10x Genomics, Inc. v. Parse Biosciences, Inc.

N OTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
10X GENOMICS, INC.,
Appellant
v.
PARSE BIOSCIENCES, INC.,
Appellee
______________________
2025-1199
______________________
Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. IPR2023-
00876.
-------------------------------------------------
10X GENOMICS, INC.,
Appellant
v.
PARSE BIOSCIENCES, INC.,
Appellee
______________________
2025-1618, 2025-1619
______________________
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 2
Appeals from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in Nos. IPR2023-
00955, IPR2023-00958.
______________________
Decided: August 19, 2026
______________________
T HOMAS SAUNDERS , Wilmer Cutler Pickering Hale and
Dorr LLP, Washington, DC, argued for appellant. Also rep-
resented by G ARY M. F OX , O MAR K HAN, New York, NY;
BENJAMIN M ORRIS , Boston, MA.
EDWARD R. REINES , Jones Day, Palo Alto, CA, argued
for appellee. Also represented by CONCORD CHEUNG;
D EREK C. WALTER , San Francisco, CA.
______________________
Before T ARANTO, BRYSON, and CUNNINGHAM , Circuit
Judges.
CUNNINGHAM , Circuit Judge.
10x Genomics (“10x”) appeals final written decisions by
the Patent Trial and Appeal Board in inter partes reviews
(“IPRs”) brought by Parse Biosciences, Inc. (“Parse”). The
Board determined that all claims of U.S. Patent
No. 10,155,981 (“the ’981 patent”), U.S. Patent
No. 10,240,197 (“the ’197 patent”), and U.S. Patent
No. 10,697,013 (“the ’013 patent”), are unpatentable as ob-
vious. Parse Biosciences, Inc. v. 10x Genomics, Inc.,
No. IPR2023-00876, 2024 WL 4218540, at *1 (P.T.A.B.
Sep. 17, 2024) (“’981 Decision”); Parse Biosciences, Inc.
v. 10x Genomics, Inc., No. IPR2023-00955, 2025 WL
355170, at *1 (P.T.A.B. Jan. 31, 2025) (“’197 Decision”);
Parse Biosciences, Inc. v. 10x Genomics, Inc., No. IPR2023-
00958, 2025 WL 383299, at *1 (P.T.A.B. Feb. 3, 2025)
(“’013 Decision”). For the reasons below, we affirm.
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 3
I. BACKGROUND
The patents claim methods for analyzing nucleic acids
from single cells. ’981 patent col. 30 ll. 19–62; ’197 patent
col. 30 l. 16 to col. 32 l. 25; ’013 patent col. 30 l. 38 to col. 32
l. 59.1 Claims 1 and 5 of the ’981 patent recite:
1. A method of analyzing nucleic acids from a plu-
rality of single cells, the method comprising:
(a) providing a sample comprising a plural-
ity of single cells, wherein each single cell
of the plurality of single cells comprises a
plurality of sample polynucleotides;
(b) generating a plurality of tagged polynu-
cleotides from the plurality of sample poly-
nucleotides, wherein each tagged polynu-
cleotide comprises:
(i) a sequence from a sample poly-
nucleotide of the plurality of sam-
ple polynucleotides; and
(ii) a multiplex identifier (MID) se-
quence comprising:
I. a first tag sequence asso-
ciated with the single cell
from which the sample pol-
ynucleotide is derived,
wherein the first tag se-
quence is a different se-
quence for different single
1 The ’197 patent is a continuation of the ’981 patent,
and the ’013 patent is in the same patent family. All three
patents share a specification, and citations to the specifica-
tion will be to that of the ’981 patent.
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 4
cells in the plurality of sin-
gle cells; and
II. a second tag sequence
distinguishing the sample
polynucleotide from other
sample polynucleotides de-
rived from the same single
cell;
(c) sequencing the plurality of tagged poly-
nucleotides to obtain a plurality of identi-
fied polynucleotide sequences;
(d) using the first tag sequence to correlate
the identified polynucleotide sequence with
the single cell from which the identified pol-
ynucleotide sequence is derived; and
(e) using the second tag sequence to corre-
late the identified polynucleotide sequence
with the sample polynucleotide from which
the identified polynucleotide sequence is
derived.
5. The method of claim 1, wherein the tagged pol-
ynucleotides are generated through at least one li-
gation reaction.
’981 patent col. 30 ll. 19–48, 56–57 (emphases added).
Claims 1 and 5 of the ’197 patent recite:
1. A method of counting nucleic acids in a sample,
the method comprising:
(a) providing a sample comprising a plural-
ity of cells, wherein a cell of the plurality of
cells comprises a plurality of sample poly-
nucleotides;
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 5
(b) generating a plurality of tagged polynu-
cleotides from the plurality of sample poly-
nucleotides of said cell and a plurality of
oligonucleotide tags, wherein a tagged pol-
ynucleotide of the plurality of tagged poly-
nucleotides comprises:
(i) a sample sequence from a sam-
ple polynucleotide of the plurality
of sample polynucleotides;
(ii) a first tag sequence distinguish-
ing said sample polynucleotide
from sample polynucleotides from
other cells; and
(iii) a second tag sequence distin-
guishing said sample polynucleo-
tide from other sample
polynucleotides from said cell;
(c) sequencing the tagged polynucleotide to
determine the sample sequence, the first
tag sequence, and the second tag sequence;
and
(d) using the first tag sequence and the sec-
ond tag sequence to count a number of sam-
ple polynucleotides in said plurality of
sample polynucleotides of said cell.
5. The method of claim 1, wherein the plurality of
tagged polynucleotides is generated through at
least one ligation reaction.
’197 patent col. 30 ll. 16–39, 47–49 (emphasis added).
Claim 1 of the ’013 patent recites:
1. A method for multiplexed analysis of nucleic ac-
ids from single cells, the method comprising:
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 6
(a) providing a sample comprising a plural-
ity of cells, wherein a single cell of the plu-
rality of cells comprises a plurality of
sample polynucleotides;
(b) performing combinatorial tagging to
generate a plurality of tagged polynucleo-
tides from said plurality of sample polynu-
cleotides and a plurality of oligonucleotide
tags, wherein a tagged polynucleotide of
the plurality of tagged polynucleotides is
generated by:
(A) providing an extension product
by primer extension using a first ol-
igonucleotide tag and a sample pol-
ynucleotide of said plurality of
sample polynucleotides, and
(B) ligating a second oligonucleo-
tide tag to said extension product,
and
wherein said tagged polynucleotide
of the plurality of tagged polynucle-
otides comprises:
(i) a sample sequence corre-
sponding to said sample
polynucleotide of the plu-
rality of sample polynucleo-
tides;
(ii) a first tag sequence dis-
tinguishing said sample
polynucleotide from sample
polynucleotides from other
cells; and
(iii) a second tag sequence
distinguishing said sample
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 7
polynucleotide from other
sample polynucleotides
from said cell;
(c) amplifying said tagged polynucleotide,
thereby generating a plurality of amplified
polynucleotides corresponding to the
tagged polynucleotide; and
(d) sequencing said plurality of amplified
polynucleotides to determine sequences of
the amplified polynucleotides correspond-
ing to the sample sequence, the first tag se-
quence, and the second tag sequence of the
tagged polynucleotide; and
(e) using the sequences determined in step
(d) to count sample polynucleotides for
multiple different sample polynucleotides
of multiple different single cells of said plu-
rality of cells.
’013 patent col. 30 l. 38 to col. 31 l.9 (emphasis added).
In its final written decisions, the Board determined
that all claims of the ’981 patent, claims 1–12, 20–26 of the
’197 patent, and claims 1–12 and 19–28 of the ’013 patent
are unpatentable as obvious over the combination of Lin-
narsson2 and McCloskey.3 ’981 Decision at *23; ’197 Deci-
sion at *32; ’013 Decision at *23. Additionally, the Board
determined that the remaining claims of the ’197 and ’013
patents are unpatentable as obvious over the combination
2 PCT Patent Pub. No. WO 2010/117620 (filed
Mar. 30, 2010; published Oct. 14, 2010), 25-1199
J.A. 1119–89 (“Linnarsson”).
3 Megan L. McCloskey et al., Encoding PCR Prod-
ucts with Batch-stamps and Barcodes, 45 BIOCHEM G ENET
761–67 (2007), 25-1199 J.A. 1190–96 (“McCloskey”).
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 8
of Linnarsson, McCloskey, and McCloskey II.4 ’197 Deci-
sion at *32; ’013 Decision at *23.
The Board found a motivation to combine Linnarsson
and McCloskey in all decisions. ’981 Decision at *14–17;
’197 Decision at *15–20; ’013 Decision at *15–19. For all
three patent IPRs, the Board also found motivation to com-
bine Linnarsson and McCloskey using ligation as a design
choice to improve flexibility. ’981 Decision at *20–22; ’197
Decision at *27–28; ’013 Decision at *16–19. Additionally,
for the ’981 patent IPR, the Board determined that the
combination of Linnarsson and McCloskey discloses the
“correlate” limitations of claim 1. ’981 Decision at *13–14.
10x timely appealed. We have jurisdiction under
28 U.S.C. § 1295(a)(4)(A).
II. STANDARD OF REVIEW
“We review the Board’s legal conclusions de novo and
its fact findings for substantial evidence.” Game & Tech.
Co. v. Wargaming Grp. Ltd., 942 F.3d 1343, 1348 (Fed. Cir.
2019). “Whether a claimed invention is unpatentable as
obvious is a question of law that is reviewed de novo, based
on underlying findings of fact reviewed for substantial evi-
dence.” Redline Detection, LLC v. Star Envirotech, Inc.,
811 F.3d 435, 449 (Fed. Cir. 2015). Whether a person of
ordinary skill in the art would have been motivated to com-
bine prior art references is a factual question that we re-
view for substantial evidence. Intel Corp. v. PACT XPP
Schweiz AG, 61 F.4th 1373, 1378 (Fed. Cir. 2023).
“Substantial evidence means such relevant evidence as
a reasonable mind might accept as adequate to support a
conclusion.” FanDuel, Inc. v. Interactive Games LLC,
4 U.S. Patent App. Pub. No. 2007/0020640 (filed July
21, 2005; published Jan. 25, 2007), 25-1618 J.A. 3272–90
(“McCloskey II”).
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 9
966 F.3d 1334, 1343 (Fed. Cir. 2020) (internal quotation
marks and citation omitted). “The substantial evidence
standard . . . involves examination of the record as a whole,
taking into account evidence that both justifies and de-
tracts from an agency’s decision.” OSI Pharms., LLC
v. Apotex Inc., 939 F.3d 1375, 1381 (Fed. Cir. 2019) (inter-
nal quotation marks and citation omitted).
III. D ISCUSSION
10x raises four challenges to the Board’s final written
decisions. First, for the ’013 patent IPR, 10x argues that
the Board never made a finding that a person of ordinary
skill in the art would have been motivated to combine Lin-
narsson and McCloskey to reduce amplification bias and to
use ligation to attach the second tag sequence. No. 25-1618
Appellant’s Br. 31–32. Second, for the ’197 patent and ’981
patent IPRs, 10x argues that the Board erred in finding
that a person of ordinary skill in the art would have found
that a reduction of amplification bias or a design choice pro-
vides a motivation to combine Linnarsson and McCloskey.
Id. at 32–61; No. 25-1199 Appellant’s Br. 30–57. Third, for
the ’981 patent IPR, 10x argues that the Board erred in de-
termining that the combination of Linnarsson and McClos-
key discloses the “correlate” limitations. No. 25-1199
Appellant’s Br. 57–61. Fourth, for the ’197 patent and ’981
patent IPRs, 10x argues that the Board erred in finding
that a person of ordinary skill in the art would have been
motivated to combine Linnarsson and McCloskey using li-
gation as a “design choice” that increased “flexibility.” Id.
at 61–65; No. 25-1618 Appellant’s Br. 61–66. We address
each argument in turn.
A.
10x argues that, for the ’013 patent IPR, the Board
committed reversible error because it never made any find-
ing regarding the motivation to combine Linnarsson and
McCloskey to add a second tag sequence and only discussed
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 10
the motivation for modifying that combination to use liga-
tion. No. 25-1618 Appellant’s Br. 31–32. We disagree.
The Board did not err in addressing the motivation-to-
combine challenges that 10x raised before it. Before the
Board, 10x never raised the motivation-to-combine chal-
lenges that it is raising before us now. Instead, 10x focused
its motivation-to-combine arguments before the Board on
utilization of ligation to add a tag and the length of the sec-
ond tag from McCloskey that would be applied to Linnar-
son. No. 25-1618 J.A. 13356–61, 13382. Accordingly, the
Board did not err by addressing the specific challenges that
10x raised. ’013 Decision at *16–18; see Novartis AG
v. Torrent Pharms. Ltd., 853 F.3d 1316, 1327–28 (Fed. Cir.
2017).
Additionally, 10x does not show reversible Board error
in the motivation-to-combine discussion. “[T]o prevail[,
10x] must not only show the existence of error, but also
show that the error was in fact harmful because it affected
the decision below.” In re Watts, 354 F.3d 1362, 1369–70
(Fed. Cir. 2004). In this case, the Board acknowledged
Parse’s proposed motivations to combine, engaged specifi-
cally with the arguments that 10x disputed, and ultimately
agreed with Parse’s motivations to combine. ’013 Decision
at *15–19. The Board’s finding in the ’013 patent IPR that
there was a motivation to combine McCloskey and Linnars-
son is also consistent with the outcome of its findings for
the ’981 patent and ’197 patent IPRs, where the Board
found that there was a motivation to combine McCloskey
and Linnarsson based on similar rationales that Parse
raised for the ’013 patent IPR, and which we discuss below.
Id.; ’981 Decision at *14–17; ’197 Decision at *15–20. Com-
pare No. 25-1618 J.A. 11056–58 with No. 25-1618
J.A. 13050–52 (arguing the same amplification bias moti-
vation-to-combine rationale in the ’197 patent and ’013 pa-
tent petitions). Accordingly, 10x does not show reversible
Board error in the motivation-to-combine discussion.
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 11
B.
10x challenges the Board’s findings that a person of or-
dinary skill in the art would have been motivated to com-
bine McCloskey and Linnarsson. 25-1199 Appellant’s
Br. 30–57; 25-1618 Appellant’s Br. 32–61. For the ’981 and
’197 patent IPRs, the Board found that there was a moti-
vation to combine because doing so: (1) would have been
an obvious design choice, ’981 Decision at *14–15; ’197 De-
cision at *16; and (2) would have solved the problem of am-
plification bias, disclosed in Linnarsson, ’981 Decision
at *15–17; ’197 Decision at *16–20; No. 25-1199 J.A. 1121
p. 2 ll. 11–13. Amplification refers to “a process by which
extra or multiple copies of a particular polynucleotide are
formed,” No. 25-1199 J.A. 1131 p. 12 ll. 17–18, and ampli-
fication bias can lead to a “source-uncertainty problem for
DNA sequences.” No. 25-1199 J.A. 1190. 10x argues that
the combination would not reduce amplification bias be-
cause McCloskey does not have enough barcodes to
uniquely tag substantially all messenger RNA (“mRNA”)
molecules of Linnarsson. No. 25-1199 Appellant’s Br. 30–
48; No. 25-1618 Appellant’s Br. 32–53. Specifically, 10x ar-
gues that: (1) the Board improperly deviated from the pe-
tition by relying on barcodes longer than the seven-
nucleotide barcodes discussed in McCloskey, No. 25-1199
Appellant’s Br. 32–37, No. 25-1618 Appellant’s Br. 34–40;
(2) eliminating amplification bias requires tagging sub-
stantially all mRNA molecules in a given cell, No. 25-1199
Appellant’s Br. 37–44, No. 25-1618 Appellant’s Br. 40–48;
and (3) the Board erred by relying on Parse’s arguments
regarding bacteria and yeast, No. 25-1199 Appellant’s
Br. 44–48, No. 25-1618 Appellant’s Br. 49–53. As ex-
plained below, we disagree.
i.
Substantial evidence supports the Board’s findings
that McCloskey is not limited to seven-nucleotide barcodes.
As an initial matter, 10x is incorrect in arguing that Parse
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 12
relied on seven-nucleotide barcodes. Parse’s petitions do
not explicitly limit the number of nucleotides for the bar-
code. No. 25-1199 J.A. 8067 (discussing “McCloskey’s
teachings” rather than specifying a nucleotide count);
No. 25-1618 J.A. 11058 (same). Furthermore, McCloskey
itself does not teach only seven-nucleotide barcodes—alt-
hough McCloskey states that it “currently use[s] seven nu-
cleotides for the barcode,” No. 25-1199 J.A. 1193.
McCloskey also teaches the relationship between barcode
length and the number of different molecules and how to
change the number of distinguishable barcodes: “[t]he
number of distinguishable barcodes in a population of oli-
gonucleotides used in a reaction is determined by the num-
ber of random bases, n. This enables one to distinguish
among 4 n allele copies per reaction.” Id.; see also No. 25-
1199 J.A. 3676–78; No. 25-1618 J.A. 3694–96. Accord-
ingly, substantial evidence supports the Board’s findings
that McCloskey is not limited to seven-nucleotide barcodes.
ii.
10x argues that the Board erred in not finding that the
rationale of reducing amplification bias requires substan-
tially all the mRNA molecules present in a cell to be tagged
because: (1) the Board “failed to address Linnarsson’s
teaching of tagging substantially all mRNA molecules,”
No. 25-1199 Appellant’s Br. 38–40; No. 25-1618 Appel-
lant’s Br. 41–44; and (2) the Board failed to explain “how
tagging less than substantially all mRNA molecules in a
cell would address amplification bias,” No. 25-1199 Appel-
lant’s Br. 40–44; No. 25-1618 Appellant’s Br. 44–48. We
address each argument in turn.
First, the Board did not fail to address Linnarsson’s
teaching of tagging substantially all mRNA molecules. The
Board addressed 10x’s argument and considered whether
Parse’s proposed combination required tagging each poly-
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 13
nucleotide or merely each sample polynucleotide5 to ad-
dress amplification bias. ’981 Decision at *16–17; ’197 De-
cision at *18–19.
Second, substantial evidence supports the Board’s find-
ings that Parse’s rationale of reducing amplification bias
does not require all the mRNA molecules present in a cell
to be tagged. 10x concedes that the claims do not require
all the mRNA molecules present in a cell to be tagged.
No. 25-1199 J.A. 8407 (“[T]he claims don’t require ‘tagging
all the mRNA molecules[.]’” (internal citation omitted) (em-
phases omitted)); No. 25-1618 J.A. 11584 (same). Addi-
tionally, Parse’s rationale of reducing amplification bias
does not require tagging substantially all the mRNA mole-
cules present in a cell. In its petitions, Parse explains that
McCloskey addresses amplification bias “[b]y incorporating
a second tag in an oligonucleotide that uniquely identifies
each sample polynucleotide prior to amplification.” No. 25-
1199 J.A. 8066; No. 25-1618 J.A. 11057–58; see also No. 25-
1199 J.A. 1190, 1195. Parse consistently refers to tagging
each sample polynucleotide in its petitions, not each, every,
or all polynucleotides. No. 25-1199 J.A. 8066 (referring to
tagging “each sample polynucleotide”); No. 25-1618
J.A. 11057 (same). Furthermore, expert testimony that the
method would associate a tag with substantially every
sample mRNA molecule supports the amplification-bias ra-
tionale. No. 25-1199 J.A. 1096. Accordingly, substantial
evidence supports the Board’s finding that not all the poly-
nucleotides present in a cell must be tagged to support the
rationale of reducing amplification bias.
5 “[S]ample polynucleotides are the polynucleotides
in a cell that are being sampled (i.e., the polynucleotides of
interest)[.]” ’197 Decision at *18 (internal citation omitted)
(emphasis omitted).
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 14
iii.
Substantial evidence supports the Board’s findings
that Linnarsson is not limited to mammalian cells. As an
initial matter, this argument is not new or improperly
raised in the reply. Parse explains in its petitions that
“Linnarsson explains that the sample of single cells can
take various forms” and can be obtained “from a tissue of
interest, or from a biopsy, blood sample, or cell culture.”
No. 25-1199 J.A. 8050–51 (quoting No. 25-1199 J.A. 1132
p. 13 ll. 11–12); No. 25-1618 J.A. 11044 (same). Linnars-
son itself is also not limited to mammalian cells. No. 25-
1199 J.A. 1132 p. 13 ll. 14–16 (“Furthermore, in general,
cells from any population can be used in the methods, such
as a population of prokaryotic or eukaryotic single celled
organisms including bacteria or yeast.”). Accordingly, sub-
stantial evidence supports the Board’s finding that Lin-
narsson is not limited to mammalian cells. ’981 Decision
at *16 (“Linnarsson is not limited to mammalian cells. Nor
is the Petition’s reliance on Linnarsson limited to mamma-
lian cells.”); ’197 Decision at *18 (same, additionally ex-
plaining that the Petition’s reliance on Linnarsson is not
limited to eukaryotic cells).
Because we conclude that the Board’s findings of a mo-
tivation to combine McCloskey and Linnarsson to reduce
amplification bias are supported by substantial evidence,
we do not reach 10x’s arguments regarding a “design
choice” rationale for ground 1 of the ’981 patent and ’197
patent IPRs, No. 25-1199 Appellant’s Br. 49–57; No. 25-
1618 Appellant’s Br. 53–61, as the Board found amplifica-
tion bias to be an independent motivation to combine, ’981
Decision at *14 (finding the amplification-bias-reduction
and obvious-design-choice rationales “independently suffi-
cient to support the proposed modification”); ’197 Decision
at *15 (same).
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 15
C.
10x argues that the Board erred in determining that
the combination of Linnarsson and McCloskey discloses
the “correlate” limitations of the ’981 patent because
McCloskey’s batch-stamp tracks batches, not individual
cells. No. 25-1199 Appellant’s Br. 57–61. We disagree.
Substantial evidence supports the Board’s determina-
tion that the prior art discloses the “correlate” limitations
of the ’981 patent. The petition relies on Linnarsson for
teaching the cell-specific tag, not McCloskey. No. 25-1199
J.A. 8069–70 (discussing Linnarsson as disclosing the
“first tag sequence”); No. 25-1199 J.A. 8070–71 (identifying
the combination of Linnarsson and McCloskey as disclos-
ing the “second tag sequence”); see also ’981 Decision
at *14. Moreover, the proposed modification is that “Lin-
narsson’s native tag would be conceptually divided into two
portions, wherein the first portion performs the function of
McCloskey’s ‘batch-stamp,’ used to track individual cells.”
’981 Decision at *13 (citing No. 25-1199 J.A. 1097) (cleaned
up). Because Linnarsson’s native tag tracks a polynucleo-
tide to its source “cell,” No. 25-1199 J.A. 1138 p. 19 ll. 9–10,
1170 fig. 3, Linnarsson alone satisfies the “first tag . . . cor-
relate” limitation. ’981 Decision at *14; ’981 patent col. 30
l. 40. Accordingly, substantial evidence supports the
Board’s determination that the prior art discloses the “cor-
relate” limitations.
D.
10x argues that the Board erred in finding that a per-
son of ordinary skill in the art would be motivated to use
ligation in the combination of Linnarsson and McCloskey
for claim 5 of the ’981 and ’197 patents and claim 1 of the
’013 patent as a “design choice” to increase “flexibility.”
No. 25-1199 Appellant’s Br. 61–65; No. 25-1618 Appel-
lant’s Br. 61–66. We disagree.
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10X GENOMICS, INC. v. PARSE BIOSCIENCES, INC. 16
Substantial evidence supports the Board’s findings
that a person of ordinary skill in the art would be motivated
to introduce a “second tag” through ligation as an obvious
design choice to add flexibility. The patents themselves ex-
plained that “[s]uch conventional techniques include . . . li-
gation.” ’981 patent col. 13 ll. 37–39. Additionally, expert
testimony supports the statement that a person of ordinary
skill in the art would be motivated to introduce a “second
tag” to “address the problem of amplification bias, as ex-
pressly taught in McCloskey,” and “[t]here are only two
ways to include this second tag,” one of which is ligation.
No. 25-1199 J.A. 3689 (Dr. Cooper reply declaration);
No. 25-1618 J.A. 3712 (same); No. 25-1618 J.A. 10374–75
(same); No. 25-1199 J.A. 1113–17 (Dr. Cooper declaration);
No. 25-1618 J.A. 1112–16 (same); No. 25-1618 J.A. 10078–
81 (same); ACCO Brands Corp. v. Fellowes, Inc., 813 F.3d
1361, 1367 (Fed. Cir. 2016) (explaining that when a person
of ordinary skill in the art is left with two design choices,
“[e]ach of these two design choices is an obvious combina-
tion of prior-art elements”). Regarding flexibility, the peti-
tions explain that the benefit of added flexibility is the
option to add a second tag sequence later in the process,
No. 25-1199 J.A. 8080; No. 25-1618 J.A. 11074; No. 25-
1618 J.A. 13054, and expert testimony supports this ra-
tionale, No. 25-1199 J.A. 1116; No. 25-1618 J.A. 1115–16;
No. 25-1618 J.A. 10081. Accordingly, substantial evidence
supports the Board’s findings that a person of ordinary
skill in the art would be motivated to introduce a “second
tag” through ligation as an obvious design choice to im-
prove flexibility.
IV. CONCLUSION
We have considered 10x’s remaining arguments and
find them unpersuasive. We affirm.
AFFIRMED
Case: 25-1199 Document: 47 Page: 16 Filed: 08/19/2026

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