Table 2.

The in vivo effect of orally administered BSA versus chemically modified PAL variants, on plasma Phe concentrations, in the PKU mouse model

	Total Dose(I.U.)a	Pre-dosing plasma[Phe] (uM ± s.e.m.)	Time of measure(hour post initial dosing)	Reduction in plasma [Phe] (pre- versus post-initial dosing)
				(uM ± s.e.m.)	p value	compared with control treatment*(uM)
BSA-Control – highest concentration (46.0 mg/ml)	0	959.2 ±44.3	6	−44.6 ±99	NA	NA
BSA-Control – lowest concentration (5.5 mg/ml)	0	812.6 ±35	5	122 ± 26	NA	NA
			6	15.3 ± 44	NA	NA
Rt-PAL+ aprotinin	2.88	1147.6± 108	3	303.5 ±30	0.0005	251.8
Av-p.C503S/p.C565S PAL + aprotinin	0.99	1251.7±68	3	468.6 ±15	<0.0001	371.1
20 kDa PEGylated-Av- p.C503S/p.C565S PAL	0.99	1159.7± 80	3	239.0 ±62	0.1673	70.8
Av-p.C503S/p.C565S/p.F18A PAL+ aprotinin	11.34	826.3 ±26	5	496.7 ±129	0.0172	432.3
5 kDa PEGylated-Av- p.C503S/p.C565S/p.F18A PAL	14.34	1052.4± 74	5	425.5 ±66	0.0029	470.2
10 kDa PEGylated-Av- p.C503S/p.C565S/p.F18A PAL	9.54	750.4 ±91	5	286.9±115	0.2235	222.5
20 kDa PEGylated-Av- p.C503S/p.C565S/p.F18A PAL	7.59	866.6 ±42	5	385.8 ±180	0.0657	321.4
20 kDa PEGylated-Av- p.C503S/p.C565S/p.F18A PAL + aprotinin	6.03	853.1 ±159	5	503.3 ±119	0.0212	354.6
			6	311.9 ±88	0.6024	89.3
Hydrogel protected nanoparticles of Av-p.C503S/p.C565S/p.F18A PAL	11.34	722.0 ±99	5	100.6 ±36	0.8270	36.1
Barium Alginate Microspheres of Av-p.C503S/p.C565S/p.F18A PAL	4.35	816.5 ±79	5	178.5 ±93	0.7128	55.7
			6	−36.2 ±187	0.7181	−51.5
Amorphous Silica particles of Av- p.C503S/p.C565S/p.F18A PAL	3.18	1029.7± 61	6	−53.1 ±95	0.4704	−117.7
PTD-AvPAL TM fusion Av- p.C503S/p.C565S/p.F18A PAL + aprotinin	17.25	1002.1±42	6	441.5 ±38	0.1324	289.9

^aDose was formulation dependant and was determined based on the highest volume administrable to the ENU2 mouse.

^*These values take into account the time equivalent, plasma [Phe] of control treated mice exposed to the same regimen of dosing.