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. 2023 Apr 7;299(5):104685. doi: 10.1016/j.jbc.2023.104685

Figure 4.

Figure 4

Effect of antibody epitope and off-rate on targeted enzyme activity. A, summary of kinetic parameters and EC50 values for the anti-Aβ antibody off-rate series. EC50's are presented as average and standard error from duplicates. B, faster anti-Aβ antibody off-rates lead to improved targeted Aβ proteolytic cleavage in the IgG-CTF-2 fusion format as shown in the in vitro Aβ(1–40) cleavage assay. Targeting of NEP with crenezumab (kd 4.1 × 10−3 1/s) leads to a 3-fold improvement in the EC50 value for Aβ(1–40) cleavage compared to targeting with solanezumab (1.4 × 10−4 1/s). C, correlation between the EC50 value for Aβ(1–40) cleavage and the off-rate for the anti-Aβ targeting antibody. Aβ, amyloid-β; CTF, C-terminal fusion; NEP, neprolysin.