UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`OXFORD NANOPORE TECHNOLOGIES, INC.,
`Petitioner,
`v.
`PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
`Patent Owner
`
`Case IPR No. IPR2018-01792
`U.S. Patent No. 9,738,929
`
`
`
`
`
`PATENT OWNER PACIFIC BIOSCIENCES OF CALIFORNIA, INC.’S
`PRELIMINARY RESPONSE
`
`
`
`
`
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`OXFORD NANOPORE TECHNOLOGIES, INC.,
`Petitioner,
`v.
`PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
`Patent Owner
`
`Case IPR No. IPR2018-01792
`U.S. Patent No. 9,738,929
`
`
`
`
`
`PATENT OWNER PACIFIC BIOSCIENCES OF CALIFORNIA, INC.’S
`PRELIMINARY RESPONSE
`
`
`
`
`
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`
`
`
`
`
`
`I.
`
`II.
`
`TABLE OF CONTENTS
`
`Page
`
`INTRODUCTION .......................................................................................... 1
`
`THE BOARD SHOULD EXERCISE ITS DISCRETION TO DENY
`INSTITUTION PURSUANT TO §§ 314(A) AND 324(A) ............................ 5
`
`A.
`
`B.
`
`C.
`
`Strategic Delay in Filing the Petition .................................................... 6
`
`Status of District Court Litigation ......................................................... 7
`
`The Board Has Broad Discretion to Deny Institution Under 35
`U.S.C. §§ 314(a) and 324(a) ................................................................. 8
`
`D.
`
`The General Plastic Factors Also Weigh Against Institution ............ 10
`
`III. BACKGROUND ........................................................................................... 13
`
`A. Overview Of Sequencing Technology And The State Of The Art
` ............................................................................................................. 13
`
`B.
`
`C.
`
`1.
`
`2.
`
`Prior Art Ensemble Sequencing Techniques ............................ 13
`
`Single-Molecule Sequencing .................................................... 16
`
`Overview Of The ’929 Patent ............................................................. 21
`
`Overview Of The Cited Prior Art ........................................................ 23
`
`1.
`
`2.
`
`3.
`
`4.
`
`U.S. Patent 6,087,099 (“Gupte”) .............................................. 23
`
`U.S. Patent Publication 2005/0142559 (“Makrigiorgos”) ........ 25
`
`In DNA
`Determination Of Nucleotide Sequences
`(“Sanger”) ................................................................................. 28
`
`U.S. Patent Publication 2006/0063171 (“Akeson”) ................. 29
`
`IV. REASONS WHY THE PETITION SHOULD BE DENIED ....................... 32
`
`A. GROUNDS 1-3: The Combination Of Akeson With Gupte .............. 32
`i
`
`
`
`1.
`
`2.
`
`3.
`
`Gupte Does Not Teach Determining A Single-Molecule
`Consensus Sequence ................................................................. 32
`
`A Person Of Ordinary Skill In The Art Would Not Be
`Motivated To Combine Akeson with Gupte ............................. 37
`
`A Person Of Ordinary Skill In The Art Would Not Have
`Had A Reasonable Expectation Of Success In The
`Combination .............................................................................. 44
`
`B.
`
`GROUNDS 4-7: The Combination Of Akeson, Sanger, And
`Makrigiorgos ....................................................................................... 46
`
`1.
`
`2.
`
`3.
`
`Neither Sanger Nor Makrigiorgos Teach Determining A
`Single-Molecule Consensus Sequence ..................................... 46
`
`A Person Of Ordinary Skill In The Art Would Not Be
`Motivated To Combine Akeson with Sanger and
`Makrigiorgos ............................................................................. 49
`
`A Person Of Ordinary Skill In The Art Would Not Have
`Had A Reasonable Expectation Of Success In The
`Combination .............................................................................. 53
`
`V. CONCLUSION ............................................................................................ 54
`
`
`
`
`ii
`
`
`
`
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`Cases
`Alphonso, Inc. v. Free Stream Media, Corp.,
`IPR2017-01731, 2018 WL 566832 (P.T.A.B. Jan. 25, 2018) ............................. 40
`Arctic Cat Inc. v. Bombardier Recreational Prod. Inc.,
`876 F.3d 1350 (Fed. Cir. 2017) ..................................................................... 45, 54
`Cheese Sys., Inc. v. Tetra Pak Cheese & Powder Sys.,
`725 F.3d 1341 (Fed. Cir. 2013) ............................................................................ 37
`General Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha,
`Case IPR2016-01357, Paper 19 at 16-17 (PTAB Sept. 6, 2017) ................. passim
`
`Honeywell Int'l Inc. v. Mexichem Amanco Holding S.A. De C.V.,
`865 F.3d 1348 (Fed. Cir. 2017) ..................................................................... 45, 54
`In re Nuvasive, Inc.,
`842 F.3d 1376 (Fed. Cir. 2016) ..................................................................... 41, 50
`
`Initiative for Medicines, Access & Knowledge (I-MAK), Inc., v. Gilead Pharmasset
`LLC,
`Case IPR2018-00211, Paper 7 (PTAB June 20, 2018) ................................. 44, 54
`Institut Pasteur v. Focarino,
`738 F.3d 1337 (Fed. Cir. 2013) ............................................................................ 45
`InTouch Technologies, Inc. v. VGO Comms.,
`751 F. 3d 1327 (Fed. Cir. 2014) ........................................................................... 47
`Kinetic Concepts, Inc. v. Smith & Nephew, Inc.
`688 F.3d 1342 (Fed. Cir. 2012) ..................................................................... 38, 50
`
`KSR Intern. Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007) ............................................................................................. 37
`Microsoft Corp. v. Enfish, LLC,
`662 Fed. Appx. 981 (Fed. Cir. 2016) ................................................................... 40
`
`iii
`
`
`
`Microsoft Corp. v. Koninkijke Philips N.V.,
`Case IPR2018-00277, Paper 10 (June 8, 2018) ..................................................... 5
`NetApp, Inc. v. Realtime Data LLC,
`Case IPR2017-01195, Paper 9 (PTAB Oct. 12, 2017) ........................... 11, 12, 13
`
`NHK Spring Co. Ltd. v. Intri-plex Techs., Inc.,
`Case IPR2018-00752, Paper 8 (PTAB Sept. 12, 2018) .......................... 6, 8, 9, 10
`NPF Ltd. v. Smart Parts, Inc.,
`187 Fed. Appx. 973 (Fed. Cir. June 27, 2006) .................................................... 44
`Outdry Techs. Corp. v. Geox S.p.A.,
`859 F.3d 1364 (Fed. Cir. 2017) ............................................................................ 41
`Princeton Biochemicals, Inc. v. Beckman Coulter, Inc.,
`411 F.3d 1332 (Fed. Cir. 2005) ............................................................................ 53
`Trustees of Columbia Univ. in City of New York v. Illumina, Inc.,
`620 F. App'x 916 (Fed. Cir. 2015) ....................................................................... 44
`Vivid Techs., Inc., v. American Science & Engineering,
`200 F.3d 795 (Fed. Cir. 1999) ................................................................................ 9
`Statutes
`35 U.S.C. § 314(a) ............................................................................................ 5, 6, 8
`35 U.S.C. § 316(a)(11) ............................................................................................. 11
`35 U.S.C. § 324(a) ............................................................................................ 5, 6, 8
`35 U.S.C. § 326(b) ..................................................................................................... 8
`35 U.S.C. §§ 316(b) ................................................................................................... 8
`
`
`
`iv
`
`
`
`
`
`
`
`EXHIBIT LIST
`
`Exhibit #
`Description
`Ex. 2001 Amendment and Response to Office Action regarding Patent
`Application No. 13/147,159, Docket No. JKJ-027USRCE
`
`Ex. 2002
`
`Ex. 2003
`
`Ex. 2004
`
`Ex. 2005
`
`Complaint for Patent Infringement arising under U.S. Patent No.
`9,546,400, Pacific Biosciences of California, Inc. v. Oxford
`Nanopore Technologies, Inc., Case No. 1:17-cv-00275 (D. Del.),
`Docket No. 1
`
`Complaint for Patent Infringement arising under U.S. Patent No.
`9,678,056, Pacific Biosciences of California, Inc. v. Oxford
`Nanopore Technologies, Inc., Case No. 1:17-cv-01353 (D. Del.),
`Docket No. 1
`
`Oxford Nanopore Technologies, Inc.’s Initial Invalidity
`Contentions, Pacific Biosciences of California, Inc. v. Oxford
`Nanopore Technologies, Inc., Case Nos. 1:17-cv-00275 (D. Del.)
`and 1:17-cv-01353 (D. Del.)
`
`Docket text for Oral Order Rescheduling Markman Hearing,
`Pacific Biosciences of California, Inc. v. Oxford Nanopore
`Technologies, Inc., Case Nos. 1:17-cv-00275 (D. Del.) and 1:17-
`cv-01353 (D. Del.)
`
`Ex. 2006 Exhibit number not used
`
`Ex. 2007
`
`Scheduling Order, Pacific Biosciences of California, Inc. v. Oxford
`Nanopore Technologies, Inc., Case No. 1:17-cv-01353 (D. Del.),
`Docket No. 35
`
`Ex. 2008
`
`Deposition Excerpts of Patrick Hrdlicka, Ph.D., dated October 23,
`2018, Pacific Biosciences of California, Inc. v. Oxford Nanopore
`Technologies, Inc., Case Nos. 1:17-cv-00275 (D. Del.) and 1:17-
`cv-01353 (D. Del.)
`
`v
`
`
`
`
`
`I.
`
`INTRODUCTION
`Patent Owner, Pacific Biosciences of California, Inc. (“PacBio”), submits this
`
`Preliminary Response to Petition for Inter Partes Review of U.S. Patent No.
`
`9,738,929 (“the Petition”). As explained herein, the Board should not institute
`
`review.
`
`U.S. Patent No. 9,738,929 (“the ’929 patent”) is one of a suite of patents
`
`awarded to PacBio for revolutions in single molecule sequencing including nanopore
`
`sequencing of DNA. In particular, the ’929 patent offered a major improvement in
`
`the accuracy of nanopore sequencing by teaching the use of double-stranded DNA
`
`templates that include redundant sequence information. As disclosed and claimed
`
`in the ’929 patent, by sequencing both strands of a single DNA template molecule
`
`and generating redundant sequence information, one can generate a “consensus
`
`sequence” from a single molecule that is substantially more accurate than the
`
`sequence one would obtain by simply sequencing a single strand of the DNA.
`
`According to Petitioner, the “notion of using nanopores to sequence
`
`polynucleotides, such as DNA and RNA, has been around for decades.” Petition at
`
`10. Likewise, Petitioner asserts that “[e]ven as early as 1980, sequencing of both
`
`strands of a double-stranded nucleic acid was known to improve the accuracy of
`
`sequencing.” Id. at 12.
`
`
`
`
`
`
`
`One would think, then, that Petitioner would cite countless prior art references
`
`teaching nanopore sequencing of both strands of a double-stranded nucleic acid
`
`molecule. Yet, Petitioner fails to cite even a single prior art reference suggesting the
`
`use of a consensus sequence from a double-stranded DNA template molecule with
`
`any kind of single-molecule sequencing, let alone nanopore sequencing. Petitioner’s
`
`failure to identify any such art is not the result of oversight, but a result of the fact
`
`that the ’929 patent represents a genuine advance over anything that was known in
`
`the prior art.
`
`Indeed, to try and achieve the claimed invention, Petitioner is forced to rely
`
`on obviousness. Petitioner starts with a generic nanopore sequencing reference
`
`(Akeson) that makes no mention of techniques for improving accuracy, let alone the
`
`determination of a consensus sequence using a double-stranded DNA template
`
`molecule. Petitioner then attempts to combine this with two references (Gupte and
`
`Sanger) that have nothing to do with single-molecule sequencing. This combination
`
`is defective and is based purely on hindsight.
`
`The defects in Petitioner’s obviousness theory are exposed by the Petition
`
`itself, which is bereft of any meaningful reasoning or analysis to justify Petitioner’s
`
`proposed combination. At most, the Petition includes some conclusory assertions
`
`about motivation to combine, followed by a paint-by-numbers exposition of where
`
`2
`
`
`
`
`
`each claim element is allegedly found in the prior art. See, e.g., Petition at 24. This
`
`falls far short of meeting the requirements to prove obviousness under KSR.
`
`What’s more, as Petitioner’s expert confirmed at deposition, Gupte and
`
`Sanger do not even disclose a consensus sequence, much less a single molecule
`
`consensus sequence.1 Likewise, Petitioner has confirmed during prosecution of its
`
`own patents that Akeson “fails to teach or suggest sequencing both strands of a
`
`denatured double-stranded nucleic acid template (with sense and anti-sense strands
`
`connected by a hairpin) and actively combining the current data for each position in
`
`the sense and anti-sense strands to generate a higher quality aggregate call for both
`
`bases at each position, as compared with a single observation.” Ex. 2001
`
`[13/147,149 12/17/14 OA Response] at 12. If anything, Akeson teaches away from
`
`consensus sequencing based on the use of a double-stranded DNA template. In this
`
`regard, the Petition does not even make a basic showing that each of the claim
`
`elements are disclosed in the art.
`
`Ultimately, any contention that the claimed invention is obvious is belied by
`
`Petitioner’s own characterization of the very approach covered by the ’929 patent,
`
`which Petitioner has tried to patent for itself. In seeking to do so, Petitioner was
`
`
`1 Although this is only a preliminary response, Petitioner’s expert has been
`questioned on some aspects of his opinions in this case in connection with claim
`construction proceedings in co-pending district court litigation. Some of this
`deposition testimony is presented herein.
`3
`
`
`
`
`
`clear that there are “surprising and unexpected advantages” to be gleaned from
`
`sequencing both strands of a double-stranded nucleic acid template. These
`
`advantages, Petitioner urged, were not taught in the prior art:
`
`Linking the two strands of a double stranded nucleic acid template with a
`hairpin-containing adaptor prior to sequencing provides a number of
`surprising and unexpected advantages that are neither taught nor
`disclosed by the cited references. Interrogating each position in the original
`template nucleic twice (once on the sense strand and once on the antisense
`strand) gives greater certainty that each position in the nucleic acid has been
`observed. Combining the current data for each position in the sense and anti-
`sense strands generates an aggregate call of a greater quality score than
`would be possible with a single observation. This ensures that the quality of
`the sequence data generated is much higher, with a reduced potential for
`misidentified base calls or completely missed bases.
`Id. at 11 (emphasis added).
`
`While Petitioner now contends the ’929 patent is obvious, its prior
`
`representations to the Patent Office, the limited disclosure in the art, and the lack of
`
`meaningful reasoning in the Petition confirm that any assertion of obviousness is
`
`based on nothing but hindsight. The ’929 patent represents an important invention,
`
`the benefits of which are so substantial that Petitioner has adopted it for use in its
`
`own products.
`
`The patent is the subject of co-pending district court litigation that has been
`
`pending since September 2017, with trial set for March 2020. Had Petitioner truly
`
`believed the ’929 patent was obvious, it surely would have promptly sought review
`
`before this tribunal. Yet, Petitioner waited almost a year into the district court
`
`4
`
`
`
`
`
`litigation, delaying its IPR filing until the last possible day. Petitioner’s delay was
`
`so substantial that the Board will not complete its review before the district court has
`
`fully adjudicated the validity of the ’929 patent. The Board should not allow this
`
`IPR to proceed further, not just because the merits of the request are so weak, but
`
`also because the district court will fully adjudicate validity before this tribunal will
`
`have a chance to do so.
`
`II. THE BOARD SHOULD EXERCISE ITS DISCRETION TO DENY
`INSTITUTION PURSUANT TO §§ 314(A) AND 324(A)
`While the Petition is substantively deficient, and institution should be denied
`
`on the merits, the Board should also exercise its discretion and deny this petition
`
`under 35 U.S.C. §§ 314(a) and 324(a) because it would be a waste of the Board’s
`
`finite resources and fundamentally unfair to Patent Owner to institute a trial that
`
`would result in a final written decision after the conclusion of the same validity
`
`challenge in the related district court litigation.
`
`The efficient resolution of patent challenges is foundational to the IPR system
`
`and the AIA generally. To this end, it is “an objective of the AIA . . . to provide an
`
`effective and efficient alternative to district court litigation.” General Plastic Indus.
`
`Co., Ltd. v. Canon Kabushiki Kaisha, Case IPR2016-01357, Paper 19 at 16-17
`
`(PTAB Sept. 6, 2017) (precedential); see also Microsoft Corp. v. Koninkijke Philips
`
`N.V., Case IPR2018-00277, Paper 10 at 7 (PTAB June 8, 2018) (explaining that
`
`“AIA proceedings ‘are not to be used as tools for harassment or a means to prevent
`5
`
`
`
`
`
`market entry through repeated litigation and administrative attacks on the validity of
`
`a patent. Doing so would frustrate the purpose of the section as providing quick and
`
`cost effective alternatives to litigation’” quoting H.R. Rep. No. 112-98, pt. 1, at 48
`
`(2011)).
`
`This purpose is frustrated when, as here, a party delays filing a Petition until
`
`such time that the IPR, if instituted, would result in a final written decision only after
`
`the same validity issues have been resolved by a district court. See NHK Spring Co.
`
`Ltd. v. Intri-Plex Techs., Inc., Case IPR2018-00752, Paper 8 at 19-20 (PTAB Sept.
`
`12, 2018). The Board has also recognized “the potential for abuse of the review
`
`process by repeated attacks on patents” in deciding to exercise its discretion under
`
`§§ 314(a) and 324(a). See Gen. Plastic, IPR2016-01357, Paper 19 at 16-17 (“Our
`
`intent in formulating the factors [used in determining whether to exercise discretion]
`
`was to take undue inequities and prejudices to Patent Owner into account.”).
`
`A.
`Strategic Delay in Filing the Petition
`Patent Owner filed suit against Petitioner in district court for infringement of
`
`one of its nanopore sequencing patents, the ’400 Patent, on March 15, 2017. On
`
`September 25, 2017, Patent Owner filed a second action asserting infringement of
`
`the ’929 and ’056 Patents. Exs. 2002, 2003. The two litigations were subsequently
`
`consolidated by the Court. On July 13, 2018, Petitioner served its invalidity
`
`contentions for all of the asserted patents, alleging invalidity of the ’929 Patent based
`
`6
`
`
`
`
`
`on Akeson, Gupte, Sanger, and Makrigiorgos, the same exact references at issue
`
`here. Ex. 2004 [Inv. Cont. Cover Doc].
`
`Petitioner filed its first IPR petition related to the patents in suit on March 15,
`
`2018, more than six months before it filed the current petition. See IPR2018-00789
`
`Paper 1. Petitioner’s delay in filing this Petition allowed it to review both the patent
`
`owner preliminary response and the Board’s denial of institution in its earlier filed
`
`petition before filing this one. See IPR2018-00789, Paper 7 (July 5, 2018); IPR2018-
`
`00789, Paper 8 (Sept. 25, 2018). Petitioner’s delay in filing of this Petition can be
`
`seen as a way of gaming the system to gain an unfair advantage.
`
`B.
`Status of District Court Litigation
`Due to Petitioner’s delay in filing the current Petition, the district court
`
`litigation is at an advanced stage, and trial will conclude before a final written
`
`decision will issue in this proceeding. The district court Markman hearing has been
`
`held, and the Court’s claim construction order is likely to be issued prior to any
`
`institution decision in this proceeding. Ex. 2005 [Markman Scheduling Order].
`
`Trial is set for five days starting on March 9, 2020. Ex. 2007 [Scheduling Order].
`
`Thus, the district court will reach a verdict on the validity of the ’929 Patent based
`
`on the same prior art before the completion of this proceeding.
`
`7
`
`
`
`
`
`C. The Board Has Broad Discretion to Deny Institution Under 35
`U.S.C. §§ 314(a) and 324(a)
`The Board has discretion under §§ 314(a) and 324(a) to deny institution of a
`
`petition. This “discretion is informed by 35 U.S.C. §§ 316(b) and 326(b), which
`
`require the Director to ‘consider the effect of any such regulation [under this section]
`
`on the economy, the integrity of the patent system, the efficient administration of the
`
`Office, and the ability of the Office to timely complete proceedings instituted under
`
`this chapter.’” August 2018 Update to the Office Patent Trial Practice Guide at 9
`
`(Aug. 13, 2018) (“August 2018 Trial Practice Guide Update”). In discussing this
`
`discretion, the August 2018 Trial Practice Guide Update recognizes that the “AIA
`
`was ‘designed to establish a more efficient and streamlined patent system that will
`
`improve patent quality and limit unnecessary and counterproductive litigation
`
`costs.’” Id. (citing H.R. Rep. No. 112-98, pt. 1, at 40 (2001), 2011 U.S.C.C.A.N.
`
`67, 69).
`
`The Board has applied its discretion to deny institution under §§ 314(a) and
`
`324(a) on facts substantially identical to those presented here. See NHK Spring Co.,
`
`Case IPR2018-00752, Paper 8. In NHK Spring, like the instant case, (1) the parties
`
`were engaged in District Court litigation on the same patent, (2) the petitioner was
`
`relying on the same prior art in the petition as in the litigation, and (3) the District
`
`Court trial would conclude before the IPR. Id. at 19-20. The Board cited the
`
`“advanced state of the district court proceedings” and concluded that the “Patent
`8
`
`
`
`
`
`Owner argues persuasively that instituting a trial under the facts and circumstances
`
`here would be an inefficient use of Board resources.” Id. at 20. In NHK Spring, the
`
`Board noted that “[i]nstitution of an inter partes review under these circumstances
`
`would not be consistent with ‘an objective of the AIA . . . to provide an effective and
`
`efficient alternative to district court litigation’” and denied institution. Id.
`
`Here, the parties are currently engaged in District Court litigation on the same
`
`patent, and Petitioner relies on the same primary references—Akeson, Gupte,
`
`Sanger, and Makrigiorgos—for invalidity. Moreover, a trial on the validity of the
`
`’929 Patent in the District Court will be complete before a final written decision
`
`would be issued if this proceeding were instituted. Ex. 2007 [Scheduling Order].
`
`The only distinction between NHK Spring and the instant case is that the ’929 Patent
`
`is not expired (i.e., the broadest reasonable interpretation applies in claim
`
`construction). This is a distinction without a difference. Petitioner and Patent
`
`Owner agree that there are no claim construction issues to be resolved in this
`
`proceeding. As such, all terms should be given their ordinary meaning. See Vivid
`
`Techs., Inc., v. American Science & Engineering, 200 F.3d 795, 803 (Fed. Cir. 1999).
`
`Thus, there is no claim construction necessary and no relevant difference in the claim
`
`construction standards to be applied.
`
`9
`
`
`
`
`
`As in NHK Spring, the Board should exercise its discretion not to institute trial
`
`here, as it would be a waste of both the Board’s and the Parties’ resources and
`
`fundamentally at odds with Congress’s intent for IPR proceedings.
`
`D. The General Plastic Factors Also Weigh Against Institution
`In addition to the factors identified in NHK Spring, the Board has identified a
`
`set of non-exclusive factors to determine whether a discretionary denial is
`
`appropriate when multiple IPR petitions have been filed on the same patent. General
`
`Plastic Industrial Co., Ltd. v. Canon Kabushiki Kaisha, Case IPR2016-01357, Paper
`
`19 (PTAB Sept. 6, 2017) (precedential as to § II.B.4.i). These factors are:
`
`whether the same petitioner previously filed a petition
`1.
`directed to the same claims of the same patent;
`
`whether at the time of filing of the first petition the
`2.
`petitioner knew of the prior art asserted in the second petition or should
`have known of it;
`
`whether at the time of filing of the second petition the
`3.
`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;
`
`the length of time that elapsed between the time the
`4.
`petitioner learned of the prior art asserted in the second petition and the
`filing of the second petition;
`
`10
`
`
`
`
`
`whether the petitioner provides adequate explanation for
`5.
`the time elapsed between the filings of multiple petitions directed to the
`same claims of the same patent;
`
`6.
`
`the finite resources of the Board; and
`
`the requirement under 35 U.S.C. § 316(a)(11) to issue a
`7.
`final determination not later than 1 year after the date on which the
`Director notices institution of review.
`
`Id. at 9-10.
`
`While these factors were articulated in the context of multiple petitions filed
`
`on the same patent by the same party, the Board has subsequently applied these
`
`factors in other contexts. See NetApp, Inc. v. Realtime Data LLC, Case IPR2017-
`
`01195, Paper 9 (PTAB Oct. 12, 2017) at 10 (“[O]ur discretion under [§ 314(a)] and
`
`37 C.F.R. § 42.108(a) is not limited to situations where the same party files multiple
`
`petitions ….”); see also August 2018 Trial Practice Guide Update at 10 (“The
`
`General Plastics factors are also not exclusive and are not intended to represent all
`
`situations where it may be appropriate to deny a petition.”). Here, while there have
`
`not been multiple IPR petitions filed on the ’929 Patent, the General Plastic factors
`
`still weigh against institution.
`
`As acknowledged by the Board in NetApp, Factor 1 weighs slightly in favor
`
`of institution because Petitioner has not previously filed a Petition challenging the
`
`11
`
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`
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`’929 Patent; however, factor 2 is neutral in light of factor 1. NetApp, Inc., IPR2017-
`
`01195, Paper 9 at 10.
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`Factor 3 weighs strongly against institution. Here, Petitioner had the
`
`advantage of reviewing both Patent Owner’s preliminary responses and the Board’s
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`denial of institution in a related IPR proceeding before filing the current Petition.
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`This is the exact kind of unfair advantage that the Board was concerned with in
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`General Plastic.
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`Factor 4 also weighs against institution. Petitioner was aware of the primary
`
`prior art relied upon in the Petition no later than July 13, 2018 when it served its
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`invalidity contentions based on the same references. See Ex. 2004. Petitioner
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`nonetheless delayed in filing its petition, allowing it to obtain an unfair advantage.
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`Factor 5 weighs against institution or is neutral. Here, only one petition for
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`IPR has been filed. Nonetheless, Petitioner has offered no explanation for its delay
`
`in filing the current Petition after it had already developed its invalidity positions.
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`Factors 6 and 7 also weigh against institution. As discussed above,
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`Petitioner’s validity challenges will be fully resolved via jury trial in District Court
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`before the Board would reach its determination. Moreover, Petitioner had ample
`
`opportunity to file a petition for inter partes review during the spring of 2018,
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`allowing the IPR proceedings to complete before the District Court litigation.
`
`12
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`
`
`
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`Due to Petitioner’s delay in filing its Petition and the time limit for issuance
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`of a final written decision, instituting an inter partes review at this time would
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`require the Board to conduct a proceeding involving issues that will already be
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`resolved. See NetApp, Inc., IPR2017-01195, Paper 9 at 13. “The result would be a
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`significant waste of the Board’s resources” with “no offsetting conservation” of
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`judicial resources “because any final written decision in this proceeding would not
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`issue until well after the scheduled trial date.” Id.
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`Based on these facts, the General Plastic factors weigh in favor of denial of
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`institution. This Petition is the antithesis of the “effective and efficient alternative
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`to district court litigation” contemplated by the AIA. The Board should exercise its
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`discretion and deny institution.
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`III. BACKGROUND
`A. Overview Of Sequencing Technology And The State Of The Art
`1.
`Prior Art Ensemble Sequencing Techniques
`Techniques to sequence DNA molecules first arose in the mid-1970s. Around
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`that time, Dr. Frederick Sanger developed a method that became widely adopted
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`because it was relatively easy to use and provided reproducible data.
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`The Sanger method is based on a signal from a multitude of single-stranded
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`DNA molecules. The method begins with a DNA sample where the double-stranded
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`DNA helices have been separated into their constituent single strands by, for
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`13
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`
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`
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`example, heating. These single-stranded molecules are then copied millions of times
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`to create a “clonal population.” As originally implemented, the clonal population of
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`single-stranded DNA molecules to be sequenced is divided up into four separate
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`vials, each of which will be used in a separate sequencing reaction where a
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`polymerase enzyme will be used to synthesize complementary DNA. Each of the
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`four reactions will include the sample single-stranded DNA molecules, the
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`polymerase enzyme, and the nucleotide building blocks needed to synthesize DNA.
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`The four reactions differ from each other, however, in that each of them also
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`includes a different kind of “terminator” nucleotide. Briefly, DNA polymerases can
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`incorporate not just natural nucleotides, but also analogues of nucleotides. One such
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`analogue is referred to as a “terminator.” When a terminator nucleotide is
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`incorporated into the growing DNA strand, the polymerase becomes blocked and is
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`no longer capable of adding additional nucleotides; the polymerization reaction
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`based on that particular template DNA then comes to an end.
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`As the polymerization reaction proceeds, at some point a terminator
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`nucleotide will be incorporated, and the reaction will end selectively at A, C, G, or
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`T depending on whether the reaction is the one that includes the A, C, G, or T
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`terminator. Therefore, each sequencing reaction will produce sets, or ensembles, of
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`different-sized nucleic acid chains, each of which contains all of the molecules
`
`14
`
`
`
`
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`whose reactions end at the position where the particular terminator nucleotide
`
`happened to be incorporated.
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`The product from each of the four separate sequencing reactions is added to a
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`separate lane of the agarose gel, and the different sized products are physically
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`separated. A typical gel that results from the Sanger sequencing process is shown
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`below. Each band in the gel represents the ensemble of thousands of nucleic acids
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`that were terminated at that size. For instance, reading the gel below from top to
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`bottom yields the sequence CGTTATCTTC… and so on.
`
`
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`The saturation of the band is a function of the number of nucleic acids that were
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`terminated at that size.
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`Importantly, the signal in each band in the gel above derives from thousands
`
`of sequencing reactions occurring in synchrony; each error that occurs during the
`15
`
`
`
`
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`sequencing of any single molecule within the population is averaged out by the
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`signal from thousands of other molecules where there was no error. Accordingly,
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`the sequence can be easily and accurately read from the gel shown above.
`
`2.
`Single-Molecule Sequencing
`Unlike traditional sequencing techniques such as Sanger sequencing, single-
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`molecule sequencing techniques produces data from individual molecules of DNA,
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`not an ensemble made up of thousands of DNA molecules.
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`One such single-molecule sequencing approach is Patent Owner’s SMRT®
`
`(“Single Molecule Real-Time”) sequencing approach. In SMRT® sequencing, a
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`single-stranded DNA template molecule is contacted with a single DNA polymerase
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`enzyme that is anchored to the bottom of a very small hole. The activity of the
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`enzyme is then monitored in real time as it synthesizes a complementary strand of
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`DNA using fluorescently labeled nucleotides. To determine the sequence, the
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`fluorescence given off during incorporation of individually labeled nucleotides is
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`monitored by focusing excitation illumination into the bottom of the tiny hole, as
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`shown below:
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`16
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`
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`The type of signal that arises from the SMRT® sequencing approach is
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`illustrated in the schematic below, which shows the incorporation of two different
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`nucleotides:
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`17
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`As shown above, with each nucle
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