Filed December 8, 2017
`
`Filed on behalf of:
`Illumina, Inc.
`By: Kerry S. Taylor
`Michael L. Fuller
`KNOBBE, MARTENS, OLSON & BEAR, LLP
`2040 Main Street, 14th Floor
`Irvine, CA 92614
`Telephone: 949-760-0404
`Facsimile: 949-760-9502
`Email: BoxIllumina@knobbe.com
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________________________
`
`ILLUMINA, INC.
`Petitioner,
`
`v.
`
`THE TRUSTEES OF COLUMBIA UNIVERSITY
`IN THE CITY OF NEW YORK
`Patent Owner.
`
`Case No. IPR2018-00291
`U.S. Patent No. 9,718,852
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,718,852
`Columbia Ex. 2034
`Illumina, Inc. v. The Trustees
`of Columbia University
`in the City of New York
`IPR2020-01177
`
`

`

`TABLE OF CONTENTS
`
`Page No.
`
`I.
`
`II.
`
`INTRODUCTION ......................................................................................... 1 
`
`BACKGROUND REGARDING THE ’852 PATENT ................................. 3 
`
`A. 
`
`Prosecution History and Patent Owner Estoppel ................................ 4 
`
`1. 
`
`2. 
`
`3. 
`
`The double patenting rejection and patent owner
`estoppel ..................................................................................... 4 
`
`Lack of written description support .......................................... 5 
`
`Columbia incorrectly asserted “small” was inventive,
`and did not address Tsien .......................................................... 6 
`
`III. THE BOARD SHOULD PRECULDE COLUMBIA FROM
`PARTICIPATING IN THIS PROCEEDING ............................................... 6 
`
`IV. CLAIM CONSTRUCTION .......................................................................... 7 
`
`V.
`
`LEVEL OF ORDINARY SKILL IN THE ART ........................................... 7 
`
`VI. STATE OF THE ART ................................................................................... 8 
`
`A.  Deoxyribonucleotides Were Known ................................................... 8 
`
`B. 
`
`Nucleotide Analogues Were Known ................................................. 10 
`
`1. 
`
`Nucleotide analogues having a 3′-OH cap and a
`labeled base were known ........................................................ 11 
`
`a. 
`
`b. 
`
`Small 3′-capping groups were desirable ....................... 11 
`
`7-Substituted deaza-purine labels were
`common ........................................................................ 12 
`
`VII. THERE IS A REASONABLE LIKELIHOOD THAT THE
`CHALLENGED CLAIM IS UNPATENTABLE ....................................... 14 
`
`-i-
`
`

`

`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`A. 
`
`B. 
`
`The Asserted References Are Prior Art ............................................ 14 
`
`Grounds Of Challenges ..................................................................... 15 
`
`VIII. GROUND 1: OBVIOUSNESS OVER TSIEN IN VIEW OF
`PROBER ...................................................................................................... 15 
`
`A. 
`
`B. 
`
`Introduction to Tsien and Prober ....................................................... 15 
`
`Claim 1 is Obvious Over Tsien in view of Prober ............................ 16 
`
`1. 
`
`The structure depicted in Claim 1 is not new ......................... 16 
`
`a. 
`
`Tsien in view of Prober renders obvious the
`nucleotide depicted in Claim 1 ..................................... 19 
`
`Limitation R(a): “wherein R(a) represents a small,
`chemically cleavable, chemical group capping the
`oxygen at the 3′ position of the deoxyribose of the
`deoxyribonucleotide analogue” .............................................. 21 
`
`Limitation R(b): “wherein R ... (b) does not interfere
`with recognition of the analogue as a substrate by a
`DNA polymerase” ................................................................... 24 
`
`Limitations “wherein R ... (c) is stable during a DNA
`polymerase reaction” and “wherein the covalent bond
`between the 3′-oxygen and R is stable during a DNA
`polymerase reaction” .............................................................. 25 
`
`Limitations “wherein R ... (d) does not contain a
`ketone group” and “wherein OR is not a methoxy
`group or an ester group” ......................................................... 26 
`
`Limitation “wherein tag represents a detectable
`fluorescent moiety” ................................................................. 26 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`-ii-
`
`

`

`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`7. 
`
`8. 
`
`9. 
`
`Limitation Y is a “chemically cleavable, chemical
`linker” ...................................................................................... 27 
`
`Limitation Y(a): “wherein Y ... (a) does not interfere
`with recognition of the analogue as a substrate by a
`DNA polymerase” ................................................................... 28 
`
`Limitation Y(b): “wherein Y ... (b) is stable during a
`DNA polymerase reaction” ..................................................... 29 
`
`10.  Limitation i): “wherein the adenine
`deoxyribonucleotide analogue: i) is recognized as a
`substrate by a DNA polymerase” ............................................ 30 
`
`11.  Limitation ii): “wherein the adenine
`deoxyribonucleotide analogue ... ii) is incorporated at
`the end of a growing strand of DNA during a DNA
`polymerase reaction” .............................................................. 31 
`
`12.  Limitation iii): “wherein the adenine
`deoxyribonucleotide analogue ... iii) produces a 3′-
`OH group on the deoxyribose upon cleavage of R” ............... 31 
`
`13.  Limitation iv): “wherein the adenine
`deoxyribonucleotide analogue ... iv) no longer
`includes a tag on the base upon cleavage of Y” ..................... 32 
`
`14.  Limitation v): “wherein the adenine
`deoxyribonucleotide analogue ... v) is capable of
`forming hydrogen bonds with thymine or a thymine
`nucleotide analogue” ............................................................... 32 
`
`15.  There was motivation to combine Tsien and Prober .............. 33 
`
`a. 
`
`The motivation here was not present in
`IPR2013-00517 ............................................................. 36 
`
`-iii-
`
`

`

`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`16.  There was a reasonable expectation of success ...................... 36 
`
`C. 
`
`The Pharmaceutical “Lead Compound” Analysis Does Not
`Apply ................................................................................................. 38 
`
`1. 
`
`2. 
`
`3. 
`
`A pharmaceutical “lead compound” analysis
`compares compounds having specific arrangements
`of atoms ................................................................................... 40 
`
`Claim 1 does not define a compound having a
`specific arrangement of atoms ................................................ 40 
`
`Columbia’s §112 arguments cut against a “lead
`compound” analysis ................................................................ 42 
`
`D. 
`
`Tsien’s 3′-O-allyl dATP is a Lead Compound .................................. 42 
`
`1. 
`
`Tsien’s 3′-O-acetyl dTTP also qualifies as a Lead
`Compound ............................................................................... 45 
`
`2.  Motivation to use Prober’s 7-substituted deaza-
`adenine base having a linker and label ................................... 46 
`
`3.  Motivation to use a cleavable allyl linker ............................... 48 
`
`4. 
`
`There was a reasonable expectation of success ...................... 49 
`
`IX.
`
`35 U.S.C. §325(d) IS NOT APPLICABLE ................................................. 51 
`
`A. 
`
`B. 
`
`Columbia’s improper prosecution tactics should not be
`rewarded ............................................................................................ 51 
`
`The Petition provides arguments and evidence not cited
`during prosecution ............................................................................. 52 
`
`X. GROUND 2: OBVIOUSNESS BASED ON DOWER IN VIEW
`OF PROBER AND METZKER .................................................................. 54 
`
`-iv-
`
`

`

`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`A. 
`
`B. 
`
`Introduction to Dower, Prober, and Metzker .................................... 54 
`
`Claim 1 is Obvious Over Dower in view of Prober and
`Metzker .............................................................................................. 55 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`The structure depicted in Claim 1 is not new ......................... 55 
`
`Limitation R(a) ........................................................................ 58 
`
`a. 
`
`Dower ........................................................................... 58 
`
`b.  Metzker ......................................................................... 59 
`
`Limitation R(b) ....................................................................... 60 
`
`Limitations R(c) and “wherein the covalent bond
`between the 3′-oxygen and R is stable during a DNA
`polymerase reaction” .............................................................. 61 
`
`Limitations R(d) and “wherein OR is not a methoxy
`group or an ester group” ......................................................... 62 
`
`Limitation “wherein tag represents a detectable
`fluorescent moiety” ................................................................. 63 
`
`Limitation Y is a “chemically cleavable, chemical
`linker” ...................................................................................... 63 
`
`Limitations Y(a) and Y(b) ...................................................... 64 
`
`Limitation i) ............................................................................ 65 
`
`10.  Limitation ii) ........................................................................... 66 
`
`11.  Limitation iii) .......................................................................... 68 
`
`12.  Limitation iv) .......................................................................... 68 
`
`-v-
`
`

`

`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`13.  Limitation v) ........................................................................... 68 
`
`14.  A POSA would have been motivated to combine
`Dower, Prober and Metzker .................................................... 70 
`
`15.  There would have been a reasonable expectation of
`success ..................................................................................... 73 
`
`XI. GROUNDS 1 AND 2 ARE NOT REDUNDANT ...................................... 74 
`
`XII. THERE IS NO EVIDENCE OF SECONDARY
`CONSIDERATIONS ................................................................................... 74 
`
`XIII. MANDATORY NOTICES PURSUANT TO 37 C.F.R.
`§42.8(A)(1) .................................................................................................. 74 
`
`A. 
`
`B. 
`
`C. 
`
`D. 
`
`Real Party-In-Interest (37 C.F.R. §42.8(b)(1)) ................................. 74 
`
`Related Matters (37 C.F.R. §42.8(b)(2)) ........................................... 74 
`
`Lead and Backup Counsel (37 C.F.R. §42.8(b)(3)) .......................... 77 
`
`Service Information (37 C.F.R. §42.8(b)(4)) .................................... 77 
`
`XIV. PAYMENT OF FEES PURSUANT TO 37 C.F.R. §42.103 ...................... 78 
`
`XV. REQUIREMENTS FOR REVIEW UNDER 37 C.F.R. §42.104 ............... 78 
`
`XVI. CONCLUSION ............................................................................................ 78 
`
`
`
`-vi-
`
`

`

`TABLE OF AUTHORITIES
`
`Page No(s).
`
`Actavis LLC v. Abraxis Bioscience LLC,
`IPR2017-01101 (P.T.A.B. 2017) ........................................................................ 53
`
`Advanced Display Sys., Inc. v. Kent State Univ.,
`212 F.3d 1272 (Fed. Cir. 2000) .......................................................................... 70
`
`Altana Pharma AG v. Teva Pharms. USA, Inc.,
`566 F.3d 999 (Fed. Cir. 2009) ...................................................................... 42, 45
`
`Amerigen Pharms. Ltd. v. Janssen Oncology, Inc.,
`IPR2016-00286 (P.T.A.B. 2016) ........................................................................ 54
`
`Apotex Inc. v. Novartis AG,
`IPR2017-00854 (P.T.A.B. 2017) ........................................................................ 53
`
`Boehringer Ingelheim Int’l GmbH v. AbbVie Biotech. Ltd.,
`IPR2016-00408 (P.T.A.B. 2016) ........................................................................ 54
`
`Boston Sci. Scimed, Inc. v. Cordis Corp.,
`554 F.3d 982 (Fed. Cir. 2009) ...................................................................... 34, 36
`
`Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014) ...................................................................... 44, 47
`
`Ex parte Cao,
`Appeal No. 2010-004081 (B.P.A.I. Sept. 21, 2011) ........................................... 40
`
`Ex parte Dong,
`Appeal No. 2011-010047 (P.T.A.B. 2013) ................................................... 43, 45
`
`Guardian Indus. Corp. v. Pilkington Deutschland AG,
`IPR2016-01635 (P.T.A.B. 2017) ........................................................................ 53
`
`Hospira, Inc. v. Genentech, Inc.,
`IPR2017-00804 (P.T.A.B. 2017) ........................................................................ 53
`
`-vii-
`
`

`

`TABLE OF AUTHORITIES
`(cont’d)
`
`Page No(s).
`
`Illumina Cambridge Ltd. v. Intelligent Bio-Systems, Inc.,
`638 Fed. Appx. 999 (Fed. Cir. 2016) .................................................................. 76
`
`Illumina v. Columbia,
`IPR2012-00006 & IPR2013-00011(P.T.A.B. 2014) .......................................... 75
`
`Illumina v. Columbia,
`IPR2012-00007 (P.T.A.B. 2014) ........................................................................ 75
`
`Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd.,
`821 F.3d 1359 (Fed. Cir. 2016) .................................................................... 36, 76
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................... 39, 70
`
`Lupin Ltd. v. Horizon Therapeutics, Inc.,
`IPR2016-00829 (P.T.A.B. 2016) ........................................................................ 54
`
`New Hampshire v. Maine,
`532 U.S. 742 (2001) .............................................................................................. 5
`
`Otsuka Pharm. Co. v. Sandoz, Inc.,
`678 F.3d 1280 (Fed. Cir. 2012) .................................................................... 40, 43
`
`In re Petering,
`301 F.2d 676 (C.C.P.A. 1962) ............................................................................ 44
`
`PharmaStem Therapeutics, Inc. v. ViaCell, Inc.,
`491 F.3d 1342 (Fed. Cir. 2007) .......................................................................... 23
`
`In re Swinehart,
`439 F.2d 210 (C.C.P.A. 1971) ............................................................................ 41
`
`Trustees of Columbia Univ. v. Illumina, Inc.,
`620 Fed. Appx. 916 (Fed. Cir. 2015) .............................................................. 1, 76
`
`-viii-
`
`

`

`TABLE OF AUTHORITIES
`(cont’d)
`
`Page No(s).
`
`Trustees of Columbia Univ. v. Illumina, Inc.,
`C.A. No. 12-cv-376 (D. Del.) ............................................................................. 75
`
`Trustees of Columbia Univ. v. Illumina, Inc.,
`C.A. No. 17-cv-973-GMS (D. Del.) ................................................................... 75
`
`TRW Auto. US LLC v. Magna Elects. Inc.,
`IPR2014-00293 (P.T.A.B. 2014) ........................................................................ 78
`
`Unified Patents Inc. v. Berman,
`IPR2016-01571 (P.T.A.B. 2016) ........................................................................ 52
`
`OTHER AUTHORITIES
`
`35 U.S.C. §102 ......................................................................................................... 14
`
`35 U.S.C. §103 ......................................................................................................... 15
`
`35 U.S.C. §112 ................................................................................................... 42, 48
`
`35 U.S.C. §315 ......................................................................................................... 78
`
`35 U.S.C. §325 ............................................................................................. 51, 52, 74
`
`37 C.F.R. §42.1 ........................................................................................................ 52
`
`37 C.F.R. §42.8 .................................................................................................. 74, 77
`
`37 C.F.R. §42.15 ...................................................................................................... 77
`
`37 C.F.R. §42.73 ............................................................................................ 2, 4, 6, 7
`
`37 C.F.R. §42.103 .................................................................................................... 77
`
`37 C.F.R. §42.104 .................................................................................................... 78
`
`M.P.E.P. §2143 .................................................................................................. 40, 43
`
`-ix-
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`
`TABLE OF EXHIBITS
`
`
`
`Exhibit No. Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`U.S. Patent No. 9,718,852 (“Ju”) – (Claim 1 is an adenine claim)
`
`U.S. Patent No. 9,708,358 (“Ju”) – (Claim 1 is a cytosine claim)
`
`U.S. Patent No. 9,719,139 (“Ju”) – (Claim 1 is a thymine claim)
`
`U.S. Patent No. 9,725,480 (“Ju”) – (Claim 1 is a guanine claim)
`
`2014-03-06 IPR2012-00007, Paper 140, Final Written Decision
`
`2014-03-06 IPR2012-00006, Paper 128, Final Written Decision
`
`2014-03-06 IPR2013-00011, Paper 130, Final Written Decision
`
`2015-07-17 Federal Circuit Opinion Affirming IPR2012-00006,
`IPR2012-00007 and IPR2013-00011
`
`Excerpts from Prosecution History of U.S. Patent No. 9,718,852
`(“Ju”)
`
`U.S. Patent No. 7,790,869 (“Ju”)
`
`Alberts, et al., “Molecular Biology of the Cell”, Third Edition,
`Garland Publishing Inc., New York (1994)
`
`Declaration of Floyd Romesberg, Ph.D.
`
`WO 91/06678 (“Tsien”)
`
`Prober, et al., “A System for Rapid DNA Sequencing with
`Flourescent Chain-Terminating Dideoxynucleotides”, Science,
`238:336-341 (1987) (“Prober”)
`
`1015
`
`U.S. Patent No. 5,547,839 (“Dower”)
`
`Table of Exhibits, Page 1
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`Metzker, et al., “Termination of DNA synthesis by novel 3’-
`modified-deoxyribonucleoside 5’-triphosphates”, Nucleic Acids
`Research, 22:4259-67 (1994) (“Metzker”)
`
`1016
`
`1017
`
`1018
`
`1019
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`1020
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`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`Wu and Metzker, et al., “Termination of DNA synthesis by N6-
`alkylated, not 3’-O-alkylated, photocleavable 2’-deoxyadenosine
`triphosphates”, Nucleic Acids Research, 35:6339-6349 (2007)
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`
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`(“Sanger”)
`
`U.S. Patent No. 7,270,951 (“Stemple”)
`
`U.S. Patent No. 5,302,509 (“Cheeseman”)
`
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`Polymerase β, a DNA Template-Primer, and ddCTP”, Science,
`264:1891-1903 (1994) (“Pelletier”)
`
`Declaration of Jingyue Ju from Prosecution History of U.S. Patent
`No. 9,718,852 (“Ju”)
`
`for
`Welch, et al., “Syntheses of Nucleosides Designed
`Combinatorial DNA Sequencing”, Chem. Eur. J., 5:951-960
`(1999) (“Welch”)
`
`Welch, et al., “Corrgenda – Syntheses of Nucleosides Designed for
`Combinatorial DNA Sequencing”, Chem. Eur. J., 11:7136-7145
`(2005) (“Welch Corrigenda”)
`
`Seela, et al., “7-Deazapurine containing DNA”, Nucleic Acids
`Research, 20:55-61 (1991) (“Seela 1991”)
`
`U.S. Patent No. 4,804,748 (“Seela Patent”)
`
`Rosenblum, et al., “New dye-labeled terminators for improved
`DNA sequencing patterns”, Nucleic Acid Research, 25:4500-4504
`(1997) (“Rosenblum”)
`
`Table of Exhibits, Page 2
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`Excerpts from 2013-09-04 Deposition Transcript of Dr. George L.
`Trainor in IPR2012-00007
`
`1028
`
`1029
`
`U.S. Patent No. 5,151,507 (“Hobbs”)
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`Ramzaeva, et al., “88. 7-Substituted 7-Deasa-2’-deoxyguanosines:
`Regioselective Halogenation of Pyrrolo[2,3-d] pyrimidine
`Nucleosides”, Helvetica Chimica Acta, 78:1083-1090 (1995)
`(“Ramzaeva 1995”)
`
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`7-Substituents of 7-Deazaguanine Bases”, Bioorganic &
`Mechanical Chemistry Letters, 5:3049-3052 (1995) (“Seela 1995”)
`
`Seela, et al., “Duplex Stability of Oligonucleotides Containing 7-
`Substituted 7-Deaza- and 8-Aza-7-Deazapurine Nucleosides”,
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`(“Seela 1997”)
`
`Ramzaeva, et al., “123. 7-Deazaguanine DNA: Oligonucleotides
`with Hydrophobic or Cationic Side Chains”, Helvetica Chimica
`Acta, 80:1809-1822 (1997) (“Ramzaeva 1997”)
`
`2013-06-25 Declaration of Dr. George L. Trainor from IPR2012-
`00006
`
`Boss, et al., “Cleavage of Allyl Ethers with Pd/C”, Angew. Chem.
`Int. Ed. Engl., 15:558-559 (1976) (“Boss”)
`
`Qian, et al., “Unexptected Ensymatic Fucosylation of the Hindered
`Tertiary Alcohol of 3-C-Methyl-N-Acetyllactosamine Produces a
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`American Chemical Society, 120:2184-2185 (1998) (“Qian”)
`
`Kamal, et al., “A Miled and Rapid Regeneration of Alcohols from
`their Allylic Ethers by Chlorotrimethylsilane/Sodium Iodide”,
`Tetrahedron Letters, 40:371-372 (1999) (“Kamal”)
`
`Excerpts from Prosecution History of U.S. Patent No. 9,725,480
`(“Ju”)
`
`Table of Exhibits, Page 3
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`Vollhardt, et al., “Organic Chemistry”, Second Edition, W.H.
`Freeman and Co., New York (1994) (“Vollhardt”)
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`1049
`
`1050
`
`1051
`
`Yu, et al., “Cyanine dye dUTP analogs for enzymatic labeling of
`DNA probes”, Nucleic Acids Research, 22:3226-3232 (1994)
`(“Yu”)
`
`Livak, et al., “Detection of single base differences using
`biotinylated nucleotides with very long linker arms”, Nucleic
`Acids Research, 20:4831-4837 (1992) (“Livak”)
`
`Watson, et al., “Genetical Implication of the Structure of
`Deoxyribonucleic Acid”, Nature, 171:964-967 (1953) (“Watson &
`Crick”)
`
`Zavgorodny, et al., “1-Alkylthioalkylation of Nucleoside Hydroxyl
`Functions and its Synthetic Applications: A New Versatile Method
`in Nucleoside Chemistry”, Tetrahedron Letters, 32:7593-7596
`(1991) (“Zavgorodny”)
`
`2015-02-11 Final Written Decision in IPR2013-00517
`
`2016-05-09 Federal Circuit Opinion Affirming IPR2013-00517
`
`Gigg, et al., “The Allyl Ether as a Protecting Group in
`Carbohydrate Chemistry Part II”, J. Chem. Soc. (C), 1903-1911
`(1968) (“Gigg”)
`
`2013-08-30 Substitute Columbia Patent Owner Response in
`IPR2012-00007, Paper 77
`
`2014-07-25 Final Written Decision in IPR2013-00128, Paper 92
`
`2014-10-28 Final Written Decision in IPR2013-00266, Paper 73
`
`2016-01-29 Federal Circuit Opinion Affirming IPR2013-00128
`and IPR2013-00266
`
`Greenberg, et al., “Optimization and Mechanistic Analysis of
`Oligonucleotide Cleavage from Palladium-Labile Solid-Phase
`Synthesis Supports”, J. Org. Chem., 63:4062-4068 (1998)
`(“Greenberg”)
`
`Table of Exhibits, Page 4
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`Seitz, et al., HYCRON, an Allylic Anchor for High-Efficiency
`Solid Phase Synthesis of Protected Peptides and Glycopeptides”, J.
`Org. Chem., 62:813-826 (1997) (“Seitz”)
`
`1052
`
`Gullier, et al., “Linkers and Cleavage Strategies in Solid-Phase
`Organic Synthesis and Combinatorial Chemistry”, Chem. Rev.,
`100:2091-2157 (2000) (“Gullier”)
`
`U.S. Patent No. 8,088,575 (“Ju”)
`
`Stryer, “Biochemistry”, Fourth Edition, W.H. Freeman and Co.,
`New York (1995) (“Stryer”)
`
`Columbia’s complaint for U.S. 9,718,852 and U.S. 9,719,139
`
`Curriculum Vitae of Floyd Romesberg, Ph.D.
`
`List of documents considered by Floyd Romesberg, Ph.D.
`
`Sears, et al., “CircumVent Thermal Cycle Sequencing and
`Alternative Manual and Automated DNA Sequencing Protocols
`Using the Highly Thermostable VentR (exo) DNA Polymerase”,
`BioTechniques, 13:626-633 (1992) (“Sears”)
`
`1053
`
`1054
`
`1055
`
`1056
`
`1057
`
`1058
`
`1059
`
`
`
`
`
`Table of Exhibits, Page 5
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`Illumina, Inc. requests inter partes review of Claim 1 of U.S. 9,718,852
`
`(“’852 patent,” Ex-1001) purportedly owned by The Trustees of Columbia
`
`University (“Columbia”).
`
`I. INTRODUCTION
`
`In three previous IPRs the Board held all challenged claims in related
`
`Columbia patents unpatentable over the prior art Tsien reference, or obvious over
`
`Tsien in view of Prober, as shown in the following table:
`
`Previous IPR Final Written Decision Columbia’s Patent
`7,790,869
`IPR2012-00007, Paper 140 (Ex-1005)
`(“’869 patent”)
`7,713,698
`(“’698 patent”)
`8,088,575
`(“’575 patent”)
`
`IPR2012-00006, Paper 128 (Ex-1006)
`
`IPR2013-00011, Paper 130 (Ex-1007)
`
`The Federal Circuit unanimously affirmed the Board’s decisions. Trustees of
`
`Result
`
`All challenged
`claims held
`unpatentable.
`
`Columbia Univ. v. Illumina, Inc., 620 Fed. Appx. 916, 927-28, 934 (Fed. Cir.
`
`2015) (Ex-1008).
`
`Undeterred by these results, Columbia improperly sought a second bite at
`
`the apple by filing a patent application with a claim directed to the same
`
`unpatentable subject matter. This application issued as the ’852 patent with a
`
`single claim: Claim 1. During prosecution, the Examiner rejected Claim 1 as
`
`patentably indistinct over claims held unpatentable from Columbia’s ’869 patent.
`
`Columbia did not disagree, and made no effort to substantively distinguish Claim 1
`
`-1-
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`from the ’869 patent. Instead, Columbia filed a terminal disclaimer to sidestep the
`
`rejection. It stands unrebutted that Claim 1 is patentably indistinct over
`
`unpatentable claims from the ’869 patent.
`
`Claim 1 of the ’852 patent is directed to a nucleotide analogue with: (1) a
`
`“small” 3′-OH capping group, and (2) a removably-labeled, deaza-substituted base.
`
`During prosecution, Columbia’s sole argument for nonobviousness was that it
`
`invented a nucleotide with a “small” 3′-O-capping group. Columbia made this
`
`argument while knowing that the Board had previously held Claim 31 of the ’869
`
`patent unpatentable, which recited “wherein the cleavable chemical group capping
`
`the 3′ OH group is a small chemical moiety.” Any argument that the size or
`----
`
`“smallness” of the 3′-O-capping group is inventive was fully and finally rejected
`
`by the Board.
`
`Columbia relied on a concept adjudicated by the Board to be non-inventive
`
`and filed a terminal disclaimer over claims already held to be unpatentable. This
`
`clearly violates the patent owner estoppel provisions of 37 C.F.R. §42.73(d)(3)(i).
`
`Pursuant to this regulation, a “patent applicant or owner is precluded from taking
`
`action inconsistent with [an] adverse judgment, including obtaining in any patent....
`
`[a] claim that is not patentably distinct from a finally refused or canceled claim.”
`
`The Board should rectify Columbia’s disregard of the Board’s previous final
`
`written decisions and §42.73(d)(3)(i), and cancel Claim 1 of the ’852 patent.
`
`-2-
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`II. BACKGROUND REGARDING THE ’852 PATENT
`
`The ’852 patent claims priority to the ’869 and ’575 patents via continuation
`
`applications. Ex-1001 at Title Page. The ’852, ’869, ’575, and ’698 patents
`
`contain the same specification.
`
`Claim 1 of the ’852 patent, the only claim, recites:
`
`1. An adenine deoxyribonucleotide analogue having the structure:
`
`
`wherein R (a) represents a small, chemically cleavable, chemical
`group capping the oxygen at the 3′ position of the deoxyribose of
`the deoxyribonucleotide analogue, (b) does not interfere with
`recognition of the analogue as a substrate by a DNA polymerase,
`(c) is stable during a DNA polymerase reaction, and (d) does not
`contain a ketone group;
`wherein OR is not a methoxy group or an ester group;
`wherein the covalent bond between the 3′-oxygen and R is stable
`during a DNA polymerase reaction;
`wherein tag represents a detectable fluorescent moiety;
`wherein Y represents a chemically cleavable, chemical linker which
`(a) does not interfere with recognition of the analogue as a
`substrate by a DNA polymerase and (b) is stable during a DNA
`polymerase reaction; and
`
`-3-
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`wherein the adenine deoxyribonucleotide analogue: i) is recognized as
`a substrate by a DNA polymerase, ii) is incorporated at the end of a
`growing strand of DNA during a DNA polymerase reaction, iii)
`produces a 3′-OH group on the deoxyribose upon cleavage of R,
`iv) no longer includes a tag on the base upon cleavage of Y, and v)
`is capable of forming hydrogen bonds with thymine or a thymine
`nucleotide analogue.
`
`A.
`
`Prosecution History and Patent Owner Estoppel
`
`During prosecution, the Examiner issued an office action rejecting
`
`Columbia’s claim for double patenting, lack of written description support, and
`
`obviousness. Ex-1009 at 93-106.
`
`1.
`
`The double patenting rejection and patent owner estoppel
`
`The Examiner issued an obviousness-type double patenting rejection finding
`
`Columbia’s present claim was patentably indistinct from Claims 17 and 28 of the
`
`’869 patent in view of Prober. Ex-1009 at 102. Claims 17 and 28 were previously
`
`held unpatentable by the Board and Federal Circuit. Ex-1005 at 49; Ex-1008 at 33.
`
`Under 37 C.F.R. §42.73(d)(3)(i), Columbia was bound by patent owner estoppel to
`
`refrain from taking any action to prosecute the present claim unless and until it
`
`convinced the Examiner to withdraw the patentably indistinct finding. Instead of
`
`addressing the Examiner’s finding, Columbia evaded it with a terminal disclaimer,
`
`which improperly led the Examiner to remove the rejection. Ex-1009 at 24. The
`
`-4-
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`Examiner’s patentably indistinct finding was never addressed and remains intact
`
`today.
`
`2.
`
`Lack of written description support
`
`The Examiner rejected the functional language recited for “Y” and “R” for
`
`lack of written description support. Ex-1009 at 93-96.
`
`Columbia asserted that Claim 1 is supported because it covers the same
`
`subject matter as the previously issued claims “cited in the Office Action in the
`
`obviousness-type double patenting rejection” that are presumed to be supported by
`
`the same specification. Id. at 21, n.3. The previously issued claims Columbia
`
`relied on include the patentably indistinct and now cancelled Claims 17 and 28 of
`
`the ’869 patent. The judicial estoppel rule prevents Columbia from embracing the
`
`Examiner’s patentably indistinct finding to establish written description support
`
`during prosecution without also accepting the patent owner estoppel ramifications
`
`that come with the Examiner’s finding. New Hampshire v. Maine, 532 U.S. 742,
`
`749 (2001) (“Where a party assumes a certain position in a legal proceeding, and
`
`succeeds in maintaining that position, he may not thereafter, simply because his
`
`interests have changed, assume a contrary position…. This rule, known as
`
`judicial estoppel, generally prevents a party from prevailing in one phase of a case
`
`on an argument and then relying on a contradictory argument to prevail in another
`
`phase.”).
`
`-5-
`
`

`

`Illumina v. Columbia
`IPR Petition – U.S. Patent No. 9,718,852
`3.
`Columbia incorrectly asserted “small” was inventive, and did not
`address Tsien
`
`The Examiner issued an obviousness rejection over Stemple and Tsien in
`
`view of Prober and Anazawa. Ex-1009 at 96-100. Columbia’s response focused
`
`solely on Stemple and argued nonobviousness over Stemple’s disclosure of a
`
`“large” 3′-O-2-nitrobenzyl capping group. Ex-1009 at 22-25. Columbia
`
`improperly asserted its inventive insight was the 3′-OH capping group being
`
`“small” (id. at 24), which contradicts the Board’s decision in IPR2012-00007
`
`holding unpatentable Claim 31 of Columbia’s ’869 patent that recited “wherein the
`
`cleavable chemical group capping the 3′ OH group is a small chemical moiety.”1
`
`Ex-1005 at 11; Ex-1010 at 34:48-50. The Examiner withdrew the obviousness
`
`rejection based on Columbia’s arguments regarding St