TABLE 1

Plasma pharmacokinetic parameters from subcutaneous dosing of multiple siRNAs to male (M) and female (F) rats and monkeys

siRNA	Dose	Plasma Pharmacokinetic Properties after Subcutaneous Administration to Monkeys
		C_max		AUC_last		T_max		t_1/2		Dose at C_max
		M	F	M	F	M	F	M	F	M	F
	mg/kg	ng/ml		hng/ml*		h				%
1	0.3	40.6	57.6	233	266	1	2	8.79	ND	0.159	0.225
	3	634	598	4700	3310	2	2	2.78	2.11	0.248	0.234
	10	2530	2860	15,700	16,600	2	2	1.96	5.84	0.297	0.335
2	1	89.3	173	279	465	1	1	ND	ND	0.105	0.203
	5	857	702	4820	4260	2	2	ND	ND	0.201	0.165
	10	2060	2030	11,300	10,600	1	2	3.36	ND	0.242	0.238
15	0.3	43.8	30.6	189	162	1	1	2.38	2.84	0.171	0.119
	1	96.2	112	695	686	1	1	3.24	3.37	0.113	0.131
	3	358	425	2190	2680	2	2	2.79	2.5	0.140	0.166
3	1	72.9	64	112	87	2	2	ND	ND	0.0854	0.075
	5	386	281	1930	1690	2	2	ND	ND	0.0904	0.0658
	25	2560	2130	19,700	12,000	2	1	3.79	6.13	0.120	0.0998
4	0.3	82.1	86.8	198	204	1	1	ND	ND	0.321	0.339
	1	245	311	843	949	1	0.5	2.55	1.52	0.287	0.364
	5	1140	1250	5610	5850	1	1	3.04	1.81	0.268	0.293
	20	6770	4480	44,000	38,000	2	4	8.49	ND	0.396	0.263
5	0.1	13.8	13.2	168	22.5	4	1	ND	ND	0.161	0.155
	1	181	129	12,200	1140	2	2	ND	9.94	0.212	0.151
	5	1160	985	5590	4240	2	2	ND	ND	0.272	0.231
	10	1570	2250	12,100	10,700	2	2	3.58	ND	0.184	0.263
6	0.3	42.2	37.6	119	127	0.5	2	6.22	ND	0.165	0.147
	1	90.6	99.7	586	662	4	4	ND	ND	0.106	0.117
	3	549	299	3140	1600	4	2	ND	ND	0.214	0.117
	30	7760	6920	63,100	66,100	2	4	2.7	ND	0.303	0.270
siRNA	Dose	Plasma Pharmacokinetic Properties after Subcutaneous Administration to Rats
siRNA	Dose	C_max		AUC_last		T_max		t_1/2		Dose at C_max
		M	F	M	F	M	F	M	F	M	F
	mg/kg	ng/ml		hng/ml*		h				%
1	0.3	34.7	29.1	39.6	16.8	1	1	ND	ND	0.453	0.381
	1	90.5	92.4	174	171	1	1	ND	ND	0.355	0.363
	3	290	301	494	479	1	1	ND	ND	0.379	0.395
	10	1430	1060	3740	2120	1	1	ND	1.38	0.561	0.415
2	1	98	112	141	158	0.25	0.25	ND	2.54	0.384	0.44
	1	102	113	254	164	2	1	ND	ND	0.401	0.442
	5	466	386	1400	1110	0.5	0.25	3.14	1.66	0.365	0.303
	5	568	455	1580	1240	2	1	ND	ND	0.445	0.357
	10	976	1170	2390	2980	0.25	2	3.31	ND	0.383	0.458
	10	1120	1550	4150	3820	2	2	6.33	ND	0.441	0.607
3	2.5	230	285	320	371	0.5	0.5	ND	ND	0.36	0.447
	5	514	639	934	762	1	0.5	ND	ND	0.403	0.502
	25	4450	3980	10,300	7080	1	1	1.43	ND	0.698	0.625
4	0.3	71.4	93.9	101	111	0.5	0.5	ND	ND	0.933	1.23
	1	312	207	415	262	0.5	0.5	0.969	ND	1.22	0.814
	5	943	943	1840	2020	0.25	0.5	0.931	0.83	0.739	0.741
	20	4130	4990	16,200	10,600	0.5	1	ND	1.02	0.809	0.981
5	0.1	21.7	22	15	14.2	0.5	0.5	ND	0.987	0.849	0.865
	1	271	335	381	498	0.5	0.5	1.03	ND	1.06	1.32
	5	1010	874	1820	2020	0.5	1	1.05	1.11	0.793	0.687
	10	2200	2430	4770	4620	1	0.5	0.914	ND	0.864	0.955

F, female; M, male; ND, not determined.