Agilent Technologies Inc v. Roche Sequencing Solutions Inc

1. Case Identification

• Case #: IPR Trial No.: TBD
• Patent #: 9,790,543
• Filed: September 24, 2018
• Petitioner(s): Agilent Technologies, Inc.
• Patent Owner(s): Roche Sequencing Solutions, Inc.
• Challenged Claims: 1-29

2. Patent Overview

• Title: Methods and Systems for Solution Based Sequence Enrichment
• Brief Description: The ’543 patent discloses methods for reducing the genetic complexity of a nucleic acid sample for targeted sequencing. The method involves generating a pool of nucleic acid probes from oligonucleotides immobilized on a solid support, using these free-floating probes in solution to hybridize with and capture specific target nucleic acid sequences from a sample, and then separating and eluting the captured target sequences for subsequent analysis.

3. Grounds for Unpatentability

Ground 1: Claims 1-3 and 5-29 are obvious over Fu in view of Lipshutz.

• Prior Art Relied Upon: Fu (Application # 2006/0183132) and Lipshutz (Patent 6,013,440).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the claimed method comprises two main stages: (1) generating a pool of amplified probes and (2) using that pool for in-solution target enrichment. Lipshutz allegedly taught the first stage by disclosing methods of generating a pool of probes by amplifying them from a support-immobilized "amplification template array" into solution, including using biotinylated primers. Fu allegedly taught the second stage by disclosing enrichment methods that use "multiple unique selection probes in a single medium" for in-solution hybridization to capture desired target sequences, followed by separation using an affinity system (e.g., biotin-streptavidin).
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine Lipshutz and Fu because they shared the same goal of capturing target sequences to create a reduced-complexity sample. Petitioner asserted that the approaches were compatible and that Lipshutz provided a known, efficient, and cost-effective method for generating the large, diverse pool of probes required for the in-solution enrichment method taught by Fu.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success because both references utilized compatible technologies, such as biotinylated probes and affinity partners (e.g., streptavidin) to collect hybridization complexes. Therefore, probes generated according to Lipshutz would have been expected to function as intended within the enrichment protocol of Fu.

Ground 2: Claims 1-3 and 5-29 are obvious over Noonan in view of Lipshutz.

• Prior Art Relied Upon: Noonan (a 2006 Science article on Neanderthal genomic DNA) and Lipshutz (Patent 6,013,440).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground presented a similar combination as Ground 1, but substituted Noonan for Fu. Petitioner argued Lipshutz taught the probe generation method from a solid support. Noonan taught a "direct genomic selection approach" that used in-solution hybridization with a pool of biotinylated probes to recover specific ancient DNA sequences from metagenomic libraries. Noonan explicitly disclosed hybridizing probes in solution, capturing the resulting heteroduplexes on streptavidin-coated beads, washing, and eluting the captured DNA.
  • Motivation to Combine: The motivation was again based on a shared goal of enrichment. A POSITA seeking to implement Noonan's method for analyzing ancient DNA, where preserving the original sample is critical, would have been motivated to use Lipshutz's method to generate large quantities of the necessary biotinylated probes in a cost-effective manner.
  • Expectation of Success: Success was expected because Noonan’s use of biotinylated probes and streptavidin beads for capture is entirely compatible with Lipshutz’s method for generating such probes. A POSITA would have recognized that the probe generation method of Lipshutz would work seamlessly with the in-solution capture method of Noonan.

Ground 3: Claim 4 is obvious over (Fu or Noonan) in view of Lipshutz, in further view of Patil.

• Prior Art Relied Upon: Fu (Application # 2006/0183132) or Noonan (a 2006 Science article), in view of Lipshutz (Patent 6,013,440), and in further view of Patil (Application # 2005/0100911).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground specifically addressed claim 4, which added the limitation that the probe pool comprises "overlapping sequences defining the complete sequence of the at least one genetic locus." Petitioner argued that Patil taught this specific concept by disclosing the use of overlapping probes, or "tiling," for genetic analysis. Tiling, as described in Patil, ensures that a probe set spans an entire region of interest.
  • Motivation to Combine: A POSITA implementing the enrichment methods of Fu/Lipshutz or Noonan/Lipshutz for large genetic regions (e.g., genes or chromosomes) would have been motivated to incorporate Patil's well-known tiling strategy. This would have been a predictable design choice to ensure complete and robust coverage of the target genetic locus.
  • Expectation of Success: A POSITA would have reasonably expected that applying Patil’s tiling design to the probes generated by Lipshutz would successfully promote full coverage of the target locus within the enrichment systems of Fu or Noonan.

4. Key Technical Contentions

• Rebuttal of "Unexpected Results": A central contention of the petition was that the patent owner overcame prior art rejections during prosecution by arguing the "unexpected success" of its in-solution approach, supported by a declaration from inventor Dr. Thomas Albert. The declaration asserted that a POSITA would have expected in-solution probes to cross-react and fail. Petitioner argued this was contrary to the state of the art, citing numerous pre-2007 references (including Fu, Noonan, Welcher, Gormley, and Hardenbol) that explicitly taught and successfully implemented in-solution hybridization with large, diverse probe sets for target enrichment.

5. Arguments Regarding Discretionary Denial

• New Issues of Patentability under §325(d): Petitioner argued that discretionary denial under §325(d) would be inappropriate. Although Lipshutz was considered during prosecution, the primary references forming the core of the invalidity grounds (Fu, Noonan, and Patil) were not before the Examiner. Petitioner asserted that these new references raise new issues because they directly contradict the Albert Declaration and the patent owner's arguments regarding "unexpected results," which were dispositive for allowance. Therefore, the petition presented prior art and arguments substantially different from those previously considered by the USPTO.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-29 of Patent 9,790,543 as unpatentable under 35 U.S.C. §103.