Example 6
Tg32 mice were homozygous, 8 week old, males. There were 4 mice per test article group. The test articles included CDA1-WT, CDA1-FcMut008, and CDA1-FcMut015. The mice were dosed at 10 mg/Kg by IV administration. Data were collected at thirteen time points (1 h, 8 h, 1 d, 2 d, 3 d, 4 d, 6 d, 8 d, 10 d, 13 d, 16 d, 19 d, and 22 d). Human IgG was quantified by ELISA using an anti-hIgG polyclonal antibody.
Tg32 is a human FcRn transgenic mouse model that can be used in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies. Monoclonal antibody clearance in Tg32 homozygous mice has the strongest correlation to monoclonal antibody clearance in humans (Avery et al. MAbs. 2016; 8(6):1064-78).
CDA1 (actoxumab) is known to have a half-life of >25 days in human. In vivo evaluation with additional mAbs in Tg32 model was performed. The different constructs can also be evaluated on Tg276 mice which are reported to have increased half-life differences between IgG variants. The results are shown in Table 2 and
