PTAB

IPR2018-01785

Oxford Nanopore Technologies Inc v. Pacific Biosciences Of California Inc

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods for Nucleic Acid Sequencing
  • Brief Description: The ’929 patent describes methods for nanopore-based sequencing of a polynucleotide. The methods involve using an enzyme chaperone to control the passage of a double-stranded polynucleotide through the nanopore, obtaining sequence information from both complementary strands, and determining a consensus sequence to improve accuracy.

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 taught the foundational method for nanopore sequencing of a polynucleotide, including using an enzyme chaperone (a "molecular motor") to control the rate of translocation through a nanopore in a membrane. However, to improve accuracy, a person of ordinary skill in the art (POSA) would look to known techniques such as sequencing both strands of a DNA molecule. Gupte provided this teaching, disclosing a method for generating a double-stranded DNA product with a hairpin structure that, when sequenced, yields the sequence of both complementary strands of the original DNA in a single reaction. The combination of Akeson's system with Gupte's template structure would therefore teach all limitations of independent claim 1. Dependent claims were allegedly met by Akeson's disclosure of protein channels, lipid bilayers, and altering reaction conditions to control the rate of passage, and Gupte's disclosure of linked complementary strands via a nucleotide linker.
    • Motivation to Combine: A POSITA would combine Akeson with Gupte to improve the accuracy of the nanopore sequencing technique. Gupte explicitly stated it was common to sequence both DNA strands to minimize errors, providing a clear reason to apply its template generation method to Akeson’s sequencing platform.
    • Expectation of Success: Petitioner asserted a POSITA would have a reasonable expectation of success, as this combination involved applying a known method for improving accuracy (sequencing both strands via a Gupte-style template) to a known sequencing system (Akeson's nanopore device).

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 journal article), and Makrigiorgos (Application # 2005/0142559).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented an alternative combination for the core invention. Akeson again provided the base nanopore sequencing system. Sanger, a Nobel Laureate speech, established the fundamental motivation for sequencing both strands of DNA to ensure correctness and minimize errors. Makrigiorgos taught a method for creating a "dumbbell" polynucleotide structure by ligating oligonucleotide "caps" (linkers) to both ends of a double-stranded DNA fragment. This structure links the complementary strands and is suitable for sequencing. Petitioner argued that sequencing a Makrigiorgos-style dumbbell template using Akeson's nanopore system would result in obtaining the sequence of both complementary strands. Claim 13, which required a "nick" in the linker, was allegedly taught by Makrigiorgos's disclosure that its linkers could include a strand break to initiate polymerization.
    • Motivation to Combine: A POSITA, motivated by Sanger to improve sequencing accuracy, would have sought methods to prepare templates for sequencing both strands. A POSITA would combine Makrigiorgos's method for generating sequencable dumbbell templates with Akeson's nanopore system to achieve this goal with high accuracy.
    • Expectation of Success: The combination was presented as a predictable assembly of known elements, where each component performed its expected function.

Ground 3: Obviousness over Akeson, Sanger, Makrigiorgos, and O'Dea - Claims 14 and 15 are obvious over the combination of Akeson, Sanger, and Makrigiorgos in view of O'Dea.

  • Prior Art Relied Upon: Akeson (Application # 2006/0063171), Sanger (a 1981 journal article), Makrigiorgos (Application # 2005/0142559), and O'Dea (a 2000 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built upon the Akeson/Sanger/Makrigiorgos combination to specifically address the limitations of claims 14 ("synthetic linker") and 15 ("carbon-based linker"). While Makrigiorgos taught oligonucleotide linkers, O'Dea was introduced for its explicit teaching of using synthetic, carbon-based linkers (specifically oligo(ethylene glycol) linkers) to replace loop structures at the end of a DNA molecule. Petitioner argued it would have been obvious to a POSITA to replace the nucleotide-based linkers of Makrigiorgos with the synthetic, carbon-based linkers taught by O'Dea to create the dumbbell sequencing template.
    • Motivation to Combine: A POSITA would combine O'Dea with the primary references to use an alternative, known type of linker in the template construction. O'Dea taught that its synthetic linkers were advantageous due to their hydrophilic nature, providing a technical reason for their adoption.
    • Expectation of Success: The substitution of one known type of linker (O'Dea's synthetic linker) for another (Makrigiorgos's oligonucleotide linker) was argued to be a simple and predictable design choice for a POSITA.
  • Additional Grounds: Petitioner asserted additional obviousness challenges, including grounds adding Miner (a 2004 journal article) for its teaching of "registration sequences" in linkers (claim 12), and Akeson ’433 (Patent 6,936,433) for its teaching of monitoring with multiple detection periods (claim 17).

4. Relief Requested

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