expected to be specifically activated, neutralize the local IL-1β antigen and reduce the systemic on-target toxicity during autoinflammatory disease treatment.