Trustees of Columbia Univ. v. Illumina, Inc. ( 2021 )

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NOTE: This disposition is nonprecedential.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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TRUSTEES OF COLUMBIA UNIV. v. ILLUMINA, INC. 5
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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TRUSTEES OF COLUMBIA UNIV. v. ILLUMINA, INC. 7
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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TRUSTEES OF COLUMBIA UNIV. v. ILLUMINA, INC. 9
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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TRUSTEES OF COLUMBIA UNIV. v. ILLUMINA, INC. 11
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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12 TRUSTEES OF COLUMBIA UNIV. v. ILLUMINA, INC.
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
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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