Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 1 of 502 PageID #:
`3761
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`Plaintiffs and Counter Defendants,
`
`v.
`
`CELLTRION, INC., CELLTRION,
`HEALTHCARE CO., LTD., TEVA
`PHARMACEUTICALS USA, INC., and
`TEVA PHARMACEUTICALS
`INTERNATIONAL GMBH,
`
`C.A. No. 18-95-CFC
`(CONSOLIDATED)
`
`GENENTECH, INC., CITY OF HOPE, and )
`HOFFMANN LA ROCHE INC.,
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`Defendants and Counterclaim Plaintiffs. )
`)
`GENENTECH, INC. and CITY OF HOPE, )
`)
`Plaintiffs and Counterclaim Defendants, )
`)
`)
`)
`)
`)
`)
`)
`GENENTECH, INC. and CITY OF HOPE, )
`)
`)
`)
`)
`)
`)
`)
`)
`)
`JOINT CLAIM CONSTRUCTION CHART
`APPENDIX C VOLUME 7A
`
`v.
`
`AMGEN INC.,
`
`Defendant and Counterclaim Plaintiff.
`
`Plaintiffs,
`
`v.
`
`SAMSUNG BIOEPIS CO., LTD,
`
`Defendant.
`
`C.A. No. 18-924-CFC
`
`C.A. No. 18-1363-CFC
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 2 of 502 PageID #:
`3762
`
`JA00002205
`
`

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`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 3 of 502 PageID #:
`3763
`
`JA00002206
`
`

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`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 4 of 502 PageID #:
`3764
`
`JA00002207
`
`

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`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 5 of 502 PageID #:
`3765
`
`JA00002208
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 6 of 502 PageID #:
`3766
`
`JA00002209
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 7 of 502 PageID #:
`3767
`
`JA00002210
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 8 of 502 PageID #:
`3768
`
`JA00002211
`
`

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`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 9 of 502 PageID #:
`3769
`
`JA00002212
`
`

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`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 10 of 502 PageID #:
`3770
`
`JA00002213
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 11 of 502 PageID #:
`3771
`
`JA00002214
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 12 of 502 PageID #:
`3772
`
`JA00002215
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 13 of 502 PageID #:
`3773
`
`JA00002216
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 14 of 502 PageID #:
`3774
`
`JA00002217
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 15 of 502 PageID #:
`3775
`
`JA00002218
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 16 of 502 PageID #:
`3776
`
`JA00002219
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 17 of 502 PageID #:
`3777
`
`JA00002220
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 18 of 502 PageID #:
`3778
`
`JA00002221
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 19 of 502 PageID #:
`3779
`
`JA00002222
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 20 of 502 PageID #:
`3780
`
`JA00002223
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 21 of 502 PageID #:
`3781
`
`JA00002224
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 22 of 502 PageID #:
`3782
`
`JA00002225
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 23 of 502 PageID #:
`3783
`
`JA00002226
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 24 of 502 PageID #:
`3784
`
`JA00002227
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 25 of 502 PageID #:
`3785
`
`JA00002228
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 26 of 502 PageID #:
`3786
`
`JA00002229
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 27 of 502 PageID #:
`3787
`
`JA00002230
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 28 of 502 PageID #:
`3788
`
`JA00002231
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 29 of 502 PageID #:
`3789
`
`JA00002232
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 30 of 502 PageID #:
`3790
`
`JA00002233
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 31 of 502 PageID #:
`3791
`
`JA00002234
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 32 of 502 PageID #:
`3792
`
`JA00002235
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 33 of 502 PageID #:
`3793
`
`JA00002236
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 34 of 502 PageID #:
`3794
`
`JA00002237
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 35 of 502 PageID #:
`3795
`
`JA00002238
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 36 of 502 PageID #:
`3796
`
`JA00002239
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 37 of 502 PageID #:
`3797
`
`JA00002240
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 38 of 502 PageID #:
`3798
`
`JA00002241
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 39 of 502 PageID #:
`3799
`
`JA00002242
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 40 of 502 PageID #:
`3800
`
`JA00002243
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 41 of 502 PageID #:
`3801
`
`JA00002244
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 42 of 502 PageID #:
`3802
`
`JA00002245
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 43 of 502 PageID #:
`3803
`
`JA00002246
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 44 of 502 PageID #:
`3804
`
`JA00002247
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 45 of 502 PageID #:
`3805
`
`JA00002248
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 46 of 502 PageID #:
`3806
`
`JA00002249
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 47 of 502 PageID #:
`3807
`
`JA00002250
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 48 of 502 PageID #:
`3808
`
`JA00002251
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 49 of 502 PageID #:
`3809
`
`JA00002252
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 50 of 502 PageID #:
`3810
`
`JA00002253
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 51 of 502 PageID #:
`3811
`
`JA00002254
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 52 of 502 PageID #:
`3812
`
`JA00002255
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 53 of 502 PageID #:
`3813
`
`JA00002256
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 54 of 502 PageID #:
`3814
`
`JA00002257
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 55 of 502 PageID #:
`3815
`
`JA00002258
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 56 of 502 PageID #:
`3816
`
`JA00002259
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 57 of 502 PageID #:
`3817
`
`JA00002260
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 58 of 502 PageID #:
`3818
`
`JA00002261
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 59 of 502 PageID #:
`3819
`
`JA00002262
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 60 of 502 PageID #:
`3820
`
`JA00002263
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 61 of 502 PageID #:
`3821
`
`JA00002264
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 62 of 502 PageID #:
`3822
`
`JA00002265
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 63 of 502 PageID #:
`3823
`
`JA00002266
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 64 of 502 PageID #:
`3824
`
`JA00002267
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 65 of 502 PageID #:
`3825
`
`JA00002268
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 66 of 502 PageID #:
`3826
`
`JA00002269
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 67 of 502 PageID #:
`3827
`
`JA00002270
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 68 of 502 PageID #:
`3828
`
`JA00002271
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 69 of 502 PageID #:
`3829
`
`JA00002272
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 70 of 502 PageID #:
`3830
`
`JA00002273
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 71 of 502 PageID #:
`3831
`
`JA00002274
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 72 of 502 PageID #:
`3832
`
`JA00002275
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 73 of 502 PageID #:
`3833
`
`JA00002276
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 74 of 502 PageID #:
`3834
`
`JA00002277
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 75 of 502 PageID #:
`3835
`
`JA00002278
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 76 of 502 PageID #:
`3836
`
`JA00002279
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 77 of 502 PageID #:
`3837
`
`JA00002280
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 78 of 502 PageID #:
`3838
`
`JA00002281
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 79 of 502 PageID #:
`3839
`
`JA00002282
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 80 of 502 PageID #:
`3840
`
`JA00002283
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 81 of 502 PageID #:
`3841
`
`JA00002284
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 82 of 502 PageID #:
`3842
`
`JA00002285
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 83 of 502 PageID #:
`3843
`
`JA00002286
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 84 of 502 PageID #:
`3844
`
`JA00002287
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 85 of 502 PageID #:
`3845
`
`JA00002288
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 86 of 502 PageID #:
`3846
`
`JA00002289
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 87 of 502 PageID #:
`3847
`
`JA00002290
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 88 of 502 PageID #:
`3848
`
`JA00002291
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 89 of 502 PageID #:
`3849
`
`JA00002292
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 90 of 502 PageID #:
`3850
`
`JA00002293
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 91 of 502 PageID #:
`3851
`
`JA00002294
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 92 of 502 PageID #:
`3852
`
`JA00002295
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 93 of 502 PageID #:
`3853
`
`JA00002296
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 94 of 502 PageID #:
`3854
`
`JA00002297
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 95 of 502 PageID #:
`3855
`
`JA00002298
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 96 of 502 PageID #:
`3856
`
`JA00002299
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 97 of 502 PageID #:
`3857
`
`JA00002300
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 98 of 502 PageID #:
`3858
`
`JA00002301
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 99 of 502 PageID #:
`3859
`
`JA00002302
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 100 of 502 PageID #:
`3860
`
`JA00002303
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 101 of 502 PageID #:
`3861
`
`JA00002304
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 102 of 502 PageID #:
`3862
`
`JA00002305
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 103 of 502 PageID #:
`3863
`
`JA00002306
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 104 of 502 PageID #:
`3864
`
`JA00002307
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 105 of 502 PageID #:
`3865
`
`JA00002308
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 106 of 502 PageID #:
`3866
`
`JA00002309
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 107 of 502 PageID #:
`3867
`
`JA00002310
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 108 of 502 PageID #:
`3868
`
`JA00002311
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 109 of 502 PageID #:
`3869
`
`JA00002312
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 110 of 502 PageID #:
`3870
`
`JA00002313
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 111 of 502 PageID #:
`3871
`
`JA00002314
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 112 of 502 PageID #:
`3872
`
`JA00002315
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 113 of 502 PageID #:
`3873
`
`JA00002316
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 114 of 502 PageID #:
`3874
`
`JA00002317
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 115 of 502 PageID #:
`3875
`
`JA00002318
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 116 of 502 PageID #:
`3876
`
`JA00002319
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 117 of 502 PageID #:
`3877
`
`JA00002320
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 118 of 502 PageID #:
`3878
`
`JA00002321
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 119 of 502 PageID #:
`3879
`
`JA00002322
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 120 of 502 PageID #:
`3880
`
`JA00002323
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 121 of 502 PageID #:
`3881
`
`JA00002324
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 122 of 502 PageID #:
`3882
`
`JA00002325
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 123 of 502 PageID #:
`3883
`
`JA00002326
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 124 of 502 PageID #:
`3884
`
`JA00002327
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 125 of 502 PageID #:
`3885
`
`JA00002328
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 126 of 502 PageID #:
`3886
`
`JA00002329
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 127 of 502 PageID #:
`3887
`
`JA00002330
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 128 of 502 PageID #:
`3888
`
`JA00002331
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 129 of 502 PageID #:
`3889
`
`JA00002332
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 130 of 502 PageID #:
`3890
`
`JA00002333
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 131 of 502 PageID #:
`3891
`
`JA00002334
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 132 of 502 PageID #:
`3892
`
`JA00002335
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 133 of 502 PageID #:
`3893
`
`JA00002336
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 134 of 502 PageID #:
`3894
`
`JA00002337
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 135 of 502 PageID #:
`3895
`
`JA00002338
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 136 of 502 PageID #:
`3896
`
`JA00002339
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 137 of 502 PageID #:
`3897
`
`JA00002340
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 138 of 502 PageID #:
`3898
`
`JA00002341
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 139 of 502 PageID #:
`3899
`
`JA00002342
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 140 of 502 PageID #:
`3900
`
`JA00002343
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 141 of 502 PageID #:
`3901
`
`JA00002344
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 142 of 502 PageID #:
`3902
`
`JA00002345
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 143 of 502 PageID #:
`3903
`
`JA00002346
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 144 of 502 PageID #:
`3904
`
`JA00002347
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 145 of 502 PageID #:
`3905
`
`JA00002348
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 146 of 502 PageID #:
`3906
`
`JA00002349
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 147 of 502 PageID #:
`3907
`
`JA00002350
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 148 of 502 PageID #:
`3908
`
`JA00002351
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 149 of 502 PageID #:
`3909
`
`JA00002352
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 150 of 502 PageID #:
`3910
`
`JA00002353
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 151 of 502 PageID #:
`3911
`
`JA00002354
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 152 of 502 PageID #:
`3912
`
`JA00002355
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 153 of 502 PageID #:
`3913
`
`JA00002356
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 154 of 502 PageID #:
`3914
`
`JA00002357
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 155 of 502 PageID #:
`3915
`
`JA00002358
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 156 of 502 PageID #:
`3916
`
`JA00002359
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 157 of 502 PageID #:
`3917
`
`JA00002360
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 158 of 502 PageID #:
`3918
`
`JA00002361
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 159 of 502 PageID #:
`3919
`
`JA00002362
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 160 of 502 PageID #:
`3920
`
`JA00002363
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 161 of 502 PageID #:
`3921
`
`JA00002364
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 162 of 502 PageID #:
`3922
`
`JA00002365
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 163 of 502 PageID #:
`3923
`
`JA00002366
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 164 of 502 PageID #:
`3924
`
`JA00002367
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 165 of 502 PageID #:
`3925
`
`JA00002368
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 166 of 502 PageID #:
`3926
`
`JA00002369
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 167 of 502 PageID #:
`3927
`
`JA00002370
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 168 of 502 PageID #:
`3928
`
`JA00002371
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 169 of 502 PageID #:
`3929
`
`JA00002372
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 170 of 502 PageID #:
`3930
`
`JA00002373
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 171 of 502 PageID #:
`3931
`
`JA00002374
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 172 of 502 PageID #:
`3932
`
`JA00002375
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 173 of 502 PageID #:
`3933
`
`JA00002376
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 174 of 502 PageID #:
`3934
`
`JA00002377
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 175 of 502 PageID #:
`3935
`
`JA00002378
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 176 of 502 PageID #:
`3936
`
`JA00002379
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 177 of 502 PageID #:
`3937
`
`JA00002380
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 178 of 502 PageID #:
`3938
`
`JA00002381
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 179 of 502 PageID #:
`3939
`
`JA00002382
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 180 of 502 PageID #:
`3940
`
`JA00002383
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 181 of 502 PageID #:
`3941
`
`JA00002384
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 182 of 502 PageID #:
`3942
`
`JA00002385
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 183 of 502 PageID #:
`3943
`
`JA00002386
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 184 of 502 PageID #:
`3944
`
`JA00002387
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 185 of 502 PageID #:
`3945
`
`JA00002388
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 186 of 502 PageID #:
`3946
`
`JA00002389
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 187 of 502 PageID #:
`3947
`
`JA00002390
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 188 of 502 PageID #:
`3948
`
`JA00002391
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 189 of 502 PageID #:
`3949
`
`JA00002392
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 190 of 502 PageID #:
`3950
`
`JA00002393
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 191 of 502 PageID #:
`3951
`
`JA00002394
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 192 of 502 PageID #:
`3952
`
`JA00002395
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 193 of 502 PageID #:
`3953
`
`JA00002396
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 194 of 502 PageID #:
`3954
`
`JA00002397
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 195 of 502 PageID #:
`3955
`
`JA00002398
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 196 of 502 PageID #:
`3956
`
`JA00002399
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 197 of 502 PageID #:
`3957
`
`JA00002400
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 198 of 502 PageID #:
`3958
`
`JA00002401
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 199 of 502 PageID #:
`3959
`
`JA00002402
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 200 of 502 PageID #:
`3960
`
`JA00002403
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 201 of 502 PageID #:
`3961
`
`JA00002404
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 202 of 502 PageID #:
`3962
`
`JA00002405
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 203 of 502 PageID #:
`3963
`
`JA00002406
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 204 of 502 PageID #:
`3964
`
`JA00002407
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 205 of 502 PageID #:
`3965
`
`JA00002408
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 206 of 502 PageID #:
`3966
`
`JA00002409
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 207 of 502 PageID #:
`3967
`
`JA00002410
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 208 of 502 PageID #:
`3968
`
`JA00002411
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 209 of 502 PageID #:
`3969
`
`JA00002412
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 210 of 502 PageID #:
`3970
`
`JA00002413
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 211 of 502 PageID #:
`3971
`
`JA00002414
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 212 of 502 PageID #:
`3972
`
`JA00002415
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 213 of 502 PageID #:
`3973
`
`JA00002416
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 214 of 502 PageID #:
`3974
`
`JA00002417
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 215 of 502 PageID #:
`3975
`
`JA00002418
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 216 of 502 PageID #:
`3976
`
`JA00002419
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 217 of 502 PageID #:
`3977
`
`JA00002420
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 218 of 502 PageID #:
`3978
`
`JA00002421
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 219 of 502 PageID #:
`3979
`
`JA00002422
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 220 of 502 PageID #:
`3980
`
`JA00002423
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 221 of 502 PageID #:
`3981
`
`JA00002424
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 222 of 502 PageID #:
`3982
`
`JA00002425
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 223 of 502 PageID #:
`3983
`
`JA00002426
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 224 of 502 PageID #:
`3984
`
`JA00002427
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 225 of 502 PageID #:
`3985
`
`JA00002428
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 226 of 502 PageID #:
`3986
`
`JA00002429
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 227 of 502 PageID #:
`3987
`
`JA00002430
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 228 of 502 PageID #:
`3988
`
`JA00002431
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 229 of 502 PageID #:
`3989
`
`JA00002432
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 230 of 502 PageID #:
`3990
`
`JA00002433
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 231 of 502 PageID #:
`3991
`
`JA00002434
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 232 of 502 PageID #:
`3992
`
`JA00002435
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 233 of 502 PageID #:
`3993
`
`JA00002436
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 234 of 502 PageID #:
`3994
`
`JA00002437
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 235 of 502 PageID #:
`3995
`
`JA00002438
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 236 of 502 PageID #:
`3996
`
`JA00002439
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 237 of 502 PageID #:
`3997
`
`JA00002440
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 238 of 502 PageID #:
`3998
`
`JA00002441
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 239 of 502 PageID #:
`3999
`
`JA00002442
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 240 of 502 PageID #:
`4000
`
`JA00002443
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 241 of 502 PageID #:
`4001
`
`JA00002444
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 242 of 502 PageID #:
`4002
`
`JA00002445
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 243 of 502 PageID #:
`4003
`
`JA00002446
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 244 of 502 PageID #:
`4004
`
`JA00002447
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 245 of 502 PageID #:
`4005
`
`JA00002448
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 246 of 502 PageID #:
`4006
`
`JA00002449
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 247 of 502 PageID #:
`4007
`
`JA00002450
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 248 of 502 PageID #:
`4008
`
`JA00002451
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 249 of 502 PageID #:
`4009
`
`JA00002452
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 250 of 502 PageID #:
`4010
`
`JA00002453
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 251 of 502 PageID #:
`4011
`
`JA00002454
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 252 of 502 PageID #:
`4012
`
`JA00002455
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 253 of 502 PageID #:
`4013
`
`JA00002456
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 254 of 502 PageID #:
`4014
`
`JA00002457
`
`

`

`Case 1:18-cv-01363-CFC Document 48-7 Filed 12/11/18 Page 255 of 502 PageID #:
`4015
`
`P002 694206
`
`dentification and Prevention of Antibody Distdfide
`Bond Reduction During CeO Cufture Manufacturing
`
`LQJic NOLOGY
`BIOENGINEERNG
`
`Sandy Sargis Jason Chin2 Stefanie Sze-Khoo Melissa Mun3
`Melody Tresder-Schsnidt
`Lard
`Ynog-Usiang Kao4 Michael
`Inc DNA Way South San Francisco California 94080
`fax 650-225-3880
`sdirnidt.nwlody@gene.com
`Inc South San Francisco
`Inc South San Francisco
`California
`Inc South San Francisco
`Chemistry Cenentech
`
`Late Stage Purification Cenentech
`
`tekphone
`
`650-225-5137
`
`e-mail
`
`2Early Stage Purification Cenentech
`
`Thate Stage Cell Culture Cenentech
`
`4Protein Analytical
`
`California
`
`California
`
`tlsreivetl
`
`31 July 2093 revision
`
`received
`
`23 December
`
`21305
`
`accepted
`
`February
`
`2030
`
`Pubtohed
`
`online 22 Febraaiy
`
`2010
`
`iii Wiley
`
`leterSciesee
`
`lwvvw.intersciencewiley.cnas
`
`001
`
`10IOSVbit222005
`
`ASThAT In the biopharmaccutical
`monoclonal
`
`antibodies
`
`are primarily
`
`industry
`therapeutic
`produced in mamma
`of mono
`the scale-up
`systems During
`we observed excessive
`production process
`cell shear
`as well as significant
`reduction
`of
`the
`disulfide bonds during harvest
`event
`tions This antibody reduction
`was catastrophic
`to meet
`the drug substance
`product
`the bulk product was lost Subsequent
`have demonstrated
`that cells
`subjected
`
`lian cell culture
`
`clunsi antibody
`mechanical
`
`antibodys interchain
`
`failed
`
`release
`
`cellular
`
`opera
`as the
`and
`
`specifications
`
`laboratory
`to mechanical
`
`studies
`
`shear
`
`linroduction
`
`Recombinant monoclonal
`
`prevalent
`
`as
`
`clinical
`
`the
`
`last
`
`antibodies rMAb have become
`therapy over
`20 years
`for
`and immunological
`diseases Reichert 20012002
`oncology
`Reichert and Pavolu 2004 Rcichert et al 2005 Currently
`commercialized
`in the biopharmaceutical
`for
`products
`rMAbs
`produced in mammalian cell
`are typically
`in large stainless steel fermentors up to 25-kL in scale
`et al 2002
`2007 After
`additions
`
`industry
`
`culture
`
`Benton
`
`Kelley
`
`production
`
`bioreactor
`
`various
`
`process
`
`initiating
`
`and
`
`growth
`
`that
`contribute
`to this antibody
`enzymes
`phenomenon manuscript
`submitted Kao et al
`reduction
`2009 Several
`nseshods
`to prevent
`this antibody reduction
`event
`were developed
`lab-scale model
`and
`
`the lysis
`
`reduction
`
`to reproduce
`tssing
`These methods
`events
`included
`culture media with chemicals
`modifications
`sulfate CuSO4 pre-
`e.g cupric
`flual CCF eg
`chemical
`to the cell culture
`additions
`CuSO4 EDTA L-cystine as well as lowering
`the pH and
`the harvested CCF l-ICCF These methods
`of
`sir sparging
`were evaluated
`for their effectiveness
`
`to the
`
`cell
`
`and
`
`post-harvest
`
`disulfide
`
`in preventing
`to product quality
`impact
`which yielded
`for their potential
`to be implemented
`The work
`described
`here identifies
`
`bond
`
`reduction
`
`and their
`
`tive
`
`prevention
`qualiry were evaluated
`
`methods
`
`Effec
`
`acceptable
`
`product
`
`at manufacturing-scale
`numerous
`
`effective
`
`lab-scale
`
`studies
`
`reduction
`prevention
`several of these methods
`
`measures from
`then success
`were
`
`fully translated
`into manul(cid:224)cturing
`processes
`Biotechnol Bioeng
`452461
`Inc
`2010 Wiley Periodicals
`KEYWORDS antibody disuluide redaction ccntrifugation
`shear
`
`lysis
`
`201
`
`Correspondence
`
`to
`
`Treeier-Schaidt
`
`to maximize
`performed
`parameter
`manipulations
`are
`and antibody production
`and yield suitable
`product
`and Krummen
`Andersen
`2002 Andersen and
`quality
`Reilly 2004 Birch et al 2005 Birch and Racher 2006
`Wuron
`2004 The
`rh4Abs
`and
`secreted
`are
`expressed
`into the cell culture fluid CCFAt the end of
`extracellularly
`the production phase the feedstock
`is usually harvested
`by
`followed by depth filtrati