Court Opinion

ID: 4656280
Source: CourtListenerOpinion
Date Created: 2021-02-01 16:00:45.233124+00
Date Added: 2024-06-11T08:00:49.165394
License: Public Domain

Case: 19-2302   Document: 61     Page: 1    Filed: 02/01/2021

        NOTE: This disposition is nonprecedential.

   United States Court of Appeals
       for the Federal Circuit
                 ______________________

  TRUSTEES OF COLUMBIA UNIVERSITY IN THE
            CITY OF NEW YORK,
                 Appellant

                            v.

                   ILLUMINA, INC.,
                        Appellee
                 ______________________

  2019-2302, 2019-2303, 2019-2304, 2019-2305, 2019-2452
                 ______________________

     Appeals from the United States Patent and Trademark
 Office, Patent Trial and Appeal Board in Nos. IPR2018-
 00291, IPR2018-00318, IPR2018-00322, IPR2018-00385,
 IPR2018-00797.
                  ______________________

                Decided: February 1, 2021
                 ______________________

    JOHN D. MURNANE, Venable LLP, New York, NY, ar-
 gued for appellant. Also represented by ZACHARY L.
 GARRETT, ROBERT SETH SCHWARTZ; JUSTIN J. OLIVER,
 Washington, DC; JOHN P. WHITE, Cooper & Dunham, LLP,
 New York, NY.

    EDWARD R. REINES, Weil, Gotshal & Manges LLP,
Case: 19-2302     Document: 61      Page: 2     Filed: 02/01/2021

 2               TRUSTEES OF COLUMBIA UNIV.    v. ILLUMINA, INC.

 Redwood Shores, CA, argued for appellee. Also repre-
 sented by DEREK C. WALTER; BRIAN GEORGE LIEGEL, Mi-
 ami, FL.
                ______________________

     Before LOURIE, O’MALLEY, and REYNA, Circuit Judges.
 LOURIE, Circuit Judge.
     The Trustees of Columbia University in the City of
 New York (“Columbia”) appeal from two final written deci-
 sions of the U.S. Patent and Trademark Office Patent Trial
 and Appeal Board (“the Board”) holding claim 1 of U.S pa-
 tent 9,718,852 (“the ’852 patent”), claim 1 of U.S. Patent
 9,719,139 (“the ’139 patent”), claim 1 of U.S. Patent
 9,708,358 (“the ’358 patent”), claim 1 of U.S. Patent
 9,725,480 (“the ’480 patent”), and claims 1–2 of U.S. Patent
 9,868,985 (“the ’985 patent”) unpatentable as obvious. See
 Illumina, Inc. v. Trustees of Columbia Univ. in the City of
 New York, Nos. IPR2018-00291, IPR2018-00318, IPR2018-
 00322, IPR2018-00385, 2018 WL 8619911 (P.T.A.B. June
 21, 2019) (“Decision I”), J.A. 1–81; Illumina, Inc. v. Trustees
 of Columbia Univ. in the City of New York, No. IPR2018-
 00797 (P.T.A.B. Sept. 9, 2019), J.A. 82–162 (“Decision II”).
 For the reasons detailed below, we affirm.
                         BACKGROUND
      The ’852, ’139, ’358, ’480, and ’985 patents (collectively,
 “the patents”) are directed to nucleotide analogs and a
 method of using nucleotide analogs to sequence DNA. Ap-
 pellant Br. at 2. The method is called sequencing-by-syn-
 thesis (“SBS”). Id. SBS works by “detecting the identity of
 a nucleotide analogue after the nucleotide analogue is in-
 corporated into a growing strand of DNA.” ’852 patent
 col. 4 ll. 46–48.
      The patents explain that SBS generally includes the
 following steps: First SBS requires “mak[ing] nucleotide
 analogues” by (a) “linking a unique label such as a
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 TRUSTEES OF COLUMBIA UNIV.   v. ILLUMINA, INC.               3

 fluorescent dye or a mass tag through a cleavable linker to
 the nucleotide base or an analogue of the nucleotide base”
 and (b) “us[ing] a small cleavable chemical moiety to cap
 the 3′-OH group of the deoxyribose to make it nonreac-
 tive.” 1 ’852 patent col. 3 ll. 4–11. The “nucleotide ana-
 logue[]” is incorporated “into the growing DNA strand as
 [a] terminator[].” Id. col. 3 ll. 11–13. Second, “[d]etection
 of the unique label will yield the sequence identity of the
 nucleotide,” i.e., adenine, thymine, guanine, or cytosine.
 Id. col. 3 ll. 13–14. Third “[u]pon removing the label and
 the 3′-OH capping group, the polymerase reaction will pro-
 ceed to incorporate the next nucleotide analogue and detect
 the next base.” Id. col. 3 ll. 14–17. “These steps (incorpo-
 ration of the modified nucleotide, identification of the label,
 cleavage of the capping group and the label) result in one
 nucleotide being sequenced and are known as a ‘cycle’ of
 SBS.” Appellant Br. at 10.
     Claim 1 of the ’852 patent reads as follows:
     1. An adenine deoxyribonucleotide analogue having the
 structure:

         wherein R (a) represents a small, chemically
     cleavable, chemical group capping the oxygen at the
     3′ position of the deoxyribose of the deoxyribonucle-
     otide analogue, (b) does not interfere with

     1   Because the patents share a substantially similar
 specification, all citations are to the ’852 patent unless oth-
 erwise noted. Decision, 2018 WL 8619911, at *2.
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 4              TRUSTEES OF COLUMBIA UNIV.    v. ILLUMINA, INC.

     recognition of the analogue as a substrate by a
     DNA polymerase, (c) is stable during a DNA poly-
     merase reaction, and (d) does not contain a ketone
     group;
         wherein OR is not a methoxy group or an ester
     group;
         wherein the covalent bond between the 3′-oxy-
     gen and R is stable during a DNA polymerase reac-
     tion;
        wherein tag represents a detectable fluorescent
     moiety;
         wherein Y represents a chemically cleavable,
     chemical linker which (a) does not interfere with
     recognition of the analogue as a substrate by a
     DNA polymerase and (b) is stable during a DNA
     polymerase reaction; and
         wherein the adenine deoxyribonucleotide ana-
     logue:
             i) is recognized as a substrate by a DNA
         polymerase,
             ii) is incorporated at the end of a grow-
         ing strand of DNA during a DNA polymer-
         ase reaction,
             iii) produces a 3′-OH group on the deox-
         yribose upon cleavage of R,
            iv) no longer includes a tag on the base
         upon cleavage of Y, and
             v) is capable of forming hydrogen bonds
         with thymine or a thymine nucleotide ana-
         logue.
 ’852 patent col. 34 l. 2–col. 35 l. 4 (emphases added).
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      The ’139, ’358, and ’480 patents recite substantially the
 same claim as claim 1 of the ’852 patent but with a different
 base: ’139 (thymine), ’358 (cytosine), and ’480 (guanine).
 See ’139 patent col. 34 l. 2–col. 35 l. 6; ’358 patent col 34 l.
 2–col. 35 l. 4; ’480 patent col. 34 l. 2–col. 35 l. 4; Appellant
 Br. at 24. Lastly, the ’985 patent includes method claims
 for sequencing DNA using the nucleotide analogs claimed
 in the other four patents. Independent claim 1 of the ’985
 patent recites, in relevant part, “[a] method for sequencing
 a nucleic acid which comprises detecting the identity of a
 nucleotide analogue incorporated into the end of a growing
 strand of DNA in a polymerase reaction . . . .” ’985 patent
 col. 34 l. 2–col. 36. l. 28.
     This appeal primarily centers on one aspect of the
 claims: the use of a capping group that is “small,” and not
 a “ketone group,” “a methoxy group, or an ester group.”
 ’852 patent col. 34 ll. 18–26; ’139 patent col. 34 ll. 18–26;
 ’358 patent col 34 ll. 17–24; ’480 patent col. 34 ll. 19–25;
 ’985 patent col. 35 l. 27–col. 36 l. 1; see also Appellant Br.
 at 21–22. According to Columbia, the inventors discovered
 that a capping group should have these characteristics in
 order to “work for SBS.” Appellant Br. at 22. Relevant to
 this appeal an “allyl capping group” is small, and is not ke-
 tone, methoxy, or ester. See Decision I, 2018 WL 8619911,
 at *7, *28.
      Illumina, Inc. (“Illumina”) filed petitions for inter
 partes review of the ’852, ’139, ’358, ’480, and ’985 patents.
 In the petitions, it asserted that certain combinations of
 prior art references would have rendered obvious the use
 of a labeled nucleotide analog with an allyl capping group.
 The prior art references include (1) Tsien et al., WO
 91/06678 (May 16, 1991) (“Tsien”), (2) James M. Prober et
 al., A System for Rapid DNA Sequencing with Fluorescent
 Chain-Terminating Dideoxynucleotides, 238 SCIENCE 336–
 41 (Oct. 16, 1987) (“Prober”), (3) Michael L. Metzker et al.,
 Termination of DNA synthesis by novel 3′- modified-deoxy-
 ribonucleoside 5’-triphosphates, 22 NUCLEIC ACIDS
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 6              TRUSTEES OF COLUMBIA UNIV.   v. ILLUMINA, INC.

 RESEARCH 4259–67 (1994) (“Metzker”), and (4) Dower et
 al., U.S. Patent 5,547,839, Aug. 20, 1996 (“Dower”).
      Like the patents, Tsien discloses that DNA can be se-
 quenced using the SBS method. See J.A. 3412–13; Decision
 I, 2018 WL 8619911, at *9; Appellant Br. at 27. Tsien spe-
 cifically teaches that allyl capping groups can be used for
 SBS. See J.A. 3430; see also Decision I, 2018 WL 8619911,
 at *16.
     Dower similarly teaches that DNA can be sequenced
 with the SBS method. See J.A. 3491; Decision I, 2018 WL
 8619911, at *8. Dower discloses that “small” capping
 groups can be used for SBS. J.A. 3497.
      Metzker discloses a method of sequencing DNA “equiv-
 alent to SBS.” Decision I, 2018 WL 8619911, at *10; J.A.
 3500. Metzker describes an experiment in which “eight 3′-
 modified dNTPs” with different capping groups were “ex-
 amined for their ability to terminate DNA synthesis.” J.A.
 3500. The presumption in Metzker is that capping groups
 that terminated DNA synthesis would potentially be good
 candidates for use with DNA sequencing. In Metzker’s ex-
 periment, 3′-O-allyl nucleotides (nucleotides with allyl cap-
 ping groups) showed “Termination*.” Id. at 3504. Metzker
 explains that the asterisk after termination means that
 “activity was incomplete at a final concentration of 250
 μM.” Id. (emphasis added). In contrast to the 3′-O-allyl
 nucleotides, Metzker’s experiment shows that nucleotides
 with other capping groups demonstrated “Termination”
 (without an asterisk). Id. Metzker reports that those other
 capping groups were “interesting” and “were further eval-
 uated.” J.A. 3504, 3506. Prober discloses limitations not
 at issue in this appeal. See Appellant Br. at 26 n.6.
     The Board issued two final written decisions, one re-
 garding the patents with nucleotide analog claims and one
 regarding the patent with method claims. The Board first
 concluded that claim 1 of the ’852 patent would have been
 obvious over the combination of (1) Tsien and Prober, or (2)
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 Prober, Dower, and Metzker. See Decision I, 2018 WL
 8619911, at *21, *23. The Board further concluded that the
 claims of the other four patents are unpatentable as obvi-
 ous, based on similar reasoning. See id. at *24; Decision II,
 slip op. at 77–78.
     In concluding that the claims would have been obvious,
 the Board first found that Tsien discloses the use of allyl
 capping groups. See Decision I, 2018 WL 8619911, at *16;
 Decision II, slip op. at 41. The Board rejected Columbia’s
 argument that Metzker’s experiment, which demonstrated
 that 3′-O-allyl nucleotides showed only “incomplete” termi-
 nation, would have negated Tsien’s teaching. See Decision
 I, 2018 WL 8619911, at *18–19; Decision II, slip op. at 45.
 The Board also determined that a person of ordinary skill
 would have understood that Metzker’s experiment could be
 further improved by “increasing [nucleotide] concentration
 or reaction time.” Id. Administrative Patent Judge Worth
 dissented in both decisions, believing that “Metzker’s ex-
 periment would have discouraged a person of ordinary skill
 from pursuing an allyl nucleotide.” Decision I, 2018 WL
 8619911, at *33; J.A. 160–161. Columbia appealed to this
 court.    We have jurisdiction pursuant to 28 U.S.C.
 § 1295(a)(4)(A).
                         DISCUSSION
      We review the Board’s legal determinations de novo, In
 re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004), and the
 Board’s factual findings underlying those determinations
 for substantial evidence, In re Gartside, 203 F.3d 1305,
 1316 (Fed. Cir. 2000). A finding is supported by substan-
 tial evidence if a reasonable mind might accept the evi-
 dence to support the finding. Consol. Edison Co. v. NLRB,
 305 U.S. 197, 229 (1938).
     Obviousness is a question of law based on underlying
 facts, including the scope and content of the prior art, dif-
 ferences between the prior art and the claims at issue, the
 level of ordinary skill, and relevant evidence of secondary
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 8              TRUSTEES OF COLUMBIA UNIV.   v. ILLUMINA, INC.

 considerations. Graham v. John Deere Co., 383 U.S. 1, 17–
 18 (1966). “What the prior art teaches, whether a person
 of ordinary skill in the art would have been motivated to
 combine references, and whether a reference teaches away
 from the claimed invention are questions of fact.”
 Meiresonne v. Google, Inc., 849 F.3d 1379, 1382 (Fed. Cir.
 2017) (citing Apple Inc. v. Samsung Elecs. Co., 839 F.3d
 1034, 1047–48 (Fed. Cir. 2016) (en banc)). “The presence
 or absence of a reasonable expectation of success is also a
 question of fact.” PAR Pharm., Inc. v. TWi Pharms., Inc.,
 773 F.3d 1186, 1196 (Fed. Cir. 2014).
     Columbia challenges the Board’s determination re-
 garding the obviousness of the claims in three respects.
 First, Columbia asserts that the Board erred in determin-
 ing that a person of ordinary skill would have been moti-
 vated to pursue an allyl capping group for use with SBS.
 Second, Columbia argues that the Board erred in determin-
 ing that a person of ordinary skill would have had a rea-
 sonable expectation of success in using an allyl capping
 group for SBS. Third, Columbia argues that the Board
 erred in determining that person of ordinary skill would
 have had a reasonable expectation of success in specifically
 incorporating 3′-O-allyl thymine, cytosine, or guanine nu-
 cleotides into a DNA strand during SBS. We address each
 argument in turn.
                               I
     Columbia first argues that the Board erred in deter-
 mining that a person of ordinary skill “would have been
 motivated to pursue the allyl capping group for [use with]
 SBS.” Appellant Br. at 31. Columbia contends that the
 Board’s error stemmed from its “misapprehension” of Metz-
 ker’s experiment. Id. at 34–35. According to Columbia, the
 asterisk after “Termination*” in Metzker’s experiment in-
 dicated that 3′-O-allyl nucleotides were inefficiently incor-
 porated into the DNA strand and resulted in poor
 termination. See id. at 16–17. Columbia asserts that such
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 a result would have discouraged a person of ordinary skill
 from using an allyl capping group because SBS requires ef-
 ficient incorporation of nucleotides. As support for its ar-
 gument, Columbia points to Metzker’s disclosure that only
 nucleotides with capping groups that showed “Termina-
 tion” (without an asterisk) were advanced for further test-
 ing. Columbia further points out that other scientists
 allegedly ceased experimenting with allyl capping groups
 after Metzker was published, instead choosing to pursue
 “non-allyl capping groups, such as 2-nitrobenzyl.” Id. at 40.
 Columbia thus argues that Metzker’s experiment pointed
 away from Tsien’s 2 disclosure that allyl capping groups can
 be used for SBS. Id. at 35.
      Illumina responds that the Board’s determination was
 supported by substantial evidence. It contends that Metz-
 ker’s experiment would not have discouraged a person of
 ordinary skill from pursuing an allyl capping group. Ac-
 cording to Illumina, Metzker’s experiment expressly
 showed that 3′-O-allyl nucleotides achieved some measure
 of termination. Illumina asserts that the asterisk, which
 signifies that termination was not complete, does not nul-
 lify Metzker’s essential teaching.
     We agree with Illumina that the Board’s conclusion
 was supported by substantial evidence. Teaching away re-
 quires “‘clear discouragement’ from implementing a tech-
 nical feature.” Univ. of Md. Biotechnology Inst. v. Presens
 Precision Sensing GmbH, 711 F. App’x. 1007, 1011 (Fed.
 Cir. 2017) (quoting In re Ethicon, Inc., 844 F.3d 1344, 1351
 (Fed. Cir. 2017)). Columbia has not demonstrated that

     2    Columbia asserts that “[t]he Board’s obviousness
 framework was the same for Illumina’s [g]rounds focusing
 on Tsien and those focusing on Dower. As such, [Colum-
 bia’s] arguments herein apply to all [g]rounds.” Appellant
 Br. at 27 n.8; see also Appellant Reply Br. at 13 n.6. Ac-
 cordingly, our analysis here also applies to both grounds.
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 10             TRUSTEES OF COLUMBIA UNIV.    v. ILLUMINA, INC.

 there was any such clear discouragement. First, as an ini-
 tial matter, the Board determined that Tsien discloses allyl
 capping groups for use with DNA sequencing, which Co-
 lumbia does not substantively dispute. See Decision I, 2018
 WL 8619911, at *16; Decision II, slip op. at 41. Second, the
 Board carefully evaluated Metzker and found that it con-
 firms rather than negates Tsien’s teachings. Decision I,
 2018 WL 8619911, at *18; Decision II, slip op. at 45. The
 Board’s determination was supported by ample evidence.
 Metzker’s experiment reports that 3′-O-allyl nucleotides
 showed “Termination*,” indicating that they terminated
 DNA synthesis. J.A. 3504. Columbia places much weight
 on the asterisk after “Termination*.” However, the aster-
 isk merely indicates that although termination was
 achieved, it was not complete in the conditions used for the
 particular experiment. Id. Metzker never describes the
 experiment with allyl capping groups as a failure. On the
 contrary, when describing the results of the experiment,
 Metzker expressly states that 3′-O-allyl nucleotides were
 “incorporated” by polymerase. Id. at 3506.
     Lastly, while it may be true that Metzker and other sci-
 entists ultimately chose to research alternative capping
 groups, “just because better alternatives exist in the prior
 art” does not mean that an inferior alternative “is inapt for
 obviousness purposes.” In re Mouttet, 686 F.3d 1322, 1334
 (Fed. Cir. 2012) (citing In re Gurley, 27 F.3d 551, 553 (Fed.
 Cir. 1994)). Accordingly, the Board’s determination was
 supported by substantial evidence.
                              II
     We turn next to Columbia’s second argument. Colum-
 bia argues that the Board erred in determining that a per-
 son of ordinary skill would have had a reasonable
 expectation of success in using labeled 3′-O-allyl nucleo-
 tides for SBS. Appellant Br. at 46. Specifically, Columbia
 asserts that “Tsien’s prophetic disclosures from 1991 would
 [not] have provided” an expectation that labeled 3′-O-allyl
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 nucleotides would work successfully for SBS, “i.e., would be
 capable of at least twenty cycles of sequencing.” Id. at 46–
 47. As support for its argument, Columbia asserts that in
 a prior reexamination, Solexa (which was acquired by Illu-
 mina) asserted that Tsien provided no expectation that al-
 lyl capping groups could work successfully for SBS.
 Columbia also again asserts here that Metzker negates
 Tsien’s teaching.
      We disagree with Columbia. First it should be said
 that a reasonable expectation of success does not mean
 achieving the best of all possible results. Success may not
 have only one definition. And the Board’s determination
 regarding reasonable expectation of success was supported
 by substantial evidence. Overall, Columbia’s arguments
 here are largely duplicative of its motivation arguments.
 As discussed above, Columbia does not dispute that Tsien
 discloses allyl capping groups for use with SBS. Moreover,
 we are unpersuaded by Columbia’s argument that Illu-
 mina’s statements in the separate reexamination are evi-
 dence that Tsien would not have provided a person of
 ordinary skill with a reasonable expectation of success.
 The Board evaluated Columbia’s argument but found it un-
 convincing because the previous reexamination concerned
 an earlier priority date than Columbia’s patents had. The
 Board thus determined that arguments made in the reex-
 amination “would not necessarily be relevant to the level of
 skill in the art and the reasonable expectation of success . .
 . [at] the time of filing of the ’852 patent.” Decision I, 2018
 WL 8619911, at *31; see also Decision II, slip op. at 75. We
 agree. 3 And we further reject Columbia’s argument that

     3   Columbia additionally contends that in another
 separate proceeding, Illumina made statements that alleg-
 edly “undercut” its arguments in this proceeding. Colum-
 bia Motion at 1, ECF No. 51. Columbia has in fact made a
 motion asking us to take judicial notice of those
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 the differences in the priority dates are “inconsequential”
 because the priority date considered in the separate ex
 parte reexamination was September 2000, only a month
 apart from the October 2000 priority date of Columbia’s pa-
 tents. Appellant Br. at 57. Columbia ignores that the
 Board examined the record and determined that “there is
 no evidence that the Examiner adopted a finding based on
 the level of skill in September 2000.” Decision I, 2018 WL
 8619911, at *31 n.44. Rather, the Board found that “the
 examiner’s findings” in the reexamination “considered the
 level of skill in the art (and reasonable expectations based
 thereon) as of September 2, 1994.” Decision I, 2018 WL
 8619911, at *31; see also Decision II, slip op. at 75 n.43.
      Second, the Board found that although Metzker’s ex-
 periment demonstrated that 3′-O-allyl nucleotides showed
 only “Termination*,” a person of ordinary skill would have
 understood how to improve incorporation efficiency. Spe-
 cifically, the Board found that a person of ordinary skill
 would have known that “increasing concentration [of nu-
 cleotides] or reaction time could help incorporation effi-
 ciency.” Decision I, 2018 WL 8619911, at *19; Decision II,
 slip op. 45. The Board’s determination was adequately sup-
 ported by the testimony of Dr. Romesberg, whom the Board
 found credible. Id. Columbia makes an array of arguments
 as to why the Board erred in relying on Dr. Romesberg’s
 testimony, all unconvincing. For example, Columbia as-
 serts that Dr. Romesberg’s testimony regarding increasing
 nucleotide concentration is irrelevant because, inter alia
 (1) “Dr. Romesberg relied on experiments done with a
 methoxy nucleotide (3′-O-methyl) rather than a 3′-O-allyl
 nucleotide” and (2) it is known that increasing nucleotide
 concentration can “increase[] mutation rate.” Appellant
 Br. at 50–52. However, the Board considered these

 proceedings. Id. We decline to do so. We limit ourselves
 to the present record.
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 TRUSTEES OF COLUMBIA UNIV.   v. ILLUMINA, INC.               13

 arguments. It reasonably found that “[a]lthough some ev-
 idence indicates that use of high concentration can cause
 problems, the weight of the evidence does not support a
 finding that these problems would have discouraged the
 skilled artisan . . . .” Decision I, 2018 WL 8619911, at *19
 (internal citation omitted); Decision II, slip op. at 46. Co-
 lumbia effectively urges us to reweigh the evidence pre-
 sented to the Board and reach a different conclusion. But
 “[t]his court does not reweigh evidence on appeal.” Celgene
 Corp. v. Peter, 931 F.3d 1342, 1352 (Fed. Cir. 2019) (quot-
 ing In re NTP, Inc., 654 F.3d 1279, 1292 (Fed. Cir. 2011)).
      Third, the specifications of Columbia’s patents provide
 further evidence that a person of ordinary skill would have
 had a reasonable expectation of success in using allyl cap-
 ping groups for SBS. Although Columbia now argues that
 Metzker was discouraging, its patents’ disclosures contra-
 dict Columbia’s assertion. Specifically, the patents cite
 Metzker (the same prior art reference at issue here) as ev-
 idence that allyl groups can be “used to cap the 3′-OH group
 using well-established synthetic procedures.” ’852 patent
 col. 26 ll. 22–25 (emphasis added). The patents addition-
 ally state that Metzker showed incorporation of 3′-O-allyl
 nucleotides “in the growing strand of DNA.” See, e.g., ’852
 patent col. 3 ll. 28–30 (“3′-O-allyl-dATP was also shown to
 be incorporated by Ventr(exo−) DNA polymerase in the
 growing strand of DNA (Metzke[r] et al. 1994).”). We are
 unpersuaded by Columbia’s argument that the patents’ ci-
 tation of Metzker is immaterial because “whether a [person
 of ordinary skill] would have known the synthetic chemis-
 try to make the claimed nucleotides is irrelevant . . . to
 whether a [person of ordinary skill] would reasonably ex-
 pect such nucleotides to work for SBS.” Appellant Br. at
 60. Here, the patents cite Metzker without mentioning
 concerns regarding the use of allyl capping groups. See
 PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d
 1342, 1362 (Fed. Cir. 2007) (“Admissions in the specifica-
 tion regarding the prior art are binding on the patentee for
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 14             TRUSTEES OF COLUMBIA UNIV.   v. ILLUMINA, INC.

 purposes of a later inquiry into obviousness.” (citing Con-
 stant v. Advanced Micro-Devices, Inc., 848 F.2d 1560, 1570
 (Fed. Cir. 1988)). Indeed, as the Board pointed out, alt-
 hough the patents cite Metzker, they do not otherwise “pro-
 vide data establishing good incorporation or efficiency of an
 allyl group.” Decision I, 2018 WL 8619911, at *3; see also
 id. at *19 (quoting Trustees of Columbia Univ. in the City
 of New York v. Illumina, Inc., 620 F. App’x. 916, 933 (Fed.
 Cir. 2015) (“[I]f novel and nonobvious chemistry was
 needed to practice the claimed inventions [the patentee]
 would have been obligated to disclose this chemistry in the
 patent.”)); Decision II, slip op. at 6, 46.
      Columbia additionally asserts that the Board erred in
 “fail[ing] to properly consider” that Metzker only discloses
 a “3′-O-allyl nucleotide [that is] unlabeled (which cannot be
 used for SBS), whereas the relevant claimed embodiment
 in the Columbia patents is a labeled 3′-O-allyl nucleotide.”
 Appellant Br. at 54 (emphases in original) (internal cita-
 tions omitted). However, we have held “on multiple occa-
 sions that failure to explicitly discuss every issue or every
 piece of evidence does not alone establish that the tribunal
 did not consider it.” Novartis AG v. Torrent Pharms. Ltd.,
 853 F.3d 1316, 1328 (Fed. Cir. 2017). Although the Board
 did not expressly reference Columbia’s label argument, it
 was not obliged to discuss every argument that Columbia
 raised. And regardless, Tsien discloses labeled nucleotides.
 J.A. 3419.
     In sum, although Columbia faults the Board for both
 “misapprehending” Metzker and for erroneously relying on
 expert testimony, Columbia has not pointed to any flaw in
 the Board’s analysis. The Board was presented with two
 alternative theories as to whether a person of ordinary skill
 would have had a reasonable expectation of success in us-
 ing an allyl capping group for SBS. “Our task is not to de-
 termine which theory we find more compelling.” See Shoes
 by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962
 F.3d 1362, 1371 (Fed. Cir. 2020). Rather, the only question
Case: 19-2302    Document: 61        Page: 15     Filed: 02/01/2021

 TRUSTEES OF COLUMBIA UNIV.   v. ILLUMINA, INC.               15

 before us is whether the Board’s conclusion was supported
 by substantial evidence. Here, we conclude that it was.
                               III
      Finally, we turn to Columbia’s argument that the
 Board erred in holding that a person of ordinary skill would
 have expected to succeed in incorporating “labeled 3′-O-al-
 lyl thymine, cytosine, and guanine nucleotides” into a DNA
 strand, as required by the ’139, ’358, and ’480 patent
 claims, respectively. Appellant Br. at 62. Columbia con-
 tends that Metzker only discloses the inefficient incorpora-
 tion of 3′-O-allyl adenine nucleotides.       According to
 Columbia, Metzker provided no evidence that a “labeled 3′-
 O-allyl thymine, cytosine, or guanine nucleotide would
 have any polymerase activity at all.” Id. at 63.
     We disagree. The Board carefully weighed the evi-
 dence and found that the references “collectively suggest
 that the analogues discussed therein are capable of being
 incorporated at the end of a growing strand of DNA.” De-
 cision I, 2018 WL 8619911, at *24; Decision II, slip op. at
 52. Indeed, Tsien discloses that allyl capping groups can
 be used for all base types without distinction. See, e.g., J.A.
 3412–13, 3430; see also Decision I, 2018 WL 8619911, at
 *24. Similarly, Dower teaches SBS without indicating that
 different base types can raise unique issues. See, e.g., J.A.
 3481; see also Decision I, 2018 WL 8619911, at *24. Accord-
 ingly, the Board’s determination was supported by sub-
 stantial evidence.
                         CONCLUSION
     We have considered Columbia’s remaining arguments
 and find them unpersuasive. The Board’s decisions were
 supported by substantial evidence and were not erroneous
 as a matter of law. For the foregoing reasons, the decisions
 of the Board are affirmed.
                         AFFIRMED