1
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`October 3, 2017
`
`U.S. Patent No. 6,900,221
`
`IPR2016-01284
`
`OSI Pharmaceuticals, Inc.
`
`v.
`
`(cid:50)(cid:54)(cid:44)(cid:3)(cid:21)(cid:19)(cid:23)(cid:28)
`(cid:36)(cid:83)(cid:82)(cid:87)(cid:72)(cid:91)(cid:3)(cid:89)(cid:17)(cid:3)(cid:50)(cid:54)(cid:44)
`(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:21)(cid:27)(cid:23)
`
`Apotex Inc., Apotex Corp., Apotex Pharmaceuticals
`
`Holdings Inc., & Apotex Holdings, Inc.
`
`PATENTTRIALANDAPPEALBOARD
`
`UNITEDSTATESPATENTANDTRADEMARKOFFICE
`
`
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`October 3, 2017
`
`U.S. Patent No. 6,900,221
`
`IPR2016-01284
`
`OSI Pharmaceuticals, Inc.
`
`v.
`
`(cid:50)(cid:54)(cid:44)(cid:3)(cid:21)(cid:19)(cid:23)(cid:28)
`(cid:36)(cid:83)(cid:82)(cid:87)(cid:72)(cid:91)(cid:3)(cid:89)(cid:17)(cid:3)(cid:50)(cid:54)(cid:44)
`(cid:44)(cid:51)(cid:53)(cid:21)(cid:19)(cid:20)(cid:25)(cid:16)(cid:19)(cid:20)(cid:21)(cid:27)(cid:23)
`
`Apotex Inc., Apotex Corp., Apotex Pharmaceuticals
`
`Holdings Inc., & Apotex Holdings, Inc.
`
`PATENTTRIALANDAPPEALBOARD
`
`UNITEDSTATESPATENTANDTRADEMARKOFFICE
`
`
`
`2
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`3.Motion to Exclude
`
`Objective Indicia of Non-Obviousness
`No Reasonable Expectation of Success
`No Motivation to Combine
`
`–
`
`–
`
`–
`
`2.Claims 44-46 and 53 of the ’221 Patent are Non-Obvious
`
`Claim Construction
`Person of Ordinary Skill in the Art
`Background
`
`–
`
`–
`
`–
`
`1.The Claimed Invention
`OVERVIEW
`
`
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`3
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`THE CLAIMED INVENTION
`
`
`
`4
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`’221 Patent col. 35:26-36, 35:64-65 (Ex. 1001)
`
`(cid:131)Representative claims:
`A METHOD OF TREATMENT OF NSCLC
`
`The ’221 Patent (Ex. 1001)
`
`
`
`5
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`(cid:131)Before the ’221 patent, chemotherapy was the standard of care for
`
`Paper 39 at 2, 4
`Bunn Decl. ¶ 29 (Ex. 2021); Ex. 2036 at 5813; Paper 20 at 8; Giaccone Dep., 25:3-9, 34:1-11 (Ex. 2048);
`advanced NSCLC
`
`Bunn Decl. ¶ 29 (Ex. 2021); Paper 7 at 6-7, 42-43; Paper 20 at 8; Ex. 2001 at 825
`
`(cid:131)Advanced stage at diagnosis and limited treatment options
`
`Paper 39 at 3-4
`Bunn Decl. ¶ 87 (Ex. 2021); Ex. 2019 at 449; Paper 20 at 8; Giaccone Dep., 69:13-70:5, 76:15-77:10 (Ex. 2048);
`
`(cid:131)Before targeted therapies, the survival rate was very poor
`
`Bunn Decl. ¶¶ 28, 91 (Ex. 2021); Paper 7 at 42; Paper 20 at 8; Paper 33 at 12; Ex. 2010 at Ex. 2010-0027
`
`(cid:131)NSCLC was the leading cause of cancer death in the U.S.
`STATE OF THE ART
`
`Non-Small Cell Lung Cancer
`
`
`
`6
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep., 44:11-13 (Ex. 2020); Giaccone Decl. ¶¶ 52-53 (Ex. 1002); Paper 20 at 27-28
`
`(cid:131)Dr. Giaccone only applied his own definition
`
`Bunn Decl. ¶ 23 (Ex. 2021); Paper 20 at 27
`in the art” is adopted
`patent are the same regardless of which definition of the level of skill
`(cid:131)Dr. Bunn testified that his opinions “regarding the validity of the ’221
`CLAIMED INVENTION
`OSI’S DEFINITION IS CONSISTENT WITH THE
`
`The Level of Skill in the Art
`
`
`
`7
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`’221 Patent, 35:26-36 (Ex. 1001)
`
`Claim Construction
`
`
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`8
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`(cid:131)Parties agree that treatment is defined in the specification of the ’221
`
`Bunn Decl. ¶ 43 (Ex. 2021)
`’221 Patent col. 14:9-15 (Ex. 1001); Paper 20 at 28-29; Paper 33 at 9 n.3; Giaccone Reply Decl. ¶ 2 (Ex. 1053);
`patent
`
`Paper 3 at 13; Paper 7 at 17; Paper 20 at 28-29; Bunn Decl. ¶ 43 (Ex. 2021)
`
`(cid:131)Parties agree that plain and ordinary meaning of treatment applies
`TREATMENT APPLIES
`PLAIN AND ORDINARY MEANING OF
`
`Claim Construction
`
`
`
`9
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`’221 Patent col. 14:9-15 (Ex. 1001)
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`THE SPECIFICATION DEFINES TREATMENT
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`Claim Construction
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`
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`10
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`Giaccone Dep., 48:11-49:3 (Ex. 2020)
`
`Paper 20 at 28-29, 36-37
`Bunn Decl.¶ 43 (Ex. 2021)
`
`PRE-CLINICAL MODEL
`“TREATMENT” REQUIRES SOME EFFECT IN A
`
`Claim Construction
`
`
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`11
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep., 49:4-49:21 (Ex. 2020)
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`Paper 20 at 28-29, 36-37
`Bunn Decl.¶ 43 (Ex. 2021)
`
`A THERAPEUTIC BENEFIT
`“THERAPEUTICALLY EFFECTIVE” REQUIRES
`
`Claim Construction
`
`
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`12
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`NON-OBVIOUS
`’221 PATENT ARE
`CLAIMS 44-46 AND 53 OF THE
`
`
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`13
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Bunn Decl. ¶¶ 74, 81 (Ex. 2021)
`
`(cid:131)1,890 combinations (105 ×18 = 1,890)
`
`Paper 20 at 5, 17
`Schnur, 5:44-67, 14:1-30 (Ex. 1009); Bunn Decl. ¶¶ 46, 74, 81 (Ex. 2021); Giaccone Dep., 60:19-63:9 (Ex. 2020);
`
`(cid:131)At least 18 cancers recited (but not NSCLC)
`
`Giaccone Dep., 31:15-17 (Ex. 2048)
`Schnur, 2:1-5:43, 17:5-36:61 (Ex. 1009); Bunn Decl. ¶¶ 45-46, 69, 74, 81 (Ex. 2021); Paper 20 at 5, 17, 47, 54;
`
`(cid:131)105 compounds exemplified; genus of thousands of compounds
`OF NSCLCWITH ERLOTINIB
`SCHNUR DOES NOT DISCLOSE TREATMENT
`
`Schnur (Ex. 1009)
`
`
`
`14
`
`Patent Owner’s Demonstrative Exhibits
`Paper 39 at 2
`Bunn Decl. ¶¶ 44-48 (Ex. 2021); Giaccone Dep., 74:1-7 (Ex. 2020); Paper 20 at 5, 16, 35; Giaccone Dep., 32:1-33:22 (Ex. 2048);
`
`IPR2016-01284
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`Schnur, 15:3-10 (Ex. 1009)
`
`(cid:131)No in vitro data for any specific compound, including erlotinib
`(cid:131)No in vivo data for any compound for any cancer
`NO DATA FOR ERLOTINIB
`SCHNUR CONTAINS ONLY IN VITRO DATA AND
`
`Schnur (Ex. 1009)
`
`
`
`15
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`Giaccone Dep., 74:1-7 (Ex. 2020); Paper 20 at 5, 16, 35
`
`Giaccone Dep., 33:8-22 (Ex. 2048); Paper 39 at 2
`
`NO DATA FOR ERLOTINIB
`SCHNUR CONTAINS ONLY IN VITRO DATA AND
`
`Schnur (Ex. 1009)
`
`
`
`16
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`(Ex. 2020); Paper 20 at 2, 6-7, 19-24, 41, 47
`Ex. 2007; Bunn Decl. ¶¶ 51, 53, 56, 65, 75, 88 (Ex. 2021); Giaccone Dep., 89:4-91:1, 139:20-145:4, 159:19-160:15
`
`(cid:131)Published on January 1, 2000 before the commencement of any such trials
`
`1016 (Moyer); Ex. 2006 (Woodburn); Ex. 2024 (ASCO Abstracts); Ex. 2025 (AACR Abstracts)
`6, 99:6-10, 112:18-114:2, 126:6-12, 126:18-127:15, 160:1-15 (Ex. 2020); Paper 20 at 6-7, 19-23, 35, 37-55; Ex.
`Gibbs at 9-10, n.12, 13 (Ex. 1010); Bunn Decl. ¶¶ 25-26, 48, 53-65, 72, 83, 88-89 (Ex. 2021); Giaccone Dep., 97:2-
`provide any data from any study of erlotinib in NSCLC
`
`(cid:131)Gibbs and the references cited and referred to in Gibbs do not discuss or
`
`Giaccone Dep., 116:9-117:2 (Ex. 2020); Bunn Decl. ¶ 83 (Ex. 2021); Paper 20 at 48
`
`(cid:131)Both sides’ experts agree Gibbs must be considered in the context of the
`DATA FOR CP-358,774 IN NSCLC
`GIBBS DOES NOT DISCLOSE OR CITE TO
`
`references it cites
`
`Gibbs (Ex. 1010)
`
`
`
`Patent Owner’s Demonstrative Exhibits
`17
`Gibbs at 9 (Ex. 1010); Giaccone Dep., 94:1-95:1, 116:9-117:2 (Ex. 2020); Bunn Decl. ¶¶ 60-64 (Ex. 2021); Paper 20 at 22-23, 50-52
`
`IPR2016-01284
`
`Gibbs (1999 ASCO and AACR Abstracts)
`
`
`
`18
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`Bunn Decl. ¶ 83 (Ex. 2021); Paper 20 at 48
`
`Giaccone Dep., 116:9-117:2 (Ex. 2020)
`
`UNDERSTAND THE STATEMENTS IN GIBBS
`A POSA WOULD HAVE CONSULTED THE REFERENCES CITED TO
`
`Gibbs (Ex. 1010)
`
`
`
`19
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`Giaccone Dep., 116:9-117:2 (Ex. 2020); Bunn Decl. ¶ 83 (Ex. 2021); Paper 20 at 48
`
`Gibbs at 10 (Ex. 1010)
`
`UNDERSTAND THE STATEMENTS IN GIBBS
`A POSA WOULD HAVE CONSULTED THE REFERENCES CITED TO
`
`Gibbs (Ex. 1010)
`
`
`
`20
`
`Patent Owner’s Demonstrative Exhibits
`Paper 20 at 48-49, 55-56
`Ex. 2006 at 633 (Abstract 4251); Giaccone Dep., 107:3-108:13, 127:2-129:17 (Ex. 2020); Bunn Decl. ¶¶ 58, 64, 85 (Ex. 2021);
`
`IPR2016-01284
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`(cid:131)Woodburn specifically refers to using ZD-1839 in NSCLC tumors
`WOODBURN (#12) ONLY ADDRESSES ZD-1839
`
`Gibbs (Woodburn (Ex. 2006))
`
`
`
`21
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`(referring to Ex. 2006 at 633 (Woodburn Abstract 4251))
`
`Giaccone Dep., 108:1-8 (Ex. 2020)
`
`Paper 20 at 48-49, 55-56
`
`WOODBURN (#12) ONLY ADDRESSES ZD-1839
`
`Gibbs (Woodburn (Ex. 2006))
`
`
`
`22
`
`Patent Owner’s Demonstrative Exhibits
`Paper 7 at 15-16, 26-28; Paper 20 at 22, 48-50, 53
`Giaccone Dep., 118:15-20, 119:7-121:10, 123:11-125:5, 126:18-127:1 (Ex. 2020); Bunn Decl. ¶¶ 53, 55, 59, 84 (Ex. 2021);
`
`IPR2016-01284
`
`Ex. 1016 at 4838 (Moyer)
`
`cells in a cell culture
`tumors growing as xenografts in athymicmice and (2) human colon
`
`(cid:131)Moyer only addresses CP-358,774 in (1) human head and neck
`(cid:131)Moyer does not disclose treatment of NSCLC with erlotinib
`CP-358,774 IN NSCLC
`MOYER (#13) DOES NOT DISCLOSE
`
`Gibbs (Moyer (Ex. 1016))
`
`
`
`23
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`IPR2016-01284
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`Bunn Decl. ¶ 59 (Ex. 2021)
`
`Patent Owner’s Demonstrative Exhibits
`Paper 20 at 22, 48-50, 53
`Paper 7 at 15-16, 26-28;
`
`Giaccone Dep., 126:13-127:1 (Ex. 2020)
`
`CP-358,774 IN NSCLC
`MOYER (#13) DOES NOT DISCLOSE
`
`Gibbs (Moyer (Ex. 1016))
`
`
`
`24
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep., 116:9-117:2 (Ex. 2020); Bunn Decl. ¶ 83 (Ex. 2021); Paper 20 at 48
`
`Gibbs at 10 (Ex. 1010)
`
`THE REFERENCES IT CITES AND THE ART AS A WHOLE
`A POSA WOULD INTERPRET GIBBS IN THE CONTEXT OF
`
`Gibbs (Ex. 1010)
`
`
`
`25
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`Paper 7 at 13-16, 26-28; Paper 20 at 6-7, 19-24, 45-55
`Giaccone Dep., 87:4-88:5, 95:13-99:10; 112:18-114:2, 131:1-5 (Ex. 2020); Bunn Decl. ¶¶ 54-56, 64, 83, 87-88;
`
`Giaccone Dep., 98:18-99:10 (Ex. 2020);
`
`DETERMINE A THERAPEUTIC INDEX FOR ERLOTINIB IN NSCLC
`GIBBS DOES NOT INCLUDE INFORMATION NEEDED TO
`
`Gibbs (Ex. 1010)
`
`
`
`Patent Owner’s Demonstrative Exhibits
`26
`Ex. 2024; Giaccone Dep., 93:4-95:1, 116:9-117:2 (Ex. 2020); Bunn Decl. ¶¶ 60-65, 77, 83, 88-89 (Ex. 2021); Paper 20 at 22-23, 40, 50-53
`
`IPR2016-01284
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`1999 ASCO Abstracts (Ex. 2024)
`
`
`
`Patent Owner’s Demonstrative Exhibits
`27
`Ex. 2024; Giaccone Dep., 93:4-95:1, 116:9-117:2 (Ex. 2020); Bunn Decl. ¶¶ 60-65, 77, 83, 88-89 (Ex. 2021); Paper 20 at 22-23, 40, 50-53
`
`IPR2016-01284
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`1999 ASCO Abstracts (Ex. 2024)
`
`
`
`28
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep., 94:1-94:18 (Ex. 2020)
`
`Paper 20 at 22-23, 40, 50-53
`
`1999 ASCO ABSTRACTS ARE NOT RELEVANT
`
`Gibbs (1999 ASCO Abstracts (Ex. 2024))
`
`
`
`29
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
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`Paper 20 at 22-23, 40, 50-53
`Bunn Decl. ¶ 61 (Ex. 2021)
`
`NSCLC OR ANY OTHER TUMOR TYPE WITH ERLOTINIB
`ABSTRACTS DO NOT CONTAIN DATA FOR TREATMENT OF
`
`Gibbs (1999 ASCO Abstracts (Ex. 2024))
`
`
`
`30
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`Paper 20 at 22-23, 40, 50-53
`Ex. 2025; Giaccone Dep., 92:16-93:22, 94:19-95:2, 116:9-117:2 (Ex. 2020); Bunn Decl. ¶¶ 60-64 (Ex. 2021);
`
`INFORMATION REGARDING CP-358,774
`1999 AACR ABSTRACTS DO NOT CONTAIN
`
`Gibbs (1999 AACR Abstracts (Ex. 2025))
`
`
`
`31
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Bunn Decl. ¶ 62 (Ex. 2021); Paper 20 at 52-53
`
`Giaccone Dep., 94:19-95:1 (Ex. 2020); Paper 20 at 52
`
`TO CP-358,774
`1999 AACR ABSTRACTS IRRELEVANT
`
`Gibbs (1999 AACR Abstracts (Ex. 2025))
`
`
`
`Patent Owner’s Demonstrative Exhibits
`112:18-114:2, 126:6-12, 160:1-15 (Ex. 2020); Paper 20 at 6-7, 19-23, 48-55
`Gibbs at 10 (Ex. 1010); Bunn Decl. ¶¶ 25-26, 48, 50-65, 68, 72, 74, 76-78, 81, 83, 88-89 (Ex. 2021); Giaccone Dep., 97:2-6, 99:6-10,
`
`IPR2016-01284
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`32
`
`Gibbs Decl. ¶ 14 (Ex. 2022)
`
`CONCERNING TREATMENT OF NSCLC WITH ERLOTINIB
`DR. GIBBS’ TESTIMONY CONFIRMS NO AVAILABLE DATA
`
`Testimony of Dr. Gibbs (Ex. 2022)
`
`
`
`33
`
`Patent Owner’s Demonstrative Exhibits
`Paper 20 at 18-21, 38-42, 45-47, 52-54, 59; Bunn Decl. ¶ 36 (Ex. 2021); Giaccone Dep., 85:3-15 (Ex. 2020); Ex. 1011 at 1011-006
`
`IPR2016-01284
`
`(cid:131)Phase III trials designed to compare the efficacy of the proposed
`
`drug product with approved cancer therapies
`
`safe dosage level
`product was an effective treatment for a particular cancer type at a
`
`(cid:131)Phase IItrials designed to evaluate whether a particular drug
`
`patients
`(2) to evaluate the pharmacokinetic properties of the drug product in
`(1) to measure whether the proposed dose of a drug was safe and
`
`(cid:131)Phase Itrials designed as safety trials
`
`Different Phases of Clinical Trials
`
`
`
`34
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`Paper 20 at 2, 6-7, 19-24, 41
`Bunn Decl. ¶¶ 51, 75, 88 (Ex. 2021); Giaccone Dep., 139:20-145:4, 159:19-160:15 (Ex. 2020); Paper 7 at 8, 28;
`
`Ex. 1011 at 1011-005 to 06 (OSI 10-K)
`
`Paper 3 at 19
`
`NSCLC TRIALS WERE IN PROCESS
`OSI 10-K DOES NOTDISCLOSE THAT PHASE II
`
`OSI 10-K (Ex. 1011)
`
`
`
`35
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Bunn Decl.¶¶ 25-26, 50-52, 68, 72, 75-76 (Ex. 2021)
`
`Giaccone Dep., 86:11-18 (Ex. 2020)
`
`Paper 20 at 18-19
`
`SPECIFY WHICH INDICATION IS BEING PURSUED IN PHASE II
`OSI 10-K CONTAINS NO DATA FOR CP-358,774 AND DOES NOT
`
`OSI 10-K (Ex. 1011)
`
`
`
`36
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`Paper 20 at 2, 6-7, 19-24, 41
`Bunn Decl. ¶¶ 51, 75, 88 (Ex. 2021); Giaccone Dep., 139:20-145:4, 159:19-160:15 (Ex. 2020); Paper 7 at 8, 28;
`
`Giaccone Dep., 85:3-15 (Ex. 2020)
`
`PATIENTS HAD NOT STARTED AS OF OSI10-K
`ADMINISTRATION OF CP-358,774 TO NSCLC
`
`OSI 10-K (Ex. 1011)
`
`
`
`37
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Ex. 1011 at 1011-024 (OSI 10-K); Paper 20 at 42 n.8
`
`Ex. 1011 at 1011-003 (OSI 10-K); Paper 20 at 42 n.8
`
`OSI 10-K Describes Uncertainty Associated with Drug Development
`
`
`
`38
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`112:18-113:16, 126:6-127:1 (Ex. 2020); Paper 20 at 19, 35, 39-44, 46-55
`Bunn Decl. ¶¶ 25-26, 50-65, 68, 72, 75-78, 84-89 (Ex. 2021); Giaccone Dep., 84:14-85:15, 86:5-87:3, 88:6-10,
`
`for erlotinib in NSCLC
`response, or toxicity data necessary to determine a therapeutic index
`
`(cid:131)Gibbs and OSI 10-K do not include or refer to efficacy, clinical
`
`(cid:131)POSA would not have relied on OSI 10-K as a source of motivation
`
`Paper 20 at 32-35
`Giaccone Dep., 75:15-17; 77:4-15; 77:21-78:8; 81:17-20; 86:11-14 (Ex. 2020); Bunn Decl. ¶¶ 66-67 (Ex. 2021),
`for the development of NSCLC treatments
`
`NO MOTIVATION TO COMBINE
`
`Challenged Claims Non-Obvious Over Schnur and Gibbs or OSI 10-K
`
`
`
`39
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`Bunn Decl. ¶¶ 66-67 (Ex. 2021), Paper 20 at 32-35
`
`(cid:131)A medical oncologist would instead “focus on scientific
`
`literature” with “scientific evidence and data” (id.)
`
`(Ex. 2021))
`efficacy data from clinical trials” (Bunn Decl. ¶¶ 66-67
`filings because they are not focused on “reporting reliable
`(cid:131)A medical oncologist would not have relied on securities
`
`Dr. Bunn testified that:
`
`(cid:131)That a 10-K is “not a scientific publication and “does not
`research (Giaccone Dep.,75:11-17, 81:17-20 (Ex. 2020)
`
`(cid:131)He has never consulted or cited a 10-K in his oncology
`
`report scientific data” (id.,86:11-14)
`
`Dr. Giaccone admitted:
`OF THE OSI10-K
`BOTH EXPERTS AGREE ON THE LIMITATIONS
`
`No Motivation to Combine
`
`
`
`40
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Paper 20 at 11, 47; ; Paper 7 at 30-31, 43-44
`
`Giaccone Dep., 132:11-17 (Ex. 2020)
`
`Paper 20 at 5, 38; Paper 7 at 30-31, 43-44
`
`Giaccone Dep., 139:14-18 (Ex. 2020)
`
`OF TREATMENT FOR NSCLC WERE LOW
`THE ODDS OF FINDING A SUCCESSFUL METHOD
`
`No Reasonable Expectation of Success
`
`
`
`41
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`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Bunn Decl. ¶ 37 (Ex. 2021); Paper 20 at 11-12; Paper 7 at 30-31, 43-44
`
`UNPREDICTABLE
`THE STATE OF THE ART WAS
`
`No Reasonable Expectation of Success
`
`
`
`42
`
`IPR2016-01284
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`Patent Owner’s Demonstrative Exhibits
`
`Paper 20 at 49-50; Paper 7 at 30-31, 43-44
`
`Giaccone Dep., 56:18-21 (Ex. 2020)
`
`Paper 20 at 49-50; Paper 7 at 30-31, 43-44
`
`Bunn Decl. ¶ 84 (Ex. 2021)
`
`PREDICTIVE OF TREATMENT IN NSCLC
`STUDIES IN NON-NSCLC TUMORS ARE NOT
`
`No Reasonable Expectation of Success
`
`
`
`43
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Dr. Bunn’s Actual Testimony
`
`Bunn Decl. ¶ 79 (Ex. 2021)
`
`Petitioners’ Characterization of
`
`Patent Owner’s Argument
`
`Paper 33 at 7
`Apotex Reply,
`
`OWNER’S ARGUMENT
`PETITIONERS MISCHARACTERIZE PATENT
`
`No Reasonable Expectation of Success
`
`
`
`44
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep., 126:6-12 (Ex. 2020)
`
`Paper 20 at 53-54
`
`Giaccone Dep., 52:2-6 (Ex. 2020)
`
`Paper 20 at 4, 37
`
`WAS AVAILABLE BEFORE MARCH 30, 2000
`NO EFFICACY DATA FOR ERLOTINIB IN NSCLC
`
`No Reasonable Expectation of Success
`
`
`
`45
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep., 56:22-57:15 (Ex. 2020)
`
`Paper 20 at 54-55
`
`IN A PARTICULAR INDICATION
`PHASE I TRIALS DO NOT EVALUATE EFFICACY
`
`No Reasonable Expectation of Success
`
`
`
`46
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Bunn Decl. ¶ 30; Ex. 2036 at 5813-14; Paper 20 at 9; Giaccone Dep., 73:5-18 (Ex. 2048); Paper 39 at 4-5
`
`(cid:131)Successive rounds were less effective and more toxic
`
`Paper 20 at 8-9; Giaccone Dep., 68:18-21, 69:10-12 (Ex. 2048); Paper 39 at 4-5; Paper 7 at 6-7
`Bunn Decl. ¶¶ 30, 91 (Ex. 2021); Ex. 2036 at 5813-14; Giaccone Dep. 155:11-21 (Ex. 2020); Ex. 2019 at 449;
`
`(cid:131)Chemotherapy was dangerous and debilitating
`
`(cid:131)Chemotherapy was the standard of care even though its efficacy was
`LIMITATIONS
`CHEMOTHERAPY HAD SIGNIFICANT
`There Was a Long-Felt Unmet Need for New NSCLC Treatments
`
`Paper 39 at 3; Paper 7 at 6-7
`Bunn Decl. ¶ 29 (Ex. 2021); Ex. 2036 at 5813; Paper 20 at 8; Giaccone Dep., 45:9-12, 65:6-17 (Ex. 2048);
`limited and disease progression was inevitable
`
`
`
`47
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep., 65:18-66:5 (Ex. 2048); Paper 39 at 4
`
`Giaccone Dep. 154:6-16 (Ex. 2020); Giaccone Dep., 78:2-14, 62:21-63:2 (Ex. 2048); Paper 39 at 4
`
`(cid:131)New NSCLC treatments were “urgently needed”
`
`Ex. 2031 at 8; Ex. 2032; Ex. 2008 at 1; Ex. 1028 at 46; Paper 20 at 11, 38, 47, 59-61
`Giaccone Dep., 132:11-17, 133:16-134:21, 138:10-16 (Ex. 2020); Bunn Decl. ¶¶ 34, 93-100 (Ex. 2021);
`
`(cid:131)Overwhelming majority of NSCLC drugs failed
`
`Long-Felt Unmet Need / Failure of Others
`
`
`
`48
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`(Petitioners’ Reply)
`
`Paper 33 at 12
`
`There Was a Long-Felt Unmet Need for New NSCLC Treatments
`
`
`
`49
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`(cid:131)Approved for “treatment of patients with locally advanced or metastatic non-
`
`Ex. 2026 at 11; Bunn Decl. ¶¶ 93-97 (Ex. 2021)
`regimen.”
`small cell lung cancer after failure of at least one prior chemotherapy
`
`(cid:131)After years of development, Tarceva was approved for treatment of NSCLC
`
`velopmentTarcevawasapprovedfortre
`
`Paper 20 at 12, 24
`Ex. 2019 at 451-53 & publications cited at endnotes 29, 35-38, 41; Giaccone Dep., 156:10-161:21 (Ex. 2020);
`on November 18, 2004
`
`Tarceva Satisfied a Long-Felt Unmet Need for a New NSCLC Treatment
`
`ng-Felt Unmet Need for a New NSCLC
`
`
`
`50
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep., 34:1-16 (Ex. 2048)
`
`Paper 39 at 2
`
`NEW NSCLC THERAPY WITH CHEMOTHERAPY
`A SKILLED ARTISAN WOULD HAVE COMPARED A
`
`Long-Felt Unmet Need / Unexpected Results
`
`
`
`51
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Giaccone Dep. 163:12-164:1 (Ex. 2020)
`
`Paper 20 at 58-59
`
`Giaccone Dep., 45:1-8 (Ex. 2048)
`
`Paper 39 at 5-6
`
`Tarceva Satisfied a Long-Felt Unmet Need for a New NSCLC Treatment
`
`ng-Felt Unmet Need for a New NSCLC
`
`
`
`52
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`91-92, 106-107 (Ex. 2021)
`Giaccone Dep., 45:5-8, 68:18-21, 69:10-12, 71:17-72:7, 73:5-18 (Ex. 2048); Paper 39 at 4-5; Bunn Decl. ¶¶ 29-31,
`
`(cid:131)Tarceva caused less severe side effects compared with chemotherapy
`
`Bunn Decl. ¶¶ 29-30, 91-92, 106 (Ex. 2021)
`Giaccone Dep., 45:9-12, 61:18-62:8, 65:6-17, 69:13-70:5, 76:15-77:10, 80:16-82:7 (Ex. 2048); Paper 39 at 3-4;
`
`(cid:131)Tarceva’s success rate was comparable to the standard of care
`
`(cid:131)The majority of NSCLC patients did not have successful treatment even with
`
`Giaccone Dep., 80:16-82:7; 61:6-62:8 (Ex. 2048), Paper 39 at 4
`combination chemotherapy
`
`(cid:131)In 2000, chemotherapy offered only a marginal benefit for patients with
`TREATMENT WITH REDUCED SIDE EFFECTS
`TARCEVA OFFERED A NEW TARGETED NSCLC
`
`Giaccone Dep., 69:13-70:5, 76:15-77:10 (Ex. 2048), Paper 39 at 4
`advanced NSCLC
`
`Tarceva Satisfied a Long-Felt Unmet Need
`
`
`
`53
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`(cid:131)Tarceva was a groundbreaking therapy offering “the prospect of greater
`
`Ex. 2019 at 449; Giaccone Dep. 82:19-83:7, 155:4-155:21, 163:12-164:1 (Ex. 2020); Paper 20 at 58-61
`selectivity, more effective tumor control and reduced side effects”
`
`Paper 20 at 61; Bunn Decl. ¶¶ 108-109; Paper 7 at 42-44
`unexpected
`treating NSCLC with a therapeutically effective amount of erlotinib was
`
`(cid:131)The survival benefit to NSCLC patients provided by the method of
`
`Unexpected Results
`
`
`
`54
`
`Patent Owner’s Demonstrative Exhibits
`Ex. 2014 at 2014-0003
`Reisenauer Decl. ¶¶ 5-17 (Ex. 2023); Exs. 2033-2035; Paper 20 at 62-65; Paper 7 at 44-45; Ex. 2013 at 2013-0004;
`
`IPR2016-01284
`
`TARCEVA IS A COMMERCIAL SUCCESS
`
`Tarceva Has Been a Commercial Success
`
`
`
`55
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Paper 20 at iii
`
`(cid:131)Patent Owner’s arguments address the non-obviousness of all of the
`
`Paper 20 at iii, 1, 7, 15, 29-65
`challenged claims
`
`(cid:131)In the Patent Owner’s Response, OSI pointed out that Petitioners’
`
`Paper 20 at 15, 15 n.2
`obviousness arguments focused on the NSCLC indication
`
`(cid:131)Petitioners’ claim charts do not address any indication other than
`
`Paper 3 at Appendix A
`NSCLC
`
`OSI Did Not Waive Its Arguments Regarding the Patentability of Claims 45 and 46
`
`
`
`56
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`MOTION TO EXCLUDE
`
`
`
`57
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`Bunn Dep. 82:10-83:10, 21:5-14, 60:7-13 (Ex. 1048)
`
`Paper 37 at 1-7; Paper 33 at 14-15; Paper 43 at 1-3
`Hidalgo at 3267 (Ex. 1031); Siu (Ex. 2024, Abstract 1498); Bunn Dep. 82:10-83:10, 21:5-14, 60:7-13 (Ex. 1048);
`misleading
`
`(cid:131)Petitioners mischaracterize Hidalgo and the use of the exhibit is
`
`(cid:131)Hidalgo is not part of any instituted ground
`
`Paper 8 at 29
`
`(cid:131)Hidalgo was not cited in the Petition or any Paper prior to Petitioners’
`Hidalgo at 3267 (Ex. 1031); Bunn Dep. 82:10-83:10, 21:5-14, 60:7-13 (Ex. 1048); Paper 37 at 1-7; Paper 43 at 1-3
`
`Paper 3 at 4-5; Paper 37 at 1-7; Paper 43 at 1-3
`Reply
`
`(cid:131)Hidalgo is not prior art and is irrelevant
`
`Hidalgo (Ex. 1031) Should be Excluded
`
`
`
`58
`
`IPR2016-01284
`
`Patent Owner’s Demonstrative Exhibits
`
`Ex. 1031 (Hidalgo)
`
`Hidalgo (Ex. 1031) Should be Excluded
`
`
`
`59
`
`Patent Owner’s Demonstrative Exhibits
`Paper 43 at 1-3
`Hidalgo at 3267 (Ex. 1031);Siu (Ex. 2024, Abstract 1498); Paper 37 at 1-7; Bunn Dep. 82:15-83:10, 21:5-14, 60:12-13 (Ex. 1048);
`
`IPR2016-01284
`
`Hidalgo (Ex. 1031) Should be Excluded
`
`
`
`60
`
`IPR2016-01284
`
`Hidalgo at 3271 (Ex. 1031)
`
`Hidalgo (July 2001)
`
`40 patients
`
`Patent Owner’s Demonstrative Exhibits
`Paper 37 at 1-7; Paper 43 at 1-3;
`
`Siu (Ex. 2024, Abstract 1498)
`
`May 1999 ASCO
`
`27 patients
`
`HIDALGO AND SIU DATA DO NOT MATCH
`
`Hidalgo (Ex. 1031) Should be Excluded
`
`
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