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

1. Case Identification

• Case #: Unassigned
• Patent #: Patent 9,738,929
• Filed: September 24, 2018
• Petitioner(s): Oxford Nanopore Technologies, Inc.
• Patent Owner(s): Pacific Biosciences of California, Inc.
• Challenged Claims: 1-17

2. Patent Overview

• Title: Methods for Nanopore Sequencing of Polynucleotides
• Brief Description: The ’929 patent is directed to methods for nanopore-based sequencing of a polynucleotide. The methods use an enzyme chaperone to control the passage of the polynucleotide, which comprises a double-stranded portion, through the nanopore to obtain sequence information from both complementary strands and determine a consensus sequence.

3. Grounds for Unpatentability

Ground 1: Obviousness over Akeson and Gupte - 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 disclosed the foundational method for nanopore sequencing, including introducing a polynucleotide to a nanopore in a membrane, applying a voltage, monitoring ionic current, and using an enzyme chaperone (molecular motor) to regulate polynucleotide passage. Petitioner asserted Gupte taught creating a double-stranded DNA construct with a hairpin loop that, when sequenced, yields the sequence of both original complementary strands in a single reaction, providing the claimed redundant sequence information. For dependent claims, Petitioner argued Akeson taught using protein channels, lipid bilayer or solid-state membranes, and changing reaction conditions to alter the rate of passage.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) would combine the references to improve the accuracy of the nanopore sequencing technique taught by Akeson. Gupte explicitly taught that sequencing both DNA strands is a common method to minimize errors, providing a clear reason to apply its double-strand sequencing construct to Akeson’s advanced nanopore system.
  • Expectation of Success: A POSA would have a reasonable expectation of success because both references operated in the predictable field of molecular biology and DNA sequencing, and Gupte’s constructs were presented as suitable substrates for general sequencing methods like those in Akeson.

Ground 2: Obviousness over Akeson, Sanger, and Makrigiorgos - 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 article in Science), and Makrigiorgos (Application # 2005/0142559).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Akeson again provided the base nanopore sequencing system. Makrigiorgos was cited for disclosing methods to generate double-stranded "dumbbell" polynucleotide structures by adding oligonucleotide "caps" or linkers to a DNA fragment, which are then suitable for sequencing. Petitioner noted that Makrigiorgos also taught that these linkers could include a nick to initiate polymerization, which maps to the '929 patent's claim 13. Sanger provided the foundational teaching that sequencing both strands of DNA is necessary to minimize errors and confirm results.
  • Motivation to Combine: A POSA would be motivated by Sanger's well-established principle to seek methods for sequencing both strands to improve accuracy. Makrigiorgos provided a specific method for creating such double-stranded constructs (dumbbells). A POSA would therefore apply the dumbbell constructs from Makrigiorgos to the advanced nanopore sequencing system of Akeson to achieve the goal of high-accuracy, dual-strand sequencing.
  • Expectation of Success: The combination involved applying a known type of sequencing template (Makrigiorgos) to a compatible sequencing platform (Akeson) to achieve a well-understood goal (improved accuracy, per Sanger), presenting no obvious technical hurdles.

Ground 3: Obviousness over Akeson, Gupte, and Miner - Claim 12 is obvious over Akeson and Gupte in view of Miner.

• Prior Art Relied Upon: Akeson (Application # 2006/0063171), Gupte (Patent 6,087,099), and Miner (Miner et al., Nucleic Acids Res., 32(17):e135 (2004)).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground built upon the combination in Ground 1. Petitioner argued that Miner disclosed adding a "registration sequence" or "molecular barcode" to a DNA template using hairpin linkers. This barcode allows each ligated fragment to be distinguished from other sequences in a sample. Petitioner asserted that this known labeling technique could be readily applied to the oligonucleotide linker of the Akeson/Gupte combination to satisfy the limitation of claim 12.
  • Motivation to Combine: A POSA would be motivated to add Miner’s barcoding method to the combined Akeson/Gupte process for the known benefit of labeling and tracking individual DNA templates during sequencing, which is a common and desirable practice for improving data analysis and reliability.
  • Expectation of Success: The combination was asserted to be a straightforward application of a known labeling technique (Miner) to a known sequencing substrate (Gupte) for use in a known sequencing system (Akeson), all within the same well-developed technical field.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including:

  • Claim 17 over Akeson, Gupte, and Akeson '433 (Patent 6,936,433) for teaching multiple detection periods.
  • Claim 9 over Akeson, Gupte, and Makrigiorgos for teaching multiple repeats of a region of interest.
  • Claim 12 over Akeson, Sanger, Makrigiorgos, and Miner.
  • Claims 14-15 over Akeson, Sanger, Makrigiorgos, and O'Dea (a 2000 protocol) for teaching the use of synthetic, carbon-based linkers.

4. Relief Requested

• Petitioner requested the institution of an inter partes review and cancellation of claims 1-17 of the ’929 patent as unpatentable under 35 U.S.C. § 103.