Table 4.
Binding kinetics and pharmacokinetics of CA645 Fab graft variants. Association (ka) and dissociation (kd) rate constants and equilibrium binding constants (KD) determined by SPR. Three mice (M1-3)/group were dosed intravenously at 10 mg/kg with a single CA645 graft variant. Mean and standard deviation (SD) of each group is shown. *measured by steady-state.
| mutation |
SPR |
Half-life (h) |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| CA645 graft variants | Light chain | Heavy chain | ka x105 (1/Ms) | kd x10−4 (1/s) | KD x10−9 (M) | M1 | M2 | M3 | Mean | SD |
| gL4gH5 | – | – | 1.39 | 1.72 | 1.23 | 85 | 88 | 79 | 84 | 4.6 |
| gL5gH5 | W30A | – | 1.26 | 571 | 453 | 120 | 82 | 88 | 96.7 | 20.4 |
| gL4gH37 | – | F58E | 0.61 | 583 | 955 | 55 | 48 | 80 | 61 | 16.8 |
| gL5gH47 | W30A | T100aS | – | – | 52 µM* | 27 | 23 | 29 | 26.3 | 3.1 |
| gL5gH37 | W30A | F58E | – | – | NB | 0.54 | 0.42 | 0.47 | 0.48 | 0.06 |