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`IPR2017-02172
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`COMPLETE GENOMICS, INC.
`Petitioner
`
`v.
`
`ILLUMINA CAMBRIDGE LTD.
`Patent Owner
`
`____________
`
`Case IPR2017-02172
`Patent 7,566,537 B2
`____________
`
`
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 7,566,537 B2
`
`
`
`
`
`
`
`Columbia Ex. 2008
`Illumina, Inc. v. The Trustees
`of Columbia University
`in the City of New York
`IPR2020-01177
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`IPR2017-02172
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`TABLE OF CONTENTS
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`Page No.
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`I.
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`INTRODUCTION ........................................................................................... 1
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. §42.8 .................................... 4
`
`
`
`A.
`Real Party-In-Interest (37 C.F.R. §42.8(b)(1)) ..................................... 4
`B.
`Related Matters (37 C.F.R. §42.8(b)(2)) ............................................... 4
`
`C.
`Lead and Back-up Counsel (37 C.F.R. §42.8(b)(3)-(4)) ....................... 7
`
`D.
`Service Information (37 C.F.R. §42.8(b)(4)) ........................................ 7
`
`III. REQUIREMENTS FOR INTER PARTES REVIEW .................................... 8
`
`
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`
`
`A.
`B.
`
`C.
`
`Payment of Fees (37 C.F.R. §42.103) ................................................... 8
`Grounds for Standing (37 C.F.R. §42.104(a)) ...................................... 8
`Identification of Challenge and Precise Relief Requested (37
`C.F.R. §42.104(b)(1)-(2)) ...................................................................... 8
`IV. THE ’537 PATENT AND PRIOR PROCEEDINGS ...................................... 9
`
`
`
`The ’537 Patent ..................................................................................... 9
`A.
`Impact of Prior Proceedings Regarding the ’537 Patent ..................... 12
`B.
`
`V. DEFINITION OF A PERSON OF ORDINARY SKILL IN THE
`ART ............................................................................................................... 14
`
`VI. THE STATE OF THE ART .......................................................................... 15
`
`A.
` Advances in DNA Science .................................................................. 15
`Knowledge of a POSITA Relating to SBS ......................................... 18
`B.
`
`1.
`Use of the solid phase was well known in the art. .................... 18
`2.
`Labels and linkers were well known in the art. ........................ 20
`3.
`Enzymes capable of incorporation and conditions for their
`use were well known in the art. ................................................ 20
`A POSITA would have known how to select a suitable
`protecting group and deblocking conditions. ............................ 21
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`4.
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`5.
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`A POSITA would have known other methods to optimize
`the SBS process. ........................................................................ 22
`A POSITA Would Have Appreciated Multiple Uses for Modified
`Nucleotides .......................................................................................... 23
`VII. CLAIM CONSTRUCTION .......................................................................... 24
`
`C.
`
`
`
`VIII. ALL THE LIMITATIONS OF CLAIMS 1-6 & 8 WERE
`DISCLOSED IN THE PRIOR ART ............................................................. 25
`
`2.
`
`A.
`
`
`
`B.
`
`
`
`The “Azido” and “Azidomethyl” Protecting Groups of Claims 1
`and 6 Were Disclosed in Zavgorodny and Greene & Wuts. ............... 25
`1.
`Greene & Wuts discloses “azido” and “azidomethyl”
`protecting groups ....................................................................... 25
`Zavgorodny discloses the “azido” and “azidomethyl”
`protecting groups of Claims 1 and 6, respectively. .................. 25
`Tsien Discloses Each Limitation of Claims 1-2, 4-6, and 8 Except
`the Azido and Azidomethyl Protecting Groups. ................................. 26
`IX. THE CHALLENGED CLAIMS ARE OBVIOUS OVER THE
`PRIOR ART ................................................................................................... 30
`
`
`
`A.
`B.
`
`
`C.
`
`
`
`D.
`
`
`
`Legal Standards for Obviousness ........................................................ 30
`The Crux of this Petition is the Rationale for a “Motivation to
`Combine” ............................................................................................. 31
`Tsien’s Disclosure Must Be Considered from the Perspective of a
`POSITA ............................................................................................... 32
`Tsien’s Incorporation and Deblocking Criteria Would Have Led a
`POSITA to Modify Tsien’s SBS Method by Using the
`Azidomethyl Protecting Group of Zavgorodny and Greene &
`Wuts ..................................................................................................... 38
`1.
`A POSITA would have appreciated that each of Tsien’s
`incorporation and deblocking criteria suggest that
`azidomethyl would be a suitable alternative protecting
`group for use with Tsien’s SBS method and would therefore
`have been motivated to use an azidomethyl protecting
`group. ........................................................................................ 38
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`i.
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`The ability of a polymerase enzyme to accurately and
`efficiently incorporate the dNTPs carrying the 3′-
`blocking groups .............................................................. 38
`
`ii.
`
`Reinitiation of DNA synthesis ........................................ 41
`
`iii. Mild deblocking conditions ............................................ 41
`
`a.
`
`b.
`
`c.
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`Zavgorodny’s deblocking conditions are
`sufficiently “mild” ................................................ 42
`
`Greene & Wuts refers to Loubinoux, which
`provides alternative “mild” deblocking
`conditions ............................................................. 43
`
`A POSITA would have known that alternative
`“mild” conditions could be used to deblock an
`azidomethyl protecting group............................... 45
`
`iv. A quantitative or high yield of de-blocked 3′-OH
`groups ............................................................................. 46
`
`v.
`
`Rapid deblocking ............................................................ 50
`
`2.
`
`The obviousness of combining azidomethyl with Tsien’s
`SBS methods is further supported by the ’537 Patent and
`Illumina’s statements in other proceedings .............................. 52
`A POSITA Would Have Recognized Azidomethyl As a Known
`Element That Could Be Simply Substituted Into Tsien’s SBS
`Method to Yield Predictable Results ................................................... 53
`Ground 2: Claim 3 is Obvious Over Tsien in Combination with
`Greene & Wuts and Zavgorodny, In Further Combination with
`Prober. ................................................................................................. 55
`X. OBJECTIVE INDICIA OF NONOBVIOUSNESS DO NOT
`SUPPORT THE PATENTABILITY OF THE CHALLENGED
`CLAIMS ........................................................................................................ 57
`
`E.
`
`
`
`F.
`
`
`A.
`
` No Nexus Between the Satisfaction of a Long-Felt, Unmet Need
`and the Claimed Azidomethyl Group ................................................. 57
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`B.
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`Illumina’s Arguments for New and Unexpected Results Do Not
`Have a Sufficient Nexus to the Claims and Are Based on
`Hindsight Bias ..................................................................................... 59
`C.
`Evidence of Copying is Completely Absent ....................................... 60
`
`D.
`Praise by Others Was Likely Unrelated to the Claim Limitations ...... 61
`
`XI. CONCLUSION .............................................................................................. 61
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`TABLE OF AUTHORITIES
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` Page(s)
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`Cases
`DyStar Textilfarben GmbH v. C.H. Patrick Co.,
`464 F.3d 1356 (Fed. Cir. 2006) .................................................................... 30, 38
`
`Ilumina Cambridge Ltd. v. Intelligent Bio-Systems, Inc.,
`638 Fed. Appx. 999 (Fed. Cir. 2016) (unpublished) ............................................ 4
`
`In re Epstein,
`32 F.3d 1559 (Fed. Cir. 1994) ...................................................................... 31, 53
`
`In re GPAC,
`57 F.3d 1573 (Fed. Cir. 1995) ............................................................................ 14
`
`Institut Pasteur v. Focarino,
`738 F.3d 1337 (Fed. Cir. 2013) .......................................................................... 57
`
`Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd.,
`821 F.3d 1359 (Fed. Cir. 2016) ...................................................................passim
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ................................................................................ 30, 31, 53
`
`Merck & Co., Inc. v. Teva Pharms. USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005) .......................................................................... 57
`
`Pfizer Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .................................................................... 31, 54
`
`Standard Oil Co. v. Am. Cyanamid Co.,
`774 F.2d 448 (Fed. Cir. 1985) ............................................................................ 30
`
`Trustees of Columbia University v. Illumina, Inc.,
`620 Fed. Appx. 916 (Fed. Cir. 2015) (unpublished) ................................ 5, 27, 56
`
`Wyers v. Master Lock Co.,
`616 F.3d 1231 (Fed. Cir. 2010) .......................................................................... 61
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`Statutes and Regulations
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`37 C.F.R. § 42.8 ..................................................................................................... 4, 7
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`37 C.F.R. § 42.73 ............................................................................................... 12, 27
`
`37 C.F.R. § 42.104 ..................................................................................................... 8
`
`35 U.S.C. § 103 ...................................................................................................... 1, 8
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`IPR2017-02172
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`1004
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`1005
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`1006
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`1007
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`TABLE OF EXHIBITS
`
`Description
`Ex. No.
`1001 Shankar Balasubramanian et al., U.S. Patent No. 7,566,537 B2 (Jul. 28,
`2009) (“’537”)
`1002 Excerpts of File History of U.S. Appl. No. 11/301,478
`(downloaded from Public PAIR)
`1003 Roger Y. Tsien et al., WO 91/06678 A1 (published May 16, 1991)
`(“Tsien”)
`William J. Dower et al., U.S. Patent No. 5,547,839 (Aug. 20, 1996)
`(“Dower”)
`PROTECTIVE GROUPS IN ORGANIC SYNTHESIS (Theodora W. Greene &
`Peter G.M. Wuts eds., 3rd ed. 1999) (excerpts) (“Greene & Wuts”)
`Bernard Loubinoux et al., Protection of Phenols by the Azidomethylene
`Group Application to the Synthesis of Unstable Phenols, TETRAHEDRON
`44:6055-64 (1988), including translation, supporting affidavit and
`original publication (“Loubinoux”)
`James M. Prober et al., A System for Rapid DNA Sequencing with
`Fluorescent Chain-Terminating Dideoxynucleotides, SCIENCE 238:336-
`41 (1987) (“Prober”)
`1008 Sergey Zavgorodny et al., 1-Alkylthioalkylation of Nucleoside Hydroxyl
`Functions and Its Synthetic Applications, TETRAHEDRON LETTERS
`32:7593-96 (1991) (“Zavgorodny”)
`1009 S.G. Zavgorodny et al., S,X-Acetals in Nucleoside Chemistry, III,
`Synthesis of 2- and 3-O-Azidomethyl Derivatives of Ribonucleosides,
`NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 19:1977-91 (2000)
`(“Zavgorodny 2000”)
`J.D. Watson & F.H.C. Crick, Molecular Structure of Nucleic Acids,
`NATURE 171:737-38 (1953)
`1011 Steven M. Carr, Deoxyribose versus Ribose Sugars (2014), at
`https://www.mun.ca/biology/scarr/Ribose_sugar.html (downloaded
`Sept. 25, 2017)
`1012 Michael L. Metzker, Emerging Technologies in DNA Sequencing,
`GENOME RES. 15:1767-76 (2005) (“Metzker 2005”)
`1013 A. Kornberg et al., Enzymatic Synthesis of deoxyribonucleic acid,
`BIOCHIM. BIOPHYS. ACTA 21:197-198 (1956) (“Kornberg”)
`1014 Bruce Merrifield, Solid Phase Synthesis, SCIENCE 232:341-47 (1986)
`(“Merrifield”)
`
`1010
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`IPR2017-02172
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`1015 William C. Copeland et al., Human DNA Polymerases α and β Are Able
`to Incorporate Anti-HIV Deoxynucleotides Into DNA, J. BIOL. CHEM.
`267:21459-64 (1992) (“Copeland 1992”)
`1016 Hamilton O. Smith & K.W. Wilcox, A Restriction Enzyme from
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`BIOL. 51:379-91 (1970)
`1017 Thomas J. Kelly, Jr. & Hamilton O. Smith, A restriction enzyme from
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`MOL. BIOL. 51:393-409 (1970)
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`in DNA by Primed Synthesis with DNA Polymerase, J. MOL. BIOL.
`94:441-48 (1975) (“Sanger & Coulson”)
`1019 Allan M. Maxam & Walter Gilbert, A New Method for Sequencing
`DNA, PROC. NATL. ACAD. SCI. USA 74:560-64 (1977) (“Maxam &
`Gilbert”)
`1020 F. Sanger et al., DNA Sequencing with Chain-Termination Inhibitors,
`PROC. NATL. ACAD. SCI. USA 74:5463-67 (1977) (“Sanger”)
`1021 Radoje Drmanac et al., Sequencing of Megabase Plus DNA by
`Hybridization, GENOMICS 4:114-28 (1989) (“Drmanac”)
`1022 Edwin Southern & William Cummings, U.S. Patent 5,770,367 (June 23,
`1998)
`1023 ALDRICH HANDBOOK OF FINE CHEMICALS AND LABORATORY EQUIPMENT
`2000-2001 (Sigma Aldrich Co. 2000)
`1024 Bruno Canard & Robert S. Sarfati, DNA Polymerase Fluorescent
`Substrates with Reversible 3′-tags, GENE 148:1-6 (1994) (“Canard
`1994”)
`1025 Robert A. Stockman, Book Review, J. AM. CHEM. SOC. 122:426-26
`(reviewing Greene & Wuts) (2000)
`Joyce, C.M. Choosing the right sugar: How polymerases select a
`nucleotide substrate, PROC. NATL. ACAD. SCI. USA 94:1619-1622
`(March 1997)
`Jari Hovinen et al., Synthesis of 3'-O-(ω-Aminoalkoxymethyl)thymidine
`5'-Triphosphates, Terminators of DNA Synthesis that Enable 3'-
`Labelling, J. CHEM. SOC. PERKIN TRANS. 1:211-17 (1994)
`1028 Yuri G. Gololobov & Leonid F. Kasukhin, Recent Advances in the
`Staudinger Reaction, TETRAHEDRON 48:1353-406 (1992) (“Gololobov
`1992”)
`
`1027
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`1026
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`IPR2017-02172
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`1029 Eliana Saxon & Carolyn R. Bertozzi, Cell Surface Engineering by a
`Modified Staudinger Reaction, SCIENCE 287:2007-10 (2000) (“Saxon &
`Bertozzi”)
`1030 D.H. Dube and C.R. Bertozzi, Metabolic oligosaccharide engineering
`as a tool for glycobiology, CURR. OPIN. CHEM. BIOL. 7:616-625 (2003)
`1031 Eliana Saxon & Carolyn R. Bertozzi, U.S. Pub. 2002/0016003 A1,
`Chemoselective Ligation (published Feb. 7, 2002)
`1032 Eliana Saxon et al., Investigating Cellular Metabolism of Synthetic
`Azidosugars with the Staudinger Ligation, J. AM. CHEM. SOC.
`124:14893-902 (2002)
`1033 Saul Kit, Deoxyribonucleic Acids, ANNU. REV. BIOCHEM. 32:43–82
`(1963) (“Kit”)
`1034 Che-Hung Lee et al., Unwinding of Double-stranded DNA Helix by
`Dehydration, PROC. NATL. ACAD. SCI. USA 78:2838-42 (1981) (“Lee”)
`1035 Gordon et al., Abstract, Biophysical Society 6th Annual Meeting
`(Washington, 1962)
`1036 Lawrence Levine et al., The Relationship of Structure to the
`Effectiveness of Denaturing Agents for Deoxyribonucleic Acid,
`BIOCHEM. 2:168-75 (1963)
`1037 Derek L. Stemple et al., U.S. Patent No. 7,270,951 B1 (Sept. 18, 2007)
`(“Stemple III”)
`Jingyue Ju et al., U.S. Patent 6,664,079 B2 (Dec. 16, 2003) (“Ju”)
`1038
`1039 David Bentley et al., Accurate Whole Human Genome Sequencing
`Using Reversible Terminator Chemistry, NATURE 456:53-59 (2008)
`(“Bentley”)
`1040 Elaine R. Mardis, A Decade’s Perspective on DNA Sequencing
`Technology, NATURE 470:198-203 (2011) (“Mardis”)
`1041 Michael L., Metzker, et al., Termination of DNA synthesis by novel 3′-
`modified deoxyribonucleoside 5′-triphosphates, NUC. ACIDS RES.
`22:4259-67 (1994) (“Metzker 1994”)
`1042 Bruno Canard et al., Catalytic Editing Properties of DNA Polymerases,
`PROC. NATL. ACAD. SCI. USA 92:10859-63 (1995) (“Canard 1995”)
`1043 Fabrice Guillier et al., Linkers and Cleavage Strategies in Solid-Phase
`Organic Synthesis and Combinatorial Chemistry, CHEM. REV. 100,
`100:2091-157 (2000) (“Guillier”)
`1044 Y.G. Gololobov et al., Sixty years of Staudinger reaction,
`TETRAHEDRON 37:437-72 (1981) (“Gololobov 1981”)
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`1045 Kevin Davies, The British Invasion, in THE $1,000 GENOME: THE
`REVOLUTION IN DNA SEQUENCING AND THE NEW ERA OF PERSONALIZED
`MEDICINE 102-15 (Ch. 5), 298-99 (Ch. 5 Notes) (2010) (“Davies”)
`1046 Vincent P. Stanton et al., WO 02/21098 A2 (published Sept. 5, 2000)
`(“Stanton”)
`1047 Seela, U.S. Patent No. 4,804,748 (Feb. 14, 1989)
`1048 Declaration of Michael Cohen (Sept. 28, 2017)
`Exhibit A: Filed as Ex. 1049
`Exhibit B: Screenshot from the OCLC WorldCat database
`Exhibit C: Definition of “date entered” from OCLC website
`Exhibit D: Screenshot of University of Wisconsin-Madison Library
`System Catalog
`Exhibit E: Spreadsheet of data extracted from Voyager Integrated
`Library System
`1049 Exhibit A to Declaration of Michael Cohen:
`Travis Young, A Strategy for the Synthesis of Sulfated Peptides, A
`dissertation submitted in partial fulfillment of the requirements for the
`degree of Doctor of Philosophy (Chemistry) at the University of
`Wisconsin-Madison (2001)
`1050 Declaration of Thomas Hyatt (Sept. 28, 2017) (Attachment filed as Ex.
`1051)
`1051 Attachment to Declaration of Thomas Hyatt:
`Travis Young, A Strategy for the Synthesis of Sulfated Peptides, A
`dissertation submitted in partial fulfillment of the requirements for the
`degree of Doctor of Philosophy (Chemistry) at the University of
`Wisconsin-Madison (2001) (“Young”)
`1052 Declaration of Bonnie Phan (Sept. 28, 2017)
`Exhibit A: DISSERTATION ABSTRACTS INTERNATIONAL, Volume 62,
`Number 7 (2002) (excerpts)
`Exhibit B: Guidelines to counsel & researchers seeking discovery from
`Stanford University Libraries, at https://library.stanford.edu/using/
`special-policies/guidelines-counsel-researchers-seeking-discovery-
`stanford-university (printed Sept. 28, 2017)
`1053 Pentti Oksman et al., Solution Conformations and Hydrolytic Stability of
`2′- and 3′-Substituted 2′,3′-Dideoxyribonucleosides, Including some
`Potential Inhibitors of Human Immunodeficiency Virus, J. OF PHYSICAL
`ORGANIC CHEM. 5:741-47 (1992) (“Oksman”)
`1054 Eric F.V. Scriven et al., Azides: Their Preparation and Synthetic Uses,
`CHEMICAL REVIEWS 88:297-368 (1988)
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`1057
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`1055 Peter C. Cheeseman, U.S. Patent No. 5,302,509 (Apr. 12, 1994)
`(“Cheeseman”)
`1056 M. Vaultier et al., General Method to Reduce Azides to Primary Amines
`by Using the Staudinger Reaction, TETRAHEDRON LETTERS 24:763-64
`(1983). including translation, supporting affidavit and original
`publication (“Vaultier”)
`John A. Burns et al., Selective Reduction of Disulfides by Tris(2-
`carboxyethyl)phosphine, J. OF ORGANIC CHEM. 56:2648-2650 (1991)
`1058 Anthony L. Handlon & Norman J. Oppenheimer, Thiol Reduction of 3′-
`Azidothymidine to 3′-Aminothymidine: Kinetics and Biomedical
`Implications, PHARM. RES. 5:297-99 (1988) (“Handlon”)
`1059 Mark D. Uehling, Wanted: The $1000 Genome, Bio-IT World (Nov.
`15, 2002), http://www.bio-itworld.com/archive/111202/genome (printed
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`1060 Kevin Davies, 13 years ago, a beer summit in an English pub led to the
`birth of Solexa and—for now at least —the world’s most popular
`second-generation sequencing technology, Bio-IT World (Sept. 28,
`2010), http://www.bio-itworld.com/2010/issues/sept-oct/solexa.html
`(printed Aug. 2, 2017)
`1061 Wikipedia, Shankar Balasubramanian,
`https://en.wikipedia.org/wiki/Shankar_Balasubramanian (last visited
`Aug. 2, 2017)
`1062 Past Group Members - Balasubramanian Group,
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`2, 2017)
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`29, 2010) https://www.chemistryworld.com/news/profile-flexibility-on-
`the-move/3003307.article (printed Aug. 2, 2017)
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`1066 Xiaolin Wu, Synthesis of 5′-C- and 2′-O-Substituted
`Oligoribonucleotide Analogues and Evaluation of their Pairing
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`requirements for the degree of Doctor of Nature Science at the Swiss
`Federal Institute of Technology (ETH) Zurich (2000)
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`73678145/?ppe=1 (printed Aug. 2, 2017)
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`1073
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`1069
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`1068 The Chinese Society of Chemical Science and Technology in the UK,
`Members of the Fourth Executive Committee,
`https://www.jiscmail.ac.uk/cgi-bin/filearea.cgi?LMGT1=CHEM-
`CSCST-UK&a=get&f=/4cmmtt.htm (printed Aug. 2, 2017)
`Jonathan A. Eisen, Sequencing: The Now Generation, presentation at
`the Bodega Bay Applied Phylogenetics, slide 39 (Mar. 4, 2013),
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`EisenBodega2013.pdf
`1070 Number Not Used
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`1071
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`(downloaded Oct. 2, 2017)
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`Ch. 2 in NEXT GENERATION SEQUENCING AND SEQUENCE ASSEMBLY,
`11-39, 15 (2013)
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`(2001) (“Kwok”)
`1075 Ann-Christine Syvanen, Accessing genetic variation: genotyping single
`nucleotide polymorphisms, NATURE REVIEWS GENETICS 2:920-942
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`Immunodeficiency Virus Type 1 Reverse Transcriptase and Human DNA
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`3′-deoxythymidine, 2′,3′-Dideoxyguanosine, and 3′-Deoxythymidine, J.
`BIOL. CHEM. 266:1754-1762 (1991) (“Parker”)
`1078 Elise Burmeister Getz et al., A comparison between the Sulfhydryl
`reductants Tris(2-carboxyethyl)phosphine and Dithiothreitol for Use in
`Protein Biochemistry, ANALYTICAL BIOCHEM. 273:73-80 (1999)
`(“Getz”)
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`Terminal Aminodeoxythymidine Oligonucleotides, J. ORG. CHEM.
`40:1659-1662 (1975) (“Mungall”)
`1080 Serge Pilard et al., A stereospecific synthesis of (+) α-conhydrine and
`(+) β-conhydrine, TETRAHEDRON LETTERS 25:1555-56 (1984)
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`1081 R. Ranganathan et al., Facile conversion of adenosine into new 2′-
`substituted-2′-deoxy-arabinofuranosyladenine derivatives:
`stereospecific syntheses of 2′-azido-2′-deoxy-,2′-amino-2′deoxy-, and 2′-
`mercapto-2′deoxy-β-D-arabinofuranosyladenines, TETRAHEDRON
`LETTERS 45:4341-4344 (1978).
`1082 K.S. Kirby, A New Method for the Isolation of Deoxyribonucleic Acids:
`Evidence on the Nature of Bonds between Deoxyribonucleic Acid and
`Protein, BIOCHEM. J. 66:495-504 (1957) (“Kirby”)
`1083 David Moore & Dennis Dowhan, 2.1.1 - Manipulation of DNA in
`CURRENT PROTOCOLS IN MOLECULAR BIOLOGY (Wiley, 2002)
`(“Moore”)
`1084 G.E. Tiller et al., Dinucleotide insertion/deletion polymorphism in
`intron 50 of the COL2A1 gene, NUCLEIC ACIDS RESEARCH, 19, 4305
`(1991) (“Tiller”)
`1085 Kamada, Ltd. v. Grifols Therapeutics Inc., IPR2014-00899, Paper 22
`(Mar. 4, 2015)
`1086 Summary Table of Prior IPR Proceedings
`1087
`2014-1547, Appellee’s Brief (Dec. 29, 2014) (appeal of IPR2012-
`00006)
`IPR2013-00518, Paper 28, Illumina Request for Adverse Judgment
`(May 5, 2014)
`IPR2013-00518, Paper 29, Judgment Request for Adverse Judgment
`(May 6, 2014)
`IPR2013-00517, Paper 7, Revised Petition for Inter Partes Review of
`U.S. Pat. No. 7,566,537 (Aug. 13, 2013)
`IPR2013-00517, Paper 16, Decision - Institution of Inter Partes Review
`(Feb. 13, 2014)
`IPR2013-00517, Paper 32, Illumina’s Patent Owner Response (May 5,
`2014) (Redacted)
`IPR2013-00517, Paper 54, Petitioner IBS’s Reply (July 28, 2014)
`(Redacted)
`IPR2013-00517, Paper 87, Final Written Decision (Feb. 11, 2015)
`2015-1693, Brief of Patent Owner-Appellee Illumina Cambridge Ltd.
`(Oct. 28, 2015)
`1096 Number Not Used
`1097
`Illumina, Inc. v. Qiagen, N.V (N.D. Cal, Aug. 25, 2016) Plaintiff’s
`Reply in Support of Motion for Preliminary Injunction
`IPR2013-00517, Ex. 2011, Declaration of Floyd Romesberg, Ph.D.
`(May 5, 2014) (Redacted) (“Romesberg Decl.”)
`
`1092
`
`1093
`
`1094
`1095
`
`1098
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`
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`IPR2017-02172
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`xiii
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`1088
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`1089
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`1090
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`1091
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`
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`IPR2017-02172
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`1099
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`1100
`
`IPR2013-00517, Ex. 2089, Declaration of Dr. Kevin Burgess (May 5,
`2014) (Redacted) (“Burgess Decl.”)
`IPR2013-00517, Ex. 1026, Transcript, July 15, 2014 Deposition of
`Kevin Burgess, Ph.D. (Redacted)
`1101 Declaration of John D. Sutherland (IPR2017-02172) (“Sutherland
`Decl.”)
`1102 Curriculum Vitae of Dr. John D. Sutherland
`1103
`IPR2012-00006, Paper 128, Final Written Decision (Feb. 11, 2015)
`IPR2013-0011, Paper 4, Petition for Inter Partes Review of U.S. Pat.
`1104
`No. 8,088,575 (Aug. 3, 2012)
`
`xiv
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`IPR2017-02172
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`I.
`
`INTRODUCTION
`
`Petitioner requests inter partes review of claims 1-6, and 8 of U.S. Patent No.
`
`7,566,537 B2 (“’537,” Ex. 1001) as obvious under 35 U.S.C. § 103. The ’537 patent
`
`claims a method for labeling nucleic acid molecules where the label is attached to
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`the base via a cleavable linker, and the 3′-OH of the sugar moiety is reversibly
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`blocked with a protecting group comprising an azido group, such as azidomethyl.
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`Based on prior proceedings, there can be no dispute that all of the limitations of the
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`challenged independent claim are present in a single reference (Tsien, Ex. 1003),
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`except for the azido protecting group, which was disclosed in multiple other
`
`references—including Zavgorodny (Ex. 1008), Loubinoux (Ex. 1006), and Young
`
`(Ex. 1051)—and would have been obvious to a person of ordinary skill in the art
`
`(“POSITA”). Indeed, the ’537 patent itself admits that suitable protecting groups
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`would be apparent to a POSITA, that such groups could be formed from any suitable
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`group described in the go-to reference of Greene & Wuts (Ex. 1005), and that the
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`conditions for attaching and removing such groups were within the knowledge of a
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`POSITA. Ex. 1001, 7:57-8:4.
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`The ’537 patent was previously challenged by another party in two IPRs. One
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`resulted in cancellation of claims 7 and 11-14 in response to Illumina’s request for
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`adverse judgment. Exs. 1088 & 1089 (IPR2013-00518). The other petition was
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`instituted on the basis of Tsien or Ju (Ex. 1038) in combination with Zavgorodny,
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`but the combination of Tsien or Ju in combination with Greene & Wuts was denied
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`
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`1
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`IPR2017-02172
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`on the basis of redundancy. Ex. 1091, 5, 15 (IPR2013-00517). In the Final Written
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`Decision, the Board found that Tsien in combination with Zavgorodny disclosed
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`each element of the claims, but that the petitioner nevertheless failed to meet its
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`burden to establish obviousness. Ex. 1094, 7, 18, 21-22. On review, the Federal
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`Circuit noted that the “Board’s precise legal underpinnings are difficult to discern,”
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`and that the Board’s decision was improper to the extent it was based on an absence
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`of a reasonable expectation of success. Intelligent Bio-Systems, Inc. v. Illumina
`
`Cambridge Ltd., 821 F.3d 1359, 1365-67 (Fed. Cir. 2016). The Federal Circuit
`
`affirmed the Board’s judgment on the basis that “the petitioner’s sole argument for
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`why one of skill in the art would be motivated to combine Zavgorodny’s
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`azidomethyl group with Tsien’s [sequencing-by-synthesis (“SBS”)] method was
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`because it would meet Tsien’s quantitative deblocking requirement” and that the
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`Board had not abused its discretion in refusing to consider new arguments raised in
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`IBS’s Reply brief and evidence filed therewith. Id., 1368-70. Because many critical
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`“motivation to combine”-related issues were not adequately addressed in the
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`Petition, and were then belatedly — and still inadequately — addressed in the Reply
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`and supporting declarations, the Board’s decision and the Federal Circuit’s
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`affirmance were based on an incomplete and factually flawed record presented by
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`the prior petitioner. See id.; Ex. 1094, 14-19.
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`Nevertheless, the prior IPRs and Federal Circuit decisions demonstrate
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`several key facts. First, all of the limitations of claims 1-6 and 8 of the ’537 patent
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`are disclosed in Tsien or Tsien in combination with Prober, except the azido and
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`2
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`IPR2017-02172
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`azidomethyl protecting groups (821 F.3d at 1363-64; Ex. 1094, 22; Ex. 1091, 12),
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`which is disclosed by Zavgorodny and Greene & Wuts. 821 F.3d at 1364-65, 1368.
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`Second, none of the challenged claims require removal of the protecting group (i.e.,
`
`deblocking), much less quantitative deblocking. Id., 1367. Finally, the Federal
`
`Circuit determined that a POSITA would have had a reasonable expectation of
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`success in combining the teachings of Tsien with the azidomethyl protecting group
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`of Zavgorodny to arrive at the challenged claims. Id.
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`This petition focuses on explaining that Tsien’s reference to “quantitative
`
`deblocking” would not have deterred a POSITA from combining an azidomethyl
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`protecting group with Tsien’s SBS-related teachings. In particular, the POSITA
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`would have understood that, while high efficiency of the deblocking reactions is
`
`desirable (i.e., a high percentage of blocking groups are removed to reveal a 3′-OH),
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`Tsien itself teaches that the methods described therein will work at less than 100%
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`efficiency. Moreover, the reported yields following synthesis and purification in the
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`blocking group art were positive indicators to a POSITA that — when used with
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`conditions known to be appropriate for SBS — the azidomethyl protecting group
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`would be cleaved with high efficiency. In addition, a POSITA would have
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`appreciated that use of Tsien’s methods with an azidomethyl protecting group as
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`claimed in the ’537 patent would be useful for applications where quantitative
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`deblocking was not required, such as the detection of polymorphisms. See Ex. 1001,
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`2:7-9; Ex. 1101, ¶¶88-89. Thus, a POSITA would have had ample motivation to
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`combine Tsien with the azidomethyl group disclosed in Zavgorodny and Greene &
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`
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`3
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`
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`Wuts.
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`IPR2017-02172
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`This Petition provides new arguments, testimony, and secondary references
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`demonstrating why it would have been obvious to a POSITA to combine an
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`azidomethyl protecting group with Tsien’s methods. This Petition and the
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`Declaration of Dr. Sutherland also correct several scientific inaccuracies that appear
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`to have had a material impact on the outcome of the prior proceeding. See Part
`
`IX.D, infra; Ex. 1101. For these reasons, Petitioner respectfully requests inter partes
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`review and cancellation of the challenged claims.
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. §42.8
` Real Party-In-Interest (37 C.F.R. §42.8(b)(1))
`A.
`In accordance with 37 C.F.R. §42.8(b)(1), Petitioner Complete Genomics,
`
`Inc. (“CGI”) identifies itself and the following entities as real parties-in-interest:
`
`BGI Shenzhen Co., Ltd.; BGI Groups USA Inc.; BGI Genomics Co., Ltd.; and BGI
`
`Americas Corporation.
` Related Matters (37 C.F.R. §42.8(b)(2))
`B.
`Petitioner is concurrently filing IPR2017-02174, which challenges the ’537
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`patent on different grounds than asserted herein or in the prior proceeding.
`
`Prior proceedings between Illumina and other parties may also affect this
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`proceeding because they involved the challenged patent or patents with similar
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`disclosures and/or claims. See Intelligent Bio-Systems, Inc. v. Illumina Cambridge
`
`Ltd., 821 F.3d 1359 (Fed. Cir. 2016) (appeal from IPR2013-00517); Ilumina
`
`Cambridge Ltd. v. Intelligent Bio-Systems, Inc., 638 Fed.Appx. 999 (Fed. Cir. 2016)
`
`
`
`4
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`
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`IPR2017-02172
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`(unpublished) (appeals from IPR2013-00128 and IPR2013-00266); Trustees of
`
`Columbia University v. Illumina, Inc., 620 Fed.Appx. 916 (Fed. Cir. 2015)
`
`(unpublished) (appeals from IPR2012-00006, IPR2012-00007, and IPR2013-
`
`00011); The Trustees of Columbia University v. Illumina, Inc., 1:12-cv-00376-GMS
`
`(D.