Parse Biosciences Inc v. 10X Genomics Inc

1. Case Identification

• Case #: IPR2023-00955
• Patent #: 10,240,197
• Filed: May 25, 2023
• Petitioner(s): Parse Biosciences, Inc.
• Patent Owner(s): 10X Genomics, Inc.
• Challenged Claims: 1-26

2. Patent Overview

• Title: Methods for Analyzing Nucleic Acids from Single Cells
• Brief Description: The ’197 patent discloses methods for counting nucleic acids from individual cells within a larger sample. The method involves appending two distinct oligonucleotide tags to polynucleotides: a first tag to identify the cell of origin and a second tag to uniquely identify individual polynucleotide molecules originating from within that same cell.

3. Grounds for Unpatentability

Ground 1: Obviousness over Linnarsson and McCloskey - Claims 1-4, 6-11, 20, and 23-25 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 disclosed nearly all elements of the claimed method, including providing a sample of cells, generating tagged polynucleotides (cDNA) from the sample polynucleotides (mRNA) within those cells, and using a "cell-tag" to distinguish polynucleotides from different cells. This corresponds to the claimed "first tag." Petitioner contended that McCloskey taught the missing element: a dual-tagging system that includes a "batch-stamp" (analogous to Linnarsson's cell-tag) and a "barcode" (the claimed "second tag") specifically designed to distinguish individual polynucleotide sequences arising from the same cell or sample.
  • Motivation to Combine: Petitioner asserted a POSITA would combine these references for two primary reasons. First, they are analogous arts focused on the genetic analysis of single cells using tagged oligonucleotides. Second, Linnarsson explicitly identified the problem of "potential amplification bias" in single-cell analysis, and McCloskey’s method of using a second, unique tag (barcode) was presented as a direct solution to this exact source-uncertainty problem. McCloskey’s method allows researchers to distinguish true biological duplicates from amplification artifacts.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success because the combination required only routine modification. Petitioner argued that modifying Linnarsson’s oligonucleotide tags (CDS or TSO) to incorporate McCloskey’s second tag sequence would be a straightforward application of known techniques. This could be done by conceptually dividing Linnarsson's existing cell-tag sequence into two parts: one for the cell and one for the unique molecule.

Ground 2: Obviousness over Linnarsson, McCloskey, and McCloskey II - Claims 13-19 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 Ground 1 to address dependent claims 13-19, which require high percentages (e.g., 90%, 95%, 99%) of polynucleotides to be associated with a unique second tag sequence. Petitioner argued that while Linnarsson and McCloskey provided the dual-tagging framework, McCloskey II provided the explicit teaching needed to ensure unique tagging at high efficiency. McCloskey II taught that molecular tags could comprise up to 30 random nucleotides, which would create a vast number of unique barcode sequences (4^30, or over 10^18).
  • Motivation to Combine: A POSITA’s motivation for ensuring each molecule receives a unique tag was to increase the accuracy of molecular counting, the central purpose of the invention. By using a tag library with a number of unique sequences far exceeding the number of molecules in a cell (typically 50,000 to 360,000 mRNA molecules), a POSITA could ensure with statistical certainty that nearly every molecule would be uniquely tagged.
  • Expectation of Success: Petitioner contended that designing molecular tags with a sufficient number of random nucleotides was an obvious design choice with a high expectation of success. The ’197 patent itself acknowledged the prior art practice of using a number of distinct tags "many times greater than the actual number of molecules to be analyzed" to ensure comprehensive tagging. Therefore, applying the teachings of McCloskey II to the Linnarsson/McCloskey combination was a routine optimization.

• Additional Grounds: Petitioner asserted an additional obviousness challenge against claims 5, 12, 21-22, and 26 based on the combination of Linnarsson, McCloskey, and the general knowledge of a POSITA regarding techniques like ligation and the use of solid supports for sequencing.

4. Arguments Regarding Discretionary Denial

• §325(d) Arguments: Petitioner argued that discretionary denial under §325(d) is unwarranted because the primary prior art and arguments were not substantively considered during prosecution. McCloskey was not before the examiner at all. While Linnarsson and McCloskey II were listed on an Information Disclosure Statement (IDS), the examiner never cited, discussed, or relied upon them in any rejection or statement of allowance, meaning the specific teachings relied upon in the petition were not previously evaluated.
• Fintiv Arguments: Petitioner argued that the Fintiv factors strongly favor institution. The scheduled trial date in the parallel district court litigation (December 2, 2024) is after the statutory deadline for a Final Written Decision (FWD) in the IPR. Furthermore, investment in the district court case was minimal at the time of filing, with no claim construction orders issued and expert discovery not yet commenced. Petitioner also stated it would stipulate not to pursue any instituted IPR grounds in the district court litigation, eliminating concerns of overlapping issues.

5. Relief Requested

• Petitioner requested the institution of an inter partes review and the cancellation of claims 1-26 of the ’197 patent as unpatentable.