Case: 20-1785 Document: 80 Page: 1 Filed: 04/29/2021
`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`BIO-RAD LABORATORIES, INC.,
`Appellant
`
`v.
`
`INTERNATIONAL TRADE COMMISSION,
`Appellee
`
`10X GENOMICS INC.,
`Intervenor
`______________________
`
`2020-1785
`______________________
`
`Appeal from the United States International Trade
`Commission in Investigation No. 337-TA-1100.
`______________________
`
`Decided: April 29, 2021
`______________________
`
`BRIAN C. CANNON, Quinn Emanuel Urquhart & Sulli-
`van, LLP, Redwood Shores, CA, argued for appellant.
`Also represented by KEVIN P.B. JOHNSON; DAVID LEON
`BILSKER, ANDREW EDWARD NARAVAGE, NATHAN SUN, San
`Francisco, CA; SEAN GLOTH, II, New York, NY; S. ALEX
`LASHER, Washington, DC.
`
` BENJAMIN S. RICHARDS, Office of the General Counsel,
`United States International Trade Commission, Washing-
`ton, DC, argued for appellee. Also represented by
`
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`BIO-RAD LABORATORIES, INC. v. ITC
`
`DOMINIC L. BIANCHI, WAYNE W. HERRINGTON, SIDNEY A.
`ROSENZWEIG.
`
` MATTHEW D. POWERS, Tensegrity Law Group, LLP,
`Redwood Shores, CA, argued for intervenor. Also repre-
`sented by PAUL EHRLICH, ROBERT LEWIS GERRITY, UTSAV
`GUPTA, DANIEL RADKE, JENNIFER ROBINSON, STEFANI
`SMITH; AZRA HADZIMEHMEDOVIC, SAMANTHA A. JAMESON,
`AARON MATTHEW NATHAN, McLean, VA.
` ______________________
`
`Before TARANTO, CHEN, and STOLL, Circuit Judges.
`TARANTO, Circuit Judge.
`10X Genomics Inc. filed a complaint against Bio-Rad
`Laboratories, Inc. with the International Trade Commis-
`sion, alleging that Bio-Rad’s importation and sale of
`microfluidic systems and components used for gene se-
`quencing or related analyses violated section 337 of the
`Tariff Act of 1930, 19 U.S.C. § 1337. Invoking the stat-
`ute’s bar on importation and sale “of articles that . . .
`(i) infringe a valid and enforceable United States patent,”
`19 U.S.C. § 1337(a)(1)(B), 10X alleged that Bio-Rad in-
`fringed certain claims of several of 10X’s patents, includ-
`ing U.S. Patent Nos. 9,689,024, 9,695,468, and 9,856,530.
`The Administrative Law Judge (ALJ) determined that
`Bio-Rad violated the statute with respect to all three
`patents. Specifically, the ALJ found that Bio-Rad in-
`fringed the patent claims now at issue and also that 10X
`practiced the claims, the latter fact satisfying the re-
`quirement of a domestic industry “relating to the articles
`protected by the patent,” id. § 1337(a)(2). In addition, the
`ALJ rejected Bio-Rad’s defense that it could not be liable
`for infringement because it co-owned the asserted 10X
`patents under assignment provisions that two of the
`named inventors signed when they were employees of Bio-
`Rad (and its predecessor), even though the inventions
`claimed were not made until after the employment. The
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`Commission affirmed the ALJ’s determinations, though it
`modified some of the ALJ’s reasoning. We affirm.
`I
`A
`The first two of the three patents at issue on appeal,
`i.e., the ’024 patent and ’468 patent, share a specification.1
`Both patents are entitled “Methods for Droplet-Based
`Sample Preparation.” And both list Benjamin Hindson,
`Serge Saxonov, and Michael Schnall-Levin as the co-
`inventors. On the record and arguments before us, we
`take as a given that the conception date for the claims at
`issue was no earlier than in January 2013.
`The shared specification describes methods of prepar-
`ing samples that can include “fragmenting molecules,
`isolating molecules, and/or attaching unique identifiers to
`particular fragments of molecules.” ’024 patent, col. 1,
`lines 34–37. The material of interest (analyte)—which
`may be polynucleotides (e.g., DNA segments), cells, or
`other material—can be subdivided into “an assembly of
`partitions (e.g., microwells, droplets) that are loaded with
`microcapsules.” Id., col. 4, lines 24–27. Each partition, or
`a microcapsule in it, may contain a sample of the analyte
`and a reagent, the latter of which may be a unique identi-
`fier that enables tracking partition content in further
`processing. Id., col. 4, lines 29–44.
`In one embodiment, of central importance to the pre-
`sent matter, “a microcapsule may be a gel bead.” Id., col.
`9, lines 28–34. Analytes or reagents may be coupled to
`the interior or to the outer surface of the gel bead. See id.,
`
`
`1 Before the Commission, 10X also alleged in-
`fringement of a fourth patent, U.S. Patent No. 9,644,204,
`but the ALJ rejected the allegation, the Commission
`affirmed, and 10X has not appealed that ruling.
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`BIO-RAD LABORATORIES, INC. v. ITC
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`col. 9, lines 35–42. The analytes or reagents may then be
`released from the microcapsule via a stimulus, or “trig-
`ger,” which take the form of, e.g., chemical agents, en-
`zymes, light, heat, or magnetic fields. Id., col. 22, lines 4–
`21.
`One example of a reagent is a “molecular barcode”
`that can serve as a unique identifier. See id., col. 12, lines
`9–14. Molecular barcodes can be used to identify and
`track individual molecules of (say) the nucleic acid seg-
`ments. See id. For example, if multiple samples are
`analyzed simultaneously by pooling them, see id., col. 12,
`lines 31–39, and the analytes from each sample are
`tagged with a barcode, analytes from different samples
`can be identified and tracked in the pooled sample, id.,
`col. 12, lines 36–39. “Oligonucleotide barcodes . . . may be
`particularly useful in nucleic acid sequencing.” Id., col.
`12, lines 43–44.
`10X asserted independent claim 1 and dependent
`claims 5, 17, 19, and 22 of the ’024 patent against Bio-
`Rad. Claim 1 recites:
`1. A method for sample preparation, comprising:
`a) providing a droplet comprising a porous gel
`bead and a target nucleic acid analyte, wherein
`said porous gel bead comprises at least 1,000,000
`oligonucleotide molecules comprising barcode se-
`quences, wherein said oligonucleotide molecules
`are releasably attached to said porous gel bead,
`wherein said barcode sequences are the same se-
`quence for said oligonucleotide molecules;
`b) applying a stimulus to said porous gel bead to
`release said oligonucleotide molecules from said
`porous gel bead into said droplet, wherein upon
`release from said porous gel bead, a given oligonu-
`cleotide molecule from said oligonucleotide mole-
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`BIO-RAD LABORATORIES, INC. v. ITC
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`cules attaches to said target nucleic acid analyte;
`and
`c) subjecting said given oligonucleotide molecule
`attached to said target nucleic acid analyte to nu-
`cleic acid amplification to yield a barcoded target
`nucleic acid analyte.
`Id., col. 33, line 56, through col. 34, line 7.
`With respect to the ’468 patent, 10X asserted inde-
`pendent claim 1 and dependent claims 6, 7, 9, and 21
`against Bio-Rad. Claim 1 recites:
`1. A method for droplet generation, comprising:
`(a) providing at least 1,000,000 oligonucleotide
`molecules comprising barcode sequences, wherein
`said barcode sequences are the same sequence for
`said at least 1,000,000 oligonucleotide molecules,
`wherein said at least 1,000,000 oligonucleotide
`molecules are releasably attached to a bead,
`wherein said bead is porous;
`(b) combining said at least 1,000,000 oligonucleo-
`tide molecules and a sample comprising a nucleic
`acid analyte each in an aqueous phase at a first
`junction of two or more channels of a microfluidic
`device to form an aqueous mixture comprising
`said at least 1,000,000 oligonucleotide molecules
`attached to said bead and said sample; and
`(c) generating a droplet comprising said at least
`1,000,000[ ]oligonucleotide molecules attached to
`said bead and said sample comprising said nucleic
`acid analyte by contacting said aqueous mixture
`with an immiscible continuous phase at a second
`junction of two or more channels of said microflu-
`idic device.
`’468 patent, col. 33, line 56, through col. 34, line 9.
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`BIO-RAD LABORATORIES, INC. v. ITC
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`The third patent asserted by 10X here is the ’530 pa-
`tent, entitled “Methods and Systems for Processing Poly-
`nucleotides.” It lists Benjamin Hindson, Serge Saxonov,
`and Michael Schnall-Levin as three of six inventors. It is
`undisputed that the conception date for the inventions of
`this patent is no earlier than the January 2013 date for
`the ’024 and ’468 patents.
`Although the ’530 patent does not share a specifica-
`tion with the other two patents at issue here, the subject
`matter of the asserted claims is related to that of the
`asserted ’024 and ’468 patent claims. 10X asserted inde-
`pendent claim 1 and dependent claims 4, 11, 14, 19, 26,
`and 28 of the ’530 patent. Claim 1 recites:
`1. A method for nucleic acid preparation or analy-
`sis, comprising:
`(a) providing:
`(i) at least 1,000 gel beads;
`(ii) releasably attached to each of said at
`least 1,000 gel beads, at least 1,000 bar-
`code molecules comprising identical bar-
`code sequences that are distinct from
`barcode sequences of at least 1,000 bar-
`code molecules releasably attached to any
`other gel bead of said at least 1,000 gel
`beads; and
`(iii) a plurality of cells each comprising a
`plurality of polynucleotide molecules;
`(b) generating a plurality of droplets, wherein at
`least 1,000 droplets of said plurality of droplets
`each comprise:
`(i) a single gel bead from said at least
`1,000 gel beads; and
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`(ii) a single cell from said plurality of cells;
`and
`(c) in each of said at least 1,000 droplets, using
`said plurality of polynucleotide molecules from
`said single cell and barcode molecules of said at
`least 1,000 barcode molecules from said single gel
`bead to generate a plurality of barcoded polynu-
`cleotide molecules,
`wherein said barcode molecules become detached
`from said gel bead.
`’530 patent, col. 47, line 58, through col. 49, line 4.
`B
`By mid-2010, two of the named inventors of the 10X
`patents—Dr. Hindson and Dr. Saxonov—were working for
`a company called QuantaLife, Inc., which Dr. Hindson
`had co-founded. Each of them signed an agreement (Dr.
`Hindson in 2009, Dr. Saxonov in 2010) that provided, as
`relevant here:
`(a) Employee agrees to disclose promptly to the
`Company the full details of any and all ideas, pro-
`cesses, recipes, trademarks and service marks,
`works, inventions, discoveries, marketing and
`business ideas, and improvements or enhance-
`ments to any of the foregoing (“IP”), that Employ-
`ee conceives, develops or creates alone or with the
`aid of others during the term of Employee’s em-
`ployment with the Company . . . .
`(b) Employee shall assign to the Company, with-
`out further consideration, Employee’s entire right
`to any IP described in the preceding subsection,
`which shall be the sole and exclusive property of
`the Company whether or not patentable.
`J.A. 3199, 3209.
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`BIO-RAD LABORATORIES, INC. v. ITC
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`In 2011, Bio-Rad acquired QuantaLife, and Drs.
`Hindson and Saxonov became Bio-Rad employees. In
`October of that year, they each signed an agreement that
`provided, as relevant here:
`All inventions (including new contributions, im-
`provements, designs, developments, ideas, discov-
`eries, copyrightable material, or trade secrets)
`which I may solely or jointly conceive, develop or
`reduce to practice during the period of my em-
`ployment by Bio-Rad shall be assigned to Bio-Rad.
`J.A. 3193, 3195.
`Drs. Hindson and Saxonov left Bio-Rad in April 2012,
`and together they formed 10X in July 2012. J.A. 10042.
`By August 2012, 10X filed the first of several provisional
`patent applications that focused on using microcapsules
`in capsule partitions or droplet partitions (referred to as
`capsule-in-capsule and capsule-in-droplets architecture,
`respectively) for barcoding. See J.A. 1215. By January
`2013, the 10X inventors had conceived of a different
`architecture: “gel bead in emulsion” (GEM). See J.A.
`1215–20, 10178. The GEM architecture involves “parti-
`tioning nucleic acids, DNA or RNA, in droplets together
`with gel beads that are used to deliver the barcodes into
`the droplet,” where the “barcodes are released from the
`gel beads using a stimulus.” J.A. 269 (internal quotation
`marks omitted); see also J.A. 1215–16, 1233. The asserted
`10X patent claims all involve this architecture.
`After 10X began selling its products, including the
`GemCode and Chromium products, Bio-Rad released its
`own ddSEQ™ system, whose ordinary use, 10X alleges,
`practices its patents. See J.A. 543–44. The ddSEQ sys-
`tem uses oligonucleotide molecules that are attached to a
`gel bead and can be released from the bead via a stimu-
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`lus. J.A. 161.2 The stimulus used by Bio-Rad’s system is
`an enzyme complex that cleaves the oligonucleotides from
`the gel bead. J.A. 161.
`
`C
`The ALJ ruled for 10X in the respects relevant to the
`appeal (while resolving other issues not presented on
`appeal). J.A. 138–298. The ALJ found that ordinary use
`of Bio-Rad’s ddSEQ system infringes the asserted claims
`of the ’024, ’468, and ’530 patents, that the same is true of
`10X’s products, and that both the infringing-articles and
`domestic-industry requirements of section 337 are met.
`J.A. 159–72, 200–07, 232–59.3 The ALJ also rejected Bio-
`Rad’s contention, based on the assignment provisions,
`that it co-owned these patents and therefore could not
`infringe them. J.A. 277–93. When Bio-Rad petitioned for
`review of the ALJ’s Initial Determination, the Commis-
`sion decided to review it in part. See Certain Microfluidic
`Systems and Components Thereof and Products Contain-
`ing Same; Commission Determination To Review in Part
`a Final Initial Determination Finding a Violation of
`Section 337 and To Extend the Target Date; Schedule for
`Filing Written Submissions, 84 Fed. Reg. 56,835, 56,835
`(Oct. 23, 2019) (notice). On February 12, 2020, the Com-
`
`
`2 We use the singular “system,” even though there
`are several accused versions of ddSEQ. The versions at
`issue do not differ in a way that is material on appeal.
`3 The asserted claims are method claims, and the
`ALJ also found the requirements of indirect infringement
`met. J.A. 168–72, 204–05, 246–53. Those findings are
`not challenged on appeal. Although the claims are meth-
`od claims, in this matter we lose no needed precision by
`sometimes referring to a system or product as practicing a
`claim or meeting claim requirements or infringing a claim
`or patent.
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`BIO-RAD LABORATORIES, INC. v. ITC
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`mission affirmed the ALJ’s determinations regarding
`infringement, the domestic-industry requirement, and
`ownership. J.A. 29–137.
`
`1
`With respect to the ’024 patent, the ALJ determined
`that Bio-Rad’s ddSEQ system practices all challenged
`claims of the ’024 patent, including, as relevant on appeal,
`the second step of the method in claim 1, which requires
`“applying a stimulus to said porous gel bead to release
`said oligonucleotide molecules from said porous gel bead.”
`’024 patent, col. 33, line 65–67 (emphasis added); J.A.
`159–72. Bio-Rad contended that its system does not meet
`that claim limitation because the stimulus used in its
`system acts on the oligonucleotides rather than the gel
`bead. The ALJ disagreed, finding that “the oligonucleo-
`tides are part of the gel bead,” so that “[a]ny stimulus
`applied to the oligonucleotide is therefore also applied to
`the gel bead.” J.A. 164–65 (citing J.A. 4870 (Bio-Rad
`expert testifying that “the enzyme enters the entire
`volume of the bead”); and then citing J.A. 10074). On
`review, the Commission affirmed the ALJ’s determina-
`tion, without any modification relevant to this appeal.
`J.A. 37.
`With respect to the ’468 patent, too, the ALJ deter-
`mined that Bio-Rad’s ddSEQ system practices all chal-
`lenged claims. J.A. 200–04. As relevant on appeal, Bio-
`Rad argued to the Commission that its system does not
`meet the claim requirement of “combining said at least
`1,000,000 oligonucleotide molecules and a sample com-
`prising a nucleic acid analyte . . . at a first junction of two
`or more channels of a microfluidic device to form an
`aqueous mixture.” ’468 patent, col. 33, line 64, through
`col. 34, line 1. Citing testimony from 10X’s expert (Dr.
`Butte), Bio-Rad contended that the solutions of the oligo-
`nucleotide molecules and the sample do not form an
`aqueous mixture at the first junction, but remain sepa-
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`rate until later, when droplets form. J.A. 202 (citing J.A.
`10104); see also J.A. 10104 (Dr. Butte testifying that “it
`would be a big mess” if the two solutions mixed “without
`forming a droplet”). The ALJ disagreed and found 10X’s
`proof of satisfaction of this claim requirement persuasive,
`because 10X’s expert explained that the two solutions
`“come together and then immediately are formed into a
`droplet.” J.A. 203 (quoting J.A. 10104). On review, the
`Commission affirmed the ALJ’s determination, without
`any modification relevant to this appeal. J.A. 51.
`With respect to the ’530 patent, the ALJ likewise de-
`termined that Bio-Rad’s ddSEQ system practices all
`challenged claims. In a claim construction, the ALJ
`concluded that claim 1 requires the (second) step of gen-
`erating “at least 1,000 droplets” to be completed before
`the (third) step of “generating a plurality of barcoded
`polynucleotide molecules.” J.A. 233. Bio-Rad argued that
`its system does not meet that requirement because the
`enzymes in its droplets begin to form barcoded molecules
`immediately upon droplet formation, i.e., barcoding begins
`before at least 1,000 droplets are formed. J.A. 240. The
`ALJ rejected this argument as taking too constrained a
`view of the claim requirement. Even if the enzymes are
`active and barcoding begins immediately after a droplet is
`formed, the ALJ found, there was evidence that the
`enzymes do not work quickly enough to finish cleaving all
`barcoded molecules from the gel bead within the droplets
`before 1,000 droplets are formed. J.A. 241–44. In other
`words, the barcoding process may begin before 1,000
`droplets are formed, but claim 1 requires only that the
`barcoding process may not be completed before 1,000
`droplets are formed. See J.A. 241–44. On review, the
`Commission affirmed and made clear that the ALJ’s
`construction does not forbid any barcoding to occur in any
`droplet before at least 1,000 droplets are generated in the
`second step. See J.A. 72–81, 99–100.
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`BIO-RAD LABORATORIES, INC. v. ITC
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`Bio-Rad also argued that the domestic-industry re-
`quirement was not established for the asserted ’530
`patent claims because, Bio-Rad urged, 10X’s domestic
`products, on which 10X relied to meet this requirement,
`do not practice the independent claim 1 (or therefore the
`other asserted claims). The ALJ found that the 10X
`products do practice claim 1. J.A. 254–57. On review, the
`Commission agreed with the ALJ’s bottom-line finding
`that 10X’s products practice claim 1, even while conclud-
`ing that the particular evidence cited by the ALJ did not
`support the finding. J.A. 82–88. After its own review of
`the record, the Commission determined that enough
`barcodes in the 10X products are released after at least
`1,000 droplets have been generated: Even if gel beads
`begin to dissolve immediately after droplet generation,
`the beads do not dissolve so quickly that fewer than 1,000
`of them still have a plurality of barcodes attached upon
`the completion of droplet formation. J.A. 83–88.
`Finally, the Commission rejected Bio-Rad’s argument
`that the asserted ’530 patent claims are invalid for indefi-
`niteness. The Commission concluded that Bio-Rad had
`forfeited the argument by not timely raising it earlier.
`J.A. 89–94. In the alternative, the Commission concluded
`that the claims are not indefinite. J.A. 95–100.
`2
`As an affirmative defense, Bio-Rad argued that it co-
`owns the three 10X patents asserted against it because
`Drs. Hindson and Saxonov conceived of the ideas embod-
`ied in the patents while they were still employed by Bio-
`Rad (or its predecessor QuantaLife), with which Drs.
`Hindson and Saxonov had signed assignment agreements.
`The ALJ rejected the defense. J.A. 282–92. The ALJ
`concluded that Bio-Rad had not shown that the “inventive
`concept” of the asserted patents was conceived before the
`inventors left Bio-Rad. J.A. 282–83. That was decisive,
`the ALJ concluded, because “[n]o provision of any of the
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`applicable contracts governs future inventions” merely
`because the future inventions “are based on or developed
`from work done during employment.” J.A. 285–86. Based
`on the record, the ALJ found that it was not “more likely
`than not that conception of the inventive idea in the
`asserted patents occurred before [the two co-inventors’]
`departure” from Bio-Rad. J.A. 292.
`On review, the Commission agreed with the ALJ that
`Bio-Rad does not co-own the asserted patents. J.A. 104–
`08. The Commission stated that Bio-Rad’s identified
`“ideas” that Drs. Hindson and Saxonov worked on while
`at QuantaLife and Bio-Rad were too “generic”; they did
`not include the specifics required by the 10X patent
`claims at issue. J.A. 104–05. The Commission added that
`Bio-Rad’s own evidence showed that the inventors, while
`at Bio-Rad and QuantaLife, worked chiefly on droplet-in-
`droplet architecture, which is different from the gel-bead
`architecture to which Drs. Hindson and Saxonov later
`shifted their focus to make the inventions now at issue.4
`J.A. 105. The Commission also determined that Bio-Rad
`had not shown that any of the ideas that Drs. Hindson
`and Saxonov worked on when with Bio-Rad or QuantaLife
`remained outside the published prior art by the concep-
`tion date for the patents at issue. J.A. 106. The Commis-
`sion mentioned that many of the ideas that Bio-Rad
`identified were disclosed in U.S. Patent No. 9,347,059,
`which named Dr. Saxonov as an inventor and was as-
`signed to Bio-Rad. J.A. 106 (“Moreover, the existence of
`the ’059 patent demonstrates that Bio-Rad received the
`benefit of its bargain with respect to the employment
`agreements. For the ideas that were conceived at
`
`
`4 Droplet-in-droplet architecture uses a droplet as
`the vehicle to deliver barcodes into another droplet con-
`taining the analyte, whereas the asserted claims use a gel
`bead as the delivery vehicle. See J.A. 6216.
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`BIO-RAD LABORATORIES, INC. v. ITC
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`QuantaLife or Bio-Rad, Dr. Saxonov did assign his
`rights.”). Finally, the Commission clarified the ALJ’s use
`of the term “‘inventive concept’” to mean “‘the specific
`arrangement of elements claimed in the asserted pa-
`tents.’” J.A. 107–08 (quoting J.A. 283). The Commission
`reasoned that the inventive concept here was the combin-
`ing of several elements resulting in gel beads that deliver
`barcodes into the droplets with nucleic acid samples, in
`which the barcodes are releasably attached to the gel
`beads. J.A. 108. For those reasons, the Commission
`concluded, Bio-Rad had not shown it was entitled to an
`ownership interest in any of the asserted patents.
`Bio-Rad timely appealed. We have jurisdiction under
`19 U.S.C. § 1337(c) and 28 U.S.C. § 1295(a)(6).
`II
`We now generally refer to all determinations on re-
`view as those of the Commission, whether or not made by
`the ALJ or by the full Commission. “We review the
`Commission’s final determinations under the standards of
`the Administrative Procedure Act.” Guangdong Alison
`Hi-Tech Co. v. Int’l Trade Comm’n, 936 F.3d 1353, 1359
`(Fed. Cir. 2019); see also 19 U.S.C. § 1337(c); 5 U.S.C.
`§ 706. The Commission’s factual findings are reviewed for
`substantial-evidence support and its legal determinations
`are reviewed de novo. Guangdong, 936 F.3d at 1359. “A
`finding is supported by substantial evidence if a reasona-
`ble mind might accept the evidence as adequate to sup-
`port the finding.” Henny Penny Corp. v. Frymaster LLC,
`938 F.3d 1324, 1330 (Fed. Cir. 2019).
`A
`Bio-Rad argues that the Commission erred in finding
`that Bio-Rad infringes the asserted claims of the ’024,
`’468, and ’530 patents, in finding that 10X’s domestic
`products practice the asserted claims of the ’530 patent,
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`and in rejecting Bio-Rad’s indefiniteness challenge to the
`asserted claims of the ’530 patent. We disagree.
`1
`Bio-Rad argues that it does not infringe the asserted
`claims of the ’024 patent because its system’s stimulus is
`applied to the oligonucleotide, not the gel bead. Bio-Rad
`Opening Br. at 41–47. The Commission rejected the
`contention and found infringement. We review that
`factual finding for support by substantial evidence.
`ATEN Int’l Co. v. Uniclass Tech. Co., 932 F.3d 1364, 1367
`(Fed. Cir. 2019). We conclude that such support exists.
` Claim 1 of the ’024 patent requires a “porous gel bead
`[that] comprises at least 1,000,000 oligonucleotide mole-
`cules comprising barcode sequences, wherein said oligo-
`nucleotide molecules are releasably attached to said
`porous gel bead.” ’024 patent, col. 33, lines 58–62 (em-
`phasis added). It further requires “applying a stimulus to
`said porous gel bead to release said oligonucleotide mole-
`cules from said porous gel bead.” Id., col. 33, lines 65–67
`(emphases added). The Commission found Bio-Rad’s
`system to satisfy those requirements. The parties agreed
`that the “applying a stimulus . . .” phrase has “its plain
`and ordinary meaning.” J.A. 159. “Releasably attached”
`was construed to mean “‘attached in a manner that allows
`the attached object to be released.’” J.A. 159 (quoting J.A.
`643). That construction is not challenged on appeal.
`The evidence shows that in Bio-Rad’s system, the oli-
`gonucleotide molecules that include barcode sequences
`are contained within the gel bead. J.A. 165 (citing J.A.
`4983 (describing oligonucleotides “in the volume of the . . .
`bead”)). It further shows that the oligonucleotide mole-
`cules that
`include barcode sequences are attached
`through linking molecules to the gel bead. See J.A. 160–
`64, 1278–84. When an enzyme is applied to release
`oligonucleotides that contain barcode sequences, the
`“‘enzyme enters the entire volume of the bead,’” and it
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`releases those nucleotides. J.A. 164 (quoting Bio-Rad’s
`expert, J.A. 4870); see also J.A. 160–66, 1278–84, 3235,
`3240–51. The evidence reasonably permitted the Com-
`mission to find the claim limitation at issue met when the
`enzyme is “appl[ied],” ’024 patent, col. 33, line 65, to the
`entirety of the gel bead at a time when the bead includes
`the specified oligonucleotide molecules. J.A. 165.
`Focusing on the claim’s requirement that specified “ol-
`igonucleotide molecules are releasably attached to said
`porous gel bead,” Bio-Rad argues that two items that are
`attached to each other must not be treated as identical.
`See Bio-Rad Opening Br. at 43–44 (citing In re Cuozzo
`Speed Techs., LLC, 793 F.3d 1268, 1280 (Fed. Cir. 2015)
`(affirming Board’s construction of “integrally attached” to
`mean “discrete parts physically joined together as a unit
`without each part losing its own separate identity”)).
`That observation does not undermine the Commission’s
`finding that the claim limitation, given its plain and
`ordinary meaning, is met. The Commission did not treat
`the bead and the specified oligonucleotide as the “same
`object.” Id. at 43. The Commission properly found that,
`after the specified oligonucleotides have been releasably
`attached to the gel bead, the specified “oligonucleotides
`are part of the gel bead,” J.A. 165 (emphasis added), and
`it is after that attachment that the enzyme is applied to
`the entirety of the bead.
`Bio-Rad argues that its enzyme removes or cleaves a
`part of the oligonucleotide molecule and not some part of
`the gel material, pointing to a portion of the ’024 patent
`specification. Bio-Rad Opening Br. at 46–47 (citing ’024
`patent, col. 2, lines 20–25 (describing the gel bead as
`“degradable upon the application of a stimulus”)). But the
`claim language merely requires “applying a stimulus to
`said porous gel bead to release said oligonucleotide mole-
`cules,” the “said” molecules having only to consist of
`oligonucleotides that contain barcoding sequences (which
`may be less than the entirety of an oligonucleotide mole-
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`17
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`cule bonded with a gel bead). ’024 patent, col. 33, lines
`65–66 (emphasis added); J.A. 162. That language re-
`quires application of an enzyme to the gel bead, but it
`does not further specify which bonds must be broken to
`release the specified oligonucleotides that contain barcode
`sequences. Moreover, the specification contemplates that
`any number of stimuli could be applied, including “chemi-
`cal triggers.” ’024 patent, col. 19, lines 36–46; see also id.,
`col. 9, lines 52–56 (“For example, in the case where an
`oligonucleotide barcode is immobilized to a gel bead via a
`disulfide bond, exposure of the disulfide bond to a reduc-
`ing agent can cleave the disulfide bond and free the
`oligonucleotide barcode from the bead.”). We conclude
`that substantial evidence supports the Commission’s
`finding that Bio-Rad’s system practices the asserted
`claims of the ’024 patent.
`
`2
`Bio-Rad argues that it does not infringe the asserted
`claims of the ’468 patent because its system’s nucleic-acid-
`sample solution and reagent solution do not mix until
`droplets are formed. Bio-Rad Opening Br. at 47–51. The
`Commission reasonably found otherwise.
`Claim 1 of the ’468 patent requires both the oligonu-
`cleotide and nucleic-acid samples to be in an aqueous
`phase that meet at a “first junction . . . to form an aque-
`ous mixture.” ’468 patent, col. 33, line 64, through col. 34,
`line 3. Thereafter a droplet is generated by having the
`aqueous mixture and an “immiscible continuous phase,”
`e.g., oil, meet at a second junction. Id., col. 34, lines 4–9.
`As the Commission described, 10X’s expert testified that
`Bio-Rad’s system met the requirement of an aqueous
`mixture after the first junction, pointing to Bio-Rad
`documents that described the mixing of the two solutions.
`J.A. 201 (citing J.A. 1333–34). Bio-Rad responded that
`10X’s expert had admitted that Bio-Rad’s oligonucleotide
`solution and its nucleic-acid-sample solution are kept
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`separate until they get to the second junction where the
`droplet is formed, lest the solutions react before being
`encased in a droplet. See J.A. 202; see also J.A. 10104
`(10X expert Dr. Butte testifying that “it would be a big
`mess” if the two solutions mixed “without forming a
`droplet”). The Commission credited 10X’s expert and
`rejected Bio-Rad’s response, noting that 10X’s expert had
`explained that the potentially worrisome reaction (lysis)
`is not instantaneous and a droplet is formed soon enough
`after the solutions are combined to avoid creation of a
`mess. J.A. 203 (citing J.A. 10104).
`On appeal, Bio-Rad’s challenge to the Commission’s
`finding on this point relies crucially on a somewhat hazy
`image of the Bio-Rad system that seems to show a hori-
`zontal line between the two solutions until they are past
`the second junction—an image that, Bio-Rad argues,
`establishes that the two solu