`
`
`On behalf of Illumina Cambridge Ltd.
`By: Kerry S. Taylor
`Michael L. Fuller
`Nathanael R. Luman
`KNOBBE, MARTENS, OLSON & BEAR, LLP
`2040 Main Street, 14th Floor
`Irvine, CA 92614
`Tel.: 858-707-4000
`Email: BoxIllumina2@knobbe.com
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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
`
`
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`IPR2017-02174
`Patent 7,566,537
`
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`PRELIMINARY RESPONSE OF PATENT OWNER
`ILLUMINA CAMBRIDGE LTD.
`
`
`
`Columbia Ex. 2010
`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
`
`ILLUMINA’S CLAIMED INVENTION INCLUDES A NOVEL
`AND NONOBVIOUS 3ʹ-OH PROTECTING GROUP FOR DNA
`SEQUENCING ................................................................................................ 6
`
`III. THE BOARD, FEDERAL CIRCUIT, AND DISTRICT COURT
`PREVIOUSLY UPHELD PATENTABILITY OF THE
`CHALLENGED CLAIMS ............................................................................ 12
`
`A.
`
`B.
`
`C.
`
`The Board previously upheld the same claims in
`IPR2013-00517 ................................................................................... 12
`
`The Federal Circuit affirmed the Board’s Decision from
`IPR2013-00517 ................................................................................... 14
`
`The Northern District of California upheld the same claims
`from the same patent ........................................................................... 14
`
`IV. BGI’S SECOND FOLLOW-ON PETITION SHOULD BE
`DENIED UNDER 35 U.S.C. § 314(A) ......................................................... 15
`
`A.
`
`B.
`
`C.
`
`Factor 1: Whether the same petitioner previously filed a
`petition directed to the same claims of the same patent ...................... 19
`
`Factor 2: Whether at the time of filing of the first petition
`the petitioner knew of the prior art asserted in the second
`petition or should have known of it ..................................................... 21
`
`Factor 3: Whether the petitioner already received the patent
`owner’s preliminary response to the first petition or received
`the Board’s decision on whether to institute review in the
`first petition ......................................................................................... 22
`
`
`
`i
`
`
`
`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`D.
`
`E.
`
`F.
`
`G.
`
`Factor 4: The length of time that elapsed between the time
`the petitioner learned of the prior art asserted in the second
`petition and the filing of the second petition ....................................... 23
`
`Factor 5: Whether the petitioner provides adequate
`explanation for the time elapsed between the filings of
`multiple petitions directed to the same claims of the same
`patent ................................................................................................... 24
`
`Factor 6: The finite resources of the Board ........................................ 25
`
`Factor 7: The requirement under 35 U.S.C. § 316(a)(11) to
`issue a final determination not later than 1 year after the date
`on which the Director notices institution of review ............................ 25
`
`V. THE PERSON OF ORDINARY SKILL ...................................................... 26
`
`VI. NEW CLAIM CONSTRUCTION IS UNNECESSARY ............................. 27
`
`VII. THE LAW OF NONOBVIOUSNESS .......................................................... 27
`
`VIII. THERE WAS NO MOTIVATION TO COMBINE DOWER
`WITH ZAVGORODNY AND CHURCH .................................................... 27
`
`A.
`
`B.
`
`Introduction to Dower, Zavgorodny, and Church ............................... 28
`
`BGI Primary Issue 1: A POSITA would not have expected a
`3’-O-azidomethyl group to be efficiently and accurately
`incorporated by a polymerase ............................................................. 29
`
`1.
`
`There was no motivation to use an azidomethyl group
`in Dower’s sequencing methods because there was no
`expectation of efficient and accurate polymerase
`incorporation ............................................................................. 30
`
`
`
`ii
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`
`
`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`2.
`
`BGI has not shown there was a reasonable expectation
`of success in arriving at the claimed “incorporation” ............... 39
`
`C.
`
`BGI Primary Issue 2: A POSITA would not have expected
`azidomethyl removal conditions to be “mild” for Dower’s
`SBS method ......................................................................................... 40
`
`1.
`
`2.
`
`3.
`
`Phosphine deblocking conditions produce amines ................... 41
`
`Pyridine was a known DNA denaturant ................................... 44
`
`Young’s cleavage conditions were not mild ............................. 44
`
`D.
`
`E.
`
`BGI Primary Issue 3: A POSITA would not have expected
`azidomethyl to be cleaved with appropriate efficiency for
`SBS ...................................................................................................... 45
`
`BGI fails to address Illumina’s evidence that the
`electrophilic 3’-O-azidomethyl group would not be
`compatible with nucleophiles within the polymerase active
`site ........................................................................................................ 47
`
`IX. AZIDOMETHYL WAS NOT A SIMPLE SUBSTITUTION INTO
`DOWER’S SBS METHOD ........................................................................... 50
`
`X. MOTIVATION IS LACKING FROM BGI’S PETITION THAT
`IS PRESENT IN ILLUMINA’S PETITIONS .............................................. 52
`
`XI. THE DEPENDENT CLAIMS ARE NONOBVIOUS .................................. 54
`
`XII. THE CLAIMS ARE NOT OBVIOUS IN LIGHT OF
`SECONDARY CONSIDERATIONS OF NONOBVIOUSNESS ............... 55
`
`A.
`
`BGI was aware of Illumina’s evidence of non-obviousness,
`but failed to address the evidence ....................................................... 55
`
`iii
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`
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`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`B.
`
`C.
`
`D.
`
`BGI avoids addressing Illumina’s previously-presented
`unexpected results by using an unsupported and incorrect
`legal theory .......................................................................................... 56
`
`BGI avoids addressing Illumina’s previously-presented
`evidence of long-felt, unmet need ....................................................... 57
`
`BGI incorrectly argues that since there is no evidence of a
`competing commercial product, there can be no evidence of
`copying ................................................................................................ 59
`
`XIII. CONCLUSION .............................................................................................. 60
`
`
`
`
`
`iv
`
`
`
`TABLE OF AUTHORITIES
`
`Page No(s).
`
`Akamai Tech. Inc. v. Cable & Wireless Internet Servs. Inc.,
`344 F.3d 1186 (Fed. Cir. 2003) .......................................................................... 59
`
`In re Chu,
`66 F.3d 292 (Fed. Cir. 1995) .............................................................................. 57
`
`Demaco Corp. v. F. Von Langsdorff Licensing Ltd.,
`851 F.2d 1387 (Fed. Cir. 1988) .......................................................................... 58
`
`In re Fritch,
`972 F.2d 1260 (Fed Cir. 1992) ........................................................................... 54
`
`General Plastic Industrial Co. Ltd. v. Canon Kabushiki Kaisha,
`IPR2016-01357, Paper 19 (P.T.A.B. 2017) .................................................passim
`
`Genetics Institute, LLC v. Novartis Vaccines and Diagnostics, Inc.,
`655 F.3d 1291 (Fed. Cir. 2011) .......................................................................... 56
`
`Illumina, Inc. v. Qiagen N.V.,
`207 F.Supp.3d 1081 (N.D. Cal. 2016) ................................................ 2, 14, 16, 60
`
`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) ............................................................................................ 27
`
`LG Elecs. Inc. v. Core Wireless Licensing S.A.R.L.,
`IPR2016-00986, Paper 12 (P.T.A.B. 2016) ............................................ 17, 19, 25
`
`Merial Ltd. v. Virbac,
`IPR2014-01279, Paper 13 (P.T.A.B. 2015) ........................................................ 55
`
`NetApp Inc. v. Realtime Data LLC,
`IPR2017-01195, Paper 9 (P.T.A.B. 2017) .......................................................... 20
`
`v
`
`
`
`TABLE OF AUTHORITIES
`(cont’d)
`
`Page No(s).
`
`NetApp Inc. v. Realtime Data LLC,
`IPR2017-01196, Paper 10 (P.T.A.B. 2017) ........................................................ 21
`
`NetApp Inc. v. Realtime Data LLC,
`IPR2017-01354, Paper 16 (P.T.A.B. 2017) ........................................................ 21
`
`NVIDIA Corp. v. Samsung Elec. Co.,
`IPR2016-00134, Paper 9 (P.T.A.B. 2016) .................................................... 17, 19
`
`Omron Oilfield & Marine, Inc. v. MD/Totco,
`IPR2013-00265, Paper 11 (P.T.A.B. 2013) .................................................. 55, 57
`
`R.J. Reynolds Vapor Co. v. Fontem Holdings 1 B.V.,
`IPR2017-01117, Paper 10 (P.T.A.B. 2017) ........................................................ 24
`
`Samsung Electronics Co., Ltd. v. ELM 3DS Innovations, LLC,
`IPR2017-01305, Paper 11 (P.T.A.B. 2017) ........................................................ 21
`
`Sanofi-Aventis Deutschland GmbH v. Glenmark Pharm., Inc.,
`748 F.3d 1354 (Fed. Cir. 2014) .......................................................................... 57
`
`Starbucks Corp. v. Ameranth, Inc.,
`CBM2017-00053, Paper 7 (P.T.A.B. 2017) ....................................................... 19
`
`Stratoflex, Inc. v. Aeroquip Corp.,
`713 F.2d 1530 (Fed. Cir. 1983) .................................................................... 55, 60
`
`Unified Patents, Inc. v. Personal Web Technologies, LLC,
`IPR2014-00702, Paper 13 (P.T.A.B. 2014) ........................................................ 21
`
`Xactware Solutions., Inc. v. Eagle View Techs., Inc.,
`IPR2017-00034, Paper 9 (P.T.A.B. 2017) .......................................................... 19
`
`
`
`vi
`
`
`
`TABLE OF AUTHORITIES
`(cont’d)
`
`OTHER AUTHORITIES
`
`Page No(s).
`
`35 U.S.C. § 313 .......................................................................................................... 1
`
`35 U.S.C. § 314 .................................................................................................passim
`
`35 U.S.C. § 316 .................................................................................................. 18, 25
`
`37 C.F.R. § 42.1 ................................................................................................... 3, 25
`
`37 C.F.R. § 42.107 ..................................................................................................... 1
`
`37 C.F.R. § 42.108 ................................................................................................... 19
`
`
`
`
`
`vii
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`
`
`IPR2017-02174
`Complete Genomics v. Illumina
`
`Pursuant to 35 U.S.C. § 313, 37 C.F.R. § 42.107, and the October 23, 2017
`
`Notice of Filing Date Accorded to Petition (Paper 3), Patent Owner Illumina
`
`Cambridge Ltd. (“Illumina”) submits its Preliminary Response to the Petition for
`
`Inter Partes Review filed by Complete Genomics, Inc. and its real party-in-
`
`interest, BGI Shenzhen Co., Ltd. (collectively “BGI”). See Paper 1 (“BGI’s
`
`second follow-on petition”).
`
`I. INTRODUCTION
`This is BGI’s second attempt to challenge the ’537 Patent, and it is a prime
`
`example of a repetitive challenge to a repeatedly-upheld patent that should be
`
`denied. Further investment of scarce judicial resources is unwarranted, especially
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`given the low probability of success implied by the past outcomes upholding the
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`patent. Even beyond that, Patent Owner deserves repose after expending so much
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`time, effort and attention successfully defending its duly issued and legally valid
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`patent.
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`The very same claims of the ’537 Patent have been battle tested in the
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`crucible of district court and PTAB litigation. Seven judges have considered and
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`rejected prior art attacks on the same claims from the same patent. This includes a
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`three judge PTAB panel, a three judge Federal Circuit panel and Judge Alsup of
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`the Northern District of California.
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`1
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`
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`IPR2017-02174
`Complete Genomics v. Illumina
`
`Judge Alsup specifically addressed the validity of the ’537 Patent in granting
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`a preliminary injunction and concluded that it was unlikely to be invalidated given
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`the weakness of the prior art. Illumina, Inc. v. Qiagen N.V., 207 F.Supp.3d 1081,
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`1088-1090 (N.D. Cal. 2016). He found a “weak” showing of a motivation to
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`combine the prior art to show the claimed inventions and a low likelihood of
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`success even if one were motivated to modify the prior art. Id. Given the high
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`stakes in an injunction proceeding, it is safe to conclude that the enjoined infringer
`
`had full motivation to make the best prior art arguments it could. Yet, its
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`obviousness attack on the ’537 Patent was soundly rejected. Id. After this loss, the
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`infringer ultimately agreed to a consent decree enjoining it from infringing the
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`’537 Patent, further underlining the proven validity of the patent.
`
`Beyond that, all claims challenged by BGI’s petition withstood a full trial in
`
`IPR2013-00517. The previous petition was filed by Intelligent Bio-Systems and
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`its parent company, Qiagen, a sophisticated, multinational company based in
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`Germany with offices throughout the U.S. The Board issued a final written
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`decision upholding the patentability of all challenged claims. The Federal Circuit
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`panel unanimously affirmed the Board’s decision. Intelligent Bio-Systems, Inc.
`
`(“IBS”) v. Illumina Cambridge Ltd., 821 F.3d 1359, 1370 (Fed. Cir. 2016).
`
`BGI has been in the sequencing business for years, including, but not limited
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`to, in the U.S. through its subsidiary CGI. BGI waited until after the Federal
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`2
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`
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`IPR2017-02174
`Complete Genomics v. Illumina
`
`Circuit affirmed patentability of Illumina’s claims before filing two follow-on
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`petitions attacking the same claims for a second and third time. BGI failed to file
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`its own petition during the pendency of the prior IPR, and it did not seek to join the
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`prior proceeding. BGI sat on the sidelines and apparently wanted to reap the
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`benefit of the previous petitioner’s potential success or wait to stage its own
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`follow-on attacks to take advantage of the Board and Federal Circuit’s responses to
`
`the arguments and evidence presented in the first IPR. The Board ruled in favor of
`
`Illumina in the original IPR. BGI’s belated petitions attempt to pick up where
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`Qiagen left off with a second and third bite at the apple. BGI’s use of the previous
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`proceedings as a roadmap to retool and rehash the previous arguments should not
`
`be rewarded. Instituting another IPR proceeding would not “secure the just,
`
`speedy, and inexpensive resolution of every proceeding.” 37 C.F.R. § 42.1(b).
`
`BGI’s first follow-on petition in IPR2017-02172 is based on the same
`
`primary reference (Tsien) and secondary references (Zavgorodny and Greene &
`
`Wuts) over which the Board upheld the same claims in IPR2013-00517. This
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`present petition is BGI’s second follow-on petition, and it uses Dower as a primary
`
`reference along with Zavgorodny and Church as secondary references. All of these
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`references were cited on the face of the ’537 patent. Any reasonably diligent
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`search by BGI would have uncovered these references at least by the issue date of
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`the ’537 patent, and certainly by the time the first petition against the ’537 patent
`
`3
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`
`
`IPR2017-02174
`Complete Genomics v. Illumina
`
`was filed in IPR2013-00517. BGI makes no argument and presents no evidence
`
`showing there was any barrier to it presenting arguments based on these references
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`during the pendency of IPR2013-00517.
`
`The Board has put petitioners on notice that follow-on petitions will be
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`heavily scrutinized under 35 U.S.C. § 314(a) even if there are no district court
`
`decisions or Federal Circuit decisions upholding the invalidity of the patent. The
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`Board has issued informative and precedential decisions directing follow-on
`
`petitioners to explain why Board and Patent Owner resources should be expended
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`on their secondary (and here, tertiary) petitions. In the face of 314(a), BGI does
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`not even attempt to justify its belated secondary and tertiary petitions on the same
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`claims from the same patent, and these petitions should be rejected outright.
`
`Illumina is a U.S. company that began as a technology-driven start-up
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`company in the biotechnology hotbed of San Diego, California, and merged with a
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`similarly driven company out of Cambridge, UK – Solexa – to jointly deliver
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`ground-breaking and highly popular sequencing technology. Today, Illumina has
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`become the leading innovator in the DNA sequencing industry, employing
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`approximately 5,500 workers. The challenged claims of ’537 patent protect
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`Illumina’s highly successful sequencing products that use labeled nucleotides
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`having a reversible 3’-O-azidomethyl protecting group. Both BGI and Qiagen
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`have been developing DNA sequencers but, to-date, they have been unable to
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`4
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`
`
`IPR2017-02174
`Complete Genomics v. Illumina
`
`develop an alternative technology to effectively compete against Illumina’s
`
`reversible 3’-O-azidomethyl terminator technology in the United States.
`
`The current petitioner, BGI, and the original failed petitioner, Qiagen, are
`
`not strangers. They have business ties and an aligned interest in gaining free
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`access to the valuable inventions protected by the ’537 patent as soon as they can.
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`BGI’s follow-on petitions seek to abuse the IPR process by retreading and
`
`retooling where Qiagen lost.
`
`This petition fails to establish a prima facie case of obviousness based on
`
`Dower in view of Zavgorodny and Church. Dower discloses SBS methods that use
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`nucleotides having 3’-OH protecting groups. BGI concedes that a person of
`
`ordinary skill in the art (“POSITA”) would have focused on three primary issues
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`when selecting a reversible 3’-OH protecting group from the literature for use in
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`Dower’s SBS methods:
`
`(1) the ability of a polymerase to incorporate the nucleotide having the 3’-
`
`OH protecting group,
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`(2) the selection of deblocking conditions that would remove the 3’-OH
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`protecting group without harming the DNA, and
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`(3) the incorporation and deblocking steps must result in a yield that is
`
`reasonable for the desired application.
`
`5
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`
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`IPR2017-02174
`Complete Genomics v. Illumina
`
`This petition, however, fails to establish that an azidomethyl protecting
`
`group would have been known to satisfy these three primary requirements. This
`
`petition therefore fails to establish that a POSITA would have been motivated to
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`use an azidomethyl group as Dower’s 3’-blocking group.
`
`Not only does this petition (which is BGI’s second follow-on petition) fail to
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`establish a prima facie case of obviousness, it also fails to rebut Illumina’s
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`significant evidence of secondary considerations of non-obviousness. In the
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`previous IPR trial, Illumina raised significant evidence of secondary considerations
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`on nonobviousness, including long-felt but unmet need, unexpected results, and
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`evidence of copying. BGI fails to substantively address this evidence, and thus
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`fails to carry its burden of demonstrating obviousness. BGI’s desire to gain access
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`the claimed technology by attacking the patent that covers it only strengthens those
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`secondary considerations. For all of these reasons, the Board should deny
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`institution of BGI’s second follow-on petition.
`
`II. ILLUMINA’S CLAIMED INVENTION INCLUDES A NOVEL AND
`NONOBVIOUS 3ʹ-OH PROTECTING GROUP FOR DNA SEQUENCING
`
`Illumina is the undisputed innovative leader in the DNA sequencing
`
`industry. Illumina has been referred to as the “smartest company in the world”
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`because it “commercializes a truly innovative technology” and causes competitors
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`“to refine or rethink their strategies.” Ex-2001 at 27-29. Illumina’s novel and
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`successful methods of labeling nucleic acid molecules use a reversible 3’-O-
`
`6
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`
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`IPR2017-02174
`Complete Genomics v. Illumina
`
`azidomethyl ether protecting group in its DNA sequencing instruments. Illumina’s
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`successful sequencing instruments “account[] for the largest market share for
`
`sequencing instruments compared to other platforms.”
`
` Ex-2002 at 337.
`
`“Illumina’s highly successful suite of instruments have been the juggernaut of
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`NGS [next generation DNA sequencing], relegating technologies that could not
`
`keep pace to niche applications or outright dissolution.” Id. at 348. Indeed, where
`
`Illumina has succeeded, Complete Genomics (“CGI”) and BGI1 have failed. For
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`example, CGI and BGI instruments attempted to sequence DNA using the
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`“combinatorial probe-anchor ligation (cPAL)” technology, which CGI marketed
`
`under the name “Revelocity.” Id. at 335. The Revelocity sequencing technology
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`was not commercially viable and could not compete with Illumina’s 3’-O-
`
`azidomethyl nucleotides. Id. at 348 (“The casualties of the NGS arms race have
`
`included… the Revelocity system from Complete Genomics.”); id. at 337
`
`(“although the cPAL-based Revelocity system [from CGI] was intended to
`
`
`1 BGI, formerly Beijing Genomics Institute, is a Chinese company that
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`acquired CGI in March of 2013. Ex-2003 at 1. BGI is a real party-in-interest.
`
`Petition at 4.
`
`7
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`IPR2017-02174
`Complete Genomics v. Illumina
`
`compete with the Illumina HiSeq2 in terms of cost and throughout, its launch was
`
`suspended in 2016 and it is now only available as a service platform for human
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`WGS [whole genome sequencing]”).
`
`BGI abandoned cPAL due to inferior read lengths, and instead adopted
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`Illumina’s polymerase-based sequencing-by-synthesis (“SBS”) approach. BGI
`
`refers to its copycat polymerase approach as “combinatorial probe-anchor
`
`synthesis (cPAS).” BGI asserts cPAS provides “longer reads ... compared to the
`
`previously described combinatorial probe-anchor ligation (cPAL) chemistry.” Ex-
`
`2004 at 2. BGI’s cPAS-based BGISEQ-500 platform “is limited to mainland
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`China” (Ex-2002 at 337), apparently due to “patent issues” excluding BGI from
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`other markets. Ex-2005 at 2. BGI’s present petition seeking cancellation of the
`
`’537 patent claims that protect Illumina’s labeling methods and reversible 3’-O-
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`azidomethyl terminator technology is a strong signal that BGI wants to send its
`
`infringing sequencers into the U.S.
`
`BGI’s present petition alleges that Claims 1-6 and 8 of the ’537 patent would
`
`have been obvious to a POSITA based on a combination of Dower, Zavgorodny
`
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`2 The HiSeq instrument is one of Illumina’s flagship DNA sequencing
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`instruments and, like all of Illumina’s sequencing instruments, uses 3’-O-
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`azidomethyl protected nucleotides.
`
`8
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`IPR2017-02174
`Complete Genomics v. Illumina
`
`and Church. Dower was filed in 1990 and disclosed SBS methods using 3’-OH
`
`protected nucleotides. By August of 2002, at least 11 separate research teams had
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`tried to identify 3’-protecting groups that were effective for use in DNA
`
`sequencing:
`
`(1) Tsien investigated at least 3’-O-allyl and various other groups (Ex-1503
`
`at 21:20-31);
`
`(2) Dower (Affymax) contemplated at least “acetyl, tBOC, NBOC, and
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`NVOC” 3’-OH protecting groups (Ex-1504 at 25:47-51);
`
`(3) Metzker
`
`investigated 3’-O-methyl, 3’-O-acetyl, 3’-O-allyl, 3’-O-
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`tetrahydropyran, 3’-O-4-nitrobenzoyl, 3’-O-2-aminobenzoyl,
`
`and 3’-O-2-
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`nitrobenzyl groups (Ex-1541 at 4263);
`
`(4) Canard investigated at least 3’-O-anthranyloyl and 3’-O-anthranyl
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`derivatives (Ex-1542 at 10859);
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`(5) Stemple (ASM Scientific) investigated at least 3’-O-(2-nitrobenzyl)
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`groups (Ex-2006 at 13:18-20);
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`(6) Odedra (Amersham Pharmacia) investigated at least acetyl and
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`phenylacetamide groups (Ex-2007 at Figs. 2 & 11);
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`(7) Cheeseman (Beckman Instruments) investigated at least 3’-O-succinyl
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`and 3’-O-anhydride derivatives (Ex-1555 at 4:50-63);
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`9
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`
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`IPR2017-02174
`Complete Genomics v. Illumina
`
`(8) Kwiatkowski (Helicos BioSciences)
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`investigated at
`
`least 3’-O-
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`hydrocarbyldithiomethyl and 3’-O-“functionalized acetal” groups (Ex-2008 at
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`2:40-60; Ex-2009 at 15:11-16:24);
`
`(9) Rosenthal investigated 3’-blocking groups that “generate a 3’ hydroxyl
`
`group” (Ex-2010 at 11:3-10);
`
`(10) Rabani investigated at least a 3’-O-(4-benzoyl)benzoyl group (Ex-2011
`
`at 2:15-21); and
`
`(11) Ju investigated at least 3’-O-allyl and 3’-O-methoxymethyl groups (Ex-
`
`1538 at Fig. 7).
`
`None of these researchers investigated or even suggested a protecting group
`
`comprising an azido group that can be modified or removed to expose a 3’-OH
`
`group. These research efforts showed that the 3’-O-allyl group identified by Tsien
`
`was a reversible protecting group that could be incorporated effectively by
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`polymerases. Ex-1503 at 24:29; Ex-1541 at 4263; Ex-1538 at 3:7-22.
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`Despite the numerous research efforts by multiple teams, only Illumina
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`identified the azidomethyl group as a protecting group for DNA sequencing. Ex-
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`1501 at 19:49-20:4. Illumina found that the azidomethyl protecting group was
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`incorporated by polymerases and was surprisingly cleaved in rapid and quantitative
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`yield under conditions that permit polymerase incorporation for DNA sequencing.
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`This resulted in sequencing successes unachievable with other 3’-OH protecting
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`groups. These properties were not known in the prior art at the time the ’537
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`patent was filed, and no knowledge in the art would have led a POSITA to expect
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`that an azidomethyl group could be successful. To date, Illumina’s 3’-O-
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`azidomethyl group remains the industry-leading reversible terminator technology
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`for sequencing even though 15 years have passed since the ’537 patent was filed.
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`BGI’s follow-on petitions assert unpatentability of the same ’537 patent
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`claims the Board and Federal Circuit previously upheld in IPR213-00517. The
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`Board previously found that there was no motivation to use an azidomethyl
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`protecting group because it would not have been expected to be deblocked under
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`conditions suitable for use in the prior art sequencing methods. BGI’s follow-on
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`petitions use the previous Board and Federal Circuit decisions as a roadmap to
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`stage arguments seeking to re-litigate whether an azidomethyl protecting group
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`would have been expected to be deblocked under conditions suitable for use in
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`sequencing methods. All other considerations aside, BGI’s hindsight-driven
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`petitions are an inappropriate and an unacceptable use of the IPR process. See
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`General Plastic Industrial Co. Ltd. v. Canon Kabushiki Kaisha, IPR2016-01357,
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`Paper 19 at 17-18 (P.T.A.B. 2017) (Precedential) (“The absence of any restrictions
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`on follow-on petitions would allow petitioners the opportunity to strategically
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`stage their prior art and arguments in multiple petitions, using our decisions as a
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`roadmap, until a ground is found that results in the grant of review. All other
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`factors aside, this is unfair to patent owners and is an inefficient use of the inter
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`partes review process and other post-grant review processes.”). BGI should not be
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`permitted yet another attack on the same claims from the same patent.
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`III. THE BOARD, FEDERAL CIRCUIT, AND DISTRICT COURT
`PREVIOUSLY UPHELD PATENTABILITY OF THE
`CHALLENGED CLAIMS
`A. The Board previously upheld the same claims in IPR2013-00517
`On August 19, 2013, Intelligent Bio-Systems and its parent company,
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`Qiagen,3 filed a petition for IPR of Claims 1-6 and 8 of the ’537 patent in
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`IPR2013-00517. On August 30, 2013, they filed a revised petition. Ex-1590 at 2,
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`49.
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`Qiagen argued that “one of ordinary skill in the art, in order to improve the
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`efficiency, reliability, and robustness of the sequencing by synthesis [SBS] method
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`taught in Tsien, would have been motivated to use other protecting groups that
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`meet the criteria of Tsien, such as the azidomethyl group taught by Zavgorodny.”
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`Ex-1590 at 38. BGI’s follow-on petition relies on the same SBS motivation
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`asserted by Qiagen. Petition at 34 (“It would have been obvious to further
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`combine Dower’s SBS method with Church’s disulfide linker with Zavgorodny’s
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`azidomethyl protecting group.”); id. at 32, 52, 16, 25-26.
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`3 Qiagen acquired IBS in June of 2012. Ex-1592 at 1.
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`On May 5, 2014, Illumina filed its Patent Owner response. Illumina argued,
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`inter alia, that Claims 1-6 and 8 were nonobvious because a POSITA would not
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`have been motivated to combine the prior art SBS methods of Tsien and Ju with
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`the azidomethyl group disclosed by Zavgorodny. Ex-1592 at 12-42. Illumina
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`supported its arguments by analyzing the prior art, along with the expert testimony
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`of Dr. Romesberg and Dr. Burgess. Id. Illumina further presented significant
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`evidence of secondary considerations of nonobviousness. Id. at 43-60.
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`On February 11, 2015, the Board issued its final written decision upholding
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`the patentability of Claims 1-6 and 8. Ex-1594 at 24. Significant resources were
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`expended by the Board and Illumina in reaching this decision, including analyzing
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`over 200 exhibits, 90 papers, 4 expert witnesses, and conducting an oral hearing.
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`In the final written decision, the Board concluded “Petitioner has not shown that a
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`preponderance of the evidence supports a conclusion that an ordinary artisan would
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`have considered it obvious to use Zavgorodny’s azidomethyl protecting group in
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`the processes described in Tsien.” Id. at 18.
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`BGI’s petition argues that the Board did not consider the Reply arguments
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`submitted during the previous IPR. Petition at 2, 6-7. BGI is incorrect. The Board
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`considered the Reply arguments and found they were not persuasive. Ex-1594 at
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`16 (“Further, even if we were to overlook the procedural infirmities in Petitioner’s
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`Reply arguments, we would not find them persuasive.”);4 id. at 21 (“For the
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`reasons discussed above, we do not find Petitioner’s [Reply] arguments
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`persuasive.”).
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`B.
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`The Federal Circuit affirmed the Board’s decision from
`IPR2013-00517
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`On April 8, 2015, the Board’s final written decision from IPR2013-00517
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`was appealed to the Federal Circuit. BGI’s petition makes it seem like Illumina
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`lost on appeal. To the contrary, on May 9, 2016, the Federal Circuit
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`unanimously affirmed the Board’s decision and upheld the patentability of
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`Claims 1-6 and 8. IBS, 821 F.3d at 1370.
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`C. The Northern District of California upheld the same claims from the
`same patent
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`After the Federal Circuit upheld the Board’s final written decision, Qiagen
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`argued in the Northern District of California that the ’537 patent was obvious over
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`the prior art. Illumina, 207 F.Supp.3d at 1088. Judge Alsup found a “weak”
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`showing of a motivation to combine the prior art and a low likelihood of success
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`even if one would have been motivated to modify the prior art. Id. at 1090. He
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`concluded that the ’537 patent was unlikely to be invalidated given the weakness
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`of the prior art. Id. After this loss, Qiagen ultimately agreed to a consent decree
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`4 Emphasis supplied unless otherwise noted.
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`enjoining it from infringing the ’537 Patent, further underlining the proven validity
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`of the patent.
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`IV. BGI’S SECOND FOLLOW-ON PETITION SHOULD BE DENIED
`UNDER 35 U.S.C. § 314(A)
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`Qiagen filed the first petition challenging Claims 1-6 and 8 of the ’537
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`patent. After a full trial and Federal Circuit aff