Parse Biosciences Inc v. 10X Genomics Inc

1. Case Identification

• Case #: IPR2023-01033
• Patent #: 10,738,357
• Filed: June 6, 2023
• Petitioner(s): Parse Biosciences, Inc.
• Patent Owner(s): 10x Genomics, Inc.
• Challenged Claims: 1-30

2. Patent Overview

• Title: Methods for analyzing polynucleotides from single cells
• Brief Description: The ’357 patent pertains to compositions and methods for analyzing chromatin using a technique known as "tagmentation." This process uses an insertional enzyme, such as a transposase, to simultaneously fragment DNA and attach ("tag") sequencing adaptors, specifically as applied to a "permeabilized cell nucleus."

3. Grounds for Unpatentability

Ground 1: Obviousness over Grunenwald and Okino - Claims 1-28 and 30 are obvious over Grunenwald in view of Okino.

• Prior Art Relied Upon: Grunenwald (Application # US 2010/0120098) and Okino (WO 2010/065266).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the two key aspects of the invention were well-known in the prior art. Grunenwald taught the core tagmentation process, disclosing a method using a transposase complex (a "transposome") to fragment and tag target DNA, including an in vivo embodiment where the complex is introduced directly into a host cell via electroporation to act on chromosomal DNA. Okino taught methods for analyzing chromatin by permeabilizing a cell and its nucleus with detergents (e.g., NP40, Tween) to allow enzymes to enter and access genomic DNA. The combination of Grunenwald’s tagmentation process with Okino’s permeabilized cell nuclei allegedly rendered all limitations of the independent claims obvious.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA), seeking to apply Grunenwald’s in vivo tagmentation method, would have been motivated to use the well-known and routine detergent-based permeabilization methods taught by Okino. Petitioner contended this was a simple design choice to provide the transposase complex access to the genetic material inside the nucleus, serving as a known alternative to the electroporation method also disclosed in Grunenwald.
  • Expectation of Success: A POSA would have had a high expectation of success because both tagmentation and detergent-based cell permeabilization were well-established, routine techniques in molecular biology. The ’357 patent itself allegedly acknowledges this by only describing conventional, prior-art lysis methods.

Ground 2: Obviousness over Grunenwald, Okino, and Saleh and/or Song - Claim 29 is obvious over Grunenwald and Okino in view of Saleh and/or Song.

• Prior Art Relied Upon: Grunenwald, Okino, Saleh (a 2008 Nature Protocols article), and Song (a 2010 Cold Spring Harbor Protocols publication).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground adds the limitation of claim 29, which requires that the "permeabilized cell nucleus is isolated from a cell." Petitioner asserted that both Saleh and Song taught standard protocols for isolating cell nuclei as a preliminary step for chromatin analysis to improve the purity and yield of DNA. Notably, Petitioner argued that the nucleus isolation protocol described in the ’357 patent’s working examples was taken verbatim from Song.
  • Motivation to Combine: A POSA, having combined Grunenwald and Okino as described in Ground 1, would have been further motivated to incorporate the nuclei isolation step from Saleh or Song. This was presented as a predictable process improvement to enhance the quality of the resulting tagmented DNA library, a routine step for anyone preparing chromatin for sequencing.
  • Expectation of Success: Success would be expected, as nuclei isolation was a standard, well-established technique used to prepare samples for precisely the types of downstream analysis contemplated by Grunenwald.

Ground 3: Obviousness over Grunenwald, Okino, and Adey - Claim 16 is obvious over Grunenwald and Okino in view of Adey.

• Prior Art Relied Upon: Grunenwald, Okino, and Adey (a 2010 Genome Biology article).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground specifically addressed the limitation in claim 16 requiring that "each tagged nucleic acid fragment comprises a first sequencing adapter and second sequencing adapter." Petitioner argued that Adey disclosed a tagmentation method using Epicentre’s commercially available Nextera™ kit, which explicitly used a transposome complex carrying two different adapter sequences to prepare DNA libraries.
  • Motivation to Combine: A POSA seeking to implement Grunenwald's tagmentation method on permeabilized nuclei from Okino would have been motivated to use the specific, effective two-adapter system taught by Adey. Using a commercially successful and readily available kit like Nextera™ to perform tagmentation was an obvious choice for preparing chromatin for next-generation sequencing.
  • Expectation of Success: A POSA would have had a reasonable expectation of success because the Nextera™ kit was a proven, commercially available product known to work effectively for tagmentation. Combining this established kit with Grunenwald’s method was a predictable application of known technologies.

4. Key Claim Construction Positions

• "Insertional Enzyme Complex": Petitioner argued this term is defined by the patent specification as "a complex comprising an insertional enzyme and two adaptor molecules (the 'transposon tags') that are combined with polynucleotides to fragment and add adaptors to the polynucleotides."
• "Nucleic Acid Insert Element": Petitioner proposed the plain and ordinary meaning is "a nucleic acid for insertion in a polynucleotide by an insertional enzyme, such as transposase."

5. Arguments Regarding Discretionary Denial

• Petitioner argued against discretionary denial under §325(d), asserting that the Examiner made material errors during prosecution. Specifically, the Examiner allegedly failed to consider the in vivo embodiment of Grunenwald (applying tagmentation directly to cells) and performed no analysis of Okino whatsoever, despite it being cited.
• Petitioner also contended that the Fintiv factors strongly favor institution. The parallel district court trial date (December 2, 2024) is well after the statutory deadline for a Final Written Decision (FWD), investment in the parallel case is minimal with discovery ongoing, and Petitioner offered to stipulate not to pursue any instituted IPR ground in district court.

6. Relief Requested

• Petitioner requested institution of an inter partes review (IPR) and cancellation of claims 1-30 of the ’357 patent as unpatentable.