PTAB

IPR2014-01093

Ariosa Diagnostics Inc v. Illumina Inc

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1. Case Identification

2. Patent Overview

  • Title: Multiplex Method of Detecting Target Sequences
  • Brief Description: The ’794 patent discloses methods for simultaneously detecting at least 100 different target nucleic acid sequences in a sample. The methods involve immobilizing target sequences on a first solid support, hybridizing a set of probes, enzymatically modifying the probes, amplifying the modified probes into amplicons, and detecting the amplicons on a second solid support.

3. Grounds for Unpatentability

Ground 1: Anticipation over Fu - Claims 1-22 are anticipated by Fu under 35 U.S.C. §102.

  • Prior Art Relied Upon: Fu (Application # 2002/0172946).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Fu, particularly through its incorporated provisional application, discloses every limitation of claims 1-22. Fu taught a multiplexed method for detecting 50 to 100 genes by binding polyadenylated mRNA targets to a solid support with oligo-dT molecules, hybridizing linear oligonucleotide probes, modifying the bound probes by ligation, amplifying the resulting products with universal primers, and detecting the amplicons on a second array. The petition provided a detailed claim chart mapping each element of the challenged claims to specific disclosures in Fu.
    • Key Aspects: The argument was supported by a declaration from Professor Fu, an inventor of the Fu reference, stating that Fu's disclosure anticipates the claims of the ’794 patent.

Ground 2: Obviousness over Fu and Lizardi - Claims 1-22 are obvious over Fu in view of Lizardi under 35 U.S.C. §103.

  • Prior Art Relied Upon: Fu (Application # 2002/0172946), Lizardi (Patent 6,316,229).
  • Core Argument for this Ground:
    • Prior Art Mapping: Fu disclosed the foundational method for multiplex ligation-based detection of nucleic acids on a solid support. Lizardi taught the detection of 100 or more nucleic acids on solid substrates using specialized "padlock probes" and rolling circle amplification, including methods for enzymatic extension to fill gaps between non-adjacent probes prior to ligation. Petitioner asserted that combining Fu's general framework with Lizardi's specific padlock probe and extension-ligation techniques would arrive at the claimed invention, including embodiments taught in the ’794 patent specification.
    • Motivation to Combine: A POSITA would combine Fu and Lizardi because padlock probes and rolling circle amplification were known to be a preferred combination for certain detection experiments, offering high specificity and intense signal amplification from low levels of sample. The methods were described as naturally complementary for nucleic acid detection.
    • Expectation of Success: Both the general ligation-based assay of Fu and the padlock probe techniques of Lizardi were well-known in the art by 2000. A POSITA would have had a reasonable expectation that replacing Fu's linear probes with Lizardi's padlock probes would be successful for the multiplexed detection of at least 100 target nucleic acids.

Ground 3: Obviousness over Straus, Rothberg, and Walt - Claims 1-9 and 11-22 are obvious over Straus in view of Rothberg and Walt under §103.

  • Prior Art Relied Upon: Straus (Application # 2003/0228599), Rothberg (Patent 6,274,320), and Walt (Patent 6,859,570).
  • Core Argument for this Ground:
    • Prior Art Mapping: Straus disclosed multiplexed methods for genomic profiling that involved immobilizing single-stranded target nucleic acids, using probe sets (including both linear and padlock probes), followed by ligation, amplification, and detection on an array. Rothberg and Walt taught the specific, conventional array technologies needed to implement the detection step at the claimed scale, such as high-density arrays with at least 100 different oligonucleotides and bead-based substrates placed in wells.
    • Motivation to Combine: A POSITA would combine the genomic profiling methods of Straus with the established and widely used array platforms taught by Rothberg and Walt. This combination would enhance the multiplexing capability of the Straus assay and allow for its implementation using readily available, high-throughput detection platforms.
    • Expectation of Success: The array methods disclosed by Rothberg and Walt were conventional techniques in molecular biology at the time. A POSITA would have readily and predictably combined these standard detection platforms with the assay methods taught in Straus.
    • Key Aspects: This ground was presented as a stronger alternative to the grounds based on Fu, as Straus, Rothberg, and Walt had earlier priority dates and no inventors in common with the ’794 patent, precluding any attempt by the Patent Owner to disqualify them as prior art.

4. Key Claim Construction Positions

  • "Providing a sample which may contain at least 100 different single-stranded target sequences attached to a first solid support."
    • Petitioner argued this requires the single-stranded target sequences to be attached to the first solid support before they are contacted with the probe set in a subsequent step. Petitioner also contended that the word "may" indicates the sample is not required to actually possess 100 different target sequences for the method to be performed.
  • "Contacting said probes of the hybridization complexes with a first enzyme and forming different modified probes"
    • Petitioner defined "modified probe" as a new nucleic acid formed by the enzymatic modification (e.g., ligation, extension followed by ligation) of a probe while it is bound to its target sequence in a hybridization complex.

5. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-22 of the ’794 patent as unpatentable.