Figure 3.

Comparison of nontargeted and targeted proteolytic degradation of Aβ in different fusion formats. Antibody-targeting of C-terminal–fused NEP improves the EC₅₀ value of Aβ(1–40) (top) and Aβ(1–42) (middle) by an average of 15-fold and 9-fold, respectively, compared to nontargeted controls, while the N-terminal fusion format shows no improved activity upon targeting. All targeted formats contain the variable domain of the anti-Aβ antibody crenezumab. Formats of the same enzyme and Fab valency and enzyme fusion site are compared in each plot along with enzyme alone. The key shows the EC₅₀ values and visually depicts the targeted and nontargeted formats. Error bars represent standard error values with n = 2. Aβ, amyloid-β; CTF, C-terminal fusion; Fc, fragment crystallizable; IgG: immunoglobulin G; NEP, neprolysin; NTF, N-terminal fusion; scIgG, monovalent single-chain immunoglobulin G.