DCT

1:15-cv-00152

Bio-Rad Laboratories, Inc. v. 10X Genomics Inc.

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:15-cv-00152, D. Del., 10/21/2016
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because both Plaintiff RainDance and Defendant 10X are incorporated in Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s genetic analysis platforms infringe six patents related to the use of microfluidic droplets to perform isolated biological reactions.
  • Technical Context: The technology lies in the field of microfluidics for high-throughput genetic analysis, a foundational tool for DNA sequencing, disease research, and diagnostics.
  • Key Procedural History: The filing is a Third Amended Complaint. The complaint alleges that Defendant had pre-suit knowledge of all patents-in-suit, with the earliest knowledge dating to April 2013. It further alleges that Defendant unsuccessfully challenged the validity of several of the asserted patents in inter partes review (IPR) proceedings before the U.S. Patent and Trademark Office and continued to infringe despite these failed challenges.

Case Timeline

Date Event
2002-05-09 Priority Date for ’091, ’193, ’407, ’148, and ’083 Patents
2006-10-31 ’091 Patent Issued
2011-07-20 Priority Date for ’430 Patent
2012-11-06 ’193 Patent Issued
2012-12-11 ’407 Patent Issued
2013-04-18 Alleged 10X Knowledge of ’091, ’193, and ’407 Patents
2014-02-25 ’430 Patent Issued
2014-04-04 10X cites ’407 Patent in an Information Disclosure Statement
2014-06-06 Alleged 10X Knowledge of ’430 Patent
2014-09-02 ’148 Patent Issued
2014-10-23 Alleged 10X Knowledge of ’148 Patent
2014-11-18 ’083 Patent Issued
2015-01-14 10X presents Genomics platform at JP Morgan Healthcare Conference
2015-02-06 Alleged 10X Knowledge of ’083 Patent
2015-02-12 Original Complaint Filed
2015-02-27 10X presents GemCode platform at AGBT meeting
2015-06-30 10X announces commercial shipments of GemCode platform
2016-02-11 10X releases Chromium Controller instrument
2016-10-21 Third Amended Complaint Filed

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

U.S. Patent No. 7,129,091 - "Device and Method for Pressure-Driven Plug Transport and Reaction"

  • Issued: October 31, 2006 (Compl. ¶28).

The Invention Explained

  • Problem Addressed: The complaint describes the technical field as one requiring tools to simplify and scale complex genetic analysis (Compl. ¶12). Conventional methods for such analysis may face challenges in efficiently handling and isolating vast numbers of individual molecules for parallel reactions.
  • The Patented Solution: The invention provides microfluidic systems that partition a biological sample, such as DNA, into hundreds of thousands of discrete, nanoliter-scale droplets, referred to as "plugs" (Compl. ¶12). Each droplet serves as an independent micro-reactor, allowing enzymatic reactions like amplification to occur on the nucleic acid molecules contained within, isolated from molecules in other droplets (Compl. ¶12). This approach enables massive parallel processing of genetic material.
  • Technical Importance: This technology is presented as a method to "fundamentally enhance the way researchers and scientists study cell-based and cell-free biomarkers in cancer, infectious disease, and inherited disorders" (Compl. ¶11).

Key Claims at a Glance

  • The complaint asserts infringement of at least claims 1-3, 5-6, 11, 23, 27, 29, 31, 33, 35-39, 43, 53, and 56-58 (Compl. ¶31).
  • The complaint incorporates by reference claim chart exhibits that are not attached to the complaint; therefore, a breakdown of claim elements is not possible from the provided document (Compl. ¶31).

U.S. Patent No. 8,304,193 - "Method for Conducting an Autocatalytic Reaction in Plugs in a Microfluidic System"

  • Issued: November 6, 2012 (Compl. ¶42).

The Invention Explained

  • Problem Addressed: The complaint does not provide sufficient detail for analysis of the specific problem addressed by this patent beyond the general context of simplifying genetic analysis (Compl. ¶12).
  • The Patented Solution: The patent title indicates the invention relates specifically to performing "autocatalytic" reactions within microfluidic "plugs" (Compl. ¶42). An autocatalytic reaction, such as a polymerase chain reaction (PCR) for DNA amplification, is one where a product of the reaction also serves as a catalyst for the same reaction. The complaint describes the accused products as performing a DNA amplification reaction within droplets, which involves creating new copies of nucleic acid molecules that can then serve as templates for further copying (Compl. ¶¶12, 19).
  • Technical Importance: Applying autocatalytic reactions like PCR in a massively parallel droplet format allows for the high-throughput analysis and quantification of rare genetic material.

Key Claims at a Glance

  • The complaint asserts infringement of at least claims 1-8 and 11 (Compl. ¶45).
  • The complaint incorporates by reference claim chart exhibits that are not attached to the complaint; therefore, a breakdown of claim elements is not possible from the provided document (Compl. ¶45).

  • Multi-Patent Capsule:

    • Patent Identification: U.S. Patent No. 8,329,407, "Method for Conducting Reactions Involving Biological Molecules in Plugs in a Microfluidic System," issued December 11, 2012 (Compl. ¶56).
    • Technology Synopsis: The patent relates to methods for performing reactions with biological molecules, such as DNA or RNA, inside discrete droplets ("plugs") within a microfluidic device. This allows for the high-throughput analysis of biological samples by physically isolating reactions in miniaturized volumes (Compl. ¶¶12, 66).
    • Asserted Claims: Claims 1-5, 8-11, and 13 (Compl. ¶59).
    • Accused Features: The accused features are the partitioning of nucleic acid samples into droplets and subsequent amplification of the nucleic acid within those droplets using the GemCode platform (Compl. ¶66).

  • Multi-Patent Capsule:

    • Patent Identification: U.S. Patent No. 8,822,148, "Method of Performing PCR Reaction in Continuously Flowing Microfluidic Plugs," issued September 2, 2014 (Compl. ¶70).
    • Technology Synopsis: This patent is directed specifically to performing a Polymerase Chain Reaction (PCR), a common method for DNA amplification, within continuously flowing droplets. The complaint describes the accused process as involving a thermal cycling protocol on the droplets to achieve "a low-level of copying" of the genomic template inside (Compl. ¶19).
    • Asserted Claims: Claims 1-3 and 6-8 (Compl. ¶73).
    • Accused Features: The accused feature is the performance of a method for amplifying DNA or RNA by providing conditions suitable for a PCR reaction within the microfluidic plugs generated by the GemCode platform (Compl. ¶75).

  • Multi-Patent Capsule:

    • Patent Identification: U.S. Patent No. 8,889,083, "Device and Method for Pressure-Driven Plug Transport and Reaction," issued November 18, 2014 (Compl. ¶84).
    • Technology Synopsis: Sharing a title with the ’091 patent, this patent appears to also cover the fundamental apparatus and method for generating and transporting discrete fluid plugs (droplets) within a microchannel using pressure-driven flow. The technology allows for the creation of isolated reaction volumes from continuous fluid streams (Compl. ¶¶16, 18, 89).
    • Asserted Claims: Claims 1-2, 10-13, 20-22, 26, and 31 (Compl. ¶87).
    • Accused Features: The accused features include both the GemCode platform as an apparatus for conducting reactions in plugs and the methods of using it (Compl. ¶¶87, 89).

  • Multi-Patent Capsule:

    • Patent Identification: U.S. Patent No. 8,658,430, "Manipulating Droplet Size," issued February 25, 2014 (Compl. ¶99).
    • Technology Synopsis: This patent relates to methods for controlling the size of droplets as they are formed in a microfluidic system. The ability to form uniform droplets is important for ensuring consistent reaction conditions and predictable behavior as they flow through the device (Compl. ¶108).
    • Asserted Claims: Claims 1, 5, and 12-16 (Compl. ¶101).
    • Accused Features: The accused feature is the method of droplet formation performed by the GemCode platform when partitioning a nucleic acid sample (Compl. ¶108).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendant’s "GemCode platform" and its upgraded version, the "Chromium" system (Compl. ¶¶15, 21). The complaint defines the "GemCode platform" to include either the GemCode Instrument or the Chromium Controller combined with any of Defendant's reagent kits (Compl. ¶23).

Functionality and Market Context

  • The accused platform is a genetic analysis tool that partitions a nucleic acid sample (such as DNA) into hundreds of thousands to millions of tiny microfluidic droplets, or "partitions," each containing a unique barcode (Compl. ¶¶12, 21). A schematic in the complaint illustrates this process of "Fluid partitioning," where inputs including a barcoded primer library, DNA, and oil are combined in a microfluidic channel to form droplets called "GEMs" (Gel bead-in-emulsion) (Compl. ¶16, p. 4).
  • Inside each droplet, a biochemical reaction occurs, such as DNA amplification, which copies the DNA fragment and attaches the unique barcode (Compl. ¶¶19, 20). A diagram from Defendant's presentation shows the subsequent biochemical stages, including "Molecular barcoding in GEMs" via a thermal cycling protocol (Compl. ¶19, p. 7). After the reaction, the droplets are broken, and the barcoded DNA molecules are collected to generate "libraries" for DNA sequencing (Compl. ¶¶13, 19). An illustration from a scientific article shows the complete workflow from droplet generation in an 8-well cartridge to library construction and sequencing (Compl. ¶20, p. 8).
  • The complaint positions the accused products as direct competitors to Plaintiffs' products in the "emerging field of using microfluidic devices to deliver biological reagents so that complex genetic analysis may be simplified and scaled" (Compl. ¶12).

IV. Analysis of Infringement Allegations

The complaint alleges infringement of all six patents-in-suit but incorporates by reference preliminary claim charts (Exhibits 17-22) that are not attached to the provided complaint document (Compl. ¶¶1, 26). As the specific claim language and element-by-element infringement contentions are not available in the provided document, a claim chart summary cannot be constructed.

The general narrative theory of infringement alleges that Defendant’s GemCode and Chromium platforms practice the patented methods and embody the patented devices. The core of the accused process is the use of a microfluidic chip to partition samples (e.g., DNA) and reagents (e.g., barcoded gel beads, enzymes) into a large number of discrete aqueous droplets suspended in an immiscible oil carrier fluid (Compl. ¶¶18, 20). These droplets are alleged to be the "plugs" recited in the patents. Within these droplets, a DNA amplification reaction is performed, which is alleged to be the claimed "autocatalytic reaction" or "PCR reaction" (Compl. ¶¶19, 45, 73). The complaint further alleges that the specific device components and the overall process of generating and using these droplets for biochemical reactions infringe various apparatus and method claims across the six asserted patents (Compl. ¶26).

V. Key Claim Terms for Construction

The complaint does not provide the asserted patent claims, precluding a detailed analysis of specific terms. However, based on the patent titles and the infringement narrative, the construction of the following terms may be central to the dispute.

  • The Term: "plug"

    • Context and Importance: This term appears central to the "Ismagilov patents" (e.g., ’193, ’148 patents). The infringement theory depends on the accused "droplets," "partitions," or "GEMs" (Gel-bead in EMulsion) meeting the definition of a "plug" (Compl. ¶¶12, 16, 19, 42). Practitioners may focus on this term because its scope will determine if the specific emulsion technology used by Defendant, which involves encapsulating a gel bead, falls within the claims.
    • Intrinsic Evidence for Interpretation: The complaint does not provide sufficient detail for analysis of intrinsic evidence.

  • The Term: "autocatalytic reaction"

    • Context and Importance: This term is in the title of the ’193 Patent and is fundamental to its asserted claims (Compl. ¶¶42, 45). The complaint alleges that the DNA amplification performed within the accused droplets constitutes an "autocatalytic reaction" (Compl. ¶¶19, 48). The viability of the infringement claim for the ’193 patent may depend on whether the specific enzymatic "low-level of copying" described in Defendant's materials meets the technical definition of "autocatalytic" as understood in the context of the patent.
    • Intrinsic Evidence for Interpretation: The complaint does not provide sufficient detail for analysis of intrinsic evidence.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents.
    • Inducement: The inducement allegations are based on Defendant's alleged knowledge of the patents and specific intent that its customers infringe by using the GemCode platform. Alleged acts of inducement include disseminating promotional materials, user instructions, product brochures, and technical materials that instruct customers on how to perform the infringing methods (Compl. ¶¶33-34, 37). The complaint also points to Defendant’s distribution of open-source software for analyzing the data generated by the platform as an act of inducement (Compl. ¶36).
    • Contributory Infringement: Contributory infringement is alleged on the basis that the GemCode platform and its components (e.g., the specialized microfluidic device and reagents) are a material part of the claimed inventions, are not staple articles of commerce, and have no substantial non-infringing use (Compl. ¶¶38-39).
  • Willful Infringement: The complaint alleges willful infringement for all six asserted patents. The basis for willfulness includes allegations of Defendant’s pre-suit knowledge of each patent, with specific dates provided (e.g., April 18, 2013 for the ’091 patent) (Compl. ¶32). The complaint further supports willfulness by alleging that Defendant continued to infringe after the lawsuit was filed and after its own unsuccessful attempts to invalidate the patents via inter partes review proceedings, which Plaintiffs characterize as "egregious misconduct" (Compl. ¶¶40, 54, 68, 82, 97, 110).

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

  • A core issue will be one of definitional scope: can the term "plug," as used in the asserted patents, be construed to cover the specific "GEMs" (Gel bead-in-emulsions) generated by the accused 10X Genomics platforms? The resolution will likely depend on whether the presence of a gel bead within the aqueous droplet materially alters its structure or function in a way that removes it from the scope of the patent claims.
  • A second central question will be one of claim construction and technical operation: does the DNA amplification biochemistry performed within the accused droplets—described as a "low-level of copying" primed off a genome (Compl. ¶19)—meet the specific limitations of an "autocatalytic reaction" as claimed in the '193 patent and a "PCR reaction" as claimed in the '148 patent?
  • A key question for damages will be willfulness: given the detailed allegations of pre-suit knowledge, including citations in Defendant's own patent prosecution files and failed IPR challenges, a central issue will be whether Defendant's conduct constitutes the "egregious misconduct" required to support a finding of willful infringement and potential enhancement of damages.