Foresight Diagnostics Inc v. Personalis Inc

1. Case Identification

• Case #: IPR2023-00545
• Patent #: 11,299,783
• Filed: February 10, 2023
• Petitioner(s): Foresight Diagnostics Inc.
• Patent Owner(s): Personalis, Inc.
• Challenged Claims: 1-9, 13-19, and 21-29

2. Patent Overview

• Title: Method and System of Genetic Analysis
• Brief Description: The ’783 patent discloses methods for personalized genetic testing to monitor a subject’s health condition, such as cancer. The method involves first identifying a set of genetic variants from a biological sample and then creating a personalized probe set to selectively enrich or amplify those variants in subsequent samples for monitoring over time.

3. Grounds for Unpatentability

Ground 1: Anticipation - Claims 1-2, 5-7, 9, 14-15, 17-19, 21, 23-25, and 27 are anticipated by Ley.

• Prior Art Relied Upon: 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: Petitioner argued that Ley disclosed every element of the challenged claims. Ley described a personalized genetic testing method for an acute myeloid leukemia (AML) patient, starting with whole-genome sequencing of tumor and normal skin cells to identify genetic variants. This initial step generated sequence data used to create a "personalized probe set" of custom PCR primers. This probe set was designed to amplify specific genetic loci, comprising both newly discovered patient-specific somatic mutations (the "variable portion") and known variants in genes like BRCA2 and TP53 (the "fixed portion"). Ley then used this probe set to amplify DNA from subsequent samples (e.g., a relapse tumor) for targeted resequencing, which has a smaller sequencing footprint than the initial whole-genome analysis. The Ley publication itself, with its tables and figures showing variant frequencies, constituted a "report" identifying the health condition and informing therapy choices.

Ground 2: Obviousness over Ley - Claims 1-9, 13-19, and 21-29 are obvious over Ley.

• Prior Art Relied Upon: Ley (a 2008 article in Nature).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground incorporated the anticipation analysis from Ground 1 by reference. Petitioner further argued that, to the extent any claim element was not explicitly disclosed, it would have been obvious to a person of ordinary skill in the art (POSA) based on Ley’s teachings and the general knowledge in the field.
  • Motivation to Combine: A POSA would have been motivated to apply Ley’s established method to cancers beyond the specific AML example. It would have been an obvious and logical step to expand the "fixed portion" of the probe panel to include probes for other known tumor-driver mutations or genetic variants associated with established companion diagnostics. This combination would overcome the limitations of a purely hypothesis-driven (fixed probe-only) approach, which Ley itself noted could miss key mutations, while also ensuring known clinically relevant markers were monitored. Using plasma samples instead of tissue biopsies for easier sample collection was also a well-known and obvious modification.
  • Expectation of Success: A POSA would have had a reasonable expectation of success in applying these modifications. The underlying techniques (PCR, sequencing) were standard, and extending the method to other cancers or adding probes for known variants involved the predictable use of established techniques on known biological targets.

Ground 3: Obviousness over Forshew in view of Dawson - Claims 1-9, 13-19, and 21-29 are obvious over Forshew in view of Dawson.

• Prior Art Relied Upon: Forshew (a 2012 article in Science Translational Medicine) and Dawson (a 2013 article in the New England Journal of Medicine).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued Forshew disclosed most elements of the claimed method through its "TAm-Seq" technique for noninvasive monitoring of cancer mutations. Forshew used initial whole-genome sequencing of a metastatic breast cancer patient's tumor to identify patient-specific mutations. It then designed PCR primers (a personalized probe set with a "variable portion") to track the dynamics of these mutations in serial plasma samples over 497 days. The results were depicted in a report (Fig. 4D) showing the fraction of mutant alleles over time, informing on therapeutic response.
  • Motivation to Combine: Petitioner contended that while Forshew’s specific example focused on patient-derived "variable" probes, a POSA would have been motivated to also include a "fixed" portion in the probe panel. Forshew itself discussed the importance of the TP53 gene in other cancers and described a cost-effective method for detecting TP53 mutations in plasma. Dawson, which includes Forshew as a co-author, reinforced this by describing TP53 as "recurrently mutated in breast cancer" and applying the same TAm-Seq technique to detect it. A POSA would combine these teachings to create a comprehensive panel for a breast cancer patient that included both patient-specific variants (from Forshew's primary example) and probes for known, high-frequency mutations like TP53 (from Forshew's other teachings and Dawson).
  • Expectation of Success: A POSA would have had a high expectation of success because the combination involved applying the exact same TAm-Seq technique, as taught by the same research group, to a well-known and highly relevant cancer mutation (TP53) in the same disease context (breast cancer).

4. Key Claim Construction Positions

• "probe": Petitioner argued that based on the intrinsic record, a POSA would have understood the claimed "nucleic acid probe molecules" to encompass tools used for selectively amplifying or enriching sequences, including PCR primers and hybrid capture baits.
• "report": Petitioner asserted that the claim limitation "generating a report" is directed to printed matter and should be afforded no patentable weight because it merely conveys information (the results of the analysis) and is not functionally related to the physical substrate of the report. To the extent the limitation is considered, Petitioner argued it would be understood to include providing information for treatment and an indication of genetic variation, as disclosed in the prior art.

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-9, 13-19, and 21-29 of the ’783 patent as unpatentable.