Oxford Nanopore Technologies, Inc. v. Pacific Bioscienes of California, Inc.

1. Case Identification

• Case #: Unassigned (Related IPR: IPR2018-01785)
• Patent #: 9,738,929
• Filed: September 25, 2018
• Petitioner(s): Oxford Nanopore Technologies, Inc.
• Patent Owner(s): Pacific Biosciences of California, Inc.
• Challenged Claims: 1-17

2. Patent Overview

• Title: Nanopore-Based Polynucleotide Sequencing
• Brief Description: The ’929 patent is directed to methods for nanopore-based sequencing of a polynucleotide. The claimed methods involve using an enzyme chaperone to control the passage of a polynucleotide comprising a double-stranded portion through a nanopore, obtaining sequence information from the complementary strands of that portion, and determining a consensus sequence to improve accuracy.

3. Grounds for Unpatentability

Ground 1: Claims 1-8, 10, 11, and 16 are obvious over Akeson in view of Gupte

• Prior Art Relied Upon: Akeson (Application # 2006/0063171) and Gupte (Patent 6,087,099).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Akeson taught the foundational method for sequencing double-stranded DNA using a nanopore system where an enzyme chaperone controls the rate of DNA translocation. Gupte taught creating a specific DNA template structure containing a hairpin loop that links the two complementary strands of a DNA molecule. This structure, when sequenced, yields the sequence of both strands in a single reaction. Petitioner asserted that combining Akeson's sequencing system with Gupte's template would result in a method that meets all limitations of independent claim 1, including introducing a polynucleotide with a double-stranded portion to a nanopore, obtaining redundant sequence information from the complementary strands, and determining a consensus sequence based on that information.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) would be motivated to use the double-stranded polynucleotide templates from Gupte in the nanopore sequencing process of Akeson. Gupte explicitly taught that sequencing both strands is a common technique to minimize errors and improve accuracy. Therefore, a POSA would seek to apply this known accuracy-improving template design to Akeson’s nanopore sequencing method.
  • Expectation of Success: A POSA would have had a reasonable expectation of success in combining the references, as it involved applying a known type of sequencing template (Gupte) to a known sequencing system (Akeson) to achieve the predictable result of improved sequencing accuracy.

Ground 2: Claims 1-8, 10, 11, and 13 are obvious over Akeson in view of Sanger and Makrigiorgos

• Prior Art Relied Upon: Akeson (Application # 2006/0063171), Sanger (a 1981 Science journal article), and Makrigiorgos (Application # 2005/0142559).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground presented an alternative combination to invalidate the claims. Akeson again provided the base nanopore sequencing system. Makrigiorgos, like Gupte, taught generating a template for sequencing both strands, but through a different "dumbbell" structure where the ends of a double-stranded DNA fragment are ligated to oligonucleotide "caps." One cap could include a nick to initiate polymerization. Sanger provided the foundational rationale, stating it is necessary to sequence both DNA strands to minimize errors. Petitioner contended that sequencing the dumbbell template of Makrigiorgos using the enzyme-chaperoned nanopore system of Akeson would meet the limitations of claim 1.
  • Motivation to Combine: The general motivation, as established by Sanger for decades, was to improve sequencing accuracy by reading both strands. A POSA would have been motivated to sequence the dumbbell polynucleotides from Makrigiorgos using the nanopore methods of Akeson to achieve this well-understood benefit and analyze the nucleotide sequences of both complementary strands.
  • Expectation of Success: The combination involved known techniques for a predictable purpose. A POSA would have expected that applying a known sequencing methodology to a template designed for comprehensive sequencing would function as intended.

Ground 3: Claim 12 is obvious over Akeson, Gupte, and Miner

• Prior Art Relied Upon: Akeson (Application # 2006/0063171), Gupte (Patent 6,087,099), and Miner (a 2004 Nucleic Acids Res. article).
• Core Argument for this Ground:
  • Prior Art Mapping: This argument built upon Ground 1 by adding Miner to address the "registration sequence" limitation of dependent claim 12. Miner disclosed the use of "barcodes" (registration sequences) within hairpin linkers to label different genomic DNA fragments. This allowed for distinguishing multiple sequences within a single sample. Petitioner argued it would have been obvious to incorporate Miner's barcodes into the hairpin linker of the Gupte template before sequencing it with the Akeson system.
  • Motivation to Combine: Miner is directed to the same field of DNA sequencing. A POSA would have been motivated to combine Miner's labeling method with the Akeson/Gupte combination to gain the known advantage of labeling or multiplexing samples, a common and desirable practice for improving efficiency in sequencing workflows.
• Additional Grounds: Petitioner asserted additional obviousness challenges, including combining Akeson, Gupte, and Akeson ’433 for teaching multiple detection periods (Claim 17); combining Akeson, Gupte, and Makrigiorgos for teaching multiple repeats of a region of interest (Claim 9); and combining Akeson, Sanger, Makrigiorgos with Miner or O’Dea for teaching registration sequences or synthetic linkers (Claims 12, 14-15).

4. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-17 of the ’929 patent as unpatentable.