PTAB

IPR2023-00546

Foresight Diagnostics Inc v. Personalis Inc

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Petition
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1. Case Identification

2. Patent Overview

  • Title: Personalized Genetic Testing
  • Brief Description: The ’611 patent discloses methods for personalized genetic testing. The methods involve an initial, broad sequencing of a biological sample to identify patient-specific genetic variants, followed by the creation of a personalized probe set to target those variants for subsequent, deeper sequencing on additional samples to monitor changes over time.

3. Grounds for Unpatentability

Ground 1: Anticipation over Ley - Claims 1, 2, 4, 5, 9-11, 13, 18, 19, 28-30 are anticipated by Ley under 35 U.S.C. §102.

  • Prior Art Relied Upon: Ley (Timothy J. Ley et al., “DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome,” Nature (2008)).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Ley, which describes the whole-genome sequencing of an acute myeloid leukemia (AML) patient's tumor and normal cells, discloses every limitation of the challenged claims.
      • Initial Sequencing (Claim 1a): Ley’s whole-genome sequencing of the tumor (98 billion bases) and normal skin sample (41.8 billion bases) both far exceeded the claimed 12 gigabase (GB) threshold.
      • Computer Processing (Claim 1b): Ley disclosed using computer software (Maq and Decision Tree C4.5) to align sequence reads to a human reference genome and identify a set of somatic mutations specific to the patient's tumor.
      • Obtaining a Probe Set (Claim 1c): After identifying somatic mutations, Ley described designing and obtaining a set of polymerase chain reaction (PCR) primers (probes) to selectively amplify the specific genomic loci containing eight of these mutations.
      • Using the Probe Set (Claim 1d): Ley used this personalized probe set to enrich and amplify the target sequences from an additional biological sample—a relapse tumor sample obtained 11 months after the initial diagnosis—thereby generating a sequencing library.
      • Targeted Sequencing (Claim 1e): The resulting amplicons (sequencing library) were sequenced. Petitioner argued the total size of the targeted regions was well under the 175 kilobase (kb) limit. Further, the sequencing depth of this targeted step (ranging from 588-fold to 12,365-fold) was significantly greater than the depth of the initial whole-genome sequencing (32.7-fold).
      • Dependent Claims: Petitioner asserted Ley also disclosed outputting a report (claim 2, 9) through its tables and figures summarizing the sequencing results, performing whole-genome sequencing (claim 4), using probes with variable (patient-specific) and fixed (known cancer gene) portions (claim 5), and informing a therapeutic intervention (claim 10, 28) by identifying mutations with known clinical implications for AML treatment.

Ground 2: Anticipation over Newman - Claims 1-5, 9-11, 13, 18, 19, 28-30 are anticipated by Newman under 35 U.S.C. §102.

  • Prior Art Relied Upon: Newman (A. Newman et al., “Integrated digital error suppression for improved detection of circulating tumor DNA,” Nature Biotechnology (2016)).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner asserted that Newman’s method for “cancer personalized profiling by deep sequencing” (CAPP-Seq) anticipates the claimed method, particularly as applied to a glioblastoma (GBM) patient.
      • Initial Sequencing (Claim 1a): Newman disclosed performing whole-exome sequencing on a GBM patient’s tumor and peripheral blood lymphocyte (PBL) samples. The sequencing runs generated over 82 million reads each, which at a 150 bp read length corresponds to 12.3 GB and 13.0 GB, thus meeting the "12 GB or more" limitation.
      • Computer Processing (Claim 1b): Newman analyzed the sequencing data to identify approximately 1,500 patient-specific coding mutations by comparing the tumor sequences to a reference (the patient's germline sequence).
      • Obtaining a Probe Set (Claim 1c): Based on these mutations, Newman designed a 157-kb personalized "selector"—a probe set of biotinylated DNA oligonucleotides—configured to selectively enrich for the identified genetic variants.
      • Using the Probe Set (Claim 1d): Newman disclosed that its CAPP-Seq process is used on a first blood draw for genotyping and on "later blood draws" for tumor monitoring, which involves using the same probe set on additional biological samples.
      • Targeted Sequencing (Claim 1e): Newman applied the 157-kb selector (less than the 175 kb limit) to perform deep resequencing of the GBM tumor. The resulting sequencing depth (calculated at over 14,000-fold) was substantially greater than the median depth of the initial whole-exome sequencing (62- to 65-fold).
      • Dependent Claims: Petitioner argued Newman also disclosed generating reports via its confirmation of expected mutations (claim 2, 9), performing exome sequencing (claim 4), using probes with variable (patient-specific) and fixed (from a non-small cell lung cancer selector design) portions (claim 5), and providing a therapeutic intervention by enabling noninvasive genotyping to guide therapy selection (claim 10, 28).

  • Additional Grounds: Petitioner asserted in the alternative that claims 1-5, 9-11, 13, 18, 19, and 28-30 are obvious over Ley (Ground 2) and obvious over Newman (Ground 4). These arguments relied on the same primary disclosures, contending that to the extent any claim element was not explicitly disclosed, it would have been an obvious modification for a POSITA.

4. Key Claim Construction Positions

  • "probe": Petitioner argued that based on the intrinsic record, a POSA would understand the term "nucleic acid probe molecules" to broadly include molecules for selectively amplifying or enriching sequences, such as PCR primers and hybrid capture baits.
  • "report": Petitioner contended that a "report" includes providing information for patient treatment and indicating genetic variation, consistent with figures in the ’611 patent. Petitioner also argued the "outputting a report" limitation in claim 2 is not entitled to patentable weight under the printed matter doctrine as it merely conveys information without functional relation to the substrate.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-5, 9-11, 13, 18, 19, and 28-30 of the ’611 patent as unpatentable.