TABLE 3

Pharmacokinetic parameters for five humanized WT mAbs and the T250Q/M428L and the V308P Fc variants in cynomolgus monkeys after intravenous administration

Serum concentrations determined using validated antigen capture ELISAs. Data are the mean ± S.D. of the pharmacokinetic parameters determined from five monkeys per group for the V308P and T250Q/M428L Fc variants and 10 monkeys (across two studies with n = 5 monkeys/study) for the WT IgGs. Determined from noncompartmental pharmacokinetic analyses.

mAb	C_max	AUC_0-∞	CL	t_1/2β
	μg/ml	μg · h/ml	ml · h⁻¹ · kg⁻¹	h
A1 WT	27 ± 2	4264 ± 1242	0.25 ± 0.06	328 ± 162
A1 V308P	38 ± 8	6972 ± 1311	0.15 ± 0.04	637 ± 127
A1 T250Q/M428L	22 ± 5	5069 ± 1063	0.20 ± 0.05	285 ± 59
B1 WT	41 ± 5	5705 ± 2622	0.21 ± 0.11	268 ± 50
B1 V308P	34 ± 10	7651 ± 1505	0.14 ± 0.03	526 ± 154
B1 T250Q/M428L	30 ± 4	7850 ± 1080	0.13 ± 0.02	336 ± 146
C1 WT	25 ± 5	2843 ± 192	0.35 ± 0.02	126 ± 17
C1 V308P	20 ± 2	3503 ± 320	0.26 ± 0.05	289 ± 88
C1 T250Q/M428L	17 ± 2	3324 ± 507	0.31 ± 0.04	263 ± 59
D1 WT	28 ± 5	1905 ± 453	0.55 ± 0.14	126 ± 46
D1 V308P	19 ± 3	2588 ± 341	0.40 ± 0.05	351 ± 52
D1 T250Q/M428L	24 ± 0.6	2910 ± 587	0.35 ± 0.08	278 ± 107
E1 WT	18 ± 4	1347 ± 640	0.88 ± 0.44	94 ± 51
E1 V308P	26 ± 5	5426 ± 697	0.19 ± 0.02	310 ± 49
E1 T250Q/M428L	23 ± 3	3863 ± 849	0.27 ± 0.06	246 ± 115

C_max, maximal observed serum concentration; CL, clearance; t_1/2β, elimination half-life.