Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 1 of 415 PageID #: 2381
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`
`
`
`
`THE TRUSTEES OF COLUMBIA
`UNIVERSITY IN THE CITY OF
`NEW YORK and QIAGEN
`SCIENCES, LLC,
`
`
`v.
`
`
`ILLUMINA, INC.,
`
`
`Defendant.
`
`Plaintiffs,
`
`
`
`
`
`
`Civil Action No. 19-1681-CFC
`
`
`
`
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`
`
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`
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`
`
`
`JOINT CLAIM CONSTRUCTION APPENDIX
`
`
`
`ASHBY & GEDDES
`
`
`
`/s/ Steven J. Balick
`Steven J. Balick (#2114)
`Andrew C. Mayo (#5207)
`500 Delaware Avenue, 8th Floor
`P.O. Box 1150
`Wilmington, DE 19899
`(302) 654-1888
`sbalick@ashbygeddes.com
`amayo@ashbygeddes.com
`
`OF COUNSEL:
`
`Edward R. Reines
`Derek C. Walter
`Christopher Lavin
`WEIL, GOTSHAL & MANGES, LLP
`201 Redwood Shores Parkway
`
`
`
`
`
`MORRIS, NICHOLS, ARSHT &
`TUNNELL LLP
`
`
`/s/ Jack B. Blumenfeld
`Jack B. Blumenfeld (#1014)
`Derek J. Fahnestock (#4705)
`1201 North Market Street
`P.O. Box 1347
`Wilmington, DE 19899-1347
`(302) 658-9200
`jblumenfeld@mnat.com
`dfahnestock@mnat.com
`
`OF COUNSEL:
`
`John D. Murnane
`Robert S. Schwartz
`Justin J. Oliver
`Zachary L. Garrett
`VENABLE LLP
`
`Illumina Ex. 1158
`Illumina v. Columbia
`IPR2020-01177
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 2 of 415 PageID #: 2382
`
`Redwood Shores, CA 94065
`(650) 802-3000
`
`Attorneys for Defendant Illumina, Inc.
`
`2
`
`
`
`
`
`1290 Avenue of the Americas
`New York, NY 10104-3800
`(212) 218-2100
`
`Attorneys for Plaintiff The Trustees of
`Columbia University in the City of New
`York
`
`
`
`BALLARD SPAHR LLP
`
`/s/ Beth Moskow-Schnoll
`Beth Moskow-Schnoll (#2900)
`Brittany M. Giusini (#6034)
`919 N. Market Street, 11th Floor
`Wilmington, DE 19801-3034
`(302) 252-4465
`moskowb@ballardspahr.com
`giusinib@ballardspahr.com
`
`OF COUNSEL:
`
`Robert R. Baron, Jr.
`Marc S. Segal
`BALLARD SPAHR LLP
`1735 Market Street, 51st Floor
`Philadelphia, PA 19103-7599
`(215) 665-8500
`
`Chittam U. Thakore
`BALLARD SPAHR LLP
`999 Peachtree Street, NE.
`Suite 1600
`Atlanta, GA 30309
`(404) 420-9484
`
`Attorneys for Plaintiff QIAGEN
`Sciences, LLC
`
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 3 of 415 PageID #: 2383
`
`INDEX
`
`Joint Appendix No.
`
`Description
`
`JA0001 – JA0021
`
`U.S. Pat. 10,407,458 Excerpts
`
`JA0022 – JA0027
`
`U.S. Pat. 10,428,380 Excerpts
`
`JA0028 – JA0034
`
`’458 Patent Prosecution History, 5/5/19 Supplemental
`Communication Excerpts
`
`JA0035 – JA0041
`
`IPR2018-00291, Paper 67 (Final Written Decision)
`Excerpts
`
`JA0042 – JA0044
`
`IPR2018-00291, Ex. 1001 (U.S. Pat. 9,718,852) Excerpts
`
`JA0045 – JA0051
`
`IPR2018-00291, Paper 1 (Petition for Inter Partes
`Review) Excerpts
`
`JA0052 – JA0060
`
`IPR2018-00385, Paper 30 (Patent Owner’s Response)
`Excerpts
`
`JA0061 – JA0068
`
`’458 Patent Prosecution History, 5/5/19 Supplemental
`Communication, Ex. 1 (Declaration Under 37 C.F.R.
`§ 1.132 of Jingyue Ju, Ph.D.) Excerpts
`
`JA0069 – JA0081
`
`Ju Declaration, Exhibit A (Pelletier article)
`
`JA0082 – JA0084
`
`Ju Declaration, Exhibit C (Dr. Ju’s Analysis)
`
`JA0085
`
`’458 Patent Issue Notification
`
`JA0086 – JA0089
`
`IPR2018-00385, Paper 13 (Patent Owner’s Preliminary
`Response) Excerpts
`
`JA0090 – JA0093
`
`IPR2018-00385, Paper 66 (Final Written Decision)
`Excerpts
`
`JA0094 – JA0095
`
`IPR2018-00385 Paper 48 (Patent Owner’s Sur-Reply)
`Excerpts
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 4 of 415 PageID #: 2384
`
`JA0096 – JA0097
`
`IPR2018-00797, Paper 65 (Final Written Decision)
`Excerpts
`
`JA0098 – JA0100
`
`Amended Appendix A – Agreed To Claim Constructions
`
`JA0101 – JA112
`
`Amended Appendix B – Disputed Claim Terms and
`Proposed Constructions
`
`JA0113 – JA0117
`
`IPR2013-00266, Ex. 1011 (Declaration of Dr. Bruce P.
`Branchaud in Support of Petition for Inter Partes Review
`of U.S. Patent No. 8,158,346) Excerpts
`
`JA0118 – JA127
`
`U.S. Pat. 7,566,537 Excerpts
`
`JA0128 – JA0131
`
`Zhu, Z., et al., (1994) Directly Labeled DNA Probes
`Using Fluorescent Nucleotides With Different Length
`Linkers, Nucleic Acids Res., 22, 3418-19
`
`JA0132 – JA0133
`
`IPR2018-00291, Ex. 2141 (Patent Owner’s
`Demonstratives) Excerpts
`
`JA0134 – JA0139
`
`JA0140 – JA0142
`
`IPR2013-00266, Ex. 2004 (Declaration of Floyd
`Romesberg, Ph.D. In Support of Patent Owner’s motion
`to Amend) Excerpts
`
`IPR2020-00988, Ex. 1038 (Declaration of Floyd
`Romesberg, Ph.D. In Support of Petition for Inter Partes
`Review of U.S. Patent No. 10,407,458)
`
`JA0143 – JA0145
`U.S. Pat. 9,725,480 Notice of Allowability
`JA0146 – JA0150 Webster’s Third New International Dictionary, Merriam-
`Webster, pp. 1293, 2614 (1993)
`
`JA0151 – JA0153
`
`Oberg, E., Jones F., Shop Mathematics, p. 60 (1st ed.
`1920)
`
`JA0154 – JA0156
`
`IPR2017-02172, Paper 6 (Patent Owner Preliminary
`Response) Excerpts
`
`2
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 5 of 415 PageID #: 2385
`
`JA0157 – JA232
`
`Declaration of John Kuriyan, Ph.D. In Support of
`Plaintiffs’ Opening Claim Construction Brief (with
`Exhibits)
`
`JA0233 – JA0235
`
`IPR2018-00291, Paper 62 (Record of Oral Hearing)
`Excerpts
`
`JA0236 – JA0282
`
`Expert Declaration of Dr. Floyd Romesberg In Support of
`Illumina’s Response to Plaintiffs’ Opening Claim
`Construction Brief (with Appendix A)
`
`JA0283 – JA0294
`
`IPR2012-00007, Ex. 2094 (Trainor Dep.) Excerpts
`
`JA0295 – JA0297
`
`Plaintiffs’ Preliminary Proposed Constructions
`
`JA0298 – JA0300
`
`Defendant Illumina, Inc.’s Preliminary Disclosure of
`Proposed Claim Constructions For Disputed Claim
`Terms/Phrases
`
`JA0301 – JA0306
`
`April 14, 2020 C. Lavin Email to R. Baron
`
`JA0307 – JA0351
`
`July 15, 2020 Deposition of Floyd Romesberg, Ph.D.
`Excerpts
`
`JA0352 – JA0353
`
`Romesberg Deposition, Ex. 9
`
`JA0354 – JA0359
`
`IPR2020-00988, Ex. 1038 (Declaration of Floyd
`Romesberg, Ph.D., In Support of Petition for Inter Partes
`Review of U.S. Patent No. 10,407,458) Excerpts
`
`JA0360 – JA0397
`
`July 10, 2020 Kuriyan Deposition Excerpts
`
`JA0398 – JA0400
`
`Ex. A - Illumina's Claim Construction Sur-Reply Brief
`
`JA0401 – JA0403
`
`’458 Patent Prosecution History, 5/9/19 Supplemental
`Communication, Ex. 2 (Claim Support Table) Excerpts
`
`JA0404 – JA0405
`
`IPR2018-00797, Paper 47 (Patent Owner’s Sur-Reply)
`Excerpt
`
`3
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 6 of 415 PageID #: 2386
`
`JA0406 – JA0409
`
`IPR2018-00797, Paper 29 (Patent Owner’s Response)
`Excerpt
`
`
`
`
`
`
`
`4
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 7 of 415 PageID #: 2387
`
`1111111111111111111111010!1111110111111111111111111111111111111111
`
`US010407458B2
`
`( 12 ) United States Patent
`(12) United States Patent
`Ju et al .
`Ju et al.
`
`( 10 ) Patent No . : US 10 , 407 , 458 B2
`(10) Patent No.: US 10,407,458 B2
`( 45 ) Date of Patent :
`* Sep . 10 , 2019
`(45) Date of Patent:
`*Sep. 10, 2019
`
`( 72 )
`
`( 54 ) MASSIVE PARALLEL METHOD FOR
`MASSIVE PARALLEL METHOD FOR
`DECODING DNA AND RNA
`DECODING DNA AND RNA
`( 71 ) Applicant : The Trustees of Columbia University
`Applicant: The Trustees of Columbia University
`in the City of New York , New York ,
`in the City of New York, New York,
`NY ( US )
`NY (US)
`Inventors : Jingyue Ju , Englewood Cliffs , NJ ( US ) ;
`Inventors: Jingyue Ju, Englewood Cliffs, NJ (US);
`Zengmin Li , Flushing , NY ( US ) ; John
`Zengmin Li, Flushing, NY (US); John
`Robert Edwards , St . Louis , MO ( US ) ;
`Robert Edwards, St. Louis, MO (US);
`Yasuhiro Itagaki , New York , NY ( US )
`Yasuhiro Itagaki, New York, NY (US)
`( 73 ) Assignee : THE TRUSTEES OF COLUMBIA
`Assignee: THE TRUSTEES OF COLUMBIA
`UNIVERSITY IN THE CITY OF
`UNIVERSITY IN THE CITY OF
`NEW YORK , New York , NY ( US )
`NEW YORK, New York, NY (US)
`Subject to any disclaimer , the term of this
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`patent is extended or adjusted under 35
`U . S . C . 154 ( b ) by 0 days .
`U.S.C. 154(b) by 0 days.
`This patent is subject to a terminal dis
`This patent is subject to a terminal dis-
`claimer .
`claimer.
`( 21 ) Appl . No . : 16 / 149 , 098
`(21) Appl. No.: 16/149,098
`( 22 ) Filed :
`Oct . 1 , 2018
`(22) Filed:
`Oct. 1, 2018
`Prior Publication Data
`( 65 )
`(65)
`Prior Publication Data
`US 2019 / 0031704 A1 Jan . 31 , 2019
`US 2019/0031704 Al
`Jan. 31, 2019
`
`( * ) Notice :
`Notice:
`
`Related U . S . Application Data
`Related U.S. Application Data
`Continuation of application No . 15 / 915 , 983 , filed on
`( 60 )
`(60) Continuation of application No. 15/915,983, filed on
`Mar . 8 , 2018 , which is a continuation of application
`Mar. 8, 2018, which is a continuation of application
`No . 14 / 670 , 748 , filed on Mar . 27 , 2015 , which is a
`No. 14/670,748, filed on Mar. 27, 2015, which is a
`continuation of application No . 13 / 959 , 660 , filed on
`continuation of application No. 13/959,660, filed on
`Aug . 5 , 2013 , now Pat . No . 9 , 133 , 511 , which is a
`Aug. 5, 2013, now Pat. No. 9,133,511, which is a
`continuation of application No . 13 / 672 , 437 , filed on
`continuation of application No. 13/672,437, filed on
`Nov .
`8 , 2012 , now abandoned , which is
`a
`Nov. 8, 2012, now abandoned, which
`is a
`continuation of application No . 13 / 339 , 089 , filed on
`continuation of application No. 13/339,089, filed on
`Dec . 28 , 2011 , now abandoned , which is
`a
`Dec. 28, 2011, now abandoned, which
`is a
`continuation of application No . 12 / 804 , 284 , filed on
`continuation of application No. 12/804,284, filed on
`Jul . 19 , 2010 , now Pat . No . 8 , 088 , 575 , which is a
`Jul. 19, 2010, now Pat. No. 8,088,575, which is a
`continuation of application No . 11 / 810 , 509 , filed on
`continuation of application No. 11/810,509, filed on
`Jun . 5 , 2007 , now Pat . No . 7 , 790 , 869 , which is a
`Jun. 5, 2007, now Pat. No. 7,790,869, which is a
`continuation of application No . 10 / 702 , 203 , filed on
`continuation of application No. 10/702,203, filed on
`Nov . 4 , 2003 , now Pat . No . 7 , 345 , 159 , which is a
`Nov. 4, 2003, now Pat. No. 7,345,159, which is a
`division of application No . 09 / 972 , 364 , filed on Oct .
`division of application No. 09/972,364, filed on Oct.
`5 , 2001 , now Pat . No . 6 , 664 , 079 , which is a
`5, 2001, now Pat. No. 6,664,079, which is a
`continuation - in - part of application No . 09 / 684 , 670 ,
`continuation-in-part of application No. 09/684,670,
`filed on Oct . 6 , 2000 , now abandoned .
`filed on Oct. 6, 2000, now abandoned.
`( 60 ) Provisional application No . 60 / 300 , 894 , filed on Jun .
`(60) Provisional application No. 60/300,894, filed on Jun.
`26 , 2001 .
`26, 2001.
`
`( 51 ) Int . Ci .
`(51) Int. Cl.
`CO7H 19 / 14
`C07H 19/14
`C120 1 / 68
`C12Q 1/68
`CO7H 21 / 00
`C07H 21/00
`C12Q 1 / 686
`C12Q 1/686
`C12Q 1 / 6874
`C12Q 1/6874
`C120 1 / 6872
`C12Q 1/6872
`C12Q 1 / 6869
`C12Q 1/6869
`CO7H 19 / 10
`C07H 19/10
`
`( 2006 . 01 )
`(2006.01)
`( 2018 . 01 )
`(2018.01)
`( 2006 . 01 )
`(2006.01)
`( 2018 . 01 )
`(2018.01)
`( 2018 . 01 )
`(2018.01)
`( 2018 . 01 )
`(2018.01)
`( 2018 . 01 )
`(2018.01)
`( 2006 . 01 )
`(2006.01)
`
`( 56 )
`(56)
`
`( 2018 . 01 )
`C12Q 1 / 6876
`(2018.01)
`C12Q 1/6876
`C40B 40 / 00
`( 2006 . 01 )
`(2006.01)
`C40B 40/00
`( 52 ) U . S . CI .
`(52) U.S. Cl.
`CPC . . . . . . . . . . . . . CO7H 19 / 14 ( 2013 . 01 ) ; CO7H 19 / 10
` CO7H 19/14 (2013.01); CO7H 19/10
`CPC
`( 2013 . 01 ) ; C07H 21 / 00 ( 2013 . 01 ) ; C120 1 / 68
`(2013.01); C07H 21/00 (2013.01); C12Q 1/68
`( 2013 . 01 ) ; C12Q 1 / 686 ( 2013 . 01 ) ; C12Q
`(2013.01); C12Q 1/686 (2013.01); C12Q
`1 / 6869 ( 2013 . 01 ) ; C120 1 / 6872 ( 2013 . 01 ) ;
`1/6869 (2013.01); C12Q 1/6872 (2013.01);
`C12Q 1 / 6874 ( 2013 . 01 ) ; C12Q 1 / 6876
`C12Q 1/6874 (2013.01); C12Q 1/6876
`( 2013 . 01 ) ; COZB 2200 / 11 ( 2013 . 01 ) ; C120
`(2013.01); CO7B 2200/11 (2013.01); C12Q
`2525 / 117 ( 2013 . 01 ) ; C12Q 2525 / 186
`2525/117 (2013.01); C12Q 2525/186
`( 2013 . 01 ) ; C12Q 2535 / 101 ( 2013 . 01 ) ; C12Q
`(2013.01); C12Q 2535/101 (2013.01); C12Q
`2535 / 122 ( 2013 . 01 ) ; C12Q 2563 / 107
`2535/122 (2013.01); C12Q 2563/107
`( 2013 . 01 ) ; C12Q 2565 / 501 ( 2013 . 01 ) ; C40B
`(2013.01); C12Q 2565/501 (2013.01); C4OB
`40 / 00 ( 2013 . 01 )
`40/00 (2013.01)
`( 58 ) Field of Classification Search
`(58) Field of Classification Search
`CPC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C07H 19 / 04 ; C12Q 1 / 6869
`CPC
`CO7H 19/04; C12Q 1/6869
`USPC
`. . . . . . . . . . . . . . . . . 536 / 4 . 1 ; 435 / 6 . 1
`USPC
` 536/4.1; 435/6.1
`See an
`See application file for complete search history .
`See application file for complete search history.
`References Cited
`References Cited
`U . S . PATENT DOCUMENTS
`U.S. PATENT DOCUMENTS
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`9/1991 Hobbs, Jr. et al.
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`6/1992 Urdea
`6 / 1992 Urdea
`9 / 1992 Hobbs , Jr . et al .
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`9/1992 Hobbs, Jr. et al.
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`5,175,269
`12/1992 Stavrianopoulos
`( Continued )
`(Continued)
`FOREIGN PATENT DOCUMENTS
`FOREIGN PATENT DOCUMENTS
`4 / 2002
`2425112
`4/2002
`2425112
`11 / 2002
`2408143
`11/2002
`2408143
`( Continued )
`(Continued)
`OTHER PUBLICATIONS
`OTHER PUBLICATIONS
`Aug . 19 , 2013 Petition 2 of 2 for Inter Partes Review of U . S . Pat .
`Aug. 19, 2013 Petition 2 of 2 for Inter Partes Review of U.S. Pat.
`No . 7 , 566 , 537 , issued Aug . 19 , 2013 .
`No. 7,566,537, issued Aug. 19, 2013.
`( Continued )
`(Continued)
`Primary Examiner — Jezia Riley
` Jezia Riley
`Primary Examiner
`( 74 ) Attorney , Agent , or Firm — John P . White ; Cooper &
`(74) Attorney, Agent, or Firm John P. White; Cooper &
`Dunham LLP
`Dunham LLP
`ABSTRACT
`( 57 )
`ABSTRACT
`(57)
`This invention provides methods for attaching a nucleic acid
`This invention provides methods for attaching a nucleic acid
`to a solid surface and for sequencing nucleic acid by
`to a solid surface and for sequencing nucleic acid by
`detecting the identity of each nucleotide analog after the
`detecting the identity of each nucleotide analog after the
`nucleotide analog is incorporated into a growing strand of
`nucleotide analog is incorporated into a growing strand of
`DNA in a polymerase reaction . The invention also provides
`DNA in a polymerase reaction. The invention also provides
`nucleotide analogs which comprise unique labels attached to
`nucleotide analogs which comprise unique labels attached to
`the nucleotide analog through a cleavable linker , and a
`the nucleotide analog through a cleavable linker, and a
`cleavable chemical group to cap the OH group at the
`cleavable chemical group to cap the OH group at the
`3 ' - position of the deoxyribose .
`3'-position of the deoxyribose.
`2 Claims , 28 Drawing Sheets
`2 Claims, 28 Drawing Sheets
`Specification includes a Sequence Listing .
`Specification includes a Sequence Listing.
`
`CA
`CA
`CA
`CA
`
`JA0001
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 8 of 415 PageID #: 2388
`
`US 10 , 407 , 458 B2
`US 10,407,458 B2
`Page 25
`Page 25
`
`( 56 )
`(56)
`
`References Cited
`References Cited
`OTHER PUBLICATIONS
`OTHER PUBLICATIONS
`Fields , “ Methods for Removing the Fmoc Group , ” Methods in
`Fields, "Methods for Removing the Fmoc Group," Methods in
`Molecular Biology , vol . 35 , Peptide Synthesis Protocols , Chapter 2 ,
`Molecular Biology, vol. 35, Peptide Synthesis Protocols, Chapter 2,
`Humana Press ( 1994 ) ( Exhibit 1136 filed by Illumina in connection
`Humana Press (1994) (Exhibit 1136 filed by Illumina in connection
`with IPRs Nos . IPR 2018 - 00291 , IPR2018 - 00318 , IPR2018 - 00322 ,
`with IPRs Nos. IPR2018-00291, IPR2018-00318, IPR2018-00322,
`and IPR2018 - 00385 ) .
`and IPR2018-00385).
`IPR2012 - 00007 , Paper 79 , Substitute Columbia Motion to Amend
`IPR2012-00007, Paper 79, Substitute Columbia Motion to Amend
`under 37 C . F . R . $ 42 . 121 ( Filing Authorized to Replace Paper No .
`under 37 C.F.R. §42.121 (Filing Authorized to Replace Paper No.
`66 ) ( Aug . 30 , 2013 ) ( Exhibit 1137 filed by Illumina in connection
`66) (Aug. 30, 2013) (Exhibit 1137 filed by Illumina in connection
`with IPRs Nos . IPR 2018 - 00291 , IPR2018 - 00318 , IPR2018 - 00322 ,
`with IPRs Nos. IPR2018-00291, IPR2018-00318, IPR2018-00322,
`and IPR2018 - 00385 ) .
`and IPR2018-00385).
`List of documents reviewed by Dr . Romesberg in IPR2018 - 00291 ,
`List of documents reviewed by Dr. Romesberg in IPR2018-00291,
`- 00318 , - 00322 , - 00385 , and - 00797 ( Exhibit 1138 filed by Illumina
`-00318, -00322, -00385, and -00797 (Exhibit 1138 filed by Illumina
`in connection with IPRs Nos . IPR2018 - 00291 , IPR2018 - 00318 ,
`in connection with IPRs Nos. IPR2018-00291, IPR2018-00318,
`IPR2018 - 00322 , IPR2018 - 00385 , and IPR2018 - 00797 ) .
`IPR2018-00322, IPR2018-00385, and IPR2018-00797).
`Patent Owner ' s Sur - reply filed by The Trustees of Columbia Uni
`Patent Owner's Sur-reply filed by The Trustees of Columbia Uni-
`versity in the City of New York ( “ Columbia " ) on Feb . 5 , 2019 , in
`versity in the City of New York ("Columbia") on Feb. 5, 2019, in
`connection with IPRs Nos . IPR2018 - 00291 , IPR2018 - 00318 , IPR2018
`connection with IPRs Nos. IPR2018-00291, IPR2018-00318, IPR2018-
`00322 , and IPR2018 - 00385 .
`00322, and IPR2018-00385.
`Patent Owner ' s Sur - reply filed by Columbia on Feb . 5 , 2019 , in
`Patent Owner's Sur-reply filed by Columbia on Feb. 5, 2019, in
`connection with IPR No . IPR2018 - 00797 .
`connection with IPR No. IPR2018-00797.
`Columbia ' S Exhibit List No . 5 Under 37 C . F . R . § 42 . 63 ( e ) filed by
`Columbia'S Exhibit List No. 5 Under 37 C.F.R. § 42.63(e) filed by
`Columbia on Feb . 5 , 2019 , in connection with IPR No . IPR2018
`Columbia on Feb. 5, 2019, in connection with IPR No. IPR2018-
`00291 .
`00291.
`Columbia ' S Exhibit List No . 5 Under 37 C . F . R . $ 42 . 63 ( e ) filed by
`Columbia'S Exhibit List No. 5 Under 37 C.F.R. § 42.63(e) filed by
`Columbia on Feb . 5 , 2019 , in connection with IPR No . IPR2018
`Columbia on Feb. 5, 2019, in connection with IPR No. IPR2018-
`00318 .
`00318.
`
`Columbia ' S Exhibit List No . 5 Under 37 C . F . R . $ 42 . 63 ( e ) filed by
`Columbia'S Exhibit List No. 5 Under 37 C.F.R. § 42.63(e) filed by
`Columbia on Feb . 5 , 2019 , in connection with IPR No . IPR2018
`Columbia on Feb. 5, 2019, in connection with IPR No. IPR2018-
`00322 .
`00322.
`Columbia ’ S Exhibit List No . 5 Under 37 C . F . R . $ 42 . 63 ( e ) filed by
`Columbia'S Exhibit List No. 5 Under 37 C.F.R. § 42.63(e) filed by
`Columbia on Feb . 5 , 2019 , in connection with IPR No . IPR2018
`Columbia on Feb. 5, 2019, in connection with IPR No. IPR2018-
`00385 .
`00385.
`Columbia ’ S Exhibit List No . 5 Under 37 C . F . R . $ 42 . 63 ( e ) filed by
`Columbia'S Exhibit List No. 5 Under 37 C.F.R. § 42.63(e) filed by
`Columbia on Feb . 5 , 2019 , in connection with IPR No . IPR2018
`Columbia on Feb. 5, 2019, in connection with IPR No. IPR2018-
`00797 .
`00797.
`Metzker , et al . , “ Elimination of Residual Natural Nucleotides from
`Metzker, et al., "Elimination of Residual Natural Nucleotides from
`3 ' - O - Modified - dNTP Syntheses by Enzymatic Mop - Up , ”
`3'-O-Modified-dNTP Syntheses by Enzymatic Mop-Up,"
`Bio Techniques , 25 : 814 - 817 ( 1998 ) ( Marked at Dr . Menchen ’ s Depo
`BioTechniques, 25:814-817 (1998) (Marked at Dr. Menchen's Depo-
`sition ) ( Exhibit 2131 filed by Columbia in connection with IPRs
`sition) (Exhibit 2131 filed by Columbia in connection with IPRs
`Nos . IPR2018 - 00291 , IPR 2018 - 00318 , IPR2018 - 00322 , IPR2018
`Nos. IPR2018-00291, IPR2018-00318, IPR2018-00322, IPR2018-
`00385 , and IPR2018 - 00797 ) .
`00385, and IPR2018-00797).
`Jannasch , “ Deep sea hydrothermal vents : underwater oases , ” The
`Jannasch, "Deep sea hydrothermal vents: underwater oases," The
`NEB Transcript ( 1992 ) ( Marked at Dr . Menchen ' s Deposition )
`NEB Transcript (1992) (Marked at Dr. Menchen's Deposition)
`( Exhibit 2132 filed by Columbia in connection with IPRs Nos .
`(Exhibit 2132 filed by Columbia in connection with IPRs Nos.
`IPR2018 - 00291 , IPR2018 - 00318 , IPR2018 - 00322 , IPR2018
`IPR2018-00291, IPR2018-00318, IPR2018-00322, IPR2018-
`00385 , and IPR 2018 - 00797 ) .
`00385, and IPR2018-00797).
`Transcript for the Deposition of Dr . Floyd Romesberg , Feb . 1 , 2019 ,
`Transcript for the Deposition of Dr. Floyd Romesberg, Feb. 1, 2019,
`in IPR2018 - 00291 , - 00318 , - 00322 , - 00385 , and - 00797 ( Exhibit
`in IPR2018-00291, -00318, -00322, -00385, and -00797 (Exhibit
`2140 filed by Columbia in connection with IPRs Nos . IPR2018
`2140 filed by Columbia in connection with IPRs Nos. IPR2018-
`00291 , IPR2018 - 00318 , IPR2018 - 00322 , IPR2018 - 00385 , and
`00291, IPR2018-00318, IPR2018-00322, IPR2018-00385, and
`IPR2018 - 00797 ) .
`IPR2018-00797).
`Nov . 21 , 2018 Office Action issued in connection with U . S . Appl .
`Nov. 21, 2018 Office Action issued in connection with U.S. Appl.
`No . 14 / 670 , 748 .
`No. 14/670,748.
`Final Written Decision dated Jun . 21 , 2019 , in connection with IPRs
`Final Written Decision dated Jun. 21, 2019, in connection with IPRs
`Nos . IPR2018 - 00291 , IPR 2018 - 00318 , IPR2018 - 00322 , and IPR 2018
`Nos. IPR2018-00291, IPR2018-00318, IPR2018-00322, and IPR2018-
`00385
`00385.
`
`JA0002
`
`

`

`lualud °S11
`
`atent
`
`Sep . 10 , 2019
`
`Sheet 1 of 28
`8Z Jo 1 WIN
`
`US 10 , 407 , 458 B2
`za ssear`ot sa
`
`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 9 of 415 PageID #: 2389
`
`SIVUA
`
`template
`
`ww
`
`5 position of ddCTP
`
`5 position of ddCTP
`
`3
`
`holk N
`
`helix N
`
`3
`
`Mith
`
`!
`
`ddCTP
`
`ddCTP
`
`•
`
`primor
`
`0
`
`FIGURE 1
`
`FIGURE 1
`
`Primer
`
`Primer
`
`„+./
`O•' ****** "
`
`: 2*
`0. ....... Mel .......
`
`ON - -
`
`a
`t
`
`2
`
`Asp
`256
`
`Al
`
`hath M
`
`3 . position of ddCTP
`
`3' position of ddCTP
`
`Asp
`182 A
`Asp 180
`
`1
`
`258
`
`Asp 258
`
`OH
`
`P 192
`
`Asp
`192
`
`Asp 190
`
`Asp
`190
`
`Asp = Aspartic Acid
`
`Asp = Aspartic
`Acid
`
`JA0003
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 10 of 415 PageID #: 2390
`
`U . S . Patent
`U.S. Patent
`
`Sep . 10 , 2019
`Sep. 10, 2019
`
`Sheet 9 of 28
`Sheet 9 of 28
`
`US 10 , 407 , 458 B2
`US 10,407,458 B2
`
`FIGURE 7
`FIGURE 7
`
`NH2
`
`O
`50
`O
`0 -
`0
`- 0
`6- 0• b•
`
`WATE
`
`OR
`
`brose
`
`HO
`
`detetortowa
`
`0
`
`COON
`
`Foren A . em = 525 nmn
`x.ogrA-pa,,„ X em = 625 ftin
`
`Photocleavable Linkor
`Photocteevable Linker
`M3CH2CHNO ANHCH2CH ,
`
`H3CH 2CHN
`
`NHCH 2CH 3
`
`NH2
`
`Wy wat
`N‘
`
`0
`ON
`/
`
`0 2N
`
`\
`
`hl
`N
`
`COO'
`
`o
`0
`0
`6- 6- O'
`
`ke
`
`OR
`
`0
`
`HN
`
`0 H214-"4 N
`
`0
`
`0
`
`obok - o - bora
`ó
`ó
`o
`a-
`&
`oR
`
`7 : 07C - RED Acm - 555 nm
`555 nm
`r-oRC-nso. X
`
`( H3C ) 2N
`(H3C)2N
`
`N ( CH3 ) 2
`N(CH 3)2
`
`H
`N O
`
`0 2N
`
`/
`
`\
`
`H
`N
`
`COO'
`
`coo•
`
`- CS - Tara • GR = 585 mm
`r-oorG—T,,,, X
`585 nm
`
`0
`
`0
`
`0
`
`6- 6- a-
`
`HN
`
`OR
`
`N
`
`0 2N
`
`/
`
`H
`N
`
`CoQ
`COO"
`
`JoomT Rog i em = 604 nm
`r-orir-non x ere = 604 nm
`
`R = H , CH2OCH , ( MOM ) or CH2 - CH = CH 2 ( Allyi )
`R = H, CH2OCH 3 (MOM) or CH rCH=CH 2 (Altyl)
`
`JA0004
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 11 of 415 PageID #: 2391
`
`U . S . Patent
`U.S. Patent
`
`Sep . 10 , 2019
`Sep. 10, 2019
`
`Sheet 10 of 28
`Sheet 10 of 28
`
`US 10 , 407 , 458 B2
`US 10,407,458 B2
`
`FIGURE 8
`FIGURE 8
`
`NaN3
`
`9
`
`Na1311 4
`
`N
`
`/
`
`0 N
`
`\ /
`
`HO
`
`NH2
`
`0 N \ /
`Photocieavable Linke►
`Photoeloovabio Linker
`
`(H3C)2N
`
`N(CH 3)2
`
`0
`
`w
`
`M11-0
`
`0
`
`Nies
`
`1
`
`COO'
`
`0
`( Tar - NHS )
`(Tam-NHS)
`
`HO .
`HO
`
`(H3C)2N
`
`N(CH 3)3
`
`COO
`
`H
`N
`
`O
`
`(H3C) 2N
`
`a
`% (
`MOINS
`N(CH 3)2
`
`N.N'-diSuCtinimide carbonate/ EtN
`N . N * - disuccinimide carbonato EEN
`
`COO
`
`AL
`
`Linker . Tam
`Linker-Tam
`
`0 2N
`
`0
`
`0
`
`HN
`ech
`
`H2N
`HO
`
`OR
`
`NHCOCF
`--- =..„....,,.NHCOCF 3
`
`0
`
`HN
`
`NH2
`
`NHCOCF
`NHCOCF 3
`
`0
`
`HN
`
`H2N N
`HO
`
`OR
`
`Linker - Tam
`Linker-Tam
`iv
`
`H2N
`9
`9 9
`- 0 - 0 - 0
`O - P - 0 -
`-f - 0 -2- 0 - 1?- 0
`0" 0'
`0'
`
`OR
`
`3
`
`wwwww
`SP
`
`HUN
`O H2N
`O
`O
`hoto
`'0-f: -0 -P -O-P- O
`o-
`O.
`0 -
`
`N
`
`OR
`
`(H3C)2N
`
`ht
`
`I.
`N(CH 3)2
`
`( H3C ) 2hYya YMCH3 ) 2
`)1"
`O
`0 2N
`
`/
`
`\
`
`COO
`
`3 . 60G - Farn
`
`FROG - Faer
`r-ao-O-Taas
`
`JA0005
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 12 of 415 PageID #: 2392
`
`U . S . Patent
`U.S. Patent
`
`Sep . 10 , 2019
`Sep. 10, 2019
`
`Sheet 20 of 28
`Sheet 20 of 28
`
`US 10 , 407 , 458 B2
`US 10,407,458 B2
`
`FIGURE 16
`
`NU
`
`O
`
`H3N
`
`HO
`
`340
`mare ATXAR
`
`0
`XA
`
`COO H
`
`Ct
`
`CI
`
`COO H
`
`Ct
`
`Dlaucceanelyi Castanet*
`www
`Son ra
`iPs3NEtiOMF
`
`H033
`
`Or
`HO
`
`0
`
`NH2
`SOS
`
`°
`
`dy . com
`COOM
`COO N
`oh
`
`p
`
`HO
`
`1.
`
`2.
`
`2 .
`
`0
`
`Amtno-Cy2
`
`NHS. OEC•.OMF
`
`NHS , DEC . OMF
`
`Hosya
`
`NO 3S
`
`0
`
`evi
`
`N-0
`
`0
`
`0
`
`(V)
`
`/
`
`\
`
`NH3
`
`COO H
`
`HO
`
`oNN
`
`Ct
`
`O
`
`0
`
`SO 3.
`
`CI
`
`aucoom COOM
`
`COO M
`
`HO3S
`
`HO , S HOISYYS
`
`4
`
`9 9 9
`0 - - 0 - 80 cm
`*0-f -01 2-0 - P- 0
`0* Cr
`0*
`
`Nu,
`I \
`LN N
`
`0 3N
`
`OR
`
`„ 0
`H
`SOS
`
`O
`
`5
`
`JA0006
`
`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 13 of 415 PageID #: 2393
`
`U . S . Patent
`U.S. Patent
`
`Sep . 10 , 2019
`Sep. 10, 2019
`
`Sheet 23 of 28
`Sheet 23 of 28
`
`US 10 , 407 , 458 B2
`US 10,407,458 B2
`
`FIGURE 19
`FIGURE 19
`
`NH 2
`
`NH
`
`w
`
`9
`- O - P - O
`"0
`
`9
`P
`O' O'
`
`OR
`OR
`t
`(Nitro-Benzyl)-dATP
`Benz
`
`NH2
`
`N
`
`APU
`
`TOR
`
`0 - - 0 - - - ozot
`
`O
`
`0
`0
`O
`II
`It
`--1?-0—P—O —F)- 0
`0
`0
`0
`O'
`6 -
`o -
`
`0 - 0
`
`H
`N
`
`0
`
`0
`0 2N
`Wik
`
`MW = 120
`MW=120
`
`0
`0 2N
`
`TS
`
`—F
`
`MW = 138
`MW=138
`
`OR
`
`F - ( Nitro - Benzyl ) - dCTP
`F-(Nitro-Benzyl)-dCTP
`i
`0
`- HN
`HANN
`O
`9,
`9 H2N
`O - 2 - 0 - - 0 - p - On
`0
`0
`0
`0"
`0"
`0"
`
`HN
`
`N
`
`9
`
`RAS
`
`GERD
`
`O
`ON
`0 2N
`
`OR
`OR
`2F - ( Nitro - Benzyl ) - dGTP
`2F-(Nitro-Benzy1)-dGTP 0
`
`w
`
`noun
`
`HN
`
`0
`
`N
`
`O
`9
`9
`0 - P - 0 - P - 0 - P - 0 O - 0 - 0
`—t?-0 —17- 0 —F - 0
`0"
`0"
`0"
`
`OR
`OR
`2 ( Meo ) - ( Nitro - Benzyl ) - dTTP dir
`2(Meo)-(Nitro-Benzyl)-dTTP
`
`MW = 156
`MW=156
`
`0
`LOL
`0
`/
`ON - TO
`0 2N
`
`DOO
`
`OF
`
`waterwyl
`\ -- OMe
`- Ome
`. ernw
`OMe
`OMe
`
`L
`
`MW = 180
`MW=180
`
`R = H , MOM or Allyi
`R = H. MOM or Ailyi
`
`JA0007
`
`

`

`

`

`

`

`Case 1:19-cv-01681-CFC-SRF Document 55 Filed 08/10/20 Page 16 of 415 PageID #: 2396
`
`US 10 , 407 , 458 B2
`US 10,407,458 B2
`
`1
`2
`have also significantly improved the quality of sequencing
`MASSIVE PARALLEL METHOD FOR
`MASSIVE PARALLEL METHOD FOR
`have also significantly improved the quality of sequencing
`data ( Tabor and Richardson , 1987 , 1995 ) . Although capil
`DECODING DNA AND RNA
`data (Tabor and Richardson, 1987, 1995). Although capil-
`DECODING DNA AND RNA
`lary array DNA sequencing technology to some extent
`lary array DNA sequencing technology to some extent
`This application is a continuation of U . S . Ser . No . 15 / 915 ,
`addresses the throughput and read length requirements of
`addresses the throughput and read length requirements of
`This application is a continuation of U.S. Ser. No. 15/915,
`983 , filed Mar . 8 , 2018 , which is a continuation of U . S . Ser . 5 large scale DNA sequencing projects , the throughput and
`large scale DNA sequencing projects, the throughput and
`983, filed Mar. 8, 2018, which is a continuation of U.S. Ser.
`5
`No . 14 / 670 , 748 , filed Mar . 27 , 2015 , which is a continuation
`accuracy required for mutation studies needs to be improved
`accuracy required for mutation studies needs to be improved
`No. 14/670,748, filed Mar. 27, 2015, which is a continuation
`of U . S . Ser . No . 13 / 959 , 660 , filed Aug . 5 , 2013 , now U . S .
`for a wide variety of applications ranging from disease gene
`for a wide variety of applications ranging from disease gene
`of U.S. Ser. No. 13/959,660, filed Aug. 5, 2013, now U.S.
`Pat . No . 9 , 133 , 511 , issued Sep . 15 , 2015 , which is a con
`discovery to forensic identification . For example , electro
`discovery to forensic identification. For example, electro-
`Pat. No. 9,133,511, issued Sep. 15, 2015, which is a con-
`tinuation of U . S . Ser . No . 13 / 672 , 437 , filed Nov . 8 , 2012 ,
`phoresis based DNA sequencing methods have difficulty
`phoresis based DNA sequencing methods have difficulty
`tinuation of U.S. Ser. No. 13/672,437, filed Nov. 8, 2012,
`now abandoned , which is a continuation of U . S . Ser . No . 10 detecting heterozygotes unambiguously and are not 100 %
`10 detecting heterozygotes unambiguously and are not 100%
`now abandoned, which is a continuation of U.S. Ser. No.
`13 / 339 , 089 , filed Dec . 28 , 2011 , now abandoned , which is a
`accurate in regions rich in nucleotides comprising guanine
`accurate in regions rich in nucleotides comprising guanine
`13/339,089, filed Dec. 28, 2011, now abandoned, which is a
`continuation of U . S . Ser . No . 12 / 804 , 284 , filed Jul . 19 , 2010 ,
`or cytosine due to compressions ( Bowling et al . 1991 ;
`or cytosine due to compressions (Bowling et al. 1991;
`continuation of U.S. Ser. No. 12/804,284, filed Jul. 19, 2010,
`now U . S . Pat . No . 8 , 088 , 575 , issued Jan . 3 , 2012 , which is
`Yamakawa et al . 1997 ) . In addition , the first few bases after
`Yamakawa et al. 1997). In addition, the first few bases after
`now U.S. Pat. No. 8,088,575, issued Jan. 3, 2012, which is
`a continuation of U . S . Ser . No . 11 / 810 , 509 , filed Jun . 5 ,
`the priming site are often masked by the high fluorescence
`the priming site are often masked by the high fluorescence
`a continuation of U.S. Ser. No. 11/810,509, filed Jun. 5,
`2007 , now U . S . Pat . No . 7 , 790 , 869 , issued . Sep . 7 , 2010 , 15 signal from excess dye - labeled primers or dye - labeled ter
`15 signal from excess dye-labeled primers or dye-labeled ter-
`2007, now U.S. Pat. No. 7,790,869, issued. Sep. 7, 2010,
`which is a continuation of U . S . Ser . No . 10 / 702 , 203 , filed
`minators , and are therefore difficult to identify . Therefore ,
`minators, and are therefore difficult to identify. Therefore,
`which is a continuation of U.S. Ser. No. 10/702,203, filed
`Nov . 4 , 2003 , now U . S . Pat . No . 7 , 345 , 159 , issued Mar . 18 ,
`the requirement of electrophoresis for DNA sequencing is
`the requirement of electrophoresis for DNA sequencing is
`Nov. 4, 2003, now U.S. Pat. No. 7,345,159, issued Mar. 18,
`2008 , which is a divisional of U . S . Ser . No . 09 / 972 , 364 , filed
`still the bottleneck for high - throughput DNA sequencing and
`still the bottleneck for high-throughput DNA sequencing and
`2008, which is a divisional of U.S. Ser. No. 09/972,364, filed
`Oct . 5 , 2001 , now U . S . Pat . No . 6 , 664 , 079 ; issued Dec . 16 ,
`mutation detection projects .
`mutation detection projects.
`Oct. 5, 2001, now U.S. Pat. No. 6,664,079; issued Dec. 16,
`2003 , claiming the benefit of U . S . Provisional Application 20
`The concept of sequencing DNA by synthesis without
`20
`The concept of sequencing DNA by synthesis without
`2003, claiming the benefit of U.S. Provisional Application
`No . 60 / 300 , 894 , filed Jun . 26 , 2001 , and is a continuation
`using electrophoresis was first revealed in 1988 ( Hyman ,
`using electrophoresis was first revealed in 1988 (Hyman,
`No. 60/300,894, filed Jun. 26, 2001, and is a continuation-
`in - part of U . S . Ser . No . 09 / 684 , 670 , filed Oct . 6 , 2000 , now
`1988 ) and involves detecting the identity of each nucleotide
`1988) and involves detecting the identity of each nucleotide
`in-part of U.S. Ser. No. 09/684,670, filed Oct. 6, 2000, now
`abandoned , the contents of each of which are hereby incor
`as it is incorporated into the growing strand of DNA in a
`as it is incorporated into the growing strand of DNA in a
`abandoned, the contents of each of which are hereby incor-
`porated in its entirety into this application .
`polymerase reaction . Such a scheme coupled with the chip
`polymerase reaction. Such a scheme coupled with the chip
`porated in its entirety into this application.
`This invention was made with government support under 25 format and laser - induced fluorescent detection has the
`25 format and laser-induced fluorescent detection has the
`This invention was made with government support under
`grant no . BES0097793 awarded by the National Science
`potential to markedly increase the throughput of D