PTAB

IPR2023-00958

Parse Biosciences Inc v. 10X Genomics Inc

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1. Case Identification

2. Patent Overview

  • Title: Methods for Analyzing Nucleic Acids from Single Cells
  • Brief Description: The ’013 patent discloses methods for the multiplexed analysis of nucleic acids from single cells. The method involves appending two distinct oligonucleotide tags to polynucleotides: a first tag to identify the cell of origin and a second tag to distinguish individual polynucleotides originating from within the same cell.

3. Grounds for Unpatentability

Ground 1: Claims 1-12 and 19-28 are obvious over Linnarsson in view of McCloskey.

  • Prior Art Relied Upon: Linnarsson (WO 2010/117620) and McCloskey (a 2007 journal article titled "Encoding PCR Products with Batch-Stamps and Barcodes").
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Linnarsson discloses nearly every element of the challenged claims, including a method for single-cell gene expression analysis where nucleic acids are tagged during reverse transcription with a "cell-tag" to identify their single-cell origin. This first tag is attached via primer extension. Petitioner contended that the only element not explicitly taught by Linnarsson is the use of a second tag to distinguish individual polynucleotides from the same cell. This dual-tagging concept, Petitioner asserted, is expressly taught by McCloskey, which describes a "batch-stamp" (equivalent to Linnarsson's cell-tag) to identify the sample source and a "barcode" (the claimed second tag) to uniquely identify and distinguish polynucleotides "arising from different cell or allele copies."
    • Motivation to Combine: Petitioner asserted a POSITA would combine McCloskey's teachings with Linnarsson's method to solve the known problem of "amplification bias," which Linnarsson itself acknowledged. Linnarsson taught that amplifying the cDNA library is necessary but can distort the relative quantities of molecules. McCloskey provided the solution by teaching the use of a unique molecular barcode (the second tag) to tag polynucleotides before amplification. This allows for an accurate, quantitative count of the original molecules, thereby overcoming the amplification bias problem inherent in Linnarsson's method.
    • Expectation of Success: Petitioner argued that a POSITA would have had a high expectation of success. The combination involved applying known tagging techniques to a known analytical workflow. Specifically, Petitioner contended that ligating the second tag to the extension product, as claimed, was an obvious design choice. Ligation was a routine and well-known method for attaching tags to nucleic acids at the time of the invention, a fact Petitioner supported by citing admissions made by the Patent Owner in a prior litigation.

Ground 2: Claims 13-18 are obvious over Linnarsson in view of McCloskey and McCloskey II.

  • Prior Art Relied Upon: Linnarsson (WO 2010/117620), McCloskey (2007 journal article), and McCloskey II (Application # 2007/0020640).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built upon the combination in Ground 1 to address claims 13-18, which require a high diversity of second tags (e.g., at least 90% of tags are different, the number of tags is at least 100 times the number of sample polynucleotides, or at least 200,000 different tags). Petitioner argued that while Linnarsson and McCloskey established the fundamental dual-tagging method, McCloskey II explicitly taught how to generate a massive number of unique tags. McCloskey II, a sister publication to McCloskey, disclosed that the barcode sequence could comprise up to 30 random nucleotides, which would allow for the creation of over 10^18 unique tag sequences.
    • Motivation to Combine: The motivation was to ensure the robust and accurate counting of every individual polynucleotide molecule in a sample. A POSITA would have understood that to uniquely tag each molecule, the number of available unique tags must significantly exceed the number of molecules being analyzed. Petitioner argued it would have been a simple and obvious design choice to use the teachings of McCloskey II to create a sufficiently large pool of random barcode sequences to ensure that substantially every polynucleotide received a unique second tag, thereby fulfilling the purpose taught by McCloskey.
    • Expectation of Success: Petitioner contended success was reasonably expected, as it merely involved routine optimization. Designing oligonucleotide tags with a sufficient number of random base pairs to achieve a desired level of diversity was a standard practice. Petitioner noted that the ’013 patent’s own specification acknowledged the prior art practice of using a number of tags "many times greater than the actual number of molecules to be analyzed" to ensure comprehensive tagging.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that the Board should not exercise discretionary denial under §325(d) or Fintiv.
    • §325(d): Denial was argued to be improper because the primary prior art reference, McCloskey, was never considered by the Examiner. Petitioner asserted the Examiner made a material error by allowing the claims based on the belief that the prior art lacked a dual-tagging method, the very technique McCloskey teaches. While Linnarsson and McCloskey II were listed in an Information Disclosure Statement (IDS), they were not substantively discussed or applied during prosecution.
    • Fintiv Factors: Petitioner argued the factors favored institution. The district court trial is scheduled after the statutory deadline for a Final Written Decision (FWD), discovery in the parallel litigation is in its early stages, and Petitioner stated it would stipulate not to pursue any instituted IPR ground in the district court.

5. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-28 of the ’013 patent as unpatentable.