Table 1.
Fixed and calibrated parameters to describe whole‐body catabolic capacity for antibody
| Parameter | Value | Reference |
|---|---|---|
| Fitted | ||
| Tg32 endothelial cell number (N endo) | 14.2E8 | In same range as literature reports27, 28, 29 |
| Human endothelial cell number (N endo) | 0.86E12 | In same range as literature reports27, 28, 29 |
| k on ratio (FcRn binding #1/#2) | 83.7 | k on_2 10–1,000 fold slower due to limited membrane diffusion |
| Kd 7.4/Kd 6.0 ratio | 220 | Literature suggests values spanning 20×–250×34, 35 |
| Fixed | ||
| Transit time (T endo) (minutes) | 11 | 19, 29 |
| Uptake rate (CLup) (nL/hour/1E6 cells) | 150 | 23 |
| Prob_deg (%) | 98 | Assumed based on S. Ward personal communication (>95%) |
| FcRn tissue levels (nMoles) | 1.1/1022 | (Tg32 mouse/human)30, 31 |
| kdeg_FcRn_Ab (FcRn turnover; min−1) | 0.062 | 11.1 hour half life 31 |
CLup, pinocytotic uptake rate of endothelial cells; FcRn, neonatal Fc receptor; Kd, equilibrium constant for mAb‐FcRn binding; kdeg_FcRn_Ab, degradation rate of FcRn‐mAb complex at pH 7.4; k on, association rate constant for mAb‐FcRn binding; Prob_deg, probability of mAb degradation in the absence of FcRn binding; T endo, endosomal transit time.