PTAB

IPR2021-00212

Dropworks Inc v. Bio Rad Laboratories Inc

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Key Events
Petition

1. Case Identification

2. Patent Overview

  • Title: Digital Analyte Analysis
  • Brief Description: The ’310 patent describes methods for detecting and quantifying target nucleic acid sequences using droplet-based digital Polymerase Chain Reaction (PCR). The core technique involves partitioning a sample containing multiple target sequences into a plurality of droplets, where each droplet ideally contains no more than one target molecule, and then amplifying and detecting the sequences to quantify their presence.

3. Grounds for Unpatentability

Ground 1: Claims 1-5, 8-10, and 23 are obvious over Davies and Warren.

  • Prior Art Relied Upon: Davies (Application # 2010/0092973) and Warren (a 2006 journal article on digital RT-PCR).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Davies taught the foundational elements of the ’310 patent, including methods for digital PCR in pico-to-nanoliter scale microfluidic droplets. Davies disclosed partitioning a sample to achieve, on average, one or fewer target nucleic acid copies per droplet and then amplifying and detecting the target. Petitioner asserted that Warren taught the missing element: performing digital multiplex PCR. Warren disclosed using a plurality of different primer and probe types (for targets PU.1 and GAPDH) within each partition of a digital PCR assay, while still amplifying only a single target sequence per partition. The combination of Davies's droplet platform with Warren's multiplexing method allegedly rendered independent claim 1 obvious.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine these references to achieve a shared goal of quantifying DNA via digital PCR. The combination represented a simple substitution of Warren's microvial partitions with Davies's known droplet partitions to gain the recognized benefits of droplets (e.g., higher throughput, scalability) while applying Warren's known multiplexing technique to improve efficiency and reduce sample volume.
    • Expectation of Success: A POSA would have had a reasonable expectation of success. Warren already demonstrated that multiplexing in small, dilute partitions was feasible and mitigated issues like primer dimerization. Applying this proven concept to droplets, which the Petitioner argued serve the same basic function as microvials, was a predictable step.

Ground 2: Claims 1-5, 8-9, and 23 are obvious over Beer and Warren.

  • Prior Art Relied Upon: Beer (a 2007 journal article on picoliter droplet PCR) and Warren (a 2006 journal article on digital RT-PCR).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground presented an alternative to Ground 1, substituting Davies with Beer. Petitioner contended that Beer, like Davies, taught performing digital PCR in picoliter-scale droplets to detect single copies of target nucleic acids. Beer disclosed amplifying a single target sequence within each droplet and detecting the amplification via fluorescence. As in Ground 1, Warren supplied the teaching of using multiple different primer and probe types in a digital PCR format to enable multiplexed analysis while amplifying a single target per partition.
    • Motivation to Combine: The motivation was similar to Ground 1: improving a known technique with another known technique for predictable results. A POSA would have been motivated to implement Warren's efficient digital multiplex PCR method in Beer's picoliter-scale droplet system. Beer itself cited related multigene analysis work (Ottesen), which Petitioner argued suggested the utility of applying multiplexing to Beer's droplet system to gain benefits in efficiency, reduced reagent consumption, and improved statistics.
    • Expectation of Success: Success was reasonably expected because both were well-characterized digital PCR techniques. Warren confirmed feasibility in small-volume partitions (6.25 nL), and Beer's system operated on a similar principle, just with smaller (picoliter) droplets. Combining the two was an obvious optimization, applying Warren's multiplexing method to Beer's improved droplet platform.

  • Additional Grounds: Petitioner asserted additional obviousness challenges for claim 6 by adding Chen (a 1999 journal article) to the Davies/Warren and Beer/Warren combinations. Chen taught using quantitative PCR to determine gene copy number by comparing a target sequence to a reference sequence. Petitioner argued it would have been obvious for a POSA to apply the more advanced digital multiplex PCR methods of the primary references to perform Chen's known gene copy number analysis, which claim 6 recites.

4. Key Claim Construction Positions

  • Petitioner stated that no express claim constructions were required for the Board to find the claims unpatentable.
  • However, Petitioner noted that its analysis was consistent with constructions from a related district court litigation for two terms:
    • “nucleic acid molecule”: plain meaning.
    • “a plurality of different primer types”: “more than one set of different primer pairs.”

5. Key Technical Contentions (Beyond Claim Construction)

  • The Petitioner’s central technical contention was that the asserted invention is merely a combination of two well-known techniques. It was known to perform digital PCR by partitioning a sample into droplets to isolate single nucleic acid molecules for amplification. It was also separately known to perform multiplex PCR using multiple primer sets in a single reaction to improve efficiency.
  • Petitioner argued that the prior art, specifically Warren, had already demonstrated the solution to problems in traditional multiplex PCR (like primer-dimerization and competition) by applying it in a digital format where partitions contained only a single target molecule. Therefore, applying this known digital multiplexing technique to a known droplet-based platform (taught by Davies or Beer) was an obvious, predictable combination of familiar elements.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review (IPR) and the cancellation of claims 1-6, 8-10, and 23 of the ’310 patent as unpatentable under 35 U.S.C. §103.