Oxford Nanopore Technologies Inc v. Pacific BiosCienes Of California Inc

1. Case Identification

• Case #: IPR2018-01792
• 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 Sequencing of a Polynucleotide
• Brief Description: The ’929 patent discloses methods for nanopore-based sequencing of a polynucleotide. The claimed methods involve passing a polynucleotide containing a double-stranded portion through a nanopore, using an enzyme chaperone to control the rate of passage, and obtaining sequence information from both complementary strands to determine a high-accuracy consensus sequence.

3. Grounds for Unpatentability

Ground 1: Claims 1-8, 10-11, and 16 are obvious over Akeson and 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 of sequencing a double-stranded polynucleotide using a nanopore analysis system, including a membrane, a voltage, and an enzyme chaperone (molecular motor) to control the rate of translocation and monitor ionic current variations. Petitioner asserted Gupte taught creating a single polynucleotide construct containing both complementary strands of an original DNA molecule, linked by a hairpin loop, specifically for sequencing. Gupte allegedly disclosed that sequencing this construct yields the sequence of both original strands, which is a known method to minimize errors. The combination of Akeson's nanopore system with Gupte's linked-strand polynucleotide was argued to meet all limitations of independent claim 1, including determining a consensus sequence from the redundant information of both complementary strands. Dependent claims were allegedly met by Akeson's disclosures of protein channels, lipid bilayers, solid-state membranes, and methods for altering the rate of passage.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine Akeson and Gupte to improve the accuracy of Akeson’s nanopore sequencing method. Gupte expressly taught that sequencing both strands of DNA minimizes errors, providing a clear reason to apply its polynucleotide structure to Akeson’s sequencing platform.
  • Expectation of Success: A POSITA would have a reasonable expectation of success as both references operate in the same field of DNA sequencing and address complementary aspects of the process—Akeson provides the sequencing apparatus and Gupte provides an improved template for sequencing.

Ground 2: Claims 1-8, 10-11, and 13 are obvious over Akeson, 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: Petitioner contended this combination similarly rendered the claims obvious. Akeson was asserted to teach the base nanopore sequencing system. Makrigiorgos was argued to teach an alternative method for generating a single polynucleotide containing complementary strands by ligating hairpin "caps" to a double-stranded DNA fragment, creating a dumbbell-like structure suitable for sequencing. Sanger, a seminal work, was cited for its teaching that sequencing both strands of DNA is necessary to confirm accuracy and identify errors. Petitioner argued that applying Makrigiorgos’s dumbbell template to Akeson’s sequencing system, with Sanger providing the well-established motivation for sequencing both strands to create a consensus sequence, met all limitations of claim 1. Dependent claim 13, which requires a nick in the linker, was allegedly taught by Makrigiorgos's disclosure that its hairpin "caps" can include a strand break to initiate polymerization.
  • Motivation to Combine: A POSITA would be motivated to use the double-stranded polynucleotides of Makrigiorgos in the nanopore methods of Akeson to benefit from a template designed for sequencing. Sanger provided the fundamental rationale for doing so: to improve sequencing accuracy by analyzing both complementary strands.
  • Expectation of Success: Success was reasonably expected because the combination involved applying a known template preparation method (Makrigiorgos) to a compatible sequencing platform (Akeson) to achieve a well-understood benefit (improved accuracy, as taught by Sanger).

Ground 3: Claims 14 and 15 are obvious over Akeson, Sanger, Makrigiorgos, and O'Dea.

• Prior Art Relied Upon: Akeson (Application # 2006/0063171), Sanger (a 1981 journal article), Makrigiorgos (Application # 2005/0142559), and O'Dea (a 2000 publication).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground built upon the Akeson, Sanger, and Makrigiorgos combination by adding O'Dea to address claims 14 and 15, which require a "synthetic linker" that is "carbon-based." Petitioner argued that O'Dea explicitly disclosed the use of synthetic, carbon-based oligo(ethylene glycol) linkers to connect nucleic acid sequences, for example, to form the loop structure at the end of a DNA molecule. The argument was that it would have been an obvious design choice to substitute the hairpin linkers ("caps") of Makrigiorgos with the known synthetic, carbon-based linkers taught by O'Dea.
  • Motivation to Combine: A POSITA would combine O'Dea with the primary combination because O'Dea taught advantageous properties of its synthetic linkers, such as hydrophilicity, making them a suitable and known alternative for constructing the dumbbell polynucleotides disclosed by Makrigiorgos.
  • Expectation of Success: This was presented as a simple substitution of one known type of linker for another to create the sequencing template, carrying a high expectation of success.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including combinations substituting or adding Miner (for barcode registration sequences), Akeson ’433 (for multiple detection periods), and Gupte with Makrigiorgos.

4. Relief Requested

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