Parse Biosciences v. 10X Genomics Inc

1. Case Identification

• Case #: IPR2023-00876
• Patent #: Patent 10,155,981
• Filed: April 20, 2023
• Petitioner(s): Parse Biosciences, Inc.
• Patent Owner(s): 10X Genomics, Inc.
• Challenged Claims: 1-6

2. Patent Overview

• Title: Methods for Analyzing Nucleic Acids from Single Cells
• Brief Description: The ’981 patent discloses methods for analyzing nucleic acids from a plurality of single cells. The methods involve appending two distinct tags to polynucleotides: a first tag to identify the single cell of origin and a second tag to distinguish different polynucleotides originating from within the same cell, followed by sequencing.

3. Grounds for Unpatentability

Ground 1: Claims 1-4 and 6 are obvious over Linnarsson in view of McCloskey

• Prior Art Relied Upon: Linnarsson (International Publication No. WO 2010/117620) and McCloskey (a 2007 article titled "Encoding PCR Products with Batch-Stamps and Barcodes").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Linnarsson, a reference considered during prosecution, teaches a method for single-cell gene expression analysis that discloses every limitation of the challenged claims except for the use of a second tag to distinguish individual polynucleotides from the same cell. Linnarsson teaches using a single "cell-tag" to identify which cell a given cDNA sample originated from. Petitioner asserted that McCloskey, which was not substantively considered by the Examiner, supplies this missing element. McCloskey describes a dual-tagging system for single-cell analysis using a "batch-stamp" to identify the sample (analogous to Linnarsson's cell tag) and a "barcode" to uniquely identify individual polynucleotide molecules within that sample.
  • Motivation to Combine: A POSITA would combine Linnarsson and McCloskey because both address single-cell nucleic acid analysis. More importantly, Linnarsson acknowledged that its method was subject to "potential amplification bias," a known problem in single-cell genomics. McCloskey's method of using a unique barcode for each polynucleotide was explicitly designed to solve this exact problem by allowing researchers to count the original number of molecules before amplification, thus providing a "quantitative measure of template diversity."
  • Expectation of Success: Petitioner asserted a POSITA would have a high expectation of success in combining the references. The proposed modification involved incorporating McCloskey's known barcoding technique into Linnarsson's tagged oligonucleotides (CDS or TSO), which was a routine and predictable adaptation using standard molecular biology methods to solve a known problem.

Ground 2: Claim 5 is obvious over Linnarsson in view of McCloskey and knowledge of a POSA

• Prior Art Relied Upon: Linnarsson (WO 2010/117620), McCloskey (2007 article), and the general knowledge of a Person of Ordinary Skill in the Art (POSA).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the combination in Ground 1 to address the specific limitation of claim 5, which requires that tagged polynucleotides are generated "through at least one ligation reaction." While Linnarsson teaches generating tags via primer extension during reverse transcription, Petitioner argued that using ligation to attach nucleic acid tags was a well-known, conventional, and interchangeable method at the time. Petitioner cited the Patent Owner's own admissions from prior litigation where it characterized attaching tags via ligation as a "well-known and conventional" technique.
  • Motivation to Combine: A POSA would have been motivated to use ligation as an alternative method for attaching the dual-tags taught by the Linnarsson/McCloskey combination. It was an obvious design choice that offered added experimental flexibility.
  • Expectation of Success: Given that ligation was an undisputedly routine technique for attaching tags to polynucleotides, a POSA would have had a reasonable expectation of success in using ligation to attach the combined tag structure to Linnarsson’s constructs instead of relying solely on primer extension.

4. Key Technical Contentions (Beyond Claim Construction)

• Patent Owner's Prior Admissions: A central contention is that in a prior, unrelated litigation, the Patent Owner (10X Genomics) argued that the concept of dual-tagging nucleic acids was "as old as the scientific method" and that the methods for attaching, amplifying, and sequencing tagged DNA were merely "generic, routine, well-known laboratory techniques." Petitioner leveraged these alleged admissions to argue that the core novelty asserted for the ’981 patent was previously characterized by the Patent Owner itself as conventional and unpatentable.

5. Arguments Regarding Discretionary Denial

• §325(d) Arguments: Petitioner argued that discretionary denial under §325(d) is inappropriate because the Examiner committed material errors. Specifically, the Examiner never considered an obviousness rejection and failed to substantively evaluate McCloskey, the key reference that provides the missing "second tag" limitation not found in Linnarsson. Petitioner contended that the prosecution record shows the Examiner only considered an anticipation rejection based on Linnarsson alone.
• Fintiv Factors: Petitioner argued the Fintiv factors strongly favor institution. The district court trial date is scheduled approximately two months after the final written decision deadline, and Petitioner noted that delays are common. Investment in the parallel court proceeding was asserted to be minimal, with no claim construction orders issued and discovery incomplete. Petitioner also stated it would stipulate not to pursue any instituted IPR ground in the district court litigation, and that the petition presents a compelling case on the merits.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-6 of the ’981 patent as unpatentable.