PTAB

IPR2023-00224

Foresight Diagnostics Inc v. Personalis Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods and Systems for Genetic Analysis
  • Brief Description: The ’394 patent discloses methods for analyzing nucleic acid samples from an individual to aid in disease diagnosis and monitoring. The method involves conducting an initial whole genome sequencing assay to identify polymorphisms, followed by using capture probes based on those polymorphisms to conduct targeted sequencing on additional samples obtained at later time points.

3. Grounds for Unpatentability

Ground 1: Obviousness over Leary - Claims 1-11 and 13-19 are obvious over Leary in view of the knowledge of a POSA.

  • Prior Art Relied Upon: Leary (a 2010 article in Science Translational Medicine titled “Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing”).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Leary taught all steps of the claimed method. Leary disclosed a method called PARE (personalized analysis of rearranged ends) which involved: (1) conducting whole-genome, paired-end sequencing on a patient’s tumor and germline samples to identify patient-specific chromosomal rearrangements (polymorphisms); (2) designing PCR primers (capture probes) to specifically target the identified rearrangements; and (3) using those primers to repeatedly analyze plasma samples taken at multiple time points to monitor the patient’s disease status. Leary also disclosed generating a biomedical report (a graph) showing the fraction of rearranged DNA in plasma over time, correlating it with treatment efficacy.
    • Motivation to Combine (for §103 grounds): This ground asserted that Leary alone, interpreted through the lens of a Person of Ordinary Skill in the Art (POSA), taught the claimed invention. The motivation was inherent in Leary’s goal of developing a method for personalized tumor monitoring. A POSA would have been motivated to sequence the captured DNA at later time points to confirm the identity of the biomarker being tracked, a routine step for ensuring accuracy in clinical diagnostics.
    • Expectation of Success (for §103 grounds): A POSA would have reasonably expected success, as Leary itself demonstrated the successful application of its method to detect tumor-specific rearrangements in plasma and monitor disease burden over time.

Ground 2: Obviousness over Leary and Ley - Claims 1-11 and 13-19 are obvious over Leary in view of the knowledge of a POSA and Ley.

  • Prior Art Relied Upon: Leary (as described above) and Ley (a 2008 article in Nature titled “DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome”).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built upon the teachings of Leary by incorporating Ley. While Leary taught identifying polymorphisms from the patient’s own sample, claim 1 recites capture probes for polymorphisms “based on or extracted from one or more databases.” Petitioner argued that Ley taught this missing element by disclosing the identification and targeted re-sequencing of known, recurrent somatic mutations (SNPs and indels) in genes like FLT3 and NPM1, which would have been known from public databases.
    • Motivation to Combine (for §103 grounds): A POSA would combine Leary’s patient-specific biomarker approach with Ley’s database-driven approach to create a more robust and clinically useful monitoring panel. Combining personalized markers with known, actionable mutations from databases would increase the sensitivity of the assay and provide more comprehensive information for guiding treatment, such as identifying mutations with known therapeutic responses.
    • Expectation of Success (for §103 grounds): Success was expected because both references used well-established techniques (whole-genome sequencing and targeted re-sequencing). Combining the two approaches was a predictable extension to improve the clinical utility of the assay.

Ground 3: Obviousness over Leary, Chan, and Liao - Claims 1-19 are obvious over Leary in view of the knowledge of a POSA, Chan, and Liao.

  • Prior Art Relied Upon: Leary (as described above), Chan (a 2013 article in Clinical Chemistry), and Liao (a 2011 article in Clinical Chemistry).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground argued for modifying Leary’s method by substituting or supplementing its PCR-based capture probes with the solution-phase hybridization probes taught by Chan and Liao. Chan expressly suggested a workflow that combined an initial whole-genome sequencing step (as in Leary) with subsequent targeted monitoring using solution-phase hybridization. This modification would allow for the capture of additional polymorphism types (e.g., SNVs, CNVs) and was more amenable to multiplexed next-generation sequencing (NGS). This combination also explicitly taught claim 12, as solution-phase hybridization routinely uses probes conjugated to magnetic beads for isolation.
    • Motivation to Combine (for §103 grounds): A POSA would be motivated to modify Leary’s PCR-based protocol with the solution-phase hybridization approach taught by Chan to improve the assay’s sensitivity and scope. Chan highlighted the “numerical advantage” of detecting a wider range of mutations (passengers and drivers) and explicitly taught that targeted and shotgun (whole-genome) approaches could be used in combination for better cancer monitoring. Technological advances between Leary (2010) and the patent's priority date (2013) made NGS combined with hybridization capture a more powerful and efficient option than Sanger sequencing of individual PCR products.
    • Expectation of Success (for §103 grounds): A POSA would have a high expectation of success, as Chan and Liao demonstrated the successful use of solution-phase hybridization to enrich for target DNA sequences from plasma for subsequent sequencing.

4. Key Claim Construction Positions

  • "generating a biomedical report": Petitioner argued that this claim limitation should be afforded no patentable weight under the printed matter doctrine. The argument was that the limitation merely recites the content of information (the presence or absence of polymorphisms) and is not functionally related to the substrate on which it is presented (e.g., paper or a computer screen). As such, Petitioner contended it cannot impart patentability to an otherwise obvious process.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-19 of the ’394 patent as unpatentable under 35 U.S.C. §103.