Court Opinion

ID: 6500701
Source: CourtListenerOpinion
Date Created: 2022-07-18 15:00:40.941539+00
Date Added: 2024-06-11T09:17:24.475446
License: Public Domain

Case: 22-1027     Document: 55           Page: 1       Filed: 07/18/2022

   United States Court of Appeals
       for the Federal Circuit
                   ______________________

   CAREDX, INC., THE BOARD OF TRUSTEES OF
  THE LELAND STANFORD JUNIOR UNIVERSITY,
               Plaintiffs-Appellants

                                   v.

                      NATERA, INC.,
                     Defendant-Appellee
                   ______________________

                         2022-1027
                   ______________________

     Appeal from the United States District Court for the
 District of Delaware in Nos. 1:19-cv-00567-CFC-CJB, 1:20-
 cv-00038-CFC-CJB, Chief Judge Colm F. Connolly.

            -------------------------------------------------

   CAREDX, INC., THE BOARD OF TRUSTEES OF
  THE LELAND STANFORD JUNIOR UNIVERSITY,
               Plaintiffs-Appellants

                                   v.

                EUROFINS VIRACOR, INC.,
                    Defendant-Appellee
                  ______________________

                         2022-1028
                   ______________________
Case: 22-1027    Document: 55     Page: 2   Filed: 07/18/2022

 2                               CAREDX, INC.   v. NATERA, INC.

     Appeal from the United States District Court for the
 District of Delaware in No. 1:19-cv-01804-CFC-CJB, Chief
 Judge Colm F. Connolly.
                  ______________________

                  Decided: July 18, 2022
                  ______________________

     EDWARD R. REINES, Weil, Gotshal & Manges LLP, Red-
 wood Shores, CA, argued for plaintiffs-appellants. Also
 represented by DEREK C. WALTER; ANNA DWYER, New York,
 NY; ZACHARY TRIPP, Washington, DC.

     GABRIEL K. BELL, Latham & Watkins LLP, Washing-
 ton, DC, argued for defendant-appellee Natera, Inc. Also
 represented by ASHLEY FRY, FAN ZHANG.

     WILLIAM M. JAY, Goodwin Procter LLP, Washington,
 DC, argued for defendant-appellee Eurofins Viracor, Inc.
 Also represented by JORDAN BOCK, KEVIN JON DEJONG,
 Boston, MA; DARRYL M. WOO, San Francisco, CA.
                 ______________________

     Before LOURIE, BRYSON, and HUGHES, Circuit Judges.
 LOURIE, Circuit Judge.
      CareDx, Inc. and The Board of Trustees of the Leland
 Stanford Junior University (“Stanford”) (collectively,
 “CareDx”) appeal from a decision of the United States Dis-
 trict Court for the District of Delaware holding that U.S.
 Patents 8,703,652 (the “’652 patent”), 9,845,497 (the “’497
 patent”), and 10,329,607 (the “’607 patent”) are ineligible
 for patent under 35 U.S.C. § 101. See CareDx, Inc. v.
 Natera, Inc., 563 F. Supp. 3d 329 (D. Del. 2021) (“Deci-
 sion”). We affirm.
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 CAREDX, INC.   v. NATERA, INC.                              3

                          BACKGROUND
     Stanford owns the ’652, ’497, and ’607 patents. All
 three patents share the same specification and are entitled
 “Non-Invasive Diagnosis of Graft Rejection in Organ
 Transplant Patients.” These patents discuss diagnosing or
 predicting organ transplant status by using methods to de-
 tect a donor’s cell-free DNA (“cfDNA”). When an organ
 transplant is rejected, the recipient’s body, through its nat-
 ural immune response, destroys the donor cells, thus re-
 leasing cfDNA from the donated organ’s dying cells into the
 blood. These increased levels of donor cfDNA—which occur
 naturally as the organ’s condition deteriorates—can be de-
 tected and then used to diagnose the likelihood of an organ
 transplant rejection. Claim 1 of each patent is representa-
 tive. Claim 1 of the ’652 patent reads as follows:
     1. A method for detecting transplant rejection,
     graft dysfunction, or organ failure, the method
     comprising:
         (a) providing a sample comprising [cfDNA]
         from a subject who has received a trans-
         plant from a donor;
         (b) obtaining a genotype of donor-specific
         polymorphisms or a genotype of subject-
         specific polymorphisms, or obtaining both a
         genotype of donor-specific polymorphisms
         and subject-specific polymorphisms, to es-
         tablish a polymorphism profile for detect-
         ing donor [cfDNA], wherein at least one
         single nucleotide polymorphism (SNP) is
         homozygous for the subject if the genotype
         comprises subject-specific polymorphisms
         comprising SNPs;
         (c) multiplex sequencing of the [cfDNA] in
         the sample followed by analysis of the se-
         quencing results using the polymorphism
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 4                                 CAREDX, INC.   v. NATERA, INC.

         profile to detect donor [cfDNA] and subject
         [cfDNA]; and
         (d) diagnosing, predicting, or monitoring a
         transplant status or outcome of the subject
         who has received the transplant by deter-
         mining a quantity of the donor [cfDNA]
         based on the detection of the donor [cfDNA]
         and subject [cfDNA] by the multiplexed se-
         quencing, wherein an increase in the quan-
         tity of the donor [cfDNA] over time is
         indicative of transplant rejection, graft dys-
         function or organ failure, and wherein sen-
         sitivity of the method is greater than 56%
         compared to sensitivity of current surveil-
         lance methods for cardiac allograft vascu-
         lopathy (CAV).
 ’652 patent at col. 27 l. 39–col. 28 l. 40 (emphases
 added).
     Claim 1 of the ’497 patent is similar, except that it
 recites high-throughput sequencing or digital polymer-
 ase chain reaction (“PCR”) instead of multiplex se-
 quencing for “determining” the amount of donor cfDNA.
     1. A method of detecting donor-specific circulating
     [cfDNA] in a solid organ transplant recipient, the
     method comprising:
         (a) genotyping a solid organ transplant do-
         nor to obtain a single nucleotide polymor-
         phism (SNP) profile of the solid organ
         transplant donor;
         (b) genotyping a solid organ transplant re-
         cipient to obtain a SNP profile of the solid
         organ transplant recipient, wherein the
         solid organ transplant recipient is selected
         from the group consisting of: a kidney
         transplant, a heart transplant, a liver
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 CAREDX, INC.   v. NATERA, INC.                               5

         transplant, a pancreas transplant, a lung
         transplant, a skin transplant, and any com-
         bination thereof;
         (c) obtaining a biological sample from the
         solid organ transplant recipient after the
         solid organ transplant recipient has re-
         ceived the solid organ transplant from the
         solid organ transplant donor, wherein the
         biological sample is selected from the group
         consisting of blood, serum and plasma, and
         wherein the biological sample comprises
         circulating [cfDNA] from the solid organ
         transplant; and
         (d) determining an amount of donor-spe-
         cific circulating [cfDNA] from the solid or-
         gan transplant in the biological sample by
         detecting a homozygous or a heterozygous
         SNP within the donor-specific circulating
         [cfDNA] from the solid organ transplant in
         at least one assay, wherein the at least one
         assay comprises high-throughput sequenc-
         ing or digital polymerase chain reaction
         (dPCR), and
         wherein the at least one assay detects the
         donor-specific circulating [cfDNA] from the
         solid organ transplant when the donor-spe-
         cific circulating [cfDNA] make up at least
         0.03% of the total circulating [cfDNA] in
         the biological sample.
 ’497 patent at col. 28 l. 2–col. 29 l. 5 (emphasis added).
     Claim 1 of the ’607 patent is also similar, except that it
 recites selective amplification of the cfDNA by PCR before
 high-throughput sequencing.
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 6                              CAREDX, INC.   v. NATERA, INC.

     1. A method of quantifying kidney transplant-de-
     rived circulating [cfDNA] in a human kidney trans-
     plant recipient, said method comprising:
        (a) providing a plasma sample from said
        human kidney transplant recipient,
        wherein said human kidney transplant re-
        cipient has received a kidney transplant
        from a kidney transplant donor, wherein
        said plasma sample from said human kid-
        ney transplant recipient comprises kidney
        transplant-derived circulating [cfDNA] and
        human kidney transplant recipient-de-
        rived circulating [cfDNA];
        (b) extracting circulating [cfDNA] from said
        plasma sample from said human kidney
        transplant recipient in order to obtain ex-
        tracted circulating [cfDNA], wherein said
        extracted circulating [cfDNA] comprises
        said kidney transplant-derived circulating
        [cfDNA] and human kidney transplant re-
        cipient-derived circulating [cfDNA];
        (c) performing a selective amplification of
        target [DNA] sequences, wherein said selec-
        tive amplification of said target [DNA] se-
        quences is of said extracted circulating
        [cfDNA], wherein said selective amplifica-
        tion of said target [DNA] sequences ampli-
        fies a plurality of genomic regions
        comprising at least 1,000 single nucleotide
        polymorphisms, wherein said at least 1,000
        single nucleotide polymorphisms comprise
        homozygous single nucleotide polymor-
        phisms, heterozygous single nucleotide pol-
        ymorphisms, or both homozygous single
        nucleotide polymorphisms and heterozy-
        gous single nucleotide polymorphisms, and
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 CAREDX, INC.   v. NATERA, INC.                            7

        wherein said selective amplification of said
        target deoxyribonucleic acid sequences is
        by polymerase chain reaction (PCR);
        (d) performing a high throughput sequenc-
        ing reaction, wherein said high throughput
        sequencing reaction comprises performing
        a sequencing-by-synthesis reaction on said
        selectively-amplified target [DNA] se-
        quences from said extracted circulating
        [cfDNA], wherein said sequencing-by-syn-
        thesis reaction has a sequencing error rate
        of less than 1.5%;
        (e) providing sequences from said high
        throughput sequencing reaction, wherein
        said provided sequences from said high
        throughput sequencing reaction comprise
        said at least 1,000 single nucleotide poly-
        morphisms; and
        (f) quantifying an amount of said kidney
        transplant-derived circulating [cfDNA] in
        said plasma sample from said human kid-
        ney transplant recipient to obtain a quan-
        tified amount, wherein said quantifying
        said amount of said kidney transplant-de-
        rived circulating [cfDNA] in said plasma
        sample from said human kidney transplant
        recipient comprises using markers distin-
        guishable between said human kidney
        transplant recipient and said kidney trans-
        plant donor, wherein said markers distin-
        guishable between said human kidney
        transplant recipient and said kidney trans-
        plant donor comprises single nucleotide
        polymorphisms selected from said at least
        1,000 single nucleotide polymorphisms
        identified in said provided sequences from
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 8                                  CAREDX, INC.   v. NATERA, INC.

         said high throughput sequencing reaction,
         and wherein said quantified amount of said
         kidney     transplant-derived circulating
         [cfDNA] in said plasma sample from said
         human kidney transplant recipient com-
         prises at least 0.03% of the total circulating
         [cfDNA] from said plasma sample from
         said human kidney transplant recipient.
 ’607 patent at col. 28 l. 56–col. 30 l. 2 (emphasis added).
     In summary, the methods disclosed in the representa-
 tive claims have four steps for detecting a donor’s cfDNA in
 a transplant recipient:
     1. “obtaining” or “providing” a “sample” from the re-
        cipient that contains cfDNA;
     2. “genotyping” the transplant donor and/or recipient
        to develop “polymorphism” or “SNP” “profiles”;
     3. “sequencing” the cfDNA from the sample using
        “multiplex” or “high-throughput” sequencing; or
        performing “digital PCR”; and
     4. “determining” or “quantifying” the amount of donor
        cfDNA.
      CareDx is the exclusive licensee of the ’652, ’497, and
 ’607 patents. It sued Natera, Inc. (“Natera”), alleging that
 Natera’s kidney transplant rejection test infringed the
 ’652, ’497, and ’607 patents. CareDx also sued Eurofins Vi-
 racor, Inc. (“Eurofins”), alleging that Eurofins’ various or-
 gan transplant rejection tests infringed the ’652 patent.
 Natera and Eurofins both moved to dismiss the complaints
 for failure to state a claim due to lack of patent-eligible sub-
 ject matter under § 101.
     The motions to dismiss were referred to a magistrate
 judge, who recommended that they be denied. The magis-
 trate judge held that the claims were a “purportedly new,
 unconventional combination of steps” to detect natural
 phenomena. Decision at 336–37 (quoting J.A. 12). In light
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 CAREDX, INC.   v. NATERA, INC.                              9

 of an amendment in CareDx’s complaint against Natera,
 the district court vacated the magistrate judge’s recom-
 mendation in Natera’s action. The court then adopted the
 magistrate judge’s recommendation in the Eurofins action
 but modified the reasoning. The court noted that “lan-
 guage in the written description[] of the asserted patent[]
 suggests that the patented steps are neither new nor un-
 conventional” and that the “specifications raise[d] doubts
 about the patents’ validity.” Id. at 337 (alterations in orig-
 inal). However, the court was cautious about ruling prem-
 aturely, and denied the motion to dismiss so that the
 parties could conduct limited discovery and develop the rec-
 ord on conventionality.
     After expert discovery relating to § 101 had concluded,
 Natera and Eurofins each moved for summary judgment of
 ineligibility. The district court denied the motions, con-
 cluding that there was a factual dispute as to the conven-
 tionality of the techniques for performing the claimed
 methods. Natera and Eurofins then moved for certification
 of interlocutory appeals from the court’s order denying
 summary judgment. Following a conference with the par-
 ties regarding the motion, the court stated it would recon-
 sider its summary judgment decision in view of case law
 cited in the certification motion.
      Following reconsideration, the district court granted
 the summary judgment motions of ineligibility. The court
 first determined that the asserted claims were directed to
 the detection of natural phenomena, specifically, the pres-
 ence of donor cfDNA in a transplant recipient and the cor-
 relation between donor cfDNA and transplant rejection.
 The court concluded that, based on the specification’s nu-
 merous admissions, the claims recited only conventional
 techniques.
     CareDx appealed the district court’s grant of Natera’s
 and Eurofins’ summary judgment motions. We have juris-
 diction under 28 U.S.C. § 1295(a)(1).
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 10                                CAREDX, INC.   v. NATERA, INC.

                         DISCUSSION
      We review the district court’s grant of summary judg-
 ment de novo under Third Circuit law. SRI Int’l, Inc. v.
 Cisco Sys., Inc., 930 F.3d 1295, 1306 (Fed. Cir. 2019). Sum-
 mary judgment is appropriate when “there is no genuine
 dispute as to any material fact and the movant is entitled
 to judgment as a matter of law.” Fed. R. Civ. P. 56(a). Pa-
 tent eligibility under § 101 is ultimately a question of law
 that this court reviews de novo. Berkheimer v. HP Inc.,
 881 F.3d 1360, 1365 (Fed. Cir. 2018).
                               I
     Section 101 provides that “Whoever invents or discov-
 ers any new and useful process, machine, manufacture, or
 composition of matter, or any new and useful improvement
 thereof, may obtain a patent therefor, subject to the condi-
 tions and requirements of this title.” 35 U.S.C. § 101.
 Given the expansive terms of § 101, “Congress plainly con-
 templated that the patent laws would be given wide scope”;
 the legislative history likewise indicated that “Congress in-
 tended statutory subject matter to ‘include anything under
 the sun that is made by man.’” Diamond v. Chakrabarty,
 447 U.S. 303, 308–09 (1980) (internal citation omitted).
     The Supreme Court has held that § 101 “contains an
 important implicit exception. ‘[L]aws of nature, natural
 phenomena, and abstract ideas’ are not patentable.” Mayo
 Collaborative Servs. v. Prometheus Lab’ys, Inc., 566 U.S.
 66, 70 (2012) (alteration in original) (quoting Diamond v.
 Diehr, 450 U.S. 175, 185 (1981)). These exceptions exist
 because monopolizing the basic tools of scientific work
 “might tend to impede innovation more than it would tend
 to promote it.” Id. at 71. However, the Supreme Court has
 advised that these exceptions must be applied cautiously,
 as “too broad an interpretation of this exclusionary princi-
 ple could eviscerate patent law.” Id.
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 CAREDX, INC.   v. NATERA, INC.                               11

     Laws of nature and natural phenomena are not patent-
 able, but applications and uses of such laws and phenom-
 ena may be patentable. A claim to otherwise eligible
 statutory subject matter does not become ineligible by its
 use of a law of nature or natural phenomenon. See Diehr,
 450 U.S. at 187; Parker v. Flook, 437 U.S. 584, 590 (1978).
 On the other hand, adding “conventional steps, specified at
 a high level of generality,” to a law of nature or natural
 phenomenon does not make a claim to the law or phenom-
 enon patentable. Mayo, 566 U.S. at 82.
     To distinguish claims to patent-eligible applications of
 laws of nature and natural phenomena from claims that
 impermissibly tie up such laws and phenomena, we apply
 the two-part test set forth by the Supreme Court. First, we
 examine whether the claims are “directed to” a law of na-
 ture or natural phenomenon. Alice Corp. Pty. Ltd. v. CLS
 Bank Int’l, 573 U.S. 208, 217 (2014). If—and only if—they
 are, then we proceed to the second inquiry, where we ex-
 amine whether the limitations of the claim apart from the
 law of nature or natural phenomenon, considered individ-
 ually and as an ordered combination, “‘transform the na-
 ture of the claim’ into a patent-eligible application.” Id.
 (quoting Mayo, 566 U.S. at 78).
                                  II
     CareDx argues that, regarding Alice/Mayo step one,
 the patents’ claimed advance is not the discovery of a nat-
 ural correlation between organ rejection and the donor’s
 cfDNA levels in the recipient’s blood. Rather, the claimed
 advance is improved measurement methods spelled out in
 the claims as superior to the inadequate prior art measure-
 ment techniques. CareDx adds that the district court did
 not properly perform the step one analysis because it con-
 cluded that step one is essentially the same as step two and
 centers on conventionality. It asserts that there is no basis
 in the law for a one-step application of Alice/Mayo.
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 12                               CAREDX, INC.   v. NATERA, INC.

      Regarding Alice/Mayo step two, CareDx argues that
 using digital PCR and next-generation sequencing (“NGS”)
 to identify and measure donor-specific SNPs was an in-
 ventive breakthrough and that the patents claim this spe-
 cific and useful application. CareDx notes that the district
 court itself acknowledged that there was a factual dispute
 as to the conventionality of the claimed techniques when it
 initially denied summary judgment. Lastly, CareDx asks
 us to reverse the court’s decision rather than remand be-
 cause of what it refers to as a record of irregular proceed-
 ings, such as the court backtracking on its denial of
 summary judgment and improperly making credibility de-
 terminations.
     Natera responds that CareDx’s asserted claims are di-
 rected to detecting natural phenomena—the presence of an
 organ donor’s cfDNA in the blood of a transplant recipient
 and the correlation between elevated levels of that cfDNA
 and organ transplant rejection. It adds that the claims re-
 cite performing this detection using collection and meas-
 urement techniques that the specification admits are
 conventional and further admits can be performed using
 existing technology without modification. As such, Natera
 argues, these claims are indistinguishable from other diag-
 nostic method claims that the Supreme Court found ineli-
 gible in Mayo and that we found ineligible on multiple
 occasions. Natera’s Resp. at 17 (citing Athena Diagnostics,
 Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743 (Fed.
 Cir. 2019); Genetic Veterinary Scis., Inc. v. LABOKLIN
 GmbH & Co. KG, 933 F.3d 1302 (Fed. Cir. 2018); Roche
 Molecular Sys., Inc. v. CEPHEID, 905 F.3d 1363 (Fed. Cir.
 2018); Cleveland Clinic Found. v. True Health Diagnostics
 LLC, 859 F.3d 1352 (Fed. Cir. 2017); Ariosa Diagnostics,
 Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015)).
      Natera adds that the district court properly applied Al-
 ice step one and relied on the express use of the word “de-
 tecting” in the claims, and our case law addressing similar
 “detecting” claims, to conclude that the claims are directed
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 CAREDX, INC.   v. NATERA, INC.                             13

 to a natural phenomenon. Natera further adds that the
 court recognized that Alice step one can overlap with step
 two.
     Lastly, Natera asserts that the procedural background
 of this case confirms that we should affirm. Natera notes
 that early in this case, the district court determined that it
 was premature to resolve the eligibility question without
 affording the parties an opportunity to develop the record.
 Subsequently, the court recognized that CareDx’s expert
 testimony and other extrinsic evidence was contrary to,
 and therefore could not overcome, the admissions in the
 specification. Natera points out that the court’s reconsid-
 eration of its summary judgment decision demonstrates
 that it thoughtfully and thoroughly considered that issue.
 Eurofins largely echoes Natera’s arguments.
      We agree with Natera and Eurofins. This is not a case
 involving a method of preparation or a new measurement
 technique. See Illumina, Inc. v. Ariosa Diagnostics, Inc.,
 952 F.3d 1367, opinion modified by 967 F.3d 1319, 1327
 (Fed. Cir. 2020) (holding that a new and improved “method
 for preparing” an unnaturally enriched fetal cfDNA frac-
 tion from a pregnant woman by separating smaller fetal
 cfDNA fragments from larger (and likely maternal) frag-
 ments was unlike claims merely “directed to starting with
 a sample that contains” cfDNA and “seeing that the
 [cfDNA] exists”). CareDx also concedes that it did not in-
 vent or discover the relationship between donor cfDNA and
 the likelihood of organ transplant rejection. See Appel-
 lant’s Br. at 1 (“[S]ince at least 1998, scientists recognized
 that higher concentrations of donor cfDNA in the organ re-
 cipient’s bloodstream may be a marker for organ rejec-
 tion.”). Furthermore, as the district court noted, the
 patents’ written description expressly states that the tech-
 niques referred to in the claimed steps are, “unless other-
 wise indicated, conventional techniques of immunology,
 biochemistry, chemistry, molecular biology, microbiology,
 cell biology, genomics, and recombinant DNA, which are
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 14                                 CAREDX, INC.   v. NATERA, INC.

 well within the skill of art.” Decision at 335 (citing ’652
 patent at col. 5 ll. 36–40). Specifically, the written descrip-
 tion is replete with characterizations of the claimed tech-
 niques in terms that confirm their conventionality. 1 Thus,

      1   See, e.g., ’652 patent at col. 9 ll. 8–14 (stating that
 “[d]etection, identification and/or quantitation of the do-
 nor-specific markers (e.g.[,] polymorphic markers such as
 SNPs) can be performed using real-time PCR, chips
 (e.g., SNP chips), high throughput shotgun sequencing of
 circulating nucleic acids (e.g.[,] [cfDNA]), as well as other
 methods known in the art”); id. at col. 10 ll. 11–12 (stating
 that, to obtain cfDNA samples, “any technique known in
 the art may be used, e.g. a syringe or other vacuum suction
 device”); id. at col. 13 ll. 51–53 (stating that step 2 of
 claimed methods can be performed “using existing genotyp-
 ing platforms know[n] in the art”); id. at col. 15 ll. 6–8 (stat-
 ing that techniques recited in step 2 of claimed methods
 “can be accomplished through classic Sanger sequencing
 methods which are well known in the art”); id. at col. 13
 ll. 58–61 (stating that “[c]ompanies (such as Applied Bio-
 systems, Inc.) currently offer both standard and custom-
 designed TaqMan probe sets for SNP genotyping that can
 in principle target any desired SNP position for a PCR-
 based assay”); id. at col. 20 ll. 31–34 (stating that genotyp-
 ing recited in claimed methods “may be performed by any
 suitable method known in the art including those described
 herein such as sequencing, nucleic acid array or PCR”); id.
 at col. 15 ll. 22–65 (discussing commercial high throughput
 sequencing products); id. at col. 14 ll. 58–67 (citing articles
 from 2006 and 2007 as supporting the statement that “dig-
 ital PCR is a much more accurate and reliable method to
 quantitate nucleic acid species”); id. at col. 18 l. 55–col. 19
 l. 2 (stating that “[m]ethods for quantifying nucleic acids,”
 including high throughput genotyping, “are known in the
 art”); id. at col. 21 ll. 5–9 (stating that “[t]he presence or
 absence of one or more nucleic acids from the transplant
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 CAREDX, INC.   v. NATERA, INC.                           15

 CareDx’s patents apply conventional measurement tech-
 niques to detect a natural phenomenon—the level of donor
 cfDNA and the likelihood of organ transplant rejection.
      The claimed methods are indistinguishable from other
 diagnostic method claims the Supreme Court found ineligi-
 ble in Mayo and that we found ineligible on multiple occa-
 sions. See Mayo, 566 U.S. at 82 (applying conventional
 diagnostic methods to observe a natural correlation is not
 patent eligible subject matter). Similarly, Ariosa involved
 claims reciting methods for making a diagnosis of certain
 fetal characteristics based on detecting paternally inher-
 ited cell-free fetal DNA (“cffDNA”) in the blood of a preg-
 nant female. 788 F.3d at 1376. In Ariosa, as here, it was
 undisputed that the existence of cffDNA in maternal blood
 was a natural phenomenon. Id. And, as here, the recited
 steps in Ariosa included amplifying the cfDNA—in that
 case cffDNA in the mother’s blood—using PCR. Id.
 at 1374. What followed was detecting the paternally inher-
 ited cffDNA, again a natural phenomenon. Id. at 1373–74.
 The specification asserted that analyzing cffDNA permit-
 ted more efficient determination of genetic defects and that
 a pregnant woman carrying a fetus with certain genetic de-
 fects will have more cffDNA in her blood than will a woman
 with a normal fetus. Id. We held that the claims were di-
 rected to a natural phenomenon, identifying the presence
 of cffDNA, at Alice/Mayo step one, and ultimately ineligi-
 ble. Id. at 1376, 1378.
     Here, as in Ariosa, the claims boil down to collecting a
 bodily sample, analyzing the cfDNA using conventional
 techniques, including PCR, identifying naturally occurring
 DNA from the donor organ, and then using the natural

 donor in the transplant recipient may be determined by
 any suitable method known in the art including those de-
 scribed herein such as sequencing, nucleic acid arrays or
 PCR”).
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 16                               CAREDX, INC.   v. NATERA, INC.

 correlation between heightened cfDNA levels and trans-
 plant health to identify a potential rejection, none of which
 was inventive. The claims here are equally as ineligible as
 those in Ariosa.
      CareDx’s step one arguments are unavailing. Its argu-
 ment that the district court “disregarded the [s]tep [o]ne
 analysis entirely,” Appellant’s Br. at 33–34, is contradicted
 by the record. The court reviewed the claim language
 (e.g., “detecting” and “quantifying” donor cfDNA in a trans-
 plant recipient), along with CareDx’s own characteriza-
 tions, and concluded that the claims recite methods for
 detecting natural phenomena. Decision at 341–42. Based
 on our precedent, the court noted that claims applying con-
 ventional methods “directed to” natural phenomena satisfy
 Alice/Mayo step one.
      CareDx also incorrectly characterizes our precedent as
 limiting the conventionality inquiry to step two. On the
 contrary, and as the district court recognized, we have re-
 peatedly analyzed conventionality at step one as well. See
 Athena, 915 F.3d at 751 (stating that, at step one “the spec-
 ification describes the claimed concrete steps for observing
 the natural law as conventional”); see also Cleveland
 Clinic, 859 F.3d at 1361 (stating that, at step one the
 claims contained “no meaningful non-routine steps”). In-
 deed, we have explained that “the two stages are plainly
 related: not only do many of our opinions make clear that
 the two stages involve overlapping scrutiny of the content
 of the claims, but . . . there can be close questions about
 when the inquiry should proceed from the first stage to the
 second.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d
 1350, 1353 (Fed. Cir. 2016) (citations omitted). As such,
 our precedent rejects CareDx’s effort to draw a bright line
 between the two steps.
     CareDx argues that the patents’ claims are directed not
 to natural phenomena, but to improved laboratory tech-
 niques. CareDx contends that the “claimed advance” is “an
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 CAREDX, INC.   v. NATERA, INC.                            17

 improved, human-devised method for measuring increases
 in donor cfDNA in a recipient’s body to identify organ re-
 jection.” Appellant’s Br. at 27. In particular, CareDx iden-
 tifies the use of digital PCR, NGS, and selective
 amplification to more accurately measure donor SNPs of
 cfDNA in transplant recipients. However, CareDx does not
 actually claim any improvements in laboratory tech-
 niques—rather, as previously discussed, the actual claims
 of the patent merely recite the conventional use of existing
 techniques to detect naturally occurring cfDNA. Further-
 more, the specification admits that the laboratory tech-
 niques disclosed in the claims require only conventional
 techniques and off-the-shelf technology. See supra note 1.
     For these reasons, we affirm the district court’s holding
 that the ’652, ’497, and ’607 patents’ asserted claims are
 directed to natural phenomena under Alice/Mayo step one.
      Regarding Alice/Mayo step two, we also agree with the
 district court and hold that the asserted claims add nothing
 inventive because they merely recite standard, well-known
 techniques in a logical combination to detect natural phe-
 nomena. The court thoroughly considered whether any of
 the claims’ additional elements were unconventional and,
 based on the specification’s admissions, properly found
 that they were not. See Decision at 345–46. The specifica-
 tion admits that each step in the purported invention re-
 quires only conventional techniques and commercially
 available technology: (1) collecting the patient’s sample us-
 ing “any technique known in the art,” ’652 patent at col. 10
 l. 11; (2) genotyping the donor and recipient to create SNP
 profiles using “any suitable method known in the art,” id.
 at col. 20 ll. 31–33; (3) sequencing the cfDNA using “well
 known” techniques and off-the-shelf tools, id. at col. 15
 ll. 6–8, col. 15 ll. 22–67; and (4) quantifying the donor
 cfDNA using methods “known in the art,” id. col. 18 l. 55–
 col. 19 l. 2. See supra note 1. There is no genuine dispute
 that the claimed techniques add nothing inventive to the
 natural phenomenon being detected.
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 18                                CAREDX, INC.   v. NATERA, INC.

      We have repeatedly held that applying standard tech-
 niques in a standard way to observe natural phenomena
 does not provide an inventive concept. In Ariosa, the spec-
 ification stated that the preparation and amplification of
 DNA sequences in plasma, including by PCR were “stand-
 ard” techniques. 788 F.3d at 1377. In Athena, the specifi-
 cation expressly described the recited immunoassay
 techniques as “standard” or “known per se in the art.”
 915 F.3d at 753–54. And in Roche, the specification stated
 that the methods for detecting the bacterium used “stand-
 ard PCR techniques” and failed to disclose “any ‘new and
 useful’ improvement to PCR protocols or DNA amplifica-
 tion techniques.” 905 F.3d at 1372.
     As in each of these cases, CareDx’s asserted claims add
 nothing inventive at step two because they recite detection
 methods that “simply append[] conventional steps, speci-
 fied at a high level of generality” to natural phenomena.
 Mayo, 566 U.S. at 82. Each of the methods in the recited
 steps was already being performed by those in the art. Fur-
 thermore, the claimed combination of steps adds nothing
 inventive. The specification confirms that the claimed com-
 bination of steps—collecting a sample, genotyping, se-
 quencing, and quantifying—was a straightforward, logical,
 and conventional method for detecting cfDNA previously
 used in other contexts, including cancer diagnostics and
 prenatal testing. See ’652 patent at col. 6 l. 57–col. 7 l. 46.
 Thus, the practice of the asserted method claims does not
 result in an inventive concept that transforms the natural
 phenomena into a patentable invention. For these reasons,
 we affirm the district court’s holding with regard to Al-
 ice/Mayo step two.
     Lastly, we note that CareDx’s procedural complaints
 are without merit. First, CareDx asserts that the district
 court did not “explain[] why it departed from the magis-
 trate judge’s reasoning.” Appellant’s Br. at 54. However,
 the court explained that it agreed with the magistrate
 judge insofar as he found it was premature to resolve § 101
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 CAREDX, INC.   v. NATERA, INC.                               19

 on the pleadings. The court then went on to express doubt
 about the magistrate judge’s recommendation on finding
 eligibility in light of the specification’s disclosures suggest-
 ing the conventionality of the claimed methods. The court
 also indicated that it viewed CareDx’s claims as akin to in-
 eligible claims in Athena. J.A. 60. Moreover, the court’s
 final decision explained why the claims are indeed ineligi-
 ble.
      Second, CareDx points out the irregularity of the dis-
 trict court backtracking on its initial denial of summary
 judgment and contends that the court erroneously decided
 issues of fact. However, as Natera and Eurofins argue, the
 court was entitled to reconsider its summary judgment de-
 cision. The court initially denied summary judgment be-
 cause the warring extrinsic evidence from CareDx, Natera,
 and Eurofins appeared to create a fact issue. However, the
 court later found this fact issue non-genuine due to the ex-
 plicit contradiction between CareDx’s extrinsic evidence
 and the numerous admissions of conventionality in the in-
 trinsic record.
                           CONCLUSION
     We have considered CareDx’s remaining arguments
 but find them unpersuasive. Because the asserted claims
 in the ’652, ’497, and ’607 patents are directed to a natural
 law together with conventional steps to detect or quantify
 the manifestation of that law, they are ineligible under
 § 101. For the foregoing reasons, we affirm the judgment
 of the district court.
                           AFFIRMED