Court Opinion

ID: 4685654
Source: CourtListenerOpinion
Date Created: 2021-05-11 15:00:51.756187+00
Date Added: 2024-06-11T08:04:29.440610
License: Public Domain

Case: 20-2155    Document: 42     Page: 1   Filed: 05/11/2021

   United States Court of Appeals
       for the Federal Circuit
                  ______________________

   PACIFIC BIOSCIENCES OF CALIFORNIA, INC.,
                Plaintiff-Appellant

                             v.

    OXFORD NANOPORE TECHNOLOGIES, INC.,
    OXFORD NANOPORE TECHNOLOGIES, LTD.,
              Defendants-Appellees
             ______________________

                   2020-2155, 2020-2156
                  ______________________

     Appeals from the United States District Court for the
 District of Delaware in Nos. 1:17-cv-00275-LPS, 1:17-cv-
 01353-LPS, Chief Judge Leonard P. Stark.
                  ______________________

                  Decided: May 11, 2021
                  ______________________

     EDWARD R. REINES, Weil, Gotshal & Manges LLP, Red-
 wood Shores, CA, argued for plaintiff-appellant. Also rep-
 resented by ROBERT S. MAGEE, DEREK C. WALTER.

    MICHAEL HAWES, Baker Botts, LLP, Houston, TX, ar-
 gued for defendants-appellees.   Also represented by
 ELIZABETH FLANNERY; STEPHEN M. HASH, Austin, TX.
                ______________________

    Before LOURIE, TARANTO, and STOLL, Circuit Judges.
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 2    PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES

 TARANTO, Circuit Judge.
      Pacific Biosciences of California, Inc. (PacBio) sued Ox-
 ford Nanopore Technologies, Inc. and Oxford Nanopore
 Technologies, Ltd. (collectively, Oxford), accusing Oxford of
 infringing several of its patents, including U.S. Patent Nos.
 9,546,400 and 9,772,323. A jury found all asserted claims
 infringed but also determined that they are invalid under
 35 U.S.C. § 112 for lack of enablement. The district court
 denied PacBio’s motion for judgment as a matter of law
 (and for a new trial) on enablement. The district court also
 denied PacBio’s request that the court grant a new trial be-
 cause of Oxford’s improper remarks during opening, re-
 marks that included references to the potential
 applications of its accused products to the then-emerging
 global COVID-19 crisis. PacBio argued that the remarks
 caused prejudice that could not be remedied by the curative
 instruction the district court gave at PacBio’s request. We
 affirm.
                               I
      PacBio owns the ’400 and ’323 patents, which share a
 specification, so we generally cite only the ’400 patent’s
 specification. The patents describe methods for sequencing
 a nucleic acid, such as deoxyribonucleic acid (DNA). The
 methods use nanopore technology, described in one form as
 follows: nucleic acids are drawn through nanometer-sized
 holes formed in a substrate, and while they transit the
 holes, their sequences of nucleotides are identified or char-
 acterized based on changes in electric current passing
 through the substrate. See ’400 patent, col. 1, lines 25–27;
 id., col. 8, lines 55–61. The ’323 patent issued from a con-
 tinuation of a continuation of the application that issued as
 the ’400 patent; and both claim priority to a provisional ap-
 plication filed on April 10, 2009.
     The patents, in discussing the prior art, explain that
 “rapid determination of the nucleotide sequence . . . is a
 major goal of researchers seeking to obtain the sequence
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES          3

 for the entire genome of an organism.” Id., col. 1, lines 19–
 22. The patents’ solution includes a system with “upper
 and lower fluidic regions” above and below a membrane
 having a nanopore passage from one region to the other,
 with electrodes that permit application of a voltage to cre-
 ate a potential difference that causes molecules to “trans-
 locate” between the two regions. Id., col. 8, lines 35–38, 48–
 61; id., col. 9, lines 6–15, 47–53; id., col. 10, line 64 through
 col. 11, line 5. The membrane in which the nanopores are
 formed, as described by the patents, can use lipid or solid-
 state materials and may include “hybrid” nanopores,
 formed by treating substrate material with organic mole-
 cules, such as proteins, that serve as “spacers” to narrow
 the nanopores so that only single strands of DNA (ssDNA)
 or ribonucleic acid (ssRNA) pass through, “in a sequential,
 single file order.” Id., col. 1, lines 28–31; id., col. 14, lines
 1–60; id., col. 15, lines 3–10; id., col. 17, lines 42–53; see
 also id., Fig. 5.
      The patents further describe using “processive DNA-
 binding enzyme[s] to enzymatically regulate the rate of
 ssDNA translocation through the nanopore.” Id., col. 25,
 lines 11–13; see also id., col. 24, lines 53–54 (“In certain
 embodiments, polymerases are used to modulate the pas-
 sage of a nucleic acid strand through a nanopore.”). Too
 fast a rate may impair accuracy, and enzymes can “promote
 efficient sequence detection, e.g., by allowing a reaction to
 proceed at a rate that provides for a desirable balance be-
 tween accuracy and throughput.” Id., col. 25, lines 3–10.
 The patents state that enzymes can bind to ssDNA in the
 fluid, then combine with the protein “spacer” in the na-
 nopore to “act as a plug,” but that “[a]pplying a strong
 enough [electric] potential can rip the ssDNA from the
 tightly bound exonuclease, advancing the ssDNA through
 the nanopore.” Id., col. 25, lines 29–34; see also id., Fig.
 25(A) & (B). Pulses that alternate large and small poten-
 tial differences, when used in connection with the enzyme,
 “can pull the ssDNA through the nanopore in steps, for
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 4    PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES

 example one base at a time. The rate and duty cycle of the
 pulses could be altered to optimize the translocation rate
 and measurement duration.” Id., col. 25, lines 34–40.
      For the sequencing of ssDNA (identifying the sequence
 of its individual nucleotides), the patents describe use of
 “an array of electrical/CMOS [complementary metal-oxide-
 semiconductor] components (amplifiers)” that measure as-
 pects of a current through the substrate—e.g., amplitude
 and duration of “current blockage,” and “interpulse dura-
 tion”—as ssDNA moves through the nanopore. Id., col. 20,
 lines 6–9; id., col. 29, lines 43–46; id., col. 41, lines 46–56.
 The patents note, however, that such measurements “can
 overlap significantly” between different nucleotides, creat-
 ing “miscall errors.” Id., col. 29, lines 46–50; see also id.,
 col. 41, lines 60–63 (“Thus, if the probability distribution of
 current blockage (likely Gaussian-like) for a nucleotide is
 highly overlapping with that of a different nucleotide, then
 there may be a large probability of miscall if only this met-
 ric is used.”). This problem, the patents state, prevented
 prior art systems from “achiev[ing] single nucleotide reso-
 lution, especially in embodiments that might be scaled to a
 commercially viable DNA sequencing system.” Id., col. 39,
 lines 49–51.
      The patents state a reason for the resolution troubles:
 “[T]he amplitude of electric current passing through the
 nanopore (which constitutes the signal) depends on the
 identity of several bases that reside in the pore throughout
 the duration of the current measurement.” Id., col. 39,
 lines 52–55. Given that there are four different nucleo-
 tides, there are 4N possibly different current levels if
 “N=the number of bases that affect the current measure-
 ment.” Id., col. 39, lines 55–60; see also id., col. 41, lines
 46–56. But, the patents note, there may not be 4N distinct
 current levels for the 4N possible N-long nucleotide se-
 quences (“some of [the possibilities] may be degenerate”).
 Id., col. 39, lines 59–60.
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES       5

     The sole independent claim of the ’400 patent, claim 1,
 recites:
     1. A method for sequencing a nucleic acid template
        comprising:
        a) providing a substrate comprising a nanopore
        in contact with a solution, the solution compris-
        ing a template nucleic acid above the nanopore;
        b) providing a voltage across the nanopore;
        c) measuring a property which has a value that
        varies for N monomeric units of the template
        nucleic acid in the pore, wherein the measuring
        is performed as a function of time, while the
        template nucleic acid is translocating through
        the nanopore, wherein N is three or greater; and
        d) determining the sequence of the template nu-
        cleic acid using the measured property from
        step (c) by performing a process including com-
        paring the measured property from step (c) to
        calibration information produced by measuring
        such property for 4 to the N sequence combina-
        tions.
 ’400 patent, col. 47, line 37 through col. 48, line 6. Depend-
 ent claim 4 of the ’400 patent includes the additional re-
 quirement that “the translocation rate through the pore is
 enzymatically controlled.” Id., col. 48, lines 11–12. The
 sole independent claim of the ’323 patent, claim 1, is simi-
 lar to claim 1 of the ’400 patent, but not identical: for ex-
 ample, it requires a “plurality of template nucleic acids
 above the nanopore” and includes an “enzymatically con-
 trolled” limitation (as in dependent claim 4 of the ’400 pa-
 tent). See ’323 patent, col. 47, lines 13–34. PacBio asserted
 claims 1, 4, and 15 of the ’400 patent, and claims 1, 4, and
 18 of the ’323 patent. The parties agree that the patents
 and the asserted claims are materially similar for purposes
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 6   PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES

 of the issues on appeal. See PacBio Opening Br. 22 n.3;
 Oxford Br. 3 n.1.
                              B
     PacBio sued Oxford in the District of Delaware in 2017,
 asserting in two separately filed cases that Oxford in-
 fringed the ’400 and ’323 patents, as well as two other pa-
 tents (U.S. Patent Nos. 9,678,056 and 9,738,929) that are
 not at issue on appeal. Before trial, the district court
 granted a PacBio motion in limine (MIL) “to prevent [Ox-
 ford] from using ‘pejorative’ terms (such as ‘non-practicing
 entity,’ ‘NPE,’ and ‘paper patents’) and from presenting ev-
 idence about the consequences of this litigation.” J.A. 27
 (MIL Order). The court’s order continued, “it would be in-
 appropriate to put before the jury evidence or argument
 about the potential impact of a verdict in favor of PacBio—
 such as higher prices or slower medical research—as these
 issues are not for the jury to decide . . . .” Id.
     The trial began on March 9, 2020, as concerns about
 the new coronavirus SARS-CoV-2, causing COVID-19,
 were already rampant but had not yet produced the large-
 scale shutdowns that would occur in a matter of days. The
 opening statements from both parties acknowledged
 COVID-19 and the relevance of the DNA-sequencing tech-
 nology at issue to dealing with this virus and others; and it
 is undisputed that Oxford told PacBio the night before the
 openings that it would mention such relevance, and that
 PacBio did not object in advance. PacBio, in its opening,
 mentioned the new coronavirus in passing. J.A. 1073 (Tr.
 120:24–121:11 (PacBio mentioning coronavirus and se-
 quencing can “[m]aybe help develop a vaccine”)). Then Ox-
 ford did so much more extensively (than PacBio did and
 than prefigured in Oxford’s pre-opening notice to PacBio)
 and with specific factual assertions. See J.A. 1079 (Tr.
 145:4–12), 1081–82 (Tr. 153:3–156:25 (Oxford discussing
 “infectious disease monitoring” and telling a story about
 sending products to Wuhan, China, at the outset of the
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES       7

 coronavirus outbreak)). Oxford made those remarks as
 part of its references to PacBio seeking to exclude Oxford’s
 products and to previous litigation between the parties on
 other patents. J.A. 1079 (Tr. 143:2–145:12), 1084 (Tr.
 165:9–12), 1085 (Tr. 169:2–17).
     PacBio objected to Oxford’s opening, mentioning both
 the reference to previous litigation and the statement that
 PacBio was “attempting to exclude it from the market,
 which [the MIL Order] said that the effect of the case and
 the possible ramifications was clearly an implication.”
 J.A. 1084–85 (Tr. 165:13–166:11); see also J.A. 1089
 (Tr. 185:3–9 (preserving objection)). The next day, PacBio
 argued in favor of its motion for two curative instructions
 to counteract “the exploitation of the violation of the MIL
 [Order].” J.A. 1153 (Tr. 279:2–3). 1 The district court

     1    See J.A. 1153 (Tr. 279:2–19) (“The issue is the clear
 vio—that is the exploitation of the violation of the MIL. I
 mean, it’s so cynical. The violation of the MIL is not the
 mention of coronavirus. I knew they were going to do. We
 did it. We’ve done that same work. We weren’t flamboyant
 about it. They were. Over the top, one might say. [¶] But
 leaving that aside, that’s just exploiting the violation. The
 violation is we specifically said they shouldn’t be stating
 that we’re trying to exclude nanopore sequencing. That is
 exactly what the Court ordered. That is exactly what [Ox-
 ford’s counsel] knowingly, intentionally, and willfully did
 to the jury, knowing, like we all know, the bell can’t be un-
 rung. Presumably, a happy client somewhere. And that
 that is what they did. [¶] And the media [in a report of the
 previous day’s opening] said that the trial is about PacBio
 trying to take the coronavirus technology off the market.
 Why? Because that is the only way to understand the tran-
 script.”); J.A. 1155 (Tr. 287:23–288:3) (“Your Honor, there
 was a clear violation of the order and the statement of ex-
 ploiting it for the Coronavirus is very different. It’s not a
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 8   PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES

 criticized Oxford for violating the MIL Order, recognizing
 that the COVID-19 references were part of that violation,
 and agreed to give the curative instructions that PacBio
 had requested. J.A. 1156–57 (Tr. 292:17–294:12).
     One instruction addressed the reference to other pro-
 ceedings. J.A. 1159 (Tr. 303:10–15). The other stated:
          In opening statement, [Oxford] argued that
     this isn’t the first time that PacBio has tried to use
     its patents to exclude nanopore sequencing. How-
     ever, if you find [Oxford] liable for patent infringe-
     ment, you are not—you are only being asked to
     award monetary compensation to PacBio. You are
     not being asked to exclude any [Oxford] product
     from the market or to stop any research work being
     performed on [Oxford] products.
 J.A. 1159 (Tr. 303:17–24). Before giving the instructions,
 the court also warned both parties about “turn[ing] this re-
 ally into a trial about an ongoing global health crisis that
 has to be on the minds of the jury,” which would be “unfair”
 and “improper” and would “inflam[e] the jury” and “would
 create a real risk of a verdict” not based on the evidence.
 J.A. 1157 (Tr. 293:22–294:5). The court required the par-
 ties, from then on, to disclose to each other “any reference,
 any evidence, any suggestion that you think you’re going to
 make to Coronavirus” and bring any disputes to the court’s
 attention “before the witnesses take the stand.” J.A. 1157
 (Tr. 294:6–12).
     PacBio did not seek a new trial at that time. During
 closing, Oxford used words such as “exclude” and “block,”
 borrowing words from PacBio testimony or documents, see
 J.A. 1105 (Tr. 247:3–6), 1503 (Tr. 1225:11–1226:3), and the

 violation of any order to mention the word, although it may
 come to that if this continues. And so that’s confusing, that
 they’re mushing the two things together.”).
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES      9

 closing was not found to be improper. See J.A. 1686–88 (Tr.
 1612:21–1618:21), 1689 (Tr. 1622:3–25); see also J.A. 1989–
 90, 1996–97. Moreover, PacBio has not identified any post-
 opening COVID-19 comment made by Oxford to the jury,
 and the district court noted that Oxford did not violate the
 MIL Order after the opening. See J.A. 53 (7/30/20 Tr. 17:9–
 14); Pac. Biosciences of Cal., Inc. v. Oxford Nanopore
 Techs., Inc., Nos. 1:17-cv-00275, 1:17-cv-01353, 2020 WL
 4699049, at *5 (D. Del. Aug. 13, 2020) (Post-Trial Decision).
     The case went to the jury on March 17, 2020, J.A. 1706,
 and the jury returned its verdict on March 18, 2020, J.A.
 1741–43; see J.A. 399–414 (verdict). The jury found all as-
 serted claims of the ’400 and ’323 patents infringed, and
 also supported by the written description, but also deter-
 mined that all of the asserted claims are invalid for lack of
 enablement. J.A. 401–03, 407–08. The district court en-
 tered judgment for Oxford based on the jury’s verdict on
 March 31, 2020.
     After trial, PacBio renewed its motion for judgment as
 a matter of law (JMOL) on enablement lodged during trial
 under Federal Rule of Civil Procedure 50. J.A. 27,435–60.
 PacBio also moved for a new trial under Rule 59, arguing
 that the jury’s enablement verdict was unsupported and
 that Oxford’s statements regarding COVID-19 violated the
 MIL Order and were so prejudicial that the case should be
 retried. Id. The district court denied PacBio’s motion.
 Post-Trial Decision, 2020 WL 4699049, at *1.
     For JMOL on the enablement verdict, the court noted
 a statement by Oxford’s expert, Dr. Nick Goldman, on cross
 examination, that a relevant artisan, having a particular
 piece of prior art, could perform the method of claim 1 of
 the ’400 patent in 2009, and the court also noted Dr. Gold-
 man’s statement that he did not know the factors specified
 in In re Wands, 858 F.2d 731 (Fed. Cir. 1988). Post-Trial
 Decision, 2020 WL 4699049, at *1. But the court concluded
 that the record “as a whole” did “contain substantial
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 10   PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES

 evidence to support the verdict” of non-enablement. Id. at
 *2. The district court identified evidence beyond Dr. Gold-
 man’s testimony that was relevant to the Wands factors
 and could support the jury’s verdict; and the court noted
 Dr. Goldman’s testimony that the claims at issue were not
 enabled and stressed that the jury was free to consider Dr.
 Goldman’s credibility and all the evidence. Id. at *2–3.
      The court similarly rejected PacBio’s motion for a new
 trial based on references to COVID-19 made in Oxford’s
 opening statement. Acknowledging that such references
 implicated the possible consequences of the jury’s verdict
 in violation of the MIL Order, the court explained, “[t]here
 is just no indication . . . that this jury was inflamed, that it
 was not careful,” or that the jury otherwise failed to
 properly consider the evidence because of the mentions of
 COVID-19. Id. at *8–9 (alteration in original).
     The court entered final judgment on August 13, 2020.
 Id. at *1. PacBio timely appealed. We have jurisdiction
 under 28 U.S.C. § 1295(a)(1).
                                II
     On appeal, PacBio argues that the jury’s verdict find-
 ing that the ’400 and ’323 patents lack enabling disclosure
 is unsupported by the evidence, requiring JMOL in its fa-
 vor. See PacBio Opening Br. 21–41. PacBio also argues
 summarily for a new trial based on the enablement evi-
 dence. Id. at 42. Much more fully, PacBio argues for a new
 trial based on Oxford’s statements about COVID-19. Id. at
 42–60. We reject these challenges.
                                A
      We review a district court’s decision on a JMOL motion
 de novo, following the law of the regional circuit, here the
 Third Circuit. Leader Techs., Inc. v. Facebook, Inc., 678
 F.3d 1300, 1305 (Fed. Cir. 2012). “[V]iewing the record in
 the light most favorable to the verdict winner and drawing
 all reasonable inferences in its favor,” id., we ask whether
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES        11

 “a reasonable jury would not have a legally sufficient evi-
 dentiary basis to find for the party,” Fed. R. Civ. P. 50(a)(1).
 See also In re Lemington Home for the Aged, 777 F.3d 620,
 626 (3d Cir. 2015) (JMOL may be granted “only if, as a mat-
 ter of law, the record is critically deficient of that minimum
 quantity of evidence from which a jury might reasonably
 afford relief” to the verdict winner). “[W]hether a patent
 satisfies the enablement requirement is a question of law
 based on underlying factual findings.” McRO, Inc. v. Ban-
 dai Namco Games America Inc., 959 F.3d 1091, 1096 (Fed.
 Cir. 2020). Here, “we review the factual underpinnings of
 enablement for substantial evidence.” Idenix Pharms. LLC
 v. Gilead Sciences Inc., 941 F.3d 1149, 1154 (Fed. Cir. 2019)
 (internal quotation marks omitted). With no greater detail
 in the verdict, we treat the jury as having made all verdict-
 supporting factual findings that are supported by substan-
 tial evidence. See Martek Biosciences Corp. v. Nutrinova,
 Inc., 579 F.3d 1363, 1378 (Fed. Cir. 2009) (describing “im-
 plicit factual findings” approach); Kinetic Concepts, Inc. v.
 Smith & Nephew, Inc., 688 F.3d 1342, 1359–60 (Fed. Cir.
 2012) (same for obviousness).
     “The requirement of enablement, stated in 35 U.S.C.
 § 112, enforces the essential ‘quid pro quo of the patent bar-
 gain’ by requiring a patentee to teach the public how ‘to
 practice the full scope of the claimed invention.’” McRO,
 959 F.3d at 1099–100 (quoting AK Steel Corp. v. Sollac, 344
 F.3d 1234, 1244 (Fed. Cir. 2003)); see also J.E.M. Ag Sup-
 ply, Inc. v. Pioneer Hi-Bred Int’l, Inc., 534 U.S. 124, 142
 (2001). A claim is not enabled if (as it is the challenger’s
 burden to prove by clear and convincing evidence) a rele-
 vant artisan would not be able to practice the claimed in-
 vention “without undue experimentation,” Amgen Inc. v.
 Sanofi, 987 F.3d 1080, 1084 (Fed. Cir. 2021) (internal quo-
 tation marks omitted), a determination typically guided by
 the following “factual considerations”: “(1) the quantity of
 experimentation necessary, (2) the amount of direction or
 guidance presented, (3) the presence or absence of working
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 12   PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES

 examples, (4) the nature of the invention, (5) the state of
 the prior art, (6) the relative skill of those in the art, (7) the
 predictability or unpredictability of the art, and (8) the
 breadth of the claims,” id. (quoting Wands, 858 F.2d at
 736–37). “[A] patentee chooses broad claim language at the
 peril of losing any claim that cannot be enabled across its
 full scope of coverage.” MagSil Corp. v. Hitachi Glob. Stor-
 age Techs., Inc., 687 F.3d 1377, 1381 (Fed. Cir. 2012);
 Amgen, 987 F.3d at 1084; Idenix, 941 F.3d at 1154; Trustees
 of Boston Univ. v. Everlight Elecs. Co., 896 F.3d 1357, 1362
 (Fed. Cir. 2018); Crown Operations Int’l, Ltd. v. Solutia
 Inc., 289 F.3d 1367, 1378–79 (Fed. Cir. 2002); Nat’l Recov-
 ery Techs. Inc. v. Magnetic Separation Systems, Inc., 166
 F.3d 1190, 1196 (Fed. Cir. 1999).
     Although PacBio seems to suggest otherwise at some
 points, it is not enough for enablement here that relevant
 artisans knew how to perform some “nanopore sequencing”
 before the priority date of the ’400 and ’323 patents. What
 matters is the scope of the asserted claims, which (taken as
 a whole, as PacBio does) claim methods of “determining the
 sequence of the template nucleic acid,” without limiting the
 character of that “template nucleic acid,” by measuring cer-
 tain properties (in particular, electric current properties)
 as the nucleic acid passes through a nanopore, using a de-
 termination of the number of nucleotides that affect the
 current (N), and using enzymes to control the rate of pas-
 sage through the nanopore. See supra pp. 5–6. Notably,
 PacBio acknowledges that the ’400 and ’323 patents do not
 differentiate between “particular types of DNA.” PacBio
 Opening Br. 39.
     In arguing for JMOL, PacBio places principal reliance
 on the following exchange from the deposition of Oxford’s
 expert, Dr. Goldman, introduced at trial during cross-ex-
 amination of Dr. Goldman:
      ‘Question: A person of ordinary skill in the art in
      2009 with the Akeson grant in front of them you
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES       13

     believe would be able to successfully perform the
     method of claim 1 of the ’400 patent?
     ‘Answer: Yes.’
 J.A. 1480 (Tr. 1134:2–6). The “Akeson grant” was a grant
 application to the National Institutes of Health filed by an-
 other Oxford witness, Dr. Mark Akeson, before 2009. See
 J.A. 1836. PacBio asserts that, in the quoted exchange,
 “Dr. Goldman admitted on cross-examination that the
 claims of the ’400 and ’323 Patents were enabled.” PacBio
 Opening Br. 14; see also id. at 22 & n.3 (“Dr. Goldman
 squarely admitted that a person skilled in the art in 2009
 would be able to successfully perform the method of claim
 1 of the ’400 Patent.”; footnote attached, stating: “For pur-
 poses of enablement, there is no difference between the
 ’400 and ’323 Patent[s].”); id. at 18.

      The jury was not required to give Dr. Goldman’s an-
 swer, even understood in isolation, the broad meaning Pac-
 Bio now gives it. It is enough to say that, in the absence of
 further elaboration of the point, the jury could have under-
 stood Dr. Goldman to be saying no more than that a rele-
 vant artisan could have “perform[ed] the method of claim 1
 of the ’400 patent,” J.A. 1480, on the particular subset of
 nucleic acids addressed in the Akeson grant, namely, “DNA
 hairpins,” which were synthesized nucleic acids used to
 test the viability of such sequencing technologies. J.A.
 1836–54. Especially in light of other evidence about the
 difference between the synthetic nucleic acids Akeson ad-
 dressed and biological DNA, the jury could properly under-
 stand the specific answer to the specific question on which
 PacBio relies not to be conceding that a skilled artisan
 could make and use the full scope of the invention (even of
 claim 1 of the ’400 patent, let alone all the asserted claims),
 including the full range of “nucleic acid templates.” In fact,
 just before that question and answer, the jury heard Dr.
 Goldman answer “no” to the question whether “a person of
 ordinary skill in the art with the ’400 patent in front of
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 14   PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES

 them trying to use the claim 1 method, including adding
 everything, if they had access to the Akeson grant, . . .
 would have been able to use the invention[,] . . . [t]o be able
 to successfully perform the method . . . of the ’400 and ’323
 [patents].” J.A. 1480 (Tr. 1133:1–9).
     The jury’s task was not to view one portion of Dr. Gold-
 man’s testimony in isolation, but to consider all the evi-
 dence, including any portion of the evidence that might
 clarify how to understand other portions. And there was
 substantial evidence that supported non-enablement. Dr.
 Goldman himself testified that the asserted claims of the
 ’400 and ’323 patents lack enablement because of the re-
 quired element of determining “N” (how many nucleotides
 affect the current measurement during transit of a nucleic
 acid through the nanopore). J.A. 1475 (Tr. 1113:1–23).
     Even aside from the “N” claim limitation, the jury had
 substantial evidence of non-enablement of the full claim
 scope. For example, Dr. Akeson testified that his research,
 leading to the “Akeson grant,” was limited to “DNA hair-
 pin[s],” see J.A. 1406–07 (Tr. 934:17–935:16); J.A. 1405 (Tr.
 930:1–13), and that the first successful nanopore sequenc-
 ing of biological DNA molecules, to his knowledge, did not
 occur until 2011, see J.A. 1408 (Tr. 940:3–941:12); J.A. 1421
 (Tr. 992:9–17); and there is no indication, or argument by
 PacBio, that the 2011 success was made possible by the dis-
 closure in the ’400 and ’323 patents, see Everlight Elecs.,
 896 F.3d at 1363–64. Another of Oxford’s witnesses, Dr.
 James Clarke, testified that “nobody was” able to use na-
 nopore sequencing to sequence biological DNA until 2011.
 J.A. 1423 (Tr. 1001:23–1002:4); see also J.A. 1293 (Tr.
 674:2–6) (Dr. Willcocks); J.A. 1491–92 (Tr. 1180:25–
 1182:3) (Dr. Ha). There also was evidence that, when Ox-
 ford announced its success in 2012 at a large meeting of
 scientific professionals in the field, three years after the
 priority date of the patents at issue here, the audience of
 700 reacted in a way that suggests that the advance
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES     15

 regarding nanopore sequencing with biological DNA was a
 major one. See J.A. 1409 (Tr. 943:1–944:14).
     We therefore conclude that there was ample evidence
 to support a finding that, before the 2009 priority date of
 the ’400 and ’323 patents, relevant artisans did not know
 how to perform nanopore sequencing for more than a nar-
 row range of the full scope of nucleic acids covered by the
 asserted claims. See Idenix, 941 F.3d at 1161 (“Where, as
 here, working examples are present but are ‘very narrow,
 despite the wide breadth of the claims at issue,’ this factor
 weighs against enablement.” (quoting Enzo Biochem, Inc.
 v. Calgene, Inc., 188 F.3d 1362, 1374 (Fed. Cir. 1999))); cf.
 Union Carbide Chems. & Plastics Tech. Corp. v. Shell Oil
 Co., 308 F.3d 1167, 1186 n.9 (Fed. Cir. 2002).
     Notably, PacBio had no evidence of actual reduction to
 practice of its own that would undermine Oxford’s evidence
 of non-enablement. As PacBio acknowledged, its reduction
 to practice was constructive only, i.e., took the form of its
 description in patent applications, without any accompany-
 ing real-world reduction to practice. See Oral Arg. 0:35–
 0:55. The jury heard from named inventor Dr. Turner that
 PacBio never performed nanopore sequencing in 2009, J.A.
 1104 (Tr. 244:10–15), and also heard stipulations of uncon-
 tested facts that PacBio had never performed the claimed
 methods, J.A. 1501 (Tr. 1217:7–1219:6); J.A. 5013–14. The
 jury had evidence, as well, that conveyed an intent by Pac-
 Bio to “tangle . . . up” and “fool” competitors with its pa-
 tents, language that might be understood to point away
 from PacBio’s having achieved an enabled method. J.A.
 1989; J.A. 1105 (Tr. 247:12–13).
     Viewing the facts most favorably to Oxford, we think
 that the record supports the legal conclusion that the dis-
 closures of the ’400 and ’323 patents, even when combined
 with knowledge of relevant artisans, required undue exper-
 imentation to enable the full scope of the relevant claims.
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                               B
      We review a decision denying a motion for a new trial
 for abuse of discretion, following the law of the regional cir-
 cuit, here, the Third Circuit. See Vectura Ltd. v Glax-
 oSmithKline LLC, 981 F.3d 1030, 1035 (Fed. Cir. 2020); see
 also Jester v. Hutt, 937 F.3d 233, 238 (3d Cir. 2019). “Un-
 der Third Circuit law, a district court should grant a new
 trial only if the jury’s verdict is against the great weight of
 evidence and either is a miscarriage of justice or cries out
 to be overturned.” Vectura, 981 F.3d at 1035; Leonard v.
 Stemtech Int’l Inc., 834 F.3d 376, 386 (3d Cir. 2016). The
 district court has broad discretion in not setting the verdict
 aside. Leonard, 834 F.3d at 386.
                               1
      PacBio first seeks a new trial based on the jury’s ver-
 dict that the asserted claims are invalid for lack of enable-
 ment. See PacBio Opening Br. 42. PacBio’s two-sentence
 argument summarily asserts, as a basis for a new trial,
 that Dr. Goldman “offered only ‘general and vague’ state-
 ments regarding enablement” and “admitted that” he could
 not recall specific examples showing a lack of enablement.
 Id. For the reasons explained above, Dr. Goldman’s testi-
 mony does not stand alone, and the jury could reasonably
 rely on the evidence as a whole to determine that the claims
 at issue were not enabled. We draw no different conclusion
 when asking if the district court abused its discretion in
 deeming the evidence sufficient for purposes of the new-
 trial standard.
                               2
    PacBio also argues that a new trial is necessary based
 on Oxford’s references to COVID-19 and the possible con-
 sequences of an infringement verdict for COVID-19. See
 PacBio Opening Br. 44–53. A new trial based on improper
 remarks is proper if “the appellee made prejudicial re-
 marks and it is ‘reasonably probable’ those prejudicial
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES      17

 remarks influenced the jury’s verdict.” Vectura, 981 F.3d
 at 1042 (quoting Draper v. Airco, Inc., 580 F.2d 91, 97 (3d
 Cir. 1978)). “On the issue of the impact of improper con-
 duct at trial, the views of the judge who supervised the trial
 proceedings are entitled to considerable weight.” Vectura,
 981 F.3d at 1044. We see no abuse of discretion in the dis-
 trict court’s determination that the opening remarks were
 not sufficiently likely to have influenced the jury to create
 a miscarriage of justice.
     As described above, PacBio, which presented its open-
 ing statement to the jury first, itself mentioned the possible
 connection between COVID-19 and the technology at issue.
 And despite knowing that Oxford would mention COVID-
 19 in its opening, PacBio did not object in advance. When
 Oxford, in its opening, made a considerably more extended
 mention of COVID-19 in connection with references to ear-
 lier litigation and PacBio’s alleged effort to exclude Ox-
 ford’s products, PacBio objected that the references to
 earlier litigation and the purported effort to exclude Ox-
 ford’s products violated the MIL Order. The next day, be-
 fore testimony commenced, PacBio and the court treated
 the references to COVID-19 as related to the MIL Order
 violation, and the court gave exactly the curative instruc-
 tion that PacBio requested. The court also required that
 the parties “carefully disclose to one another any reference,
 any evidence, any suggestion that” they might make to
 COVID-19 later in the trial and bring any disputes to the
 court’s attention before the subject was mentioned to the
 jury. J.A. 1157 (Tr. 294:6–12). The court used that proce-
 dure later during trial to prevent evidence from reaching
 the jury that it deemed prejudicial. See J.A. 1339–40 (Tr.
 860:3–864:15). Not until after the verdict did PacBio re-
 quest a new trial based on the remarks Oxford made in its
 opening. After the opening, Oxford did not refer to COVID-
 19 or violate the MIL Order.
     In denying the motion for a new trial, the district court
 did not consider the request for a new trial to have been
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 forfeited. Rather, the court addressed and rejected it on its
 merits, considering all the circumstances. See Post-Trial
 Decision, 2020 WL 4699049, at *8. The court determined
 that there was not a high enough likelihood, in light of the
 curative instructions, that Oxford’s improper opening
 tainted the jury’s consideration of the issues to justify or-
 dering a new trial. Id. at *8–9.
      The court reasonably found support for that determi-
 nation in PacBio’s own conduct and contemporaneously ex-
 pressed views about references to COVID-19 before the
 jury, including PacBio’s mention of the subject in its open-
 ing and its request for no more than curative instructions
 (which the court gave). See Post-Trial Decision, 2020 WL
 4699049, at *6–7. It reasonably found no improper conduct
 beyond the opening statement. Id. at *5. The court also
 reasonably concluded that there was “no indication of any
 sort that the jury did anything other than what it was sup-
 posed to do.” Id. at *8. The district court noted the jury’s
 care in its deliberations, reflected in the questions the jury
 asked of the court before reaching its verdict. Id. The court
 further noted that, after receiving the case on March 17
 and deliberating through the afternoon, the jury was of-
 fered the option of continuing for a few hours or instead
 returning to the courthouse the next day, and it opted to
 return on March 18, which it did, deliberating for two hours
 in the morning before returning its verdict. Id. Finally,
 the court reasoned that the jury’s careful substantive focus
 was reflected in the fact that the jury, though giving Oxford
 a bottom-line victory of invalidity, distinguished the writ-
 ten-description challenge (which it rejected) from the ena-
 blement challenge (which it accepted). Id. at *6. Although
 PacBio asserts that the distinction shows confusion, we see
 no basis for such a conclusion, as the legal standards are
 different, and the evidence allowed a conclusion that the
 problem with PacBio’s patents was not that their specifica-
 tion failed to describe the combined elements of their
 claims so as to indicate PacBio’s invention of the
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 PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES       19

 combination but, rather, that the specification, together
 with relevant artisans’ knowledge, did not enable the ac-
 tual performance of the claimed methods in their full scope.
 See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336,
 1345 (Fed. Cir. 2010) (en banc) (distinguishing the two
 standards)
      Given all the circumstances, we do not see a basis for
 disturbing the district court’s assessment that there was
 an insufficient likelihood that the improper opening re-
 marks had an adverse impact on the ultimate verdict to
 justify a new trial in this case. A contrary conclusion is not
 supported by the cases on which PacBio chiefly relies. In
 Fineman v. Armstrong World Industries, Inc., the Third
 Circuit affirmed the district court’s own assessment of prej-
 udice as warranting a retrial where, during closing (just
 before deliberations), plaintiff’s counsel “improperly testi-
 fied to his own truthfulness and trustworthiness, supplied
 ‘facts’ not in evidence about the credibility of [defendant’s]
 witnesses, accused [defendant’s] witnesses of being ‘liars’
 and ‘perjurers,’ and levied ‘an unadorned, disparaging at-
 tack’ upon defense counsel throughout his summation.”
 980 F.2d 171, 207 (3d Cir. 1992); see also id. at 208–09. In
 Blanche Road Corp. v. Bensalem Township, another affir-
 mance by the Third Circuit of a district court’s own assess-
 ment that a retrial was needed, counsel accused the trial
 judge, in front of the jury, of not treating him fairly,
 vouched for the credibility of witness testimony, and re-
 ferred to documents not in the record during closing argu-
 ments. 57 F.3d 253, 264 (3d Cir. 1995). In Draper v. Airco,
 Inc., the Third Circuit reversed the district court’s rejection
 of a new-trial motion and required a new trial, but it did so
 based on an exceptional combination of improper actions
 by plaintiff’s counsel during closing: “(1) he attempted to
 prejudice the jurors through repeated inappropriate refer-
 ences to the defendants’ wealth; (2) he asserted his per-
 sonal opinion of the justness of his client’s cause; (3) he
 prejudicially referred to facts not in evidence; and (4)
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 20   PACIFIC BIOSCIENCES   v. OXFORD NANOPORE TECHNOLOGIES

 without provocation or basis in fact, he made several prej-
 udicial, vituperative[,] and insulting references to opposing
 counsel.” 580 F.2d at 95; see also id. at 96–97 (concluding
 that counsel’s “closing address to the jury contains such nu-
 merous and serious violations of so many rules of proper
 argument” that curative instructions were not enough).
 The present case, in the timing and isolated character of
 the improper statements, along with the other circum-
 stances we have described, materially differs from PacBio’s
 authorities. See Fineman, 980 F.2d at 208 (noting cases
 where “isolated” improper remarks did not warrant a new
 trial).
      In sum, we see an inadequate basis here to substitute
 our judgment about prejudice for the judgment of the dis-
 trict court. “Because the trial judge was present and able
 to judge the impact of counsel’s remarks, we defer to his
 assessment of the prejudicial impact.” Leonard, 834 F.3d
 at 399 (citation omitted). Therefore, we affirm the denial
 of PacBio’s motion for a new trial on this ground.
                               III
     For the foregoing reasons, we affirm the judgment of
 the district court.
                        AFFIRMED