`
`Wyse I
`
`Wyse II
`
`2mg NS (Table 11)
`0.4 mg im (Table 11)
`0.4 mg iv (Table 4)
`1 mg im (Table 4)
`2mg NS (Table 4)
`
`747 Patent
`
`
`
`4 mg
`0.4 mg im
`
`Dose Normalized
`
`Wyse I
`(Table 11)
`
`2mg NS
`0.4 mg im
`ratio NS vs im
`
`Wyse II
`(Table 4)
`
`0.4 mg iv (Table 4)
`1 mg im (Table 4)
`2mg NS (Table 4)
`ratio NS vs im
`
`747 Patent 4 mg NS
`
`0.4 mg im
`ratio NS vs im
`
`
`ratio Wyse II vs im of 747
`
`
`
`
`
`33
`34
`12
`12
`12
`
`28
`28
`
`Cmax
`ng/ml
`1.78
`1.05
`3.87
`2.54
`1.95
`
`5.34
`0.91
`
`SD
`ng/ml
`0.97
`0.35
`2.72
`1.04
`1.05
`
`2.35
`0.29
`
`SE
`ng/ml
`0.17
`0.06
`0.79
`0.30
`0.30
`
`0.45
`0.05
`
`
`SE
`SD
`Cmax/D
`ng/(ml*mg) ng/(ml*mg) ng/(ml*mg)
`0.890
`0.484
`0.084
`2.625
`0.883
`0.151
`0.339
`0.217
`0.038
`
`6.800
`1.040
`0.525
`0.260
`
`0.589
`0.713
`0.319
`
`1.963
`0.300
`0.152
`0.075
`
`0.111
`0.135
`0.060
`
`9.675
`2.540
`0.975
`0.384
`
`1.335
`2.265
`0.589
`
`0.430
`
`Opiant Exhibit 2223
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 1
`
`
`
`0.700
`
`0.600
`
`0.500
`
`0.400
`
`0.300
`
`0.200
`
`0.100
`
`0.000
`
`Dose normalized ratios
`
`1
`
`2
`
`3
`
`Opiant Exhibit 2223
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 2
`
`
`
`rel SD
`%
`54.33
`33.62
`70.28
`40.94
`53.85
`
`44.1
`31.5
`
`rel SD
`%
`54.3
`33.6
`118.6
`
`70.3
`40.9
`53.8
`67.6
`
`44.1
`31.5
`54.2
`
`AUC
`ng*h/ml
`2.63
`1.67
`1.67
`4.43
`3.47
`
`8.87
`1.83
`
`SD
`ng*h/ml
`1.27
`0.36
`0.54
`1.16
`0.80
`
`3.30
`0.42
`
`SE
`ng*h/ml
`0.22
`0.06
`0.16
`0.33
`0.23
`
`0.62
`0.08
`
`SE
`SD
`AUC/D
`ng*h/(ml*mg) ng*h/(ml*mg) ng*h/(ml*mg)
`1.315
`0.635
`0.111
`4.175
`0.908
`0.156
`0.315
`0.167
`0.029
`
`1.350
`1.160
`0.400
`0.137
`
`0.825
`1.052
`0.212
`
`0.390
`0.335
`0.115
`0.039
`
`0.156
`0.199
`0.040
`
`4.175
`4.430
`1.735
`0.392
`
`2.218
`4.575
`0.485
`
`0.379
`
`rel SD
`%
`48.3
`21.7
`32.3
`26.2
`23.1
`
`37.2
`23.0
`
`rel SD
`%
`48.3
`21.7
`79.7
`
`32.3
`26.2
`23.1
`34.9
`
`37.2
`23.0
`43.7
`
`tmax
`h
`0.333
`0.167
`
`range
`h
`0.25‐0.75
`0.08‐1
`
`0.500
`0.420
`
`0.17‐1.0
`0.08‐2.0
`
`0.295129718
`0.113024036
`
`4.5
`9.71666667
`
`2.25
`
`0
`
`Opiant Exhibit 2223
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 3
`
`
`
`Cmax/D
`Wyse I (Tabl.1
`Wyse II (Table
`747 Patent
`
`0.89
`0.975
`1.335
`
`0.4835
`0.260
`0.589
`
`Wyse
`
`0.03
`0.08
`0.17
`0.25
`0.33
`0.42
`0.5
`0.75
`1
`
`Adapt
`
`
`
`
`0.042
`0.082
`0.17
`0.25
`0.342
`
`0.51
`0.75
`1
`
`Wyse I (Tabl.1
`Wyse II (Table
`747 Patent
`
`0.339
`0.384
`0.589
`
`0.038
`0.075
`0.060
`
`Wyse I (Tabl.1
`Wyse II (Table
`747 Patent
`
`31.49700599
`39.16478555
`48.46994536
`
`2.896315964
`3.944416448
`4.006201939
`
`Relative Bioavailability
`
`Wyse I (Tabl.11)
`
`Wyse II (Table. 4)
`
`747 Patent
`
`60
`
`50
`
`40
`
`30
`
`20
`
`10
`
`0
`
`Relative Bioavailability (%)
`
`Opiant Exhibit 2223
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 4
`
`
`
`Dose Normalized Cmax Ratios (NNS/IM)
`
`Wyse I (Tabl.11)
`
`Wyse II (Table. 4)
`
`747 Patent
`
`0.700
`
`0.600
`
`0.500
`
`0.400
`
`0.300
`
`0.200
`
`0.100
`
`0.000
`
`Dose normaized Cmax Ratio (NNS/IM)
`
`Opiant Exhibit 2223
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 5
`
`
`
`0.700
`
`0.600
`
`0.500
`
`0.400
`
`0.300
`
`0.200
`
`0.100
`
`0.000
`
`Dose normalized ratios
`
`1
`
`2
`
`3
`
`Opiant Exhibit 2223
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 6
`
`
`
`Cmax/Dose
`
`Wyse I
`(Tabl.11)
`
`Wyse II
`(Table. 4)
`
`747 Patent
`
`1.6
`
`1.4
`
`1.2
`
`1
`
`0.8
`
`0.6
`
`0.4
`
`0.2
`
`0
`
`Dose normaized Cmax (ng/ml)
`
`Opiant Exhibit 2223
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685, IPR2019-00688, IPR2019-00694
`Page 7
`
`