Geneoscopy Inc v. Exact Sciences Corp

1. Case Identification

• Case #: IPR2024-00459
• Patent #: 11,634,781
• Filed: January 11, 2024
• Petitioner(s): Geneoscopy, Inc.
• Patent Owner(s): Exact Sciences Corporation
• Challenged Claims: 1-20

2. Patent Overview

• Title: Method of Processing a Fecal Sample
• Brief Description: The ’781 patent is directed to methods for processing a freshly-collected fecal sample without freezing for colorectal cancer (CRC) screening. The core method involves separating a single fecal sample into two portions: one portion is combined with a buffer to preserve blood proteins for analysis, and the other portion is combined with a stabilizing buffer to preserve nucleic acids for separate analysis.

3. Grounds for Unpatentability

Ground I: Claims 1-9, 11, and 14-20 are obvious over Lenhard in view of Itzkowitz and Vilkin.

• Prior Art Relied Upon: Lenhard (a 2005 journal article), Itzkowitz (a 2007 journal article), and Vilkin (a 2005 journal article).
• Core Argument for this Ground: Petitioner argued that a person of ordinary skill in the art (POSA) would have been motivated to modify the combined fecal occult blood test (FOBT) and DNA methylation analysis method of Lenhard by incorporating the superior technologies disclosed in Vilkin and Itzkowitz to create a more sensitive, reliable, and patient-friendly CRC screening assay.
  • Prior Art Mapping: Lenhard taught separating a stool sample to test one portion for blood proteins using a guaiac-based FOBT (gFOBT) and the remaining portion for tumor-derived DNA via HIC1 gene promoter methylation. Petitioner asserted that a POSA would replace Lenhard’s outdated gFOBT with Vilkin’s superior immunochemical FOBT (iFOBT), which disclosed at-home collection of a small fecal portion into a sealable container with a hemoglobin-stabilizing buffer. Concurrently, a POSA would replace Lenhard’s laboratory-based sample collection with Itzkowitz’s method of at-home collection, where the patient defecates directly into a sealable vessel and adds a DNA-stabilizing buffer to the remaining sample to preserve nucleic acid integrity during shipment. The combination of these known elements allegedly met all limitations of the challenged independent claims.
  • Motivation to Combine: The primary motivation was to improve Lenhard’s assay. Vilkin was widely known to be superior to gFOBT, offering higher sensitivity, quantitative results, and no need for patient dietary restrictions. Itzkowitz provided a known method to improve DNA test sensitivity by using a stabilizing buffer, which prevented DNA degradation during ambient-temperature shipping and improved patient satisfaction with at-home collection.
  • Expectation of Success: A POSA would have had a high expectation of success because the combination involved replacing components of an existing assay (Lenhard) with known, superior alternatives (Vilkin’s iFOBT, Itzkowitz’s stabilization) that were already established for use on fecal samples.

Ground II: Claims 1-9, 11, and 14-20 are obvious over Shuber and Vilkin.

• Prior Art Relied Upon: Shuber (a 2005 international patent application) and Vilkin (a 2005 journal article).

• Core Argument for this Ground: Petitioner argued that it was well understood in the art that combining a DNA-based stool test with a blood protein-based test improved diagnostic sensitivity for CRC. Therefore, a POSA would have been motivated to combine the DNA analysis method of Shuber with the iFOBT of Vilkin.

  • Prior Art Mapping: Shuber disclosed a method for fecal DNA analysis where a stool sample is deposited into a sealable container, combined with a nucleic acid stabilizing solution to preserve it for various analyses (including methylation assays), and shipped to a lab without freezing. Vilkin disclosed a quantitative iFOBT where a portion of a fecal sample is removed using a sampling device and placed into a separate sealable container with a hemoglobin-stabilizing buffer. Petitioner contended that performing these two well-established assays on separate portions of the same initial fecal sample would result in the method of the challenged claims.
  • Motivation to Combine: The motivation was to improve overall diagnostic sensitivity. The petition cited multiple sources, including Lenhard and a 2008 joint guideline from the American Cancer Society, demonstrating the recognized benefit of combining DNA assays with FOBT to increase CRC detection rates. A POSA would combine these specific references to leverage the advantages of Shuber’s non-refrigerated DNA stabilization and Vilkin’s high-sensitivity iFOBT.
  • Expectation of Success: Success was reasonably expected because the combination involved performing a pair of well-established, complementary assays on separate portions of a fecal sample, a routine approach in the field of diagnostics.

• Additional Grounds: Petitioner asserted additional obviousness challenges based on adding a further reference to the primary combinations. Grounds adding Kanaoka (a 2006 patent application) argued for the obviousness of measuring RNA (claims 12-13) as another known biomarker. Grounds adding Derks (a 2006 publication) argued for the obviousness of testing for an additional methylation marker, GATA-4 (claim 10), to further improve sensitivity.

4. Key Claim Construction Positions

• "determining expression from a human gene" (claim 4): Petitioner argued this phrase must be construed to include indirect indicators of gene expression, such as testing for epigenetically-modified DNA. This construction was based on the scope of dependent claims 5 and 6, which recite testing for epigenetic modifications and methylated DNA, respectively. Petitioner asserted that since a dependent claim cannot be broader than the independent claim from which it depends, "determining expression" must encompass the specific methylation tests recited in the dependent claims.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that the Board should not exercise its discretion to deny institution under 35 U.S.C. § 325(d). The petition asserted that the arguments and combinations of art are substantially different from those considered during prosecution or reexamination. Specifically, four of the primary references (Itzkowitz, Vilkin, Derks, and Kanaoka) were never before the Examiner. While Lenhard and Shuber were listed in an Information Disclosure Statement (IDS), they were never the subject of an Examiner’s rejection or substantive discussion by the applicant, and Board precedent under the Advanced Bionics factors favors institution in such cases.

6. Relief Requested

• Petitioner requests institution of inter partes review (IPR) and cancellation of claims 1-20 of the ’781 patent as unpatentable.