DCT

1:19-cv-11587

Bio Rad Laboratories Inc v. Stilla Tech Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-11587, D. Mass., 10/11/2019
  • Venue Allegations: Venue is alleged to be proper over the domestic defendant, Stilla (US), based on its principal place of business in Beverly, Massachusetts. Venue over the foreign defendant, Stilla (FR), is alleged to be proper in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants’ Naica System for digital PCR infringes four patents related to microfluidic droplet formation, partitioning, and nucleic acid analysis.
  • Technical Context: The technology at issue is droplet digital Polymerase Chain Reaction (ddPCR), a method for precise quantification of nucleic acids by partitioning samples into thousands of discrete droplets for individual amplification reactions.
  • Key Procedural History: The complaint alleges that Plaintiff Bio-Rad is the exclusive licensee to three of the patents-in-suit, which are owned by the university co-plaintiffs, and is the owner of the fourth patent. No prior litigation or administrative proceedings are mentioned.

Case Timeline

Date Event
2002-03-14 U.S. Patent No. RE41,780 Priority Date
2002-05-09 U.S. Patent No. 9,968,933 Priority Date
2004-10-08 U.S. Patent No. 8,871,444 Priority Date
2010-02-12 U.S. Patent No. 9,127,310 Priority Date
2010-09-28 U.S. Patent No. RE41,780 Issued
2014-10-28 U.S. Patent No. 8,871,444 Issued
2015-09-08 U.S. Patent No. 9,127,310 Issued
2016-03-01 Accused Naica System Launched (approx.)
2018-05-15 U.S. Patent No. 9,968,933 Issued
2019-10-11 First Amended Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,968,933 - "Device And Method For Pressure-Driven Plug Transport And Reaction"

  • Patent Identification: U.S. Patent No. 9,968,933, "Device And Method For Pressure-Driven Plug Transport And Reaction", issued May 15, 2018 (Compl. ¶33).

The Invention Explained

  • Problem Addressed: The patent’s background section identifies the limitations of then-existing microfluidic systems, noting that pressure-driven flows suffer from "Taylor dispersion," which broadens and dilutes sample segments, while electroosmotic flows (EOF) are sensitive to surface chemistry and have difficulty handling particulates (’933 Patent, col. 1:29-54).
  • The Patented Solution: The invention claims to solve these problems by using pressure-driven flow to transport discrete "plugs" (droplets) of a sample fluid within a continuous, immiscible carrier fluid, thereby preventing the sample from contacting the channel walls and mitigating dispersion (’933 Patent, Abstract; col. 3:4-15). This approach combines the robustness of pressure-driven systems with the sample integrity of discrete partitioning.
  • Technical Importance: This method provided a way to conduct precisely controlled, multi-step chemical reactions in micro-scale volumes without the drawbacks associated with either continuous pressure-driven flow or EOF (’933 Patent, col. 2:23-29).

Key Claims at a Glance

  • The complaint alleges infringement of claims 1-20 (Compl. ¶28). Independent claim 1 is central.
  • The essential elements of independent claim 1 include:
    • A method for conducting a reaction within a substrate, comprising the steps of:
    • introducing a carrier-fluid into a first channel of the substrate;
    • introducing at least two different plug-fluids into the first channel; and
    • applying pressure to the first channel to induce a fluid flow in the substrate to form substantially identical plugs comprising a mixture of plug-fluids,
    • wherein the plug-fluids are immiscible with the carrier-fluid.
  • The complaint reserves the right to assert other claims from the ’933 Patent (Compl. ¶28).

U.S. Patent No. RE41,780 - "Chemical Amplification Based On Fluid Partitioning In An Immiscible Liquid"

  • Patent Identification: U.S. Patent No. RE41,780, "Chemical Amplification Based On Fluid Partitioning In An Immiscible Liquid", issued September 28, 2010 (Compl. ¶48).

The Invention Explained

  • Problem Addressed: The patent addresses the need for methods of chemical amplification, such as polymerase chain reaction (PCR), that can operate on very small samples or detect single copies of a target nucleic acid (’780 Patent, col. 1:15-20).
  • The Patented Solution: The invention describes a method where a sample is partitioned into a plurality of discrete sections within an immiscible fluid, followed by performing PCR on these partitioned sections (’780 Patent, Abstract). This compartmentalization isolates individual template molecules, enabling digital amplification and detection.
  • Technical Importance: This fluid partitioning approach is a foundational technique for digital PCR, allowing for absolute quantification of nucleic acids and the detection of rare genetic events by analyzing thousands of individual amplification reactions in parallel (’780 Patent, col. 2:23-26).

Key Claims at a Glance

  • The complaint alleges infringement of claims 1-3 (Compl. ¶29). Independent claim 1 is the lead asserted claim.
  • The essential elements of independent claim 1 include:
    • A method for nucleic acid amplification of a sample, comprising the steps of:
    • partitioning said sample into a plurality of partitioned sections in an immiscible fluid; and
    • subjecting said partitioned sections of said sample to polymerase chain reaction (PCR).
  • The complaint reserves the right to assert other claims from the ’780 Patent (Compl. ¶29).

U.S. Patent No. 8,871,444 - "In Vitro Evolution In Microfluidic Systems"

  • Patent Identification: U.S. Patent No. 8,871,444, "In Vitro Evolution In Microfluidic Systems", issued October 28, 2014 (Compl. ¶63).
  • Technology Synopsis: The patent addresses challenges in molecular evolution by providing a method to isolate genetic elements that encode a gene product with a desired activity (Compl. ¶30; ’444 Patent, col. 1:8-19). The solution involves compartmentalizing these genetic elements into microcapsules (droplets) and then sorting the microcapsules based on the expressed activity, with at least one step of the process occurring under microfluidic control (’444 Patent, Abstract).
  • Asserted Claims: Claims 1-5, 8, and 9 (Compl. ¶30).
  • Accused Features: The complaint alleges that the Naica System's use of microfluidic droplet formation and detection for genetic analysis infringes the patent (Compl. ¶¶30, 66).

U.S. Patent No. 9,127,310 - "Digital Analyte Analysis"

  • Patent Identification: U.S. Patent No. 9,127,310, "Digital Analyte Analysis", issued September 8, 2015 (Compl. ¶78).
  • Technology Synopsis: The patent addresses the need for multiplexed digital PCR, where multiple targets are analyzed simultaneously (Compl. ¶31; ’310 Patent, col. 2:34-37). The patented solution involves placing a single nucleic acid template into a droplet along with a plurality of primer pairs, each specific for different target sites on that single template, thereby enabling multiplexed analysis within a single partition (’310 Patent, Abstract).
  • Asserted Claims: Claims 1-6, 8-11, and 15 (Compl. ¶31).
  • Accused Features: The complaint alleges the Naica System's method for droplet formation and detection in the context of digital analyte analysis infringes the patent (Compl. ¶¶31, 80).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the Naica System (Compl. ¶26).

Functionality and Market Context

  • The complaint describes the Naica System as a digital PCR (dPCR) solution that uses "crystal digital PCR" (Compl. ¶26). The system allegedly operates by flowing a sample through a network of microchannels to partition it into a "large 2D array of 30,000 individual droplets, also called a droplet crystal." Following partitioning, PCR is performed on-chip, and the "crystal" is imaged to count positive droplets for absolute quantification of nucleic acids (Compl. ¶26). No probative visual evidence provided in complaint.
  • The complaint cites a third-party job posting that refers to the Naica System as the "premier system for Digital-PCR with decided advantages over others" and states that over 100 systems have been sold worldwide (Compl. ¶15).

IV. Analysis of Infringement Allegations

’933 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for conducting a reaction within a substrate, comprising the steps of: introducing a carrier-fluid into a first channel of the substrate; The Naica System is a microfluidic device that flows a sample and an immiscible fluid through a network of microchannels. ¶26 col. 3:4-9
introducing at least two different plug-fluids into the first channel; The Naica System introduces a sample fluid containing nucleic acids and reagents into the microchannels. ¶26 col. 3:10-11
and applying pressure to the first channel to induce a fluid flow...to form substantially identical plugs comprising a mixture of plug-fluids, wherein the plug-fluids are immiscible with the carrier-fluid. The Naica System partitions the sample into a 2D array of approximately 30,000 individual droplets within an immiscible fluid for on-chip PCR. ¶26 col. 3:12-15

’780 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for nucleic acid amplification of a sample, comprising the steps of: The Naica System is used for nucleic acid amplification and absolute quantification. ¶26 col. 2:5-7
partitioning said sample into a plurality of partitioned sections in an immiscible fluid; The Naica System flows a sample through microchannels to partition it into a 2D array of 30,000 individual droplets. ¶26 col. 2:8-10
and subjecting said partitioned sections of said sample to polymerase chain reaction (PCR). After partitioning, PCR is performed on-chip and the droplets are imaged to quantify amplified targets. ¶26 col. 2:10-12

Identified Points of Contention

  • Scope Questions: The complaint's description of the accused product forming a "2D array of 30,000 individual droplets, also called a droplet crystal" (Compl. ¶26) raises the question of whether this configuration falls within the scope of the term "plugs" as used in the ’933 Patent, which often describes mobile, sequentially flowing partitions. Similarly, it raises a question as to whether forming a "droplet crystal" constitutes "partitioning...in an immiscible fluid" as claimed in the ’780 Patent.
  • Technical Questions: The complaint alleges infringement literally or, in the alternative, under the doctrine of equivalents for all asserted patents (e.g., Compl. ¶36, ¶51). This suggests a potential dispute over whether the Naica System's on-chip formation and analysis of a "droplet crystal" is technologically identical to the methods described in the patents, or if not, whether it performs substantially the same function in substantially the same way to achieve the same result.

V. Key Claim Terms for Construction

The Term: "plugs" (from '933 Patent, claim 1)

  • Context and Importance: The definition of "plugs" is critical because the infringement allegation hinges on whether the accused Naica System's "2D array of...droplets, also called a droplet crystal" meets this limitation (Compl. ¶26). Practitioners may focus on this term because a narrow construction requiring mobility within a channel could create a non-infringement argument for a system that forms a more stationary array for on-chip analysis.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification defines a plug simply as being "formed...when a stream of at least one plug-fluid is introduced into the flow of a carrier-fluid in which it is substantially immiscible" (’933 Patent, col. 9:36-39). This broad definition does not explicitly require continuous movement after formation.
    • Evidence for a Narrower Interpretation: The patent figures and detailed descriptions consistently depict "plugs" as discrete, mobile entities flowing sequentially through channels to enable mixing, merging, and splitting (e.g., ’933 Patent, Figs. 2A-B, 4, 5). This context may support an interpretation that a "plug" is inherently a mobile, rather than arrayed, partition.

The Term: "partitioning said sample into a plurality of partitioned sections in an immiscible fluid" (from '780 Patent, claim 1)

  • Context and Importance: This term's construction is central to determining whether the accused method of creating a "droplet crystal" infringes the ’780 Patent. The dispute may turn on whether creating a 2D array on a chip is equivalent to creating "partitioned sections in an immiscible fluid," which could imply suspension within a bulk fluid rather than arrangement on a surface.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent abstract broadly describes the invention as comprising "partitioning the sample into partitioned sections and performing PCR on the partitioned sections" (’780 Patent, Abstract). This general language could be argued to encompass various methods of compartmentalization, including an on-chip array.
    • Evidence for a Narrower Interpretation: The method is described as "chemical amplification based on fluid partitioning in an immiscible liquid," and the Summary of the Invention refers to partitioning a "fluid sample" into "fluid partitions" (’780 Patent, Title; col. 2:5-8). This language could suggest that the partitions themselves must remain fluid and suspended within the liquid carrier throughout the process.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all four patents-in-suit. The inducement claims are based on allegations that Stilla offers the Naica System for sale with knowledge and specific intent that its customers will infringe, facilitated through promotional materials, user manuals, and technical documents (e.g., Compl. ¶37, ¶52). The contributory infringement claims are based on allegations that the Naica System is a material part of the inventions, is not a staple article of commerce, and is especially made or adapted for infringement (e.g., Compl. ¶38, ¶53).
  • Willful Infringement: For each patent, the complaint alleges that Stilla had knowledge of the patent as of its issue date "on information and belief that Stilla (FR) monitors patent applications and publications in the microfluidics field" (e.g., Compl. ¶39, ¶54, ¶69, ¶83). It further alleges knowledge from the filing and service of the complaint, and the prayer for relief seeks a declaration of an exceptional case (Compl. p. 23-25).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of definitional scope: can the terms "plugs" and "partitioned sections in an immiscible fluid," which appear rooted in the patents' descriptions of mobile droplets, be construed to cover the "2D array of...droplets, also called a droplet crystal" allegedly created by the accused system? The outcome of claim construction on these terms will significantly influence the infringement analysis.
  • A key evidentiary question will be one of technological operation: if the claims are construed narrowly, the case may turn on the doctrine of equivalents. This will require a factual inquiry into whether the accused system's formation of a "droplet crystal" for on-chip PCR performs substantially the same function, in substantially the same way, to achieve the same result as the claimed methods.
  • A central factual dispute for willfulness and enhanced damages will be the question of pre-suit knowledge: what evidence can Plaintiffs produce to substantiate their "information and belief" allegation that Stilla actively monitored the patent landscape and therefore knew of the patents-in-suit upon their issuance, years before the complaint was filed?