Dropworks Inc v. University Of Chicago

1. Case Identification

• Case #: IPR2021-00100
• Patent #: 8,304,193
• Filed: October 22, 2020
• Petitioner(s): Dropworks, Inc.
• Patent Owner(s): The University of Chicago
• Challenged Claims: 1-9 and 11

2. Patent Overview

• Title: Method for Conducting an Autocatalytic Reaction in Plugs in a Microfluidic System
• Brief Description: The ’193 patent discloses a method for conducting autocatalytic reactions, such as polymerase chain reaction (PCR), in discrete aqueous plugs within a microfluidic system. The method involves forming water-in-oil droplets by continuously flowing an aqueous fluid into a continuously flowing, immiscible oil carrier fluid at a channel junction.

3. Grounds for Unpatentability

Ground 1: Obviousness over Quake and Holliger - Claims 1-9 and 11 are obvious over Quake in view of Holliger.

• Prior Art Relied Upon: Quake (International Publication No. WO 02/23163) and Holliger (International Publication No. WO 02/022869).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Quake taught all elements of the claimed microfluidic system, including forming aqueous plugs (droplets) at the junction of two channels by flowing an aqueous solution into a continuously flowing oil (e.g., mineral oil). Quake expressly suggested using its device for PCR. Holliger, in turn, demonstrated that PCR amplification was successfully performed in microscopic water-in-oil droplets using mineral oil and standard surfactants (e.g., Span, Tween), the same types of materials disclosed in Quake.
  • Motivation to Combine: A person of ordinary skill in the art (POSITA) would have been motivated to implement the PCR suggested by Quake using the proven methods taught by Holliger. Quake provided a high-throughput device for creating uniform droplets, and Holliger provided an enabling disclosure confirming that PCR, including digital PCR, was feasible and successful in such droplets using conventional, biocompatible materials. Combining them was merely applying a known, successful biological technique (Holliger's emulsion PCR) to a suitable, advantageous apparatus (Quake's microfluidic device).
  • Expectation of Success: A POSITA would have had a high expectation of success because Holliger successfully performed PCR under conditions and with materials (mineral oil, standard surfactants) directly analogous to those disclosed in Quake. Holliger’s success directly refuted the alleged technical challenge of performing PCR in such systems, confirming the approach was viable.

Ground 2: Obviousness over Quake and Litborn - Claims 1-9 and 11 are obvious over Quake in further view of Litborn.

• Prior Art Relied Upon: Quake (WO 02/23163) and Litborn (Litborn et al., Micro Total Analysis Systems 2000).

• Core Argument for this Ground:

  • Prior Art Mapping: As in Ground 1, Quake was asserted to teach the claimed droplet formation method and suggested its use for PCR. Litborn was presented as teaching successful nanoscale PCR amplification in aqueous droplets flowing through a microfluidic capillary channel containing a standard hydrocarbon oil. Litborn explicitly taught using this method to reduce cross-contamination between samples.
  • Motivation to Combine: Petitioner argued a POSITA would combine Quake and Litborn to achieve a known goal: high-throughput, contamination-free PCR analysis. Litborn established the principle of performing PCR in droplets within a continuous oil flow as a simple and effective method. A POSITA would have been motivated to apply this known technique to Quake's more advanced microfluidic platform, which offered benefits of creating uniform, monodisperse droplets at high speed.
  • Expectation of Success: Litborn’s explicit statement that "[a]mplification was successful" provided a clear basis for an expectation of success. Litborn demonstrated that standard hydrocarbons were suitable carrier fluids for droplet-based PCR, confirming the feasibility of conducting the reactions suggested by Quake using the materials disclosed by Quake.

• Additional Grounds: Petitioner asserted that claims 1-9 and 11 are also obvious over Quake and Holliger in further view of Shaw Stewart (International Publication No. WO 84/02000), and over Quake and Litborn in further view of Shaw Stewart. These grounds added Shaw Stewart primarily to teach the use of fluorinated oils and surfactants as a known alternative to mineral oil for the carrier fluid, further supporting the obviousness of claims reciting these specific components (e.g., claims 6 and 8).

4. Key Technical Contentions (Beyond Claim Construction)

• Biocompatibility of Standard Hydrocarbons for PCR: A central contention was that the Patent Owner prevailed in prior reexamination by arguing that standard hydrocarbons (like mineral oil, taught in Quake) were not biocompatible and would prevent successful PCR. Petitioner argued that the newly cited art, particularly Holliger and Litborn, directly contradicted this by demonstrating successful PCR amplification in droplets formed in standard hydrocarbon oils. This evidence, not previously before the USPTO, was asserted to overcome the primary argument for patentability relied upon by the Patent Owner.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) was inappropriate because the petition presented new prior art and arguments that were materially different from those previously considered by the USPTO during prosecution, reexamination, or a prior inter partes review (IPR) filed by an unrelated party (10X Genomics).
• The core of the argument was that the new references (Holliger, Litborn) were not cumulative because they, unlike previously considered art, explicitly taught successful PCR in sub-microliter droplets using the very types of standard hydrocarbon oils that the Patent Owner had successfully argued were unsuitable. Petitioner contended this new evidence directly addressed the "reasonable expectation of success" deficiency that led to the denial of the prior IPR and refuted the arguments that persuaded the examiner during reexamination.

6. Relief Requested

• Petitioner requested institution of an IPR and cancellation of claims 1-9 and 11 of Patent 8,304,193 as unpatentable under 35 U.S.C. §103.