Figure 6
From: Long-acting antibody ligand mimetics for HER4-selective agonism
In vivo PK profiles of neuregulin fusion proteins. (A) hFcRn transgenic mice serum clearance curves are plotted for parental NRG1-MFc (black), 1F7-MFc (blue), parental antibody ligand mimetic ALM6 (red), and ALM6-1F7 (green), based on concurrent anti-NRG1 and Fc domain binding. Both monomeric Fc fusion and antibody ligand mimetic resulted in extended the serum circulation, compared to a peptide control (black circle). The HER4 selectivity engineered variant 1F7 acquired significant extension of serum half-life, with the lowest clearance rate from ALM6-1F7 (Table 3). (B) ALM6 and ALM6-1F7 serum samples were further analyzed by Fc domain and C-kappa light chain detection and compared with anti-NRG1 detection. Although both methods showed similar PK profiles for ALM6-1F7, the level of intact ALM6 molecules was lower than that of the antibody scaffold. Conc = concentration.
