Case 1:20-cv-00692-ADA Document 482 Filed 01/12/24 Page 1 of 6
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE WESTERN DISTRICT OF TEXAS
`WACO DIVISION
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`1:20-CV-00692-ADA
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`RAVGEN, INC.,
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`Plaintiff
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`-vs-
`NATERA, INC. AND NSTX, INC.,
`Defendants.
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`MEMORANDUM OPINION AND ORDER
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`Defendant Natera moves for summary judgment of invalidity of Claims 125 and 132 of the
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`’277 Patent based on patent eligibility under 35 U.S.C. § 101. Dkt. 340. The Court heard
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`the parties’ arguments during the final pretrial conference held on December 11, 2023, and
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`orally denied Natera’s motion. Consistent with the Court’s earlier oral ruling and omnibus order
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`at Dkt. 458, the Court DENIES Natera’s Motion under Mayo Step 1 for the reasons set forth
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`below.
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`Natera argues the claims are directed to natural phenomena and do not introduce any
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`meaningful non-routine steps. Dkt. 340 at 1–2. For Claim 125, Natera identifies the natural
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`phenomenon as “‘detecting the presence or absence of a fetal chromosomal abnormality’ using ‘a
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`sample from a pregnant female.’” Id. at 1 (quoting Claim 1). For Claim 132, Natera identifies
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`“determining the sequence of a locus of interest on free fetal DNA isolated from a sample from a
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`pregnant female.” Id. For the reasons discussed below, the Court disagrees that the claims are
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`directed to a natural phenomenon and finds there are genuine issues of material fact as to
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`whether the claims introduce meaningful non-routine steps.
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`Case 1:20-cv-00692-ADA Document 482 Filed 01/12/24 Page 2 of 6
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`I.
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`LEGAL STANDARD
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`The Supreme Court in Mayo Collaborative Servs. v. Prometheus Labs, Inc., 566 U.S. 70
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`(2012) set forth a framework for determining patent eligibility. The determination is based on two
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`steps: 1) whether the patent is directed to a patent-ineligible concepts, and if so, 2) whether there
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`are additional claimed elements that transfer the nature of the claim into a patent-eligible
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`application. Id. at 71-72. Step 2 requires more than “well-understood, routine, conventional
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`activity.” Id. at 73.
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`II.
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`ANALYSIS
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`Claim 125 depends from Claims 1 and 8 inter alia, which recite:
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`1. A method for detecting the presence or absence of a fetal chromosomal abnormality,
`said method comprising: quantitating a ratio of the relative amount of alleles at a
`heterozygous locus of interest in a mixture of template DNA, wherein said mixture
`comprises maternal DNA and fetal DNA, and wherein said mixture of maternal DNA and
`fetal DNA has been obtained from a sample from a pregnant female, and further wherein
`said heterozygous locus of interest has been identified by determining the sequence of
`alleles at the locus of interest, and wherein said ratio indicates the presence or absence of
`a fetal chromosomal abnormality.
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`8. The method of claim 4, wherein said sample is mixed with an agent that inhibits cell
`lysis to inhibit the lysis of cells, if cells are present, wherein the agent is selected from the
`group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor.
`Claim 125 recites:
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`125. The method of claim 10, wherein said cell lysis inhibitor is selected from
`glutaraldehyde, formaldehyde and formalin.
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`Natera argues the focus of the claim is detecting a fetal chromosomal abnormality, which is recited
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`in the preamble of Claim 1. Dkt. 361 at 4–5. Ravgen argues that the focus of the claim when
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`analyzed as a whole is “preventing cell lysis during sample preparation to improve the process of
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`preparing and analyzing cell-free DNA.” Dkt. 384 at 7. Natera responds that the only claimed
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`preparation step is the addition of an agent, and the addition of an agent is not the focus of the
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`claim because the claims provide no requirements on how to use the claimed agent such as how
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`Case 1:20-cv-00692-ADA Document 482 Filed 01/12/24 Page 3 of 6
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`much should be added, how long it should be applied, and how the sample should be handled.
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`Dkt. 427 at 2–3.
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`Both parties acknowledge that the Section 101 analysis must focus on whether the claims
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`as a whole are directed to a natural phenomenon. See Synopsis, Inc. v. Mentor Graphics Corp.,
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`839 F.3d 1138, 1149 (Fed. Cir. 2016). And both parties cite cases with claims related to biological
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`processes to support their arguments. Natera cites Ariosa Diagnostics, Inc. v. Sequenom, Inc. in
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`which the Federal Circuit held claims directed to detecting paternally inherited nucleic acid patent
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`ineligible because “the claims are directed to matter that is naturally occurring.” 788 F.3d 1371,
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`1376 (Fed. Cir. 2015). Ravgen cites Rapid Litigation Management Ltd. v. Cellzdirect, Inc. in which
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`the Federal Circuit held claims directed to freezing and thawing hepatocytes to be patent eligible.
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`827 F.3d 1042, 1048 (Fed. Cir. 2016). In Rapid Litigation, the Federal Circuit determined the
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`claims were not simply directed to observing or detecting “the ability of hepatocytes to survive
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`multiple freeze-thaw cycles,” but rather that the claims as a whole were directed to “a new and
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`useful method of preserving hepatocyte cells.” Id.
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`In both Ariosa Diagnostics and Rapid Litigation, the claims at issue recite steps in addition
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`to detecting natural phenomena. In Ariosa Diagnostics, the additional step is amplifying DNA.
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`Ariosa Diagnostics, 788 F.3d at 1373–74. In Rapid Litigation, the additional step is preserving
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`hepatocyte cells. Rapid Litigation, 827 F.3d at 1046. The parties dispute whether Claim 125 is
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`more like the claims in Ariosa Diagnostics, which were held patent ineligible, or the claims in
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`Rapid Litigation, which were held patent eligible. In this case, Claim 125, including the limitations
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`of the claims from which it depends, recites steps for preserving the cell structure of blood during
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`the process of detecting abnormalities. Because Claim 125 recites steps for preserving a sample,
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`the Court concludes it is more like the claims of Rapid Litigation rather than Ariosa Diagnostics.
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`Natera takes an unduly narrow view of Claim 125 by focusing on the preamble of Claim 1
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`rather than Claim 125 as a whole. The preamble recites detecting chromosomal abnormalities in
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`a sample, but the claim also recites preparation steps to inhibit cell lysis by mixing an agent with
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`the sample. Like the claims in Rapid Litigation, which recite steps for preserving cells, Claim 125
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`recites steps for preserving the cell structure of blood during the process of detecting abnormalities.
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`For example, Claim 8 from which Claim 125 depends, recites mixing a sample with an agent that
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`inhibits cell lysis. As the specification provides, the ability to detect fetal abnormalities was
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`hindered by the low percentage of fetal DNA in a sample, and the addition of cell lysis inhibitors
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`preserved the cell structure of fetal DNA and thereby increased the percentage of fetal DNA. ’277
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`Patent, Cols. 32:33–39, 89:1–11.
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`For the above reasons, the Court concludes Claim 125, when taken as whole, is directed to
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`a method for preserving the cell structure of blood during the process of detecting abnormalities.
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`Claim 125 is thus not directed to a natural phenomenon.
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`Even if Claim 125 were directed to a natural phenomenon, Natera fails to show that there
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`are no genuine issues of material fact as to whether the limitations of the claim transform the claim
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`into a patent-eligible application of the natural phenomenon. Again, this analysis must be based
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`on the claim as a whole. In particular, the analysis must “consider the elements of each claim both
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`individually and ‘as an ordered combination’ to determine whether additional elements ‘transform
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`the nature of the claim’ into a patent-eligible application.” Ariosa Diagnostics, 788 F.3d at 1375–
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`76 (quoting Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 78–79 (2012))
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`Natera argues that the recited limitations including sequencing, adding an agent,
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`quantitating allele ratio, and detecting abnormalities were routine and conventional. Dkt. 361 at
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`13. But aside from attorney argument, Natera does not cite any evidence that the combination of
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`the claimed elements was routine and conventional. See Dkt. 427 at 5 (“There is nothing in the
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`‘ordered combination’ of applying the indisputably known concept of using ‘agents’ like
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`formaldehyde to prevent cell lysis that makes the claims patent eligible.”) see also Dkt. 361 at 13
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`(arguing without citation that the claim “taken as a whole” is not inventive). Natera cites cases
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`finding claims in different patents to recite routine and conventional steps; however, this analysis
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`is fact intensive, and analogizing Claim 125 to other claims in other patents is not sufficient to
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`show there is no genuine issue of material fact here.
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`On the other side, Ravgen’s expert opines that using agents during sample preparation for
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`cell-free DNA applications was not a well-known routine or conventional step. See Dkt. 384-7 at
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`¶ 1919. The Court also notes that Natera filed an inter-partes review (IPR) in which the PTAB
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`found that a person of ordinary skill would not have been motivated to combine the use of a cell
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`lysis inhibiting agent with cell-free DNA analysis methods. See Dkt. 384-4 at 63. The Court
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`recognizes that the issues in dispute in the IPR are different and are not co-extensive with this
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`analysis, but the Court finds that the similarity between a claim being non-obvious and whether
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`the claim when taken as a whole is routine and conventional supports a finding that there are
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`genuine issues of material fact. In any event, on Natera’s motion for summary judgement, the
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`Court views the unrebutted evidence from Ravgen’s expert in the light most favorable to Ravgen,
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`which further supports the Court’s finding.
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`For the above reasons, the Court holds Claim 125 is not directed to a natural phenomena
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`and there are genuine issues of material facts whether the ordered combination of the steps of
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`Claim 125, when taken as a whole, is routine and conventional.
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`The parties do not make separate arguments with respect to Claim 132. For the same
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`reasons as above, the Court holds that Claim 132, which recites “an agent that inhibits cell lysis,”
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`is not directed to a natural phenomenon and there are genuine issues of material fact whether Claim
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`132, when taken as a whole, is routine and conventional.
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`III. CONCLUSION
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`For the foregoing reasons, the Court DENIES Natera’s Motion for Summary Judgement
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`of Invalidity under Mayo Step 1(Dkt. 340).
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`SIGNED this 12th day of January, 2024.
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`ALAN D ALBRIGHT
`UNITED STATES DISTRICT JUDGE
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