Table 2.
Pharmacokinetic properties of optimized decoy receptors in Tg32 mice
| Proteins produced by transiently transfected Expi293Fa | ||||
|---|---|---|---|---|
| sACE22-IgG1 protein | Enzyme treatment | t1/2βb (h) | AUC0–120h (μg/mL × h) | MRT0-inf obsc (h) |
| sACE22.v2.4-IgG1(YTE) | None | 60.1 | 330 | 43.4 |
| sACE22.S19-IgG1(YTE) | None | 73.0 | 510 | 60.8 |
| sACE22.S19-IgG1(YTE) | NA/sialidase | 30.8 | 48 | 2.1 |
| Proteins produced by stable CHOK1SV GS-KO: 8-day studya | ||||
| sACE22-IgG1 protein | t1/2βb (h) | AUC0–192h (μg/mL × h) | MRT0-inf obs (h) | C192h (μg/mL)c |
| sACE22.v2.4-IgG1(YTE) | 124 | 4100 | 160 | 10 ± 2 |
| sACE22.S19-IgG1(YTE) | 224 | 6400 | 312 | 23 ± 3 |
| sACE22.S19-IgG1(YTE) produced by stable CHOK1SV GS-KO: 14-day studyd | ||||
| Route of administration | t1/2βb (h) | AUC0–336h (μg/mL × h) | MRT0-inf obs (h) | C336h (μg/mL)c |
| i.v. | 122 | 8540 | 168 | 9 ± 1 |
| s.c. | 196 | 6170 | 263 | 8 ± 2 |
a
Proteins were administered as a single i.v. dose (10 mg/kg) to Tg32 mice. Plasma concentrations were measured by ELISA for 120 h (Expi293F protein) or 192 h (CHOK1SV GS-KO protein).
b
Beta half-life is determined from 24 to 120 h (Expi293F protein) or 24–192 h (CHOK1SV GS-KO protein).
c
MRT, mean residence time.
d
sACE22.S19-IgG1(YTE) was administered as a single i.v. or s.c. dose (10 mg/kg) to Tg32 mice. Plasma concentrations were measured by ELISA for 336 h.