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Human FcRn transgene and zygosity affect ligand persistence. (A) Percent <t>belatacept,</t> ipilimumab, and pembrolizumab in plasma compared to concentrations 1 d post IV injection from ADA-free Tg32 hom, Tg32 hemi, Tg276 hom, Tg276 hemi, and FcRn null mice (10 mg/kg), (B) Half-life from ADA-free mice, (C) and allometric scaling of Tg32 hom clearance was correlated to human. (D) Trastuzumab plasma concentrations from IV dosed F1 mice (expressed both Tg32 hemi and Tg276 hemi) with transgenic controls (5 mg/kg), (E) and their trastuzumab half-lives using WinNonlin analysis except Tg276 hemi half-life was manually calculated from two timepoint concentrations. The values represent the mean ± SD. Statistical analysis was performed using either two-way ANOVA and Tukey’s multiple comparisons test, or one-way ANOVA Kruskal–Wallis test as appropriate, where p -values < 0.05 were considered statistically significant.
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Human FcRn transgene and zygosity affect ligand persistence. (A) Percent belatacept, ipilimumab, and pembrolizumab in plasma compared to concentrations 1 d post IV injection from ADA-free Tg32 hom, Tg32 hemi, Tg276 hom, Tg276 hemi, and FcRn null mice (10 mg/kg), (B) Half-life from ADA-free mice, (C) and allometric scaling of Tg32 hom clearance was correlated to human. (D) Trastuzumab plasma concentrations from IV dosed F1 mice (expressed both Tg32 hemi and Tg276 hemi) with transgenic controls (5 mg/kg), (E) and their trastuzumab half-lives using WinNonlin analysis except Tg276 hemi half-life was manually calculated from two timepoint concentrations. The values represent the mean ± SD. Statistical analysis was performed using either two-way ANOVA and Tukey’s multiple comparisons test, or one-way ANOVA Kruskal–Wallis test as appropriate, where p -values < 0.05 were considered statistically significant.

Journal: mAbs

Article Title: Optimizing human FcRn mouse models to improve pharmacokinetic evaluation of antibody drug candidates

doi: 10.1080/19420862.2026.2649990

Figure Lengend Snippet: Human FcRn transgene and zygosity affect ligand persistence. (A) Percent belatacept, ipilimumab, and pembrolizumab in plasma compared to concentrations 1 d post IV injection from ADA-free Tg32 hom, Tg32 hemi, Tg276 hom, Tg276 hemi, and FcRn null mice (10 mg/kg), (B) Half-life from ADA-free mice, (C) and allometric scaling of Tg32 hom clearance was correlated to human. (D) Trastuzumab plasma concentrations from IV dosed F1 mice (expressed both Tg32 hemi and Tg276 hemi) with transgenic controls (5 mg/kg), (E) and their trastuzumab half-lives using WinNonlin analysis except Tg276 hemi half-life was manually calculated from two timepoint concentrations. The values represent the mean ± SD. Statistical analysis was performed using either two-way ANOVA and Tukey’s multiple comparisons test, or one-way ANOVA Kruskal–Wallis test as appropriate, where p -values < 0.05 were considered statistically significant.

Article Snippet: All biologics formulated in this study–including pharmaceutical-grade belatacept (10 mg/kg), ipilimumab (10 mg/kg), pembrolizumab (10 mg/kg), trastuzumab (5 mg/kg and 10 mg/kg), etanercept (20 mg/kg), laboratory-grade glofitamab (MedChemExpress; 2 mg/kg), mosunetuzumab (MedChemExpress; 1 mg/kg), talquetamab (MedChemExpress; 1 mg/kg), conventional IgG monospecific antibody mAb-1 (proprietary source; 3 mg/kg and 10 mg/kg), and mAb-2 (proprietary source; 3 mg/kg and 10 mg/kg)–—were diluted prior to IV administration.

Techniques: Clinical Proteomics, IV Injection, Transgenic Assay