IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In the Inter Partes Review of:
`
`Trial Number: To Be Assigned
`
`
`
`U.S. Patent No. 6,407,213
`
`Filed: November 17, 1993
`
`Issued: June 18, 2002
`
`Inventor(s): Paul J. Carter, Leonard G. Presta
`
`Assignee: Genentech, Inc.
`
`
`
`
`
`
`
`
`
`
`
`Title: Method for making humanized antibodies Panel: To Be Assigned
`
`Mail Stop Inter Partes Review
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 6,407,213
`UNDER 35 U.S.C. §311 AND 37 C.F.R. §42.100
`
`

`

`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION ......................................................................................... 1
`
`II. MANDATORY NOTICES – 37 C.F.R. §42.8(A)(1) AND (B) ................... 2
`
`A.
`
`B.
`
`C.
`
`D.
`
`37 C.F.R. §42.8(b)(1): Real Party-In-Interest ....................................... 2
`
`37 C.F.R. §42.8(b)(2): Related Matters ................................................ 2
`
`37 C.F.R. §42.8(b)(3): Lead and Back-Up Counsel ............................. 3
`
`37 C.F.R. §42.8(b)(4): Service Information .......................................... 3
`
`III. PAYMENT OF FEES – 37 C.F.R. §42.103 ................................................. 3
`
`IV. GROUNDS FOR STANDING – 37 C.F.R. §42.104(A) .............................. 4
`
`V.
`
`IDENTIFICATION OF CHALLENGE – 37 C.F.R. §42.104(B) .............. 4
`
`VI. THRESHOLD REQUIREMENT FOR INTER PARTES
`REVIEW ......................................................................................................... 6
`
`VII. STATEMENT OF REASONS FOR THE RELIEF REQUESTED ......... 7
`
`A.
`
`B.
`
`C.
`
`D.
`
`Summary of the Argument .................................................................... 7
`
`’213 Patent Background ......................................................................11
`
`1.
`
`2.
`
`The ’213 Patent .........................................................................11
`
`Prosecution History and Related Proceedings ..........................14
`
`Level of Ordinary Skill in the Art .......................................................16
`
`Claim Construction..............................................................................17
`
`1.
`
`“a humanized antibody variable domain” (claims 1, 62
`and 80), “an antibody” (claim 30) or “a humanized
`antibody” (claim 63), “a humanized variant of a non-
`human parent antibody” (claims 64 and 79) or “a
`humanized antibody heavy chain variable domain”
`(claim 66). .................................................................................17
`
`
`
`i
`
`

`

`2.
`
`3.
`
`4.
`
`“and further comprising a Framework Region (FR)
`amino acid substitution at a site selected from the group
`consisting of…” ........................................................................17
`
`“numbering system set forth in Kabat” .....................................18
`
`“up to 3-fold more” ...................................................................19
`
`E.
`
`Prior Art ...............................................................................................19
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`Queen 1989 (Ex. 1534) .............................................................19
`
`Queen 1990 (Ex. 1550) .............................................................21
`
`PBD Database ...........................................................................23
`
`Tramontano (Ex. 1551) .............................................................26
`
`Kabat 1987 (Ex. 1552) ..............................................................27
`
`Hudziak (Ex. 1521) ...................................................................27
`
`VIII. THE PRIOR ART RENDERS THE CHALLENGED CLAIMS
`OBVIOUS .....................................................................................................29
`
`B. Grounds 1 and 2: Claims 1, 2, 4, 12, 25, 29, 62–67, 69 and 71–
`81 Are Unpatentable As Obvious over Queen 1989 or Queen
`1990, In View of the PDB Database ...................................................31
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`Ground 1: Claim 1 is Obvious over Queen 1989 in view
`of the PDB Database .................................................................31
`
`Ground 2: Claim 1 is Obvious over Queen 1990 in view
`of the PDB Database .................................................................36
`
`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 ..............................................................38
`
`Ground 2: Claim 4 Is Obvious in View of Queen 1990
`and PDB Database ....................................................................40
`
`Ground 2: Claim 62 Is Obvious in View of Queen 1990
`and PDB Database ....................................................................40
`
`
`
`
`ii
`
`

`

`6.
`
`7.
`
`8.
`
`9.
`
`Grounds 1, 2: Claims 63–64 and 66 Are Obvious Over
`Queen 1989 or Queen 1990 and PDB Database .......................41
`
`Ground 2: Claim 69 Is Obvious in View of Queen 1990
`and PDB Database ....................................................................45
`
`Grounds 1, 2: Claims 67, 71–74 and 78 Are Obvious in
`View of Queen 1989 or Queen 1990 and PDB Database .........45
`
`Grounds 1, 2: Claims 75–77 and 79 Are Obvious in View
`of Queen 1989 or Queen 1990 and PDB Database ...................47
`
`10. Grounds 1 and 2: Claim 65 Is Obvious in View of Queen
`1989 or Queen 1990 and the PDB Database.............................51
`
`11. Grounds 1, 2: Claims 80 and 81 Are Obvious in View of
`Queen 1989 or Queen 1990 and PDB Database .......................52
`
`C. Grounds 3 and 4: Claims 75–77, 79, and 65 Are Obvious over
`Queen 1989 or Queen 1990 and PDB Database and Further in
`View of Tramontano. ..........................................................................53
`
`D. Ground 5: Claims 4, 62, 64 and 69 are Obvious in View of
`Queen 1989 and the PDB Database, and Further in View of
`Kabat 1987 ..........................................................................................55
`
`E.
`
`Grounds 6 and 7: Claims 30, 31, 33, 42 and 60 Are Obvious in
`View of Queen 1989 or Queen 1990; PDB Database; and
`Hudziak................................................................................................56
`
`F.
`
`Secondary Considerations Cannot Overcome Obviousness. ..............60
`
`1.
`
`2.
`
`3.
`
`The Challenged Claims Produced No Relevant
`Unexpected Results ...................................................................61
`
`The ’213 Patent Satisfied No Long-Felt but Unmet Need .......63
`
`No Nexus Between Commercial Success of Genentech
`Drugs and the Challenged Claims ............................................64
`
`IX. CONCLUSION ............................................................................................65
`
`
`
`
`
`
`iii
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 6,407,213
`
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Atlas Powder Co. v. Ireco Inc.,
`190 F.3d 1342 (Fed. Cir. 1999) .................................................................... 42, 52
`
`In re Cuozzo Speed Techs., LLC,
`793 F.3d 1268 (Fed. Cir. 2015) .......................................................................... 16
`
`Ecolochem, Inc. v. Southern California Edison Co.,
`91 F.3d 169 (Fed. Cir. 1996) .............................................................................. 17
`
`In re Hall,
`781 F.2d 897 (Fed. Cir. 1986) ............................................................................ 24
`
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .......................................................................... 62
`
`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) .......................................................................... 64
`
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006) .......................................................................... 64
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .......................................................................... 51
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .......................................................................... 60
`
`Ex Parte Takeshi Shimono,
`2015 WL 1952506, Appeal 2013–003410 (PTAB Apr. 29, 2015) .................... 61
`
`In re Wyer,
`655 F.2d 221 (C.C.P.A. 1981) ............................................................................ 24
`
`
`
`
`
`

`

`
`
`Statutes
`
`35 U.S.C. § 102(a) and (b) ....................................................................................... 24
`
`35 U.S.C. § 102(b) ............................................................................................. 14, 24
`
`35 U.S.C. § 103 .......................................................................................................... 4
`
`35 U.S.C. § 103(a) ......................................................................................... 6, 14, 15
`
`35 U.S.C. § 311 .......................................................................................................... 1
`
`35 U.S.C. § 314(a) ..................................................................................................... 6
`
`35 U.S.C. § 315 .......................................................................................................... 4
`
`Other Authorities
`
`37 C.F.R. § 42.8(A)(1) AND (B) ............................................................................... 2
`
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 2
`
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 2
`
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 3
`
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 3
`
`37 C.F.R. § 42.10(b) .............................................................................................. 1, 3
`
`37 C.F.R. § 42.15(a) ............................................................................................... 1, 3
`
`37 C.F.R § 42.24 ...................................................................................................... 67
`
`37 C.F.R. § 42.100 ..................................................................................................... 1
`
`37 C.F.R. § 42.100(b) .............................................................................................. 16
`
`37 C.F.R. § 42.103 ................................................................................................. 1, 3
`
`37 C.F.R. § 42.104(A) ............................................................................................... 4
`
`37 C.F.R. § 42.104(B) ................................................................................................ 4
`
`MPEP § 2128 ........................................................................................................... 24
`
`
`
`v
`
`

`

`
`
`MPEP § 2144.04 ...................................................................................................... 51
`
`MPEP § 2144.04 .................................................................................................... ..51MPEP § 2144.04 ...................................................................................................... 51
`
`
`
`vi
`
`ViVi
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 6,407,213
`
`
`PETITIONER’S EXHIBIT LIST
`Description
`U.S. Patent No. 6,407,213, Method for making humanized
`antibodies (filed July 17, 1993) (issued June 18, 2002)
`File History for U.S. Patent No. 6,407,213
`
`Declaration of Dr. Foote in Support of Petition for Inter Partes
`Review of Patent No. 6,407,213
`Curriculum Vitae of Dr. Foote
`Materials Reviewed by Dr. Foote
`Exhibits C–Q of Dr. Foote’s Declaration
`Declaration of Mr. Buss in Support of Petition for Inter Partes
`Review of Patent No. 6,407,213
`Curriculum Vitae of Mr. Buss
`Materials Reviewed by Mr. Buss
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`
`
`
`Exhibit No.
`1501
`
`1502 Vols.
`1–10
`1503
`
`1503A
`1503B
`1503C–Q
`1504
`
`1504A
`1504B
`1505
`1506
`1507
`1508
`1509
`1510
`1511
`1512
`1513
`1514
`1515
`1516
`1517
`1518
`1519
`1520
`
`
`
`

`

`
`
`Exhibit No.
`1521
`
`1522
`
`1523
`
`1524
`
`1525
`
`1526
`
`1527
`
`1528
`
`1529
`
`1530
`
`PETITIONER’S EXHIBIT LIST
`Description
`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 BIOLOLGY 1165–72
`(1989) (“Hudziak”)
`Köhler et al., Continuous Cultures of Fused Cells Secreting
`Antibody of Predefined Specificity, 256(5517) NATURE 495–97
`(1975)
`Prabakaran, The Quest for a Magic Bullet, 349(6246) SCIENCE 389
`(2015)
`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 572–78 (1986)
`(“Jaffers ‘86”)
`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
`accessed April 12, 2017)
`
`
`
`viii
`
`

`

`
`
`Exhibit No.
`1531
`
`1532
`
`1533
`
`1534
`
`1535
`
`1536
`
`1537
`
`1538
`
`1539
`
`1540
`
`1541
`
`
`
`PETITIONER’S EXHIBIT LIST
`Description
`Morrison et al., Chimeric Human Antibody Molecules: Mouse
`Antigen-Binding Domains With Human Constant Region Domains,
`81(21) PROC. NAT’L ACAD. SCI. USA 6851–55 (1984) (“Morrison
`‘84”)
`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”)
`Jones et al., Replacing the Complementarity-Determining Regions
`in a Human Antibody With Those From a Mouse, 321(6069)
`NATURE 522–25 (1986) (“Jones ‘86”)
`Queen et al., A Humanized Antibody That Binds to the Interleukin 2
`Receptor, 86(24) PROC. NAT’L ACAD. SCI. USA 10029–33 (1989)
`(“Queen 1989”)
`Kirkman et al., Early Experience with Anti-Tac in Clinical Renal
`Transplantation, 21(1) TRANSPLANTATION PROC. 1766–68 (1989)
`(“Kirkman ‘89”)
`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)
`Harris et al., Medical Progress: Breast Cancer, 327(5) NEW ENG. J.
`MED. 319–28 (1992) (“Harris ‘92”)
`King et al., Amplification of a Novel v-erbB-Related Gene in a
`Human Mammary Carcinoma, 229(4717) SCIENCE 974–76 (1985)
`(“King ‘85”)
`
`ix
`
`

`

`
`
`Exhibit No.
`1542
`
`1543
`
`1544
`
`1545
`
`1546
`
`1547
`
`1548
`
`1549
`
`1550
`
`1551
`
`
`
`PETITIONER’S EXHIBIT LIST
`Description
`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”)
`Coussens et al., Tyrosine Kinase Receptor with Extensive Homology
`to EGF Receptor Shares Chromosomal Location with neu
`Oncogene, 230(4730) SCIENCE 1132–39 (1985) (“Coussens ‘85”)
`Fukushige et al., Localization of a Novel v-erbB-Related Gene, c-
`erbB-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)
`Hudziak et al., Increased Expression of the Putative Growth Factor
`Receptor p185HER2 Causes Transformation and Tumorigenesis of
`NIH 3T3 Cells., 84(20) PROC. NAT’L ACAD. SCI. USA 7159–163
`(1987) (“Hudziak ‘87”)
`Shepard et al., Monoclonal Antibody Therapy of Human Cancer:
`Taking the HER2 Protooncogene to the Clinic, 11(3) J. CLINICAL
`IMMUNOLOGY, 117–27 (1991)
`Chothia et al., Conformations of Immunoglobulin Hypervariable
`Regions, 342(21) NATURE 877–83 (1989) (“Chothia ‘89”)
`Queen, International Publication No. WO 1990/07861 (published
`July 26, 1990) (“Queen 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 175–82 (1990) (“Tramontano”)
`
`x
`
`

`

`
`
`Exhibit No.
`1552
`
`1553
`1554
`1555
`
`1556
`1557
`1558
`
`1559
`
`1560
`1561
`1562
`
`1563
`
`
`
`PETITIONER’S EXHIBIT LIST
`Description
`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) (“Kabat 1987”)
`Reserved
`Reserved
`Kabat et al., 1 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, α2-MACROGLOBULINS,
`AND OTHER RELATED PROTEINS 103–338 (5th ed. 1991) (“Kabat
`1991”)
`Reserved
`Reserved
`Davies & Metzger, Structural Basics of Antibody Function, 1 ANN.
`REV. IMMUNOLOGY 87–117 (1983) (“Davies & Metzger”)
`Amit et al., Three-Dimensional Structure of an Antigen-Antibody
`Complex at 2.8 Å Resolution, 233(4765) SCIENCE 747–53 (1986)
`(“Amit ‘86”)
`Reserved
`Reserved
`Chothia & Lesk, Canonical Structures for the Hypervariable
`Regions of Immunoglobulins, 196(4) J. MOLECULAR BIOLOGY 901–
`17 (1987) (“Chothia & Lesk”)
`Chothia et al., Domain Association in Immunoglobulin Molecules:
`The Packing of Variable Domains, 186 J. MOLECULAR BIOLOGY
`651–63 (1985)
`
`xi
`
`

`

`
`
`Exhibit No.
`1564
`1565
`1566
`1567
`1568
`
`1569
`
`1570
`1571
`
`1572
`1573
`
`1574
`1575
`1576
`1577
`1578
`1579
`
`1580
`
`
`
`PETITIONER’S EXHIBIT LIST
`Description
`
`Reserved
`Reserved
`Reserved
`Reserved
`Verhoeyen et al., Reshaping Human Antibodies: Grafting an
`Antilysozyme Activity, 239(4847) SCIENCE 1534–36 (1988)
`(“Verhoeyen ‘88”)
`Riechmann et al., Reshaping Human Antibodies for Therapy,
`332(6162) NATURE 323–27 (1988) (“Riechmann ‘88”)
`Reserved
`Kurrle et al., EP Publication Number 0403156, Improved
`Monoclonal Antibodies Against the Human Alphabeta T-Cell
`Receptor, Their Production and Use (published December 19, 1990)
`(“Kurrle”)
`Reserved
`Winter et al., EP Publication Number 0239400, Recombinant
`Antibodies and Methods for Their Productions (published
`September 30, 1987)
`Reserved
`Reserved
`Reserved
`Reserved
`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, β2 MICROGLOBULINS, MAJOR HISTOCOMPATIBILITY
`ANTIGENS, THY-1, COMPLEMENT, C-REACTIVE PROTEIN,
`THYMOPOIETIN, POST-GAMMA GLOBULIN, AND α2-MACROGLOBULIN
`(1983)
`Bernstein et al., The Protein Data Bank: A Computer-based
`Archival File for Macromolecular Structures, 112(3) J. MOLECULAR
`BIOLOGY 535–42 (1977)
`
`xii
`
`

`

`
`
`Exhibit No.
`1581
`
`1582
`
`1583
`
`1584
`1585
`
`1586
`
`1587
`
`1588
`
`1589
`
`1590
`
`1591
`
`
`
`PETITIONER’S EXHIBIT LIST
`Description
`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”)
`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–
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`Immunoglobulin Molecule*, 63(1) PROC. NAT’L ACAD. SCI. USA
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`Exhibit No.
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`
`1593
`
`1594
`1595 Vols.
`1–15
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`1596
`
`1597
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`1598
`1599
`1600
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`1601
`1602
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`1603
`
`1604
`
`
`
`PETITIONER’S EXHIBIT LIST
`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)
`Reserved
`Patent Interference No. 105,744 (Senior party Application No.
`11/284,261, Inventors John Robert Adair et al., Junior Party, U.S.
`Patent 6,407,213, Inventors Paul J. Carter and Leonard G. Presta)
`(“Adair”)
`U.S. Patent No. 5,677,171, Monoclonal Antibodies Directed to the
`HER2 Receptor (filed August 5, 1994) (issued October 14, 1997)
`Sambrook et al., MOLECULAR CLONING: A LABORATORY MANUAL
`(Cold Spring Harbor Laboratory Press, 2d ed. 1989)
`Reserved
`Reserved
`Colman et al., Three-Dimensional Structure of a Complex of
`Antibody with Influenza Virus Neuraminidase, 326(6111) NATURE
`358–63 (1987) (“Colman ‘87”)
`Reserved
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`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”)
`
`xiv
`
`

`

`
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`Exhibit No.
`1605
`
`1606
`
`1607
`
`1608
`1609
`1610
`1611
`1612
`1613
`
`1614
`
`1615
`
`1616
`
`1617
`1618
`1619
`1620
`1621
`
`
`
`PETITIONER’S EXHIBIT LIST
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`Receptor and Binds Human Immunodeficiency Virus, 84 PROC.
`NAT’L. ACAD. SCI. USA 3891–95 (1987) (“Chanh ‘87”)
`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)
`Reserved
`Reserved
`Reserved
`Reserved
`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)
`Reserved
`Reserved
`Reserved
`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”)
`
`xv
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`

`

`
`
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`1622
`1623
`1624
`1625
`
`1626
`
`1627
`
`1628
`
`1629
`
`1630
`
`1631
`
`1632
`1633
`1634
`1635
`1636
`1637
`1638
`1639
`
`
`
`PETITIONER’S EXHIBIT LIST
`Description
`
`Reserved
`Reserved
`Reserved
`Furey et al., Structure of A Novel Bence-Jones Protein (Rhe)
`Fragment at 1.6Å Resolution, 167(3) J. MOLECULAR BIOLOGY 661–
`92 (1983) (“Furey”)
`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 α(L-6) Dextran Increases its Affinity for Antigen,
`168(3) J. EXPERIMENTAL MED. 1099–109 (1988) (“Wallick ‘88”)
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`Reserved
`
`xvi
`
`

`

`
`
`Exhibit No.
`1640
`1641
`1642
`1643
`1644
`1645
`1646
`1647
`1648
`1649
`1650
`1651
`1652
`1653
`1654
`1655
`1656
`1657
`1658
`1659
`1660
`1661
`1662
`1663
`1664
`1665
`1666
`1667
`1668
`1669
`
`
`
`PETITIONER’S EXHIBIT LIST
`Description
`
`Reserved
`Library of Congress Copyright Record for Cosimi ‘81
`Library of Congress Copyright Record for OMTSG ‘85
`Library of Congress Copyright Record for Jaffers ‘86
`Library of Congress Copyright Record for Morrison ‘84
`Library of Congress Copyright Record for Liu ‘87
`Library of Congress Copyright Record for Jones ‘86
`Library of Congress Copyright Record for Queen 1989
`Library of Congress Copyright Record for Kirkman ‘89
`Library of Congress Copyright Record for Waldamnn ‘93
`Library of Congress Copyright Record for Hakimi ‘91
`Library of Congress Copyright Record for Vincenti ‘98
`Library of Congress Copyright Record for Harris ‘92
`Library of Congress Copyright Record for King ‘85
`Library of Congress Copyright Record for Semba ‘85
`Library of Congress Copyright Record for Coussens ‘85
`Library of Congress Copyright Record for Slamon ‘87
`Library of Congress Copyright Record for Hudziak ‘87
`Library of Congress Copyright Record for Chothia ‘89
`Library of Congress Copyright Record for Davies & Metzger
`Library of Congress Copyright Record for Amit ‘86
`Reserved
`Reserved
`Library of Congress Copyright Record for Verhoeyen ‘88
`Library of Congress Copyright Record for Riechmann ‘88
`Reserved
`Reserved
`Library of Congress Copyright Record for Sheriff ‘87
`Library of Congress Copyright Record for Saul ‘78
`Reserved
`
`xvii
`
`

`

`
`
`Exhibit No.
`1670
`1671
`1672
`1673
`1674
`1675
`1676
`1677
`1678
`1679
`1680
`1681
`1682
`
`1683
`
`1684
`1684A
`
`1684B
`
`1684C
`
`PETITIONER’S EXHIBIT LIST
`Description
`Library of Congress Copyright Record for Padlan ‘89
`Library of Congress Copyright Record for Colman ‘87
`Library of Congress Copyright Record for Koprowski ‘84
`Library of Congress Copyright Record for Chanh ‘87
`Library of Congress Copyright Record for Schroff ‘85
`Reserved
`Reserved
`Reserved
`Library of Congress Copyright Record for Suh ‘86
`Library of Congress Copyright Record for Jones ‘85
`Library of Congress Copyright Record for Co ‘91
`Library of Congress Copyright Record for Wallick ‘88
`Bodmer, International Publication No. WO 1989/01783 (published
`March 9, 1989)
`Gorman, International Publication No. WO 1992/05274 (published
`April 2, 1992)
`Declaration of Karen Younkins
`Three-Dimensional Structure of an Antibody-Antigen Complex,
`RCSB Protein Data Bank,
`http://www.rcsb.org/pdb/explore/obsolete.do?obsoleteId=2HFL&evt
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`Bank,
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`Preliminary Refinement and Structural Analysis of the FAB
`Fragment from Human Immunoglobulin New at 2.0 Angstroms
`Resolution, RCSB Protein Data Bank,
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`
`
`
`xviii
`
`

`

`
`
`Exhibit No.
`1684D
`
`1684E
`
`1684F
`
`1684G
`
`1684H
`
`1684I
`
`1685
`
`1686
`1687
`1688
`
`PETITIONER’S EXHIBIT LIST
`Description
`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 (last
`accessed May 4, 2017)
`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
`(last accessed May 4, 2017)
`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 (last
`accessed May 4, 2017)
`Structure of an Antibody-Antigen Complex: Crystal Structure of the
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`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 (last
`accessed May 4, 2017)
`Structure of a Novel Bence-Jones Protein (Rhe) Fragment at 1.6 A
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`NAT’L CANCER INST. 1416 (1998) (“Miller ‘98”)
`Library of Congress Copyright Record for Miller ‘98
`Declaration of Amanda Hollis
`Declaration of Christopher Lowden
`
`
`
`xix
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 6,407,213
`
`I.
`
`INTRODUCTION
`
`Pursuant to 35 U.S.C. §311 and 37 C.F.R. §42.100, Petitioner Pfizer, Inc.
`
`petitions for Inter Partes Review (“IPR”) of claims 1, 2, 4, 12, 25, 29–31, 33, 42,
`
`60, 62–67, 69 and 71–81 (“Challenged Claims”) of U.S. Patent No. 6,407,213
`
`(“’213 patent,” Ex. 1501). With this Petition is a Power of Attorney pursuant to 37
`
`C.F.R. §42.10(b); and pursuant