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`US010457984B2
`
`c12) United States Patent
`Ju et al.
`
`US 10,457,984 B2
`(IO) Patent No.:
`(45) Date of Patent:
`*Oct. 29, 2019
`
`(54) MASSIVE PARALLEL METHOD FOR
`DECODING DNA AND RNA
`
`(71) Applicant: The Trustees of Columbia University
`in the City of New York, New York,
`NY (US)
`
`(72)
`
`Inventors: Jingyue Ju, Englewood Cliffs, NJ (US);
`Zengmin Li, Flushing, NY (US); John
`Robert Edwards, St. Louis, MO (US);
`Yasuhiro Itagaki, New York, NY (US)
`
`(73) Assignee: THE TRUSTEES OF COLUMBIA
`UNIVERSITY IN THE CITY OF
`NEW YORK, New York, NY (US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent is extended or adjusted under 35
`U.S.C. 154(b) by O days.
`
`This patent is subject to a terminal dis(cid:173)
`claimer.
`
`(2018.01)
`(2006.01)
`
`C12Q 116876
`C40B 40/00
`(52) U.S. Cl.
`CPC ........... C12Q 116869 (2013.01); C07H 19110
`(2013.01); C07H 19114 (2013.01); C07H
`21100 (2013.01); C12Q 1168 (2013.01); C12Q
`11686 (2013.01); C12Q 116872 (2013.01);
`C12Q 116874 (2013.01); C12Q 116876
`(2013.01); C07B 2200111 (2013.01); Cl2Q
`25251117 (2013.01); Cl2Q 2525/186
`(2013.01); Cl2Q 2535/101 (2013.01); Cl2Q
`2535/122 (2013.01); Cl2Q 2563/107
`(2013.01); Cl2Q 2565/501 (2013.01); C40B
`40/00 (2013.01)
`
`(58) Field of Classification Search
`CPC .............................. C12Q 1/6869; C07H 19/14
`USPC ............................................. 536/4.1; 435/6.1
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`(21) Appl. No.: 16/150,180
`
`(22) Filed:
`
`Oct. 2, 2018
`
`(65)
`
`Prior Publication Data
`
`US 2019/0085015 Al Mar. 21, 2019
`
`Related U.S. Application Data
`
`(60) Continuation of application No. 15/915,983, filed on
`Mar. 8, 2018, which is a continuation of application
`No. 14/670,748, filed on Mar. 27, 2015, which is a
`continuation of application No. 13/959,660, filed on
`Aug. 5, 2013, now Pat. No. 9,133,511, which is a
`continuation of application No. 13/672,437, filed on
`Nov. 8, 2012, now abandoned, which
`is a
`continuation of application No. 13/339,089, filed on
`Dec. 28, 2011, now abandoned, which
`is a
`continuation of application No. 12/804,284, filed on
`Jul. 19, 2010, now Pat. No. 8,088,575, which is a
`continuation of application No. 11/810,509, filed on
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`continuation of application No. 10/702,203, filed on
`Nov. 4, 2003, now Pat. No. 7,345,159, which is a
`division of application No. 09/972,364, filed on Oct.
`5, 2001, now Pat. No. 6,664,079, which is a
`continuation-in-part of application No. 09/684,670,
`filed on Oct. 6, 2000, now abandoned.
`
`(60)
`
`Provisional application No. 60/300,894, filed on Jun.
`26, 2001.
`
`(51)
`
`Int. Cl.
`C12Q 1168
`C07H 19114
`C12Q 116869
`C07H 21100
`C12Q 11686
`C12Q 116874
`C12Q 116872
`C07H 19110
`
`(2018.01)
`(2006.01)
`(2018.01)
`(2006.01)
`(2018.01)
`(2018.01)
`(2018.01)
`(2006.01)
`
`4,711,955 A
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`
`FOREIGN PATENT DOCUMENTS
`
`CA
`CA
`
`4/2002
`2425112
`11/2002
`2408143
`(Continued)
`
`OTHER PUBLICATIONS
`
`U.S. Pat. No. 09/266,187, filed Mar. 10, 1999, Stemple et al.
`(Continued)
`
`Primary Examiner -
`Jezia Riley
`(74) Attorney, Agent, or Firm -
`Dunham LLP
`
`John P. White; Cooper &
`
`ABSTRACT
`(57)
`This invention provides methods for attaching a nucleic acid
`to a solid surface and for sequencing nucleic acid by
`detecting the identity of each nucleotide analogue after the
`nucleotide analogue is incorporated into a growing strand of
`DNA in a polymerase reaction. The invention also provides
`nucleotide analogues which comprise unique labels attached
`to the nucleotide analogue through a cleavable linker, and a
`cleavable chemical group to cap the -OH group at the
`3'-position of the deoxyribose.
`
`2 Claims, 28 Drawing Sheets
`Specification includes a Sequence Listing.
`
`Page 1
`
`Illumina Ex. 1003
`IPR Petition - USP 10,435,742
`
`

`

`US 10,457,984 B2
`Page 2
`
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`Page 3
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`

`

`US 10,457,984 B2
`Page 4
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`IPR2012-00006.
`Apr. 26, 2013 Opposition to Request for Reconsideration (Rehear(cid:173)
`ing) Under 37 C.F.R. 42.71. (C) in connection with IPR2012-00006.
`Sep. 27, 2013 Petitioner Opposition to Motion to Amend in con(cid:173)
`nection with IPR2012-00006.
`Sep. 27, 2013 Petitioner Reply to Response to Petition in connection
`with IPR2012-00006.
`Nov. 18, 2013 Substitute Patent Owner Reply on Motion to Amend
`in Connection with IPR2012-00006.
`Prober et al. (1987), "A System for Rapid DNA Sequencing with
`Fluorescent Chain-Terminating Dideoxynucleotides", Science vol.
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`Sep. 15, 2012 Declaration of George Weinstock Under Rule 37
`C.F.R. ยง1.132 (Exhibit 1021, filed Sep. 16, 2012 in connection with
`IPR2012-00006).
`Excerpts of File History of U.S. Pat. No. 7,713,698 (Exhibit 1022,
`filed Sep. 16, 2012 in connection with IPR2012-00006).
`Columbia's Amended Complaint from The Trustees of Columbia
`University in the City of New Yorkv. Illumina, Inc., D. Del C.A. No.
`12-376 (GMS), filed Apr. 11, 2012 (Exhibit 1025, filed Apr. 30,
`2013 in connection with IPR2012-00006).
`Illumina's Answer to Amended Complaint from The Trustees of
`Columbia University in the City of New York v. Illumina, Inc., D.
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`filed Apr. 30, 2013 in connection with IPR2012-00006).
`Rosenblum et al., "New Dye-Labeled Terminators for Improved
`DNA Sequencing Patterns," Nucleic Acid Research, 1997, vol. 25,
`No. 22, pp. 4500-4504 (Exhibit 1030, filed Jun. 18, 2013 in
`connection with IPR2012-00006).
`Jun. 8, 2013 Videotaped Deposition Transcript of George M.
`Weinstock, Ph.D. (Exhibit 1034, filed Jun. 18, 2013 in connection
`with IPR2012-00006).
`"Next Generation Genomics: World Map of High-throughput Sequenc(cid:173)
`ers," Sep. 1, 2013 (Exhibit 1036, filed Sep. 27, 2013 in connection
`with IPR2012-00006).
`Videotaped Deposition Transcript of Dr. Xiaohai Liu, Mar. 20, 2013
`(Exhibit 1039, filed. Sep. 27, 2013 in connection with IPR2012-
`00006).
`Excerpt from videotaped Deposition Transcript of George M. Weinstock,
`Ph.D., Jun. 8, 2013 (Exhibit 1040, filed Sep. 27, 2013 in connection
`with IPR2012-00006).
`Seela et al., "Oligonucleotide Duplex Stability Controlled by the
`7-Substituents of 7-Deazaguanine Bases," Bioorganic & Medical
`Chemistry Letters, vol. 5, No. 24, pp. 3049-3052, 1995 (Exhibit
`1041, filed Sep. 27, 2013 in connection with IPR2012-00006).
`Rarnzaeva et al., "123. 7-Deazaguanine DNA: Oligonucleotides
`with Hydrophobic or Cationic Side Chains," Helvetica Chimica
`Acta, vol. 80, pp. 1809-1822, 1997 (Exhibit 1042, filed Sep. 27,
`2013 in connection with IPR2012-00006).
`Rarnzaeva et al., "88. ?-Substituted 7-Deaza-2'- deoxyguanosines:
`Regioselective Halogenation of Pyrrolo[2,3-d]pyrimidine Nucleosides,"
`
`Helvetica Chimica Acta, vol. 78, pp. 1083-1090, 1995 (Exhibit
`1043, filed Sep. 27, 2013 in connection with IPR2012-00006).
`Seela et al., "Duplex Stability of Oligonucleotides Containing
`?-Substituted 7-Deaza- and 8-Aza-7-Deazapurine Nucleosides,"
`Nucleosides & Nucleotides, 16(7-9), pp. 963-966, 1997 (Exhibit
`1044, filed Sep. 27, 2013 in connection with IPR2012-00006).
`Burgess et al., "Syntheses ofNucleosides Designed for Combinato(cid:173)
`rial DNA Sequencing," Chemistry-A European Journal, vol. 5,
`No. 3, pp. 951-960, 1999 (Exhibit 1045, filed Sep. 27, 2013 in
`connection with IPR2012-00006).
`Jan. 28, 2013 Declaration of Dr. Bruce P. Branchaud in Support of
`Petition for Inter Partes Review of U.S. Pat. No. 7,057,026 (Exhibit
`1049, filed Sep. 27, 2013 in connection with IPR2012-00006).
`Lee et al., "DNA sequencing with dye-labeled terminators and T7
`DNA polymerase: effect of dyes and dNTPs on incorporation of
`dye-terminators and probability analysis of termination fragments,"
`Nucleic Acids Research, vol. 20, No. 10, pp. 2471-2483, 1992
`(Exhibit 1050, filed Sep. 27, 2013 in connection with IPR2012-
`00006).
`http://www.answers.com/topic/incubate, Accessed Sep. 27, 2013
`(Exhibit 1051, filed Sep. 27, 2013 in connection with IPR2012-
`00006).
`http:// en. wikipedia. org/wiki/Fluorenylmethyloxycarbonyl_
`chloride, Accessed Sep. 27, 2013 (Exhibit 1052, filed Sep. 27, 2013
`in connection with IPR2012-00006).
`Sep. 27, 2013 Declaration of Kevin Burgess (Exhibit 1053, filed
`Sep. 27, 2013 in connection with IPR2012-00006).
`Fuji, et al., "An Improved Method for Methoxymethylation of
`Alcohols under Mild Acidic Conditions," Synthesis-The Journal
`of Synthetic Organic Chemistry, pp. 276-277, Apr. 1975 (Exhibit
`1054, filed Sep. 27, 2013 in connection with IPR2012-00006).
`Dower patent with highlights (Exhibit 2006, filed Apr. 26, 2013 in
`connection with IPR2012-00006).
`U.S. Pat. No. 7,713,698 (filed Aug. 20, 2007, issued May 11, 2010)
`(Exhibit 1001 in IPR2012-00006)(Exhibit 2011, filed Jun. 24, 2013
`in connection with IPR2012-00006).
`U.S. Pat. No. 7,790,869 (filed Jun. 5, 2007, issued Sep. 7, 2010)
`(Exhibit 1001 in IPR2012-00007) (Exhibit 2012, filed Jun. 24, 2013
`in connection with IPR2012-00006).
`Oct. 2, 2012 Declaration of George Weinstock Under 37 CFR 1.132
`(Exhibit 1021 in IPR2013-00011 )(Exhibit 2013, filed Jun. 24, 2013
`in connection with IPR2012-00006).
`Petition for Inter Partes Review of U.S. Pat. No. 8,088,575 (Paper
`4 in IPR2013-00011) (Exhibit 2014, filed Jun. 24, 2013 in connec(cid:173)
`tion with IPR2012-00006).
`Metzker et al. (1994) Termination of DNA synthesis by novel
`3'-modified-deoxyribonucleoside 5'-triphosphates. Nucleic Acids
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`Wu et al. (2007) Termination of DNA synthesis by N6-alkylated, not
`3' -O-alkylated, photocleavable 2' -deoxyadenosine triphosphates. Nucleic
`Acids Res. 35:6339-6349 (Exhibit 2016, filed Jun. 24, 2013 in
`connection with IPR2012-00006).
`Sep. 15, 2012 Declaration of George Weinstock Under 37 CFR
`1.132 (Exhibit 1021 in IPR2012-00007) (Exhibit 2017, filed Jun.
`24, 2013 in connection with IPR2012-00006).
`Sep. 15, 2012 Declaration of George Weinstock Under 37 CFR
`1.132 (Exhibit 1021 in IPR2012-00006) (Exhibit 2018, filed Jun.
`24, 2013 in connection with IPR2012-00006).
`Definition of "DN Amicroarray." http://en/wikipedia.org/wiki/DN A_
`microarray (Exhibit 2019, filed Jun. 24, 2013 in connection with
`IPR2012-00006).
`Brettin et al. (2005) Expression capable library for studies of
`Neisseria gonorrhoeae, version 1.0 BMC Microbiology. 5:50 (Exhibit
`2020, filed Jun. 24, 2013 in connection with IPR2012-00006).
`George M. Weinstock, Handbook of Molecular Microbial Ecology,
`vol. 1----Chapter 18: The Impact of Next-Generation Sequencing
`Technologies on Metagenomics 141-147 Frans J. de Bruijn ed.,
`John Wiley & Sons, Inc. (2011) (Exhibit 2021, filed Jun. 24, 2013
`in connection with IPR2012-00006).
`Sep. 16, 2012 Petition for Inter Partes Review of U.S. Pat. No.
`7,713,698 (Paper 3 in IPR2012-00006) (Exhibit 2022, filed Jun. 24,
`2013 in connection with IPR2012-00006).
`
`Page 4
`
`

`

`US 10,457,984 B2
`Page 5
`
`(56)
`
`References Cited
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`OTHER PUBLICATIONS
`
`Sep. 16, 2012 Petition for Inter Partes Review of U.S. Pat. No.
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`2013 in connection with IPR2012-00006).
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`Welch and Burgess (1999) Synthesis of Fluorescent, Photolabile
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`Canard and Sarfati (1994) DNA polymerase fluorescent substrates
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`Sarfati et al. ( 1987) Synthesis of Fluorescent or Biotinylated Nucleoside
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`Jun. 25, 2013 Substitute Declaration of Dr. George. L. Trainor
`[redacted] (Exhibit 2033, filed Aug. 30, 2013 in connection with
`IPR2012-00006).
`Jingyue Ju et. al. (2006) Four-color DNA sequencing by synthesis
`using/cleavable fluorescent nucleotide reversible terminators, Pro(cid:173)
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`Batista et al. (2008) PRG-1 and 21U-RNAs Interact to Form the
`piRNA Complex Required for Fertility in C. elegans. Molecular
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`Form 7 Review Context and Analysis, Biomedical Engineering and
`Research to Aid Persons with Disabilities Programs Dec. 19-20,
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`sive Parallel DNA Sequencing. Proposal No. BES-0097793 (Exhibit
`2036, filed Jun. 25, 2013 in connection with IPR2012-00006).
`Oct. 1, 2006 Request for opinion on manuscript by J. Ju et. al.,
`Proceedings of National Academy of Sciences, U.S.A. (Exhibit
`2037, filed Jun. 25, 2013 in connection with IPR2012-00006).
`Correspondence between George Rupp, Chancellor, Columbia Uni(cid:173)
`versity and Richard T. Schlossberg, President, The David and Lucile
`Packard Foundation (2001) (Exhibit 2038, filed Jun. 25, 2013 in
`connection with IPR2012-00006).
`The David and Lucile Packard Foundation, Packard Fellowships for
`Science and Engineering, http://www.packard.org/what-wefund/
`con serv ati on -and-sci enc e/packard-fellowships-for-science(cid:173)
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`25, 2013 in connection with IPR2012-00006).
`"Chemistry for Next-Generation Sequencing." http:/ /www.illumina.
`corn/technology/sequencing_technology.ilrnn (Exhibit 2040, filed
`Jun. 25, 2013 in connection with IPR2012-00006).
`Chiang et al. (2010) Mammalian microRNAs: experimental evalu(cid:173)
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`Seo et al. (2004) Photocleavable fluorescent nucleotides for DNA
`sequencing on a chip constructed by site-specific coupling chem(cid:173)
`istry, Proc. Natl Acad. Sci. 101(15):5488-5493 (Exhibit 2042, filed
`Jun. 25, 2013 in connection with IPR2012-00006).
`Curriculum vitae of Mr. Raymond S. Sims (Exhibit 2043, filed Jun.
`25, 2013 in connection with IPR2012-00006).
`Prior Testimony of Mr. Raymond S. Sims (Exhibit 2044, filed Jun.
`25, 2013 in connection with IPR2012-00006).
`
`Documents reviewed by Mr. Raymond S. Sims in this Proceeding
`(Exhibit 2045, filed Jun. 25, 2013 in connection with IPR2012-
`00006).
`Gary Schroth Proof of Chiang Paper (Exhibit 2052, filed Jun. 25,
`2013 in connection with IPR2012-00006).
`Information about Dr. Ju's intellectual property sent to Illumina
`(Exhibit 2074, filed Jun. 25, 2013 in connection with IPR2012-
`00006).
`IPR Default Protective Order (Exhibit 2090, filed Jun. 26, 2013 in
`connection with IPR2012-00006).
`Declaration of Raymond S. Sims (Exhibit 2091, filed Jun. 26, 2013
`in connection with IPR2012-00006).
`Rough Transcript of the Sep. 4, 2013 deposition of Dr. George L.
`Trainor (Exhibit 2092, filed Oct. 10, 2013 in connection with
`IPR2012-00006).
`Excerpt from Protective Groups in Organic Synthesis, 3rd Ed.
`(Theodora W. Greene and Peter G.M. Wuts ed., John Wiley & Sons,
`Inc. 1999) (Exhibit 2093, filed Oct. 1, 2013 in connection with
`IPR2012-00006).
`Final transcript of the Sep. 4-6, 2013 deposition of Dr. George L.
`Trainor (Exhibit 2094, filed Oct. 1, 2013 in connection with
`IPR2012-00006).
`Final transcript of the Sep. 3, 2013, deposition of Raymond S. Sims
`(Exhibit 2095, filed Oct. 1, 2013 in connection with IPR2012-
`00006).
`Nov. 12, 2013 Petitioner Motion to Exclude Evidence in connection
`with IPR2012-00006.
`Videotaped Deposition Transcript of Kevin Burgess, Ph.D., Oct. 28,
`2013, signed with errata----(Exhibit 1056, filed Nov. 19, 2013 in
`connection with IPR2012-00006).
`Nov. 12, 2013 Patent Owner Motion for Observations on the
`Cross-Examination Testimony of Kevin Burgess, Ph.D. in connec(cid:173)
`tion with IPR2012-00006.
`Nov. 12, 2013 Patent Owner Motion to Exclude Evidence in
`connection with IPR2012-00006.
`Welch, M., et al (2005) Corrigenda to Syntheses of Nucleosides
`Designed for Combinatorial DNA Sequencing Chem. Eur.J., 1999,
`951-960. Published in Chem. Eur. J, 2005, 11, 7136-7145 (Exhibit
`2099, filed Nov. 12, 2013 in connection with IPR2012-00006).
`Welch, M (1999) "Base Additions Sequencing Scheme (BASS) and
`Studies Toward New Sequencing Methodologies." PhD. Disserta(cid:173)
`tion, Texas A&M University (Exhibit 2100, filed Nov. 12, 2013 in
`connection with IPR2012-00006).
`Lu and Burgess (2006) "A Diversity Oriented Synthesis of 3'-O(cid:173)
`modified nucleoside triphosphates for DNA 'Sequencing by Syn(cid:173)
`thesis'." Bioorganic & Medicinal Chemistry Letters, 16, 3902-3905
`(Exhibit 2101, filed Nov. 12, 2013 in connection with IPR2012-
`00006).
`Advanced Sequencing Technology Awards 2004. http://www.genome.
`gov/12513162 (accessed Oct. 14, 2013) (Exhibit 2102, filed Nov.
`12, 2013 in connection with IPR2012-00006).
`Welch and Burgess (2006) Erratum to Synthesis of Fluorescent,
`Photolabile 3'-O-Protected Nucleoside Triphosphates for the Base
`Addition Sequencing Scheme, Nucleosides & Nucleotides,18:197-
`201. Published in Nucleosides, Nucleotides and Nucleic Acids,
`25:1, 119 (Exhibit 2103, filed Nov. 12, 2013 in connection with
`IPR2012-00006).
`Nov. 26, 2013 Petitioner Response to Motion for Observations in
`connection with IPR2012-00006.
`Nov. 26, 2013 Patent Owner Opposition to Petitioner's Motion to
`Exclude in connection with IPR2012-00006.
`Nov. 26, 2013 Petitioner Opposition to Motion to Exclude in
`connection with IPR2012-00006.
`Dec. 3, 2013 Petitioner Reply to Patent Owner's Opposition to
`Motion to Exclude in connection with IPR2012-00006.
`Dec. 3, 2013 Patent Owner Reply on Motion to Exclude in con(cid:173)
`nection with IPR2012-00006.
`Columbia's Demonstratives Under 42.70(b) for Dec. 17, 2013 Oral
`Hearing in connection with IPR2012-00006, IPR2012-00007, and
`IPR2013-00011 (Exhibit 21025, filed Dec. 15, 2013 in connection
`with IPR2012-00006).
`
`Page 5
`
`

`

`US 10,457,984 B2
`Page 6
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Ilumina's Invalidity Demonstratives for Final Hearing Dec. 17,
`2013 in connection with IPR2012-00006, IPR2012-00007, and
`IPR2013-00011 (Exhibit 1057, filed Dec. 16, 2013 in connection
`with IPR2012-00006).
`Feb. 10, 2014 Record of Dec. 17, 2013 Oral Hearing in connection
`with IPR2012-00006, IPR2012-00007, and IPR2013-00011.
`Mar. 6, 2014 Final Written Decision in connection with IPR2012-
`00006.
`Patent Owner Preliminary Response filed by The Trustees of
`Columbia University in the City of New York Mar. 27, 2018, in
`connection with Case No. IPR2018-00291.
`Patent Owner Preliminary Response filed by The Trustees of
`Columbia University in the City of New York Apr. 9, 2018, in
`connection with Case No. IPR2018-00318.
`Patent Owner Preliminary Response filed by The Trustees of
`Columbia University in the City of New York Apr. 9, 2018, in
`connection with Case No. IPR2018-00322.
`Patent Owner Preliminary Response filed by The Trustees of
`Columbia University in the City of New York May 4, 2018, in
`connection with Case No. IPR2018-00385.
`Patent Owner Preliminary Response filed by The Trustees of
`Columbia University in the City of New York Jul. 6, 2018, in
`connection with Case No. IPR2018-00797.
`Excerpts from the Prosecution History of U.S. Pat. No. 9,718,852
`not included in Ex-1009 (Exhibit 2005 filed by The Trustees of
`Columbia University in the City of New York with the Patent Owner
`Preliminary Response, in connection with Case No. IPR2018-
`00291).
`Excerpts from the Prosecution History of U.S. Pat. No. 9,725,480
`not included in Ex-1038 (Exhibit 2006 filed by The Trustees of
`Columbia University in the City of New York with the Patent Owner
`Preliminary Response, in connection with Case Nos. IPR2018-
`00291, IPR2018-00318, and IPR2018-00322).
`IPR2013-00517, Ex. 2011, Declaration of Floyd Romesberg, Ph.D.
`(May 5, 2014) (Exhibit 2007 filed by The Trustees of Columbia
`University in the City of New York with the Patent Owner Prelimi(cid:173)
`nary Response, in connection with Case Nos. IPR2018-00291,
`IPR2018-00318, IPR2018-00322, IPR2018-00385, and IPR2018-
`00797).
`IPR2013-00 517, Paper 3 2, Illumina' s Patent Owner Response (May
`5, 2014) (Exhibit 2008 filed by The Trustees of Columbia Univer(cid:173)
`sity in the City of New York with the Patent Owner Preliminary
`Response, in connection with Case Nos. IPR2018- 00291, IPR2018-
`00318, IPR2018-00322, IPR2018-00385, and IPR2018-00797).
`Excerpts from the Ex Parte Reexamination History of U.S. Pat. No.
`5,808,045 (Exhibit 2009 filed by The Trustees of Columbia Uni(cid:173)
`versity in the City of New York with the Patent Owner Preliminary
`Response, in connection with Case Nos. IPR2018-00291, IPR2018-
`00318, IPR2018-00322, IPR2018-00385, and IPR2018-00797).
`Assignment data in connection with U.S. Pat. No. 5,808,045 (Exhibit
`2010 filed by The

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