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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`________________
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`________________
`
`
`SAMSUNG BIOEPIS CO., LTD., Petitioner,
`
`
`v.
`
`
`GENENTECH, INC., Patent Owner.
`
`________________
`
`United States Patent No. 6,407,213
`Title: Method for Making Humanized Antibodies
`
`
`Case No.: IPR2017-02140
`
`________________
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 6,407,213
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
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`TABLE OF CONTENTS
`
`
`I.
`
`INTRODUCTION ....................................................................................... 1
`
`II. MANDATORY NOTICES ......................................................................... 1
`
`A.
`
`B.
`
`C.
`
`Petitioner and Real Party in Interest (37 C.F.R. § 42.8(b)(1)) .......... 1
`
`Related Matters (37 C.F.R. § 42.8(b)(2)) .......................................... 2
`
`Counsel and Service Information (37 C.F.R. § 42.8(b)(3) and (4)) .. 2
`
`III. FEES (37 C.F.R. § 42.15(a)) ....................................................................... 3
`
`IV. REQUIREMENTS UNDER 37 C.F.R. § 42.104 ........................................ 3
`
`A. Grounds for Standing (37 C.F.R. § 42.104(a)) ................................. 3
`
`B.
`
`Statement of relief requested (37 C.F.R. § 42.104(b)) ...................... 4
`
`V.
`
`THE LEVEL OF ORDINARY SKILL IN THE RELEVANT ART .......... 5
`
`VI. THE SCOPE AND CONTENT OF THE PRIOR ART .............................. 6
`
`A. Antibodies and Humanization ........................................................... 6
`
`B.
`
`Prior Art Cited in this Petition........................................................... 9
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`Queen 1989 ...........................................................................10
`
`Queen 1990 ...........................................................................11
`
`PDB Database .......................................................................14
`
`Tramontano ...........................................................................17
`
`Kabat 1987 ............................................................................18
`
`Hudziak .................................................................................19
`
`VII. THE ’213 PATENT ...................................................................................20
`
`VIII. CLAIM CONSTRUCTION ......................................................................22
`
`IX. DETAILED STATEMENT OF GROUNDS FOR INVALIDITY ...........25
`
`A. Grounds 1 and 2: Claims 1, 2, 4, 12, 25, 29, 62-67, 69, and 71-81
`are obvious over Queen 1989 (Ground 1) or Queen 1990 (Ground
`2) in view of the PDB Database ......................................................27
`
`1.
`
`Ground 1: Claim 1 is obvious over Queen 1989 in view of
`the PDB Database .................................................................27
`
`
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`i
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`2.
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`3.
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`4.
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`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Ground 2: Claim 1 is obvious over Queen 1990 in view of
`the PDB Database .................................................................33
`
`Grounds 1 and 2: Claims 2, 12, 25, and 29 are obvious over
`Queen 1989 and the PDB Database or Queen 1990 and the
`PDB Database .......................................................................35
`
`Ground 2: Claim 4 is obvious in view of Queen 1990 and
`PDB Database .......................................................................37
`
`Ground 2: Claim 62 is obvious in view of Queen 1990 and
`PDB Database .......................................................................38
`
`Grounds 1 and 2: Claims 63, 64, and 66 are obvious over
`Queen 1989 or Queen 1990 and the PDB Database .............38
`
`Ground 2: Claim 69 is obvious in view of Queen 1990 and
`PDB Database .......................................................................43
`
`Grounds 1 and 2: Claims 67, 71-74, and 78 are obvious in
`view of Queen 1989 or Queen 1990 and PDB Database ......44
`
`Grounds 1 and 2: Claims 75-77 and 79 are obvious in view
`of Queen 1989 or Queen 1990 and PDB Database ...............45
`
`10. Grounds 1 and 2: Claim 65 is obvious in view of Queen
`1989 or Queen 1990 and the PDB Database.........................49
`
`11. Grounds 1 and 2: Claims 80 and 81 are obvious in view of
`Queen 1989 or Queen 1990 and the PDB Database .............50
`
`B. Grounds 3 and 4: Claims 75-77, 79, and 69 are obvious over
`Queen 1989 and/or Queen 1990 in view of PDB Database and
`Tramontano .....................................................................................52
`
`C. Ground 5: Claims 4, 62, 64, and 69 are obvious over Queen 1989
`in view of the PDB Database and Kabat 1987 ................................53
`
`D. Grounds 6 and 7: Independent claim 30 and dependent claims 31,
`33, 42, and 60 are obvious over Queen 1989 (Ground 6) and/or
`Queen 1990 (Ground 7)
`in view of the PDB Database and Hudziak .....................................55
`
`E.
`
`Secondary Considerations Cannot Overcome Obviousness ...........59
`
`1.
`
`The Challenged Claims of the ’213 patent produced no
`unexpected results .................................................................60
`
`2.
`
`The ’213 patent did not satisfy a long-felt, but unmet need .63
`
`
`ii
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`
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`3.
`
`There is no nexus between the commercial success of
`Genentech drugs and the Challenged Claims of the ’213
`patent .....................................................................................64
`
`X. CONCLUSION ..........................................................................................65
`
`
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`iii
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`
`
`TABLE OF AUTHORITIES
`
`
`Cases
`
`Atlas Powder Co. v. Ireco Inc.,
`190 F.3d 1342 (Fed. Cir. 1999) .............................................................. 39, 51
`
`Cubist Pharms., Inc. v. Hospira, Inc.,
`75 F. Supp. 3d 641 (D. Del. 2014),
`aff’d 805 F.3d 1112 (Fed. Cir. 2015) ...................................................... 60, 61
`
`Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131 (2016) ...................................................................................22
`
`Ecolochem, Inc. v. S. Cal. Edison Co.,
`1996 U.S. App. LEXIS 13330 (Fed. Cir. June 5, 1996)................................23
`
`Endo Pharms., Inc. v. Depomed, Inc.,
`IPR2014-00652, Paper 38 (PTAB Sept. 16, 2015) .......................................64
`
`In re GPAC Inc.,
`57 F.3d 1573 (Fed. Cir. 1995) .......................................................................64
`
`In re Hall,
`781 F.2d 897 (Fed. Cir. 1986) .......................................................................14
`
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .....................................................................62
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .....................................................................50
`
`Merck & Cie v. Gnosis S.P.A.,
`808 F.3d 829 (Fed. Cir. 2015) .......................................................................64
`
`Merck & Co. v. Teva Pharms. USA,
`395 F.3d 1364 (Fed. Cir. 2005) .....................................................................60
`
`Norgren Inc. v. ITC,
`699 F.3d 1317 (Fed. Cir. 2012) .....................................................................63
`
`Ormco Corp. v. Align Tech., Inc.
`463 F.3d 1299 (Fed. Cir. 2006) .....................................................................64
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .....................................................................59
`
`Tokai Corp. v. Easton Enters., Inc.,
`632 F.3d 1358 (Fed. Cir. 2011) .....................................................................60
`
`
`
`
`iv
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`

`
`
`Torrent Pharms. Ltd. v. Novartis AG,
`IPR2014-00784, Paper 112 (PTAB Sept. 24, 2015) .....................................60
`
`Wyers v. Master Lock Co.,
`616 F.3d 1231 (Fed. Cir. 2010) .....................................................................64
`
`Statutes
`
`35 U.S.C. § 102 ................................................................................................ passim
`
`35 U.S.C. § 103 .......................................................................................................... 4
`
`35 U.S.C. § 120 ........................................................................................................21
`
`35 U.S.C. § 135 ........................................................................................................22
`
`35 U.S.C. §§ 311-319................................................................................................. 1
`
`Other Authorities
`
`37 C.F.R. § 42.6 ......................................................................................................... 4
`
`37 C.F.R. § 42.8 .....................................................................................................1, 2
`
`37 C.F.R. § 42.10 ....................................................................................................... 1
`
`37 C.F.R. § 42.15 ....................................................................................................... 3
`
`37 C.F.R. § 42.24 ....................................................................................................... 1
`
`37 C.F.R. § 42.104 .................................................................................................3, 4
`
`MPEP 2128 ..............................................................................................................14
`
`MPEP 2144 ..............................................................................................................50
`
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`v
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`
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`Exhibit 1002
`
`Exhibit 1003
`
`Exhibit 1004
`
`TABLE OF EXHIBITS
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Exhibit No.
`Exhibit 1001 U.S. Patent No. 6,407,213
`File History of U.S. Patent Application No. 08/146,206 (issued as
`U.S. Patent No. 6,407,213)
`Declaration of Jefferson Foote, Ph.D, submitted in support of
`IPR2017-01488
`Declaration of Timothy Buss, submitted in support of IPR2017-
`01488
`Exhibit 1005 Reserved
`Exhibit 1006 Reserved
`Exhibit 1007 Reserved
`Exhibit 1008 Reserved
`Exhibit 1009 Reserved
`Exhibit 1010 Reserved
`Exhibit 1011 Reserved
`Exhibit 1012 Reserved
`Exhibit 1013 Reserved
`Exhibit 1014 Reserved
`Exhibit 1015 Reserved
`Exhibit 1016 Reserved
`Exhibit 1017 Reserved
`Exhibit 1018 Reserved
`Exhibit 1019 Reserved
`Exhibit 1020 Reserved
`Robert Hudziak, et al., p185HER2 Monoclonal Antibody Has
`Antiproliferative Effects In Vitro and Sensitizes Human Breast
`Tumor Cells to Tumor Necrosis Factor, 9(3) Molecular & Cellular
`Biol. 1165-1172 (Mar. 1989)
`G. Köhler & C. Milstein, Continuous cultures of fused cells
`secreting antibody of predefined specificity, 256 Nature 495-497
`(Aug. 1975)
`Prabakaran, The Quest for a Magic Bullet, 349(6246) SCIENCE 389
`(2015)
`
`Exhibit 1021
`
`Exhibit 1022
`
`Exhibit 1023
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`vi
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`
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`Exhibit No.
`
`Exhibit 1024
`
`Exhibit 1025
`
`Exhibit 1026
`
`Exhibit 1027
`
`Exhibit 1028
`
`Exhibit 1029
`
`Exhibit 1030
`
`Exhibit 1031
`
`Exhibit 1032
`
`Exhibit 1033
`
`Exhibit 1034
`
`Exhibit 1035
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Marks, The Story of Cesar Milstein and Monoclonal Antibodies: A
`Healthcare Revolution in the Making,
`http://www.whatisbiotechnology.org/exhibitions/milstein (last
`accessed March 23, 2017)
`Cosimi et al., Treatment of Acute Renal Allograft Rejection with
`OKT3 Monoclonal Antibody, 32(6) TRANSPLANTATION 53539
`(1981) (“Cosimi ‘81”)
`Ortho Multicenter Transplant Study Group, A Randomized Clinical
`Trial of OKT3 Monoclonal Antibody for Acute Rejection of
`Cadveric Renal Transplants, 313(6) NEW ENG. J. MED. 337–42
`(1985) (“OMTSG ‘85”)
`Jaffers et al., Monoclonal Antibody Therapy: Anti-Idiotypic and
`Non-Anti-Idiotypic Antibodies to OKT3 Arising Despite Intense
`Immunosuppression, 41(5) Transplantation 572-578 (1986)
`Sears et al., Phase-I Clinical Trial of Monoclonal Antibody in
`Treatment of Gastrointestinal Tumours, 1 LANCET 762–65 (1982)
`Sikora, Monoclonal Antibodies in Oncology, 35(4) J. CLINICAL
`PATHOLOGY 369–75 (1982)
`Protein Data Bank - Chronology, National Science Foundation,
`https://www.nsf.gov/news/news_summ.jsp?cntn_id=100689 (last
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`S. Morrison, et al., Chimeric human antibody molecules: Mouse
`antigen-binding domains with human constant region domains, 81
`Proc. Nat’l Acad. Sci. USA 6851-6855 (Nov. 1984)
`Liu et al., Chimeric Mouse-Human IgG1 Antibody that can Mediate
`Lysis of Cancer Cells, 84(10) PROC. NAT’L ACAD. SCI. USA 3439–
`43 (1987) (“Liu ‘87”)
`P. Jones, et al., Replacing the complementarity-determining regions
`in a human antibody with those form a mouse, 321 Nature 522-525
`(May 1986)
`C. Queen, et al., A humanized antibody that binds to the interleukin
`2 receptor, 86 Proc. Nat’l Acad. Sci. USA (Dec. 1989)
`Kirkman et al., Early Experience with Anti-Tac in Clinical Renal
`Transplantation, 21(1) TRANSPLANTATION PROC. 1766–68 (1989)
`(“Kirkman ‘89”)
`
`
`
`
`vii
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`

`
`
`Exhibit No.
`
`Exhibit 1036
`
`Exhibit 1037
`
`Exhibit 1038
`
`Exhibit 1039
`
`Exhibit 1040
`
`Exhibit 1041
`
`Exhibit 1042
`
`Exhibit 1043
`
`Exhibit 1044
`
`Exhibit 1045
`
`Exhibit 1046
`
`
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Waldmann et al., The Interleukin-2 Receptor: A Target for
`Monoclonal Antibody Treatment of Human T-Cell Lymphotrophic
`Virus I-Induced Adult T-Cell Leukemia, 82(6) BLOOD 1701–12
`(1993) (“Waldman ‘93”)
`Hakimi et al., Reduced Immunogenicity and Improved
`Pharmacokinetics of Humanized ANTI-Tac in Cynomolgus
`Monkeys, 147(4) J. IMMUNOLOGY 1352–59 (1991) (“Hakimi ‘91”)
`Vincenti et al., Interleukin 2-Receptor Blockade with Daclizumab to
`Prevent Acute Rejection in Renal Transplantation, 338(3) NEW ENG.
`J. MED. 161–65 (1998) (“Vincenti ‘98”)
`SEER Stat Fact Sheets: Breast Cancer, National Cancer Institute,
`http://seer.cancer.gov/statfacts/html/breast.html (last accessed
`March 17, 2017)
`J. Harris, et al., Medical Progress: Breast Cancer, 327(5) New Eng.
`J. Med. 319-328 (1992)
`King et al., Amplification of a Novel v-erbB-Related Gene in a
`Human Mammary Carcinoma, 229(4717) SCIENCE 974–76 (1985)
`(“King ‘85”)
`Semba et al., A v-erbB-Related Protooncogene, c-erbB-2, is Distinct
`from the c-erbB-1 / Epidermal Growth Factor-Receptor Gene and is
`Amplified in a Human Salivary Gland Adenocarcinoma, 82(19)
`PROC. NAT’L ACAD. SCI. USA 6497–01 (1985) (“Semba ‘85”)
`Semba et al., A v-erbB-Related Protooncogene, c-erbB-2, is Distinct
`from the c-erbB-1 / Epidermal Growth Factor-Receptor Gene and is
`Amplified in a Human Salivary Gland Adenocarcinoma, 82(19)
`PROC. NAT’L ACAD. SCI. USA 6497–01 (1985) (“Semba ‘85”)
`Fukushige et al., Localization of a Novel v-erbB-Related Gene,
`cerbB-2, on Human Chromosome 17 and its Amplification in a
`Gastric Cancer Cell Line, 6(3) MOLECULAR CELLULAR BIOLOGY
`955–58 (1986)
`Slamon et al., Human Breast Cancer: Correlation of Relapse and
`Survival with Amplification of the HER-2/neu Oncogene, 235(4785)
`SCIENCE 177–82 (1987) (“Slamon ‘87”)
`Kraus et al., Overexpression of the EGF Receptor-Related Proto-
`Oncogene erbB-2 in Human Mammary Tumor Cell Lines by
`Different Molecular Mechanisms, 6(3) The EMBO J. 605– 10
`(1987)
`
`
`viii
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`
`
`Exhibit No.
`
`Exhibit 1047
`
`Exhibit 1048
`
`Exhibit 1049
`
`Exhibit 1050
`
`Exhibit 1051
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`R. Hudziak, et al., Increased Expression of the Putative Growth
`Factor
`Recptorp185HER2
`Causes
`Transformation
`and
`Tumorigenesis of NIH 3T3 Cells, 84(2) Proc. Nat’l Acad. Sci. USA
`7159-7163 (1987)
`H. M. Shepard, et al., Monoclonal Antibody Therapy of Human
`Cancer: Taking the HER2 Protooncogene to the Clinic, 11(3) J.
`Clinical Immunology 117-127 (1991)
`Chothia, et al., Conformations of Immunoglobulin Hypervariable
`Regions, 342(21) Nature 877-883 (1989)
`C. Queen, International Publication No. WO 1990/007861 (July 26,
`1990)
`Tramontano, et al., Framework Residue 71 is a Major Determinant
`of the Position and Conformation of the Second Hypervariable
`Region in the VH Domains of Immunoglobulins, 215(1) J. Molecular
`Biology 175-182 (1990)
`Kabat, et al., Sequences of Proteins of Immunological Interest:
`Tabulation and Analysis of Amino Acid and Nucleic Acid Sequences
`of Precursors, V-Regions, C-Regions, J-Chain, T-Cell Receptor for
`Antigen, T-Cell Surface Antigens, β2-Microglubins, Major
`Histocompatibility Antigens, Thy-1 Complement, C-Reactive
`Protein, Thymopoietin, Post-Gamma Globulin,
`and
`α2-
`Macroglobulin 41-175 (4th ed. 1987)
`Exhibit 1053 Reserved
`Exhibit 1054 Reserved
`Kabat, et al., Sequences of Proteins of Immunological Interest:
`Tabulation and Analysis of Amino Acid and Nucleic Acid Sequences
`of Precursors, V-Region, C-Regions, J-Chain, T-Cell Receptor for
`Antigen, T-Cell Surface Antigens, β2-Microglubins, Major
`Histocompatibility Antigens, Thy-1 Complement, C-Reactive
`Protein, Thymopoietin, Post-Gamma Globulin, α2-Macroglobulins,
`and Other Related Proteins 103-338 (5th ed. 1991)
`Exhibit 1056 Reserved
`Exhibit 1057 Reserved
`Davies & Metzger, Structural Basics of Antibody Function, 1 ANN.
`REV. IMMUNOLOGY 87–117 (1983) (“Davies & Metzger”)
`
`Exhibit 1052
`
`Exhibit 1055
`
`Exhibit 1058
`
`
`
`
`ix
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`
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`Exhibit No.
`
`Exhibit 1059
`
`Exhibit 1062
`
`Exhibit 1063
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`A. Amit, et al., Three-Dimensional Structure of an Antigen-
`Antibody Complex at 2.8 Å Resolution, 233 Science 747-753 (Aug.
`1986)
`Exhibit 1060 Reserved
`Exhibit 1061 Reserved
`C. Chothia & A. Lesk, Canonical Structures for the Hypervariable
`Regions of Immunoglobulins, 196 J. Mol. Biol. 901-917 (1987)
`C. Chothia, et al., Domain Association
`in Immunoglobulin
`Molecules: The Packing of Variable Domains, 186 J. Mol. Biol.
`651-663 (1985)
`Exhibit 1064 Reserved
`Exhibit 1065 Reserved
`Exhibit 1066 Reserved
`Exhibit 1067 Reserved
`M. Verhoeyen, et al., Reshaping Human Antibodies: Grafting an
`Antilysozyme Activity, 239 Science 1534-1536 (1988)
`L. Riechmann, et al., Reshaping human antibodies for therapy, 332
`Nature 323-327 (Mar. 1988)
`Exhibit 1070 Reserved
`R. Kurrle, et al. EP Publication No. 0 403 156, Improved
`Monoclonal antibodies Agasint the Human Alphabeta T-Cell
`Receptor, Their Production and Use (Dec. 19, 1990)
`Exhibit 1072 Reserved
`Winter et al., EP Publication No. 0 239 400, Recombinant
`Antibodies and Methods for Their Productions (Sept. 30, 1987)
`Exhibit 1074 Reserved
`Exhibit 1075 Reserved
`Exhibit 1076 Reserved
`Exhibit 1077 Reserved
`Exhibit 1078 Reserved
`Kabat, et al., Sequences of Proteins of Immunological Interest:
`Tabulation and Analysis of Amino Acid and Nucleic Acid Sequences
`of Precursors, V-Regions, C-Regions, J-Chain, T-Cell Receptor for
`Antigen, T-Cell Surface Antigens, β2-Microglubins, Major
`Histocompatibility Antigens, Thy-1 Complement, C-Reactive
`Protein, Thymopoietin, Post-Gamma Globulin,
`and
`α2-
`Macroglobulin 41-175 (1983)
`
`Exhibit 1068
`
`Exhibit 1069
`
`Exhibit 1071
`
`Exhibit 1073
`
`Exhibit 1079
`
`
`
`
`x
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`
`
`
`
`

`

`
`
`Exhibit No.
`
`Exhibit 1080
`
`Exhibit 1081
`
`Exhibit 1082
`
`Exhibit 1083
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Bernstein et al., The Protein Data Bank: A Computer-based
`Archival File for Macromolecular Structures, 112(3) J. MOLECULAR
`BIOLOGY 535–42 (1977)
`Sheriff et al., Three-Dimensional Structure of an Antibody- Antigen
`Complex, 84(22) PROC. NAT’L ACAD. SCI. USA. 8075–79 (1987)
`(“Sheriff ‘87”)
`Marquart et al., The Three-Dimensional Structure of Antibodies,
`3(6) IMMUNOLOGY TODAY 160–66 (1982)
`Saul et al., Preliminary Refinement and Structural Analysis of the
`Fab Fragment from Human Immunoglobulin New at 2.0 Å
`Resolution*, 253(2) J. BIOLOGICAL CHEMISTRY 585–95 (1978)
`(“Saul ‘78”)
`Exhibit 1084 Reserved
`Satow et al., Phosphocholine Binding Immunogloubulin Fab
`McPC306 An X-ray Diffraction Study at 27 Å, 190(4) J.
`MOLECULAR BIOLOGY 593–604 (1986)
`Herron et al., Three-Dimensional Structure of a Fluorescein-Fab
`Complex Crystallized in 2-Methyl-2,4-Pentanediol, 5(4) PROTEINS
`271–80 (1989)
`Padlan et al., Structure of an Antibody-Antigen Complex: Crystal
`Structure of the HyHEL-10 Fab-Lysozyme Complex, 86(15) PROC.
`NAT’L ACAD. SCI. USA 5938–42 (1989) (“Padlan ‘89”)
`Kumar et al., Regulation of Phosphorylation of the c-erbB-2/HER2
`Gene Product by Monoclonal Antibody and Serum Growth
`Factor(s) in Human Mammary Carcinoma Cells, 11(2) MOLECULAR
`CELLULAR BIOLOGY 979–86 (1991)
`Soomro et al., C-erbB-2 Expression in Different Histological Types
`of Invasive Breast Carcinoma, 44(3) J. CLINICAL PATHOLOGY 211–
`14 (1991)
`Wilson & Goulding, A BIOLOGIST‘S GUIDE TO PRINCIPLES AND
`TECHNIQUES OF PRACTICAL BIOCHEMISTRY, §Protein Sequencing,
`170–73 (3d ed. 1986)
`Edelman et al., The Covalent Structure of an Entire G
`Immunoglobulin Molecule*, 63(1) PROC. NAT’L ACAD. SCI. USA
`78–85 (1969)
`
`Exhibit 1085
`
`Exhibit 1086
`
`Exhibit 1087
`
`Exhibit 1088
`
`Exhibit 1089
`
`Exhibit 1090
`
`Exhibit 1091
`
`
`
`
`xi
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`

`
`
`Exhibit No.
`
`Exhibit 1092
`
`Exhibit 1093
`
`Exhibit 1095
`(Vols. 1-15)
`
`Exhibit 1096
`
`Exhibit 1097
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Capra & Kehoe, Variable Region Sequences of Five Human
`Immunoglobulin Heavy Chains of the VHIII Subgroup: Definitive
`Identification of Four Heavy Chain Hypervariable Regions, 71(3)
`PROC. NAT’L ACAD. SCI. USA 845–48 (1974)
`Morin, From Oncogene to Drug: Development of Small Molecule
`Tyrosine Kinase Inhibitors as Anti-Tumor and Anti-Angiogenic
`Agents, 19(56) ONCOGENE 6574– 83 (2000)
`Exhibit 1094 Reserved
`Patent Interference No. 105,744 (Senior Party, Application No.
`11/284,261, John Adair et al. and Junior Party, U.S. Patent No.
`6,407,213, Paul Carter & Leonard Presta)
`U.S. Patent No. 5,677,171, Monoclonal Antibodies Directed to the
`HER2 Receptor (filed Aug. 5, 1994 and issued Oct. 14, 1997)
`Sambrook et al., MOLECULAR CLONING: A LABORATORY MANUAL
`(Cold Spring Harbor Laboratory Press, 2d ed. 1989)
`Exhibit 1098 Reserved
`Exhibit 1099 Reserved
`Colman et al., Three-Dimensional Structure of a Complex of
`Antibody with Influenza Virus Neuraminidase, 326(6111) NATURE
`358–63 (1987) (“Colman ‘87”)
`Exhibit 1101 Reserved
`Bender et al., Immunogenicity, Efficacy and Adverse Events of
`Adalimumab in RA Patients, 27(3) RHEUMATOLOGY INT’L 269–74
`(2007)
`Brient & Nisonoff, Quantitative Investigations of Idiotypic
`Antibodies. IV. Inhibition by Specific Haptens of the Reaction of
`Anti-Hapten Antibody with Its Anti-Idiotypic Antibody, 132 J.
`EXPERIMENTAL MED. 951–61 (1970)
`Koprowski et al., Human Anti-Idiotype Antibodies in Cancer
`Patients: Is the Modulation of the Immune Response Beneficial for
`the Patient?, 81(1) PROC. NAT’L. ACAD. SCI. USA 216–19 (1984)
`(“Koprowski ‘84”)
`Chanh et al., Monoclonal Anti-Idiotypic Antibody Mimics the CD4
`Receptor and Binds Human Immunodeficiency Virus, 84 PROC.
`NAT’L. ACAD. SCI. USA 3891–95 (1987) (“Chanh ‘87”)
`
`Exhibit 1100
`
`Exhibit 1102
`
`Exhibit 1103
`
`Exhibit 1104
`
`Exhibit 1105
`
`
`
`
`xii
`
`
`
`
`
`

`

`
`
`Exhibit No.
`
`Exhibit 1106
`
`Exhibit 1107
`
`Exhibit 1113
`
`Exhibit 1114
`
`Exhibit 1115
`
`Exhibit 1116
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Schroff et al., Human Anti-Murine Immunoglobulin Responses in
`Patients Receiving Monoclonal Antibody Therapy, 45(2) CANCER
`RES. 879–85 (1985) (“Schroff ‘85”)
`Abdou et al., Network Theory in Autoimmunity. In Vitro
`Suppression of Serum Anti-DNA by Anti-idiotypic Antibody in
`Systemic Lupus Erythematosus, 67(5) J. CLINICAL INVESTIGATION
`1297–1304 (1981)
`Exhibit 1108 Reserved
`Exhibit 1109 Reserved
`Exhibit 1110 Reserved
`Exhibit 1111 Reserved
`Exhibit 1112 Reserved
`Epp et al., The Molecular Structure of a Dimer Composed of the
`Variable Portions of the Bence-Jones Protein REI Refined at 2.0-Å
`Resolution, 14(22) BIOCHEMISTRY 4943–52 (1975)
`Mian, Structure, Function and Properties of Antibody Binding Sites,
`217(1) J. MOLECULAR BIOLOGY 133–51 (1991)
`Poljak et al., The Three-Dimensional Structure of the Fab Fragment
`of A Human Myeloma Immunoglobulin at 2.0-Å Resolution, 71(9)
`PROC. NAT’L ACAD. SCI. USA. 3440–44 (1974)
`Padlan et al., Model Building Studies of Antigen-binding Sites: the
`Hapten Binding Site of MOPC-315, 41 COLD SPRING HARBOR SYMP.
`QUANTITATIVE BIOLOGY 627–37 (1977)
`Exhibit 1117 Reserved
`Exhibit 1118 Reserved
`Exhibit 1119 Reserved
`Exhibit 1120 Reserved
`Suh et al., The Galactan-Binding Immunoglobulin Fab J539: An X-
`Ray Diffraction Study at 2.6-Å Resolution, 1(1) PROTEINS 74–80
`(1986) (“Suh ‘86”)
`Exhibit 1122 Reserved
`Exhibit 1123 Reserved
`Exhibit 1124 Reserved
`W. Furey, et al., Structure of a Novel Bence-Jones Protein (Rhe)
`Fragment at 1.6 Å Resolution, 167 J. Mol. Biol. 661-692 (1983)
`
`Exhibit 1121
`
`Exhibit 1125
`
`
`
`
`xiii
`
`
`
`
`
`

`

`
`
`Exhibit No.
`
`Exhibit 1126
`
`Exhibit 1127
`
`Exhibit 1128
`
`Exhibit 1129
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Segal et al., The Three-Dimensional Structure of a
`Phosphorylcholine-Binding Mouse Immunoglobulin Fab and the
`Nature of the Antigen Binding Site, 71(11) PROC. NAT’L ACAD. SCI.
`USA 4298 (1974)
`Jones, Diffraction Methods for Biological Macromolecules.
`Interactive Computer Graphics: FRODO, 115 METHODS
`ENZYMOLOGY 157–71 (1985) (“Jones ‘85”)
`Co et al., Humanized Antibodies for Antiviral Therapy, 88(7) PROC.
`NAT’L ACAD. SCI. USA 2869–73 (1991) (“Co ‘91”)
`Excel Trick, History of Microsoft Excel 1978–2013,
`http://www.exceltrick.com/others/history-of-excel/ (last accessed
`April 13, 2017)
`U.S. Patent No. 4,891,762, Method and Apparatus for Tracking,
`Mapping and Recognition of Spatial Patterns (filed February 9,
`1988) (issued January 2, 1990)
`Wallick et al., Glycosylation of A VH Residue of a Monoclonal
`Antibody Against (L-6) Dextran Increases its Affinity for Antigen,
`168(3) J. EXPERIMENTAL MED. 1099–109 (1988) (“Wallick ‘88”)
`Exhibit 1132 Reserved
`Exhibit 1133 Reserved
`Exhibit 1134 Reserved
`Exhibit 1135 Reserved
`Exhibit 1136 Reserved
`Exhibit 1137 Reserved
`Exhibit 1138 Reserved
`Exhibit 1139 Reserved
`Exhibit 1140 Reserved
`Exhibit 1141 Library of Congress Copyright Record for Cosimi ‘81
`Exhibit 1142 Library of Congress Copyright Record for OMTSG ‘85
`Exhibit 1143 Library of Congress Copyright Record for Jaffers ‘86
`Exhibit 1144 Library of Congress Copyright Record for Morrison ‘84
`Exhibit 1145 Library of Congress Copyright Record for Liu ‘87
`Exhibit 1146 Library of Congress Copyright Record for Jones ‘86
`Exhibit 1147 Library of Congress Copyright Record for Queen 1989
`Exhibit 1148 Library of Congress Copyright Record for Kirkman ‘89
`Exhibit 1149 Library of Congress Copyright Record for Waldamnn ‘93
`Exhibit 1150 Library of Congress Copyright Record for Hakimi ‘91
`
`Exhibit 1130
`
`Exhibit 1131
`
`
`
`
`xiv
`
`
`
`
`
`

`

`
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Exhibit No.
`Exhibit 1151 Library of Congress Copyright Record for Vincenti ‘98
`Exhibit 1152 Library of Congress Copyright Record for Harris ‘92
`Exhibit 1153 Library of Congress Copyright Record for King ‘85
`Exhibit 1154 Library of Congress Copyright Record for Semba ‘85
`Exhibit 1155 Library of Congress Copyright Record for Coussens ‘85
`Exhibit 1156 Library of Congress Copyright Record for Slamon ‘87
`Exhibit 1157 Library of Congress Copyright Record for Hudziak ‘87
`Exhibit 1158 Library of Congress Copyright Record for Chothia ‘89
`Exhibit 1159 Library of Congress Copyright Record for Davies & Metzger
`Exhibit 1160 Library of Congress Copyright Record for Amit ‘86
`Exhibit 1161 Reserved
`Exhibit 1162 Reserved
`Exhibit 1163 Library of Congress Copyright Record for Verhoeyen ‘88
`Exhibit 1164 Library of Congress Copyright Record for Riechmann ‘88
`Exhibit 1165 Reserved
`Exhibit 1166 Reserved
`Exhibit 1167 Library of Congress Copyright Record for Sheriff ‘87
`Exhibit 1168 Library of Congress Copyright Record for Saul ‘78
`Exhibit 1169 Reserved
`Exhibit 1170 Library of Congress Copyright Record for Padlan ‘89
`Exhibit 1171 Library of Congress Copyright Record for Colman ‘87
`Exhibit 1172 Library of Congress Copyright Record for Koprowski ‘84
`Exhibit 1173 Library of Congress Copyright Record for Chanh ‘87
`Exhibit 1174 Library of Congress Copyright Record for Schroff ‘85
`Exhibit 1175 Reserved
`Exhibit 1176 Reserved
`Exhibit 1177 Reserved
`Exhibit 1178 Library of Congress Copyright Record for Suh ‘86
`Exhibit 1179 Library of Congress Copyright Record for Jones ‘85
`Exhibit 1180 Library of Congress Copyright Record for Co ‘91
`Exhibit 1181 Library of Congress Copyright Record for Wallick ‘88
`Bodmer, International Publication No. WO 1989/001783 (Mar. 9,
`1989)
`Gorman, International Publication No. WO 1992/005274 (Apr. 2,
`1992)
`Exhibit 1184 Declaration of Scott Weingaertner
`
`Exhibit 1183
`
`Exhibit 1182
`
`
`
`
`xv
`
`
`
`
`
`

`

`
`
`Exhibit No.
`
`Exhibit
`1184A
`
`Exhibit
`1184B
`
`Exhibit
`1184C
`
`Exhibit
`1184D
`
`Exhibit
`1184E
`
`Exhibit
`1184F
`
`Exhibit
`1184G
`
`Exhibit
`1184H
`
`Exhibit
`1184I
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Three-Dimensional Structure of an Antibody-Antigen Complex,
`RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/obsolete.do?obsoleteId=2HFL&evt
`c=Suggest&evta=PDBID&evtl=autosearch_SearchBar_querySugge
`st
`The Three-Dimensional Structure of Antibodies, RCSB Protein Data
`Bank,
`http://www.rcsb.org/pdb/explore/obsolete.do?obsoleteId=1FB4
`
`Preliminary Refinement and Structural Analysis of the FAB
`Fragment from Human Immunoglobulin New at 2.0 Angstroms
`Resolution, RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/obsolete.do?obsoleteId=3FAB
`Refined Crystal Structure of the Galactan-Binding Immunoglobulin
`Fab J539 at 1.95-Angstroms Resolution, RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/explore.do?structureId=2FBJ
`Phosphocholine Binding Immunoglobulin Fab McPC603. An X-ray
`Diffraction Study at 2.7 A, RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/explore.do?structureId=1MCP
`Three-dimensional Structure of a Fluorescein-Fab Complex
`Crystallized in 2-methyl-2,4-pentanediol, RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/explore.do?structureId=4FAB
`Structure of an Antibody-Antigen Complex: Crystal Structure of the
`HyHEL-10 Fab-lysozyme Complex, RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/explore.do?structureId=3HFM
`The Molecular Structure of a Dimer Composed of the Variable
`Portions of the Bence-Jones Protein REI Refined at 2.0-A
`Resolution, RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/explore.do?structureId=1REI
`Structure of a Novel Bence-Jones Protein (Rhe) Fragment at 1.6 A
`Resolution, RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/explore.do?structureId=2RHE
`Miller, To Build a Better Mousetrap, Use Human Parts, 90(1) J.
`NAT’L CANCER INST. 1416 (1998) (“Miller ‘98”)
`Exhibit 1186 Library of Congress Copyright Record for Miller ‘98
`Exhibit 1187 Reserved
`Exhibit 1188 Declaration of Christopher Lowden, as filed in IPR2017-01488
`
`Exhibit 1185
`
`
`
`
`xvi
`
`
`
`
`
`

`

`
`
`Petitioner Bioepis’s Exhibit List
`Document Description
`Exhibit No.
`Exhibit 1189 U.S. Patent No. 5,859,205
`Exhibit 1190 Declaration of Diljeet S. Athwal, Ph.D.
`Exhibit 1191 Declaration of Mark Gerstein, Ph.D.
`S. Roberts, et al., Generation of an antibody with enhanced affinity
`and specificity for its antigen by protein engineering, 328 NATURE
`731-34 (Aug. 1987)
`
`Exhibit 1192
`
`
`
`
`
`
`
`
`
`
`xvii
`
`
`
`
`
`

`

`
`
`I.
`
`INTRODUCTION
`
`
`
`Pursuant to 35 U.S.C. §§ 311-319 and 37 C.F.R. § 42, Samsung Bioepis Co.,
`
`Ltd. (“Bioepis” or “Petitioner”) petitions for inter partes review of claims 1, 2, 4,
`
`12, 25, 29-31, 33, 42, 60, 62-67, 69, 71-81 (the “Challenged Claims”) of United
`
`States Patent No. 6,407,213 (the “’213 patent”) (Ex. 1001). Concurrently filed
`
`with the petition is a power of attorney pursuant to 37 C.F.R. § 42.10(b).
`
`
`
`The Challenged Claims of the ’213 patent are directed to humanized
`
`antibodies with non-human residues in the Complementarity Determining Regions
`
`(“CDRs”) as well as in the framework region at certain, specified positions. This
`
`petition shows, by a preponderance of the evidence, that the Challenged Claims are
`
`unpatentable as obvious over the prior art.
`
`For the sake of completeness and efficiency, the present petition is a
`
`practical copy of the petition in IPR2017-01489. A Motion for Joinder with
`
`IPR2017-01489 is being filed concurrently with this petition.
`
`II. MANDATORY NOTICES
`
`A.
`
`Petitione