Parse BioSciences Inc v. 10X Genomics Inc

1. Case Identification

• Case #: IPR2023-XXXXX
• Patent #: 10,697,013
• Filed: May 25, 2023
• Petitioner(s): Parse Biosciences, Inc.
• Patent Owner(s): 10X Genomics, Inc.
• Challenged Claims: 1-28

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 (polynucleotides) 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: Obviousness over Linnarsson and McCloskey - 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 peer-reviewed scientific article titled "Encoding PCR Products with Batch-Stamps and Barcodes").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Linnarsson teaches nearly all elements of the claimed method, including analyzing nucleic acids from single cells, using a first oligonucleotide tag (a "cell-tag") via primer extension to identify the cell of origin, amplifying the tagged products, and sequencing them. However, Linnarsson does not explicitly teach ligating a second tag to distinguish individual molecules within the same cell. Petitioner asserted that McCloskey remedies this deficiency by teaching a dual-tagging system for single-cell analysis that includes a "batch-stamp" (analogous to Linnarsson's cell-tag) to identify the sample source and a "barcode" (the second tag) to uniquely identify individual polynucleotides. The explicit purpose of McCloskey's barcode is to solve the problem of amplification bias by enabling the accurate counting of original molecules, an issue recognized in Linnarsson.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Linnarsson and McCloskey to solve the known problem of amplification bias inherent in single-cell analysis, which Linnarsson acknowledges. McCloskey provides the exact solution by teaching the use of a unique molecular barcode to distinguish individual molecules before amplification, thereby allowing for accurate quantification. As both references address single-cell genetic analysis using tagging, they are in the same field of endeavor. Petitioner also contended that the Patent Owner had previously admitted in unrelated litigation that such tagging methods were "generic, routine, well-known laboratory techniques."
  • Expectation of Success: A POSA would have a reasonable expectation of success because the proposed combination only involves applying McCloskey’s known molecular barcode concept to Linnarsson’s single-cell analysis framework using standard, well-established laboratory techniques like oligonucleotide ligation. Petitioner emphasized that the ’013 patent itself, and the Patent Owner's own prior admissions, confirm that ligation was a conventional and routine technique for attaching tags to nucleic acids.

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

• Prior Art Relied Upon: Linnarsson (WO 2010/117620), McCloskey (2007 article), and McCloskey II (Application # 2007/0020640).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground builds on Ground 1 to address the limitations in claims 13-18, which require that the second tags be highly diverse and used in great excess (e.g., at least 90% of polynucleotides have a different second tag; the number of tag sequences is at least 10, 100, or 200,000 times the number of sample polynucleotides). Petitioner argued that while Linnarsson and McCloskey establish the fundamental dual-tagging method, McCloskey II teaches that it was a known and obvious design choice to use a vast number of unique sequences for the molecular barcodes. McCloskey II discloses that barcode sequences can comprise up to 30 random nucleotides, which would generate a massive number of unique tags (4^30), far exceeding what is needed to uniquely label every molecule in a typical mammalian cell.
  • Motivation to Combine: A POSA, seeking to implement the molecular counting method taught by McCloskey, would be motivated to ensure that each original polynucleotide receives a unique tag to maximize the accuracy of the count. The obvious way to achieve this, as taught by McCloskey II and cited art like Brenner, is to use a large excess of unique tags relative to the number of molecules being analyzed. This ensures a high probability of unique tagging for each molecule.
  • Expectation of Success: Success would be expected, as it was a simple and routine design choice to create a library of oligonucleotide tags with a sufficient number of random nucleotides to generate a large pool of unique sequences. The techniques for synthesizing such oligonucleotides were standard in the art at the time of the invention.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that the Board should not exercise its discretion to deny institution under either §325(d) or the Fintiv factors.
• §325(d): Petitioner asserted that the Examiner committed material error by allowing the claims based on the incorrect premise that prior art did not teach a dual-tagging method. The McCloskey reference, which plainly teaches this method, was never before the Examiner. While Linnarsson and McCloskey II were listed in an Information Disclosure Statement (IDS), they were never substantively considered or discussed in any rejection, meaning the core arguments of the petition are new to the Office.
• Discretionary Denial under Fintiv: Petitioner contended the Fintiv factors favor institution. The trial in the parallel district court litigation is scheduled for after the statutory deadline for a Final Written Decision (FWD). Furthermore, Petitioner stated it will seek a stay if IPR is instituted and will stipulate to not pursue any instituted grounds in the district court. Finally, Petitioner argued the petition presents a compelling case on the merits, which is a factor that weighs strongly in favor of institution.

5. Relief Requested

• Petitioner requests the institution of an inter partes review and the cancellation of claims 1-28 of Patent 10,697,013 as unpatentable.