PTAB

IPR2021-00788

Quest Diagnostics Inc v. Ravgen Inc

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods for Isolating and Analyzing Cell-Free Fetal DNA
  • Brief Description: The ’277 patent discloses methods for isolating cell-free fetal DNA (cffDNA) from a maternal plasma sample for subsequent analysis. The purported novelty is the use of agents that inhibit maternal cell lysis, thereby reducing contamination from maternal DNA and increasing the relative percentage of fetal DNA in the sample.

3. Grounds for Unpatentability

Ground I: Obviousness over Chiu, Hahn, and Abbott - Claims 81-94, 96, and 133 are obvious over Chiu, Hahn, and Abbott.

  • Prior Art Relied Upon: Chiu (a 2001 journal article), Hahn (a 2001 journal article), and Abbott (Patent 5,891,734).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination teaches all limitations of independent claim 81, a method for preparing a sample for analysis. Chiu was asserted to teach isolating free fetal nucleic acid from maternal blood samples using techniques like centrifugation. Hahn was argued to expressly identify that lysis of maternal cells "contaminates" such samples and that care should be taken to clear "maternal cellular remnants." Abbott was presented as teaching the use of an agent, such as formaldehyde (a cross-linker and cell lysis inhibitor), to fix white blood cells, prevent their lysis, and thereby avoid "interference from DNA from lysed cells" when analyzing components outside the cell.
    • Motivation to Combine (for §103 grounds): Petitioner contended a person of ordinary skill in the art (POSITA) would combine these references to solve a known problem. A POSITA starting with Chiu's method for isolating cffDNA would be directed by Hahn to the specific problem of contamination from maternal cell lysis. That POSITA would then be motivated to look for a solution and find Abbott, which explicitly taught using a well-known agent like formaldehyde to prevent cell lysis and the resulting DNA interference, a straightforward solution to the problem identified in Hahn.
    • Expectation of Success (for §103 grounds): A POSITA would have had a reasonable expectation of success because formaldehyde was a well-known and effective cell lysis inhibitor that predictably preserved cells without damaging the target cell-free DNA in the plasma.

Ground II: Obviousness over Chiu, Hahn, Abbott, and Saito - Claims 55-63, 66-69, 80, and 126-132 are obvious over Chiu, Hahn, Abbott, and Saito.

  • Prior Art Relied Upon: Chiu (a 2001 journal article), Hahn (a 2001 journal article), Abbott (Patent 5,891,734), and Saito (a 2000 journal article).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground builds upon the combination in Ground I to challenge claims requiring a sequencing step, such as independent claim 55. Petitioner argued that the combination of Chiu, Hahn, and Abbott taught preparing a maternal blood sample comprising free fetal DNA and a cell lysis inhibitor. Saito was asserted to supply the remaining limitation: "determining the sequence of a locus of interest on free fetal DNA." Saito explicitly taught performing prenatal diagnosis by determining the sequence of a specific gene (FGFR3) on cffDNA from maternal plasma to detect a mutation linked to achondroplasia.
    • Motivation to Combine (for §103 grounds): Petitioner asserted that the motivation to combine is inherent to the purpose of the underlying references. A POSITA using the Chiu/Hahn/Abbott method to prepare an improved, less-contaminated sample of cffDNA would do so for the express purpose of subsequent analysis. Saito provided a known, beneficial method for performing that very analysis—sequencing a locus of interest on cffDNA to diagnose genetic disorders. Combining the improved preparation method with a known analytical method was therefore obvious.
    • Expectation of Success (for §103 grounds): A POSITA would expect the combination to work predictably, as it involved applying a standard, well-understood sequencing technique (taught by Saito) to a sample that had been prepared using known methods (taught by Chiu, Hahn, and Abbott) to be more suitable for such analysis.

  • Additional Grounds: Petitioner asserted additional obviousness challenges (Grounds II and IV) based on Lo (a 1998 journal article) and Jen (a 2000 journal article) in place of Chiu and Hahn. Petitioner argued Lo and Jen similarly taught isolating cell-free DNA from blood and identified cell lysis as a source of contamination, providing a similar motivation to combine with Abbott and Saito.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under Fintiv would be inappropriate. The key reasons asserted were that the petition was filed expeditiously, only six months after the complaint was served and well before the one-year statutory bar. Furthermore, the parallel district court litigation in the Western District of Texas was in its infancy, with no scheduling order issued, no hearings held, and no discovery exchanged, meaning judicial and party resources had not been significantly invested. Petitioner also contended the merits of the petition were particularly strong.

5. Relief Requested

  • Petitioner requests institution of an inter partes review (IPR) and cancellation of claims 55-63, 66-69, 80, 81-94, 96, and 126-133 of the ’277 patent as unpatentable under 35 U.S.C. §103.