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

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: RainDance Technologies, Inc. (Delaware) and The University of Chicago (Illinois)
  • Defendant: 10X Genomics, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• 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 Genomics are incorporated under the laws of Delaware.
• Core Dispute: Plaintiffs allege that Defendant’s GemCode and Chromium genetic analysis platforms infringe six U.S. patents related to the formation, transport, and use of microfluidic droplets for conducting biological reactions.
• Technical Context: The technology involves microfluidics, a field focused on manipulating picoliter-to-nanoliter volumes of fluid to perform high-throughput chemical and biological analyses, which is foundational for modern genomics and single-cell analysis.
• Key Procedural History: This Third Amended Complaint follows an original complaint filed on February 12, 2015. The complaint alleges that Defendant had pre-suit knowledge of several patents-in-suit based on discovery acknowledgements and Information Disclosure Statements (IDS) filed during its own patent prosecution. It also notes that Defendant’s efforts to invalidate U.S. Patent Nos. 7,129,091 and 8,304,193 via inter partes review (IPR) were unsuccessful.

Case Timeline

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"

The Invention Explained

• Problem Addressed: The patent’s background describes the challenge of dispersion in pressure-driven microfluidic systems, where a sample plug broadens and dilutes as it flows, leading to cross-contamination and a loss of control over reaction timing ʼ091 Patent, col. 1:53-col. 2:9 Alternative electroosmotic flow (EOF) systems are slow and highly sensitive to surface contamination ʼ091 Patent, col. 1:31-52
• The Patented Solution: The invention introduces a carrier fluid that is immiscible with the sample fluid ʼ091 Patent, abstract By introducing streams of sample fluids ("plug-fluids") into the flowing carrier fluid, the system creates discrete, isolated droplets or "plugs" ʼ091 Patent, col. 2:51-65 This compartmentalization prevents the sample from contacting the channel walls, thereby eliminating Taylor dispersion and allowing for precise reaction control within each plug ʼ091 Patent, abstract Mixing within these plugs is enhanced by creating chaotic advection using non-straight channel geometries ʼ091 Patent, col. 3:6-12
• Technical Importance: This method provided a solution to the fundamental problem of dispersion in pressure-driven microfluidics, enabling high-throughput, precisely controlled reactions in nanoliter-scale volumes Compl. ¶11

Key Claims at a Glance

• The complaint asserts independent claim 1, among others Compl. ¶31
• The essential elements of independent method claim 1 include:
  • introducing a carrier-fluid into a first microchannel of a device;
  • simultaneously introducing at least two streams of plug-fluids into a first inlet in fluid communication with the first microchannel;
  • forming at least one plug in the carrier-fluid, where each plug comprises both plug-fluids;
  • wherein a first plug-fluid comprises a first reagent and a second plug-fluid comprises a second reagent, allowing a reaction to occur within the plug;
  • wherein each plug-fluid is immiscible with the carrier-fluid, and each plug is substantially surrounded by the carrier-fluid.
• The complaint asserts numerous dependent claims but does not reserve the right to assert others not listed Compl. ¶31

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

The Invention Explained

• Problem Addressed: The complaint does not provide sufficient detail for analysis of the problem described in the patent's background. However, the patent's title and the context of the infringement allegations suggest the invention addresses the challenges of performing sensitive, self-amplifying reactions (Compl. ¶¶42; 52).
• The Patented Solution: The patent title indicates the invention is a method for conducting an "autocatalytic reaction" within the discrete plugs of a microfluidic system, as generally described in the '091 Patent Compl. ¶42 The complaint alleges that amplifying nucleic acid within droplets constitutes practice of the claimed method, suggesting the patented solution involves using the plug-based system to isolate and control enzymatic amplification reactions like PCR Compl. ¶52
• Technical Importance: This approach enables massively parallel, isolated amplification reactions, which is a key technique for digital PCR and single-cell genomic analysis where individual nucleic acid molecules are compartmentalized before amplification Compl. ¶12

Key Claims at a Glance

• The complaint asserts independent claim 1, among others Compl. ¶45
• The complaint does not provide the patent or its claims. The infringement allegations suggest the elements of claim 1 involve partitioning a nucleic acid sample into droplets and then amplifying the nucleic acid within those droplets, constituting a method for "conducting an autocatalytic reaction in plugs" (Compl. ¶¶48; 52).
• The complaint asserts dependent claims 2-8 and 11 Compl. ¶45

Multi-Patent Capsules

U.S. Patent No. 8,329,407 - "Method for Conducting Reactions Involving Biological Molecules in Plugs in a Microfluidic System"

• Technology Synopsis: The patent title suggests a method for using the plug-based microfluidic platform specifically for reactions involving biological molecules, such as nucleic acids Compl. ¶66 The invention allows for partitioning a sample containing biological molecules into droplets and then conducting a reaction, such as amplification, within those droplets Compl. ¶66
• Asserted Claims: Claims 1-5, 8-11, and 13 Compl. ¶59
• Accused Features: The complaint alleges that the use of the GemCode platform for partitioning a nucleic acid sample and amplifying it within droplets infringes the '407 Patent Compl. ¶66

U.S. Patent No. 8,822,148 - "Method of Performing PCR Reaction in Continuously Flowing Microfluidic Plugs"

• Technology Synopsis: The patent title indicates a method specifically for performing Polymerase Chain Reaction (PCR) in continuously flowing plugs within a microfluidic system. This method involves amplifying DNA or RNA by providing conditions suitable for PCR within the discrete droplets Compl. ¶76
• Asserted Claims: Claims 1-3 and 6-8 Compl. ¶73
• Accused Features: The complaint alleges that using the GemCode platform to partition a nucleic acid sample and perform amplification infringes the '148 Patent Compl. ¶80

U.S. Patent No. 8,889,083 - "Device and Method for Pressure-Driven Plug Transport and Reaction"

• Technology Synopsis: Sharing a title with the '091 patent, this patent appears to cover further aspects of the core microfluidic device and method. The complaint alleges infringement by both the use of the GemCode platform (a method) and the making, selling, and/or offering for sale of the platform (an apparatus) Compl. ¶87
• Asserted Claims: Claims 1-2, 10-13, 20-22, 26, and 31 Compl. ¶87
• Accused Features: The complaint alleges that customers' use of the GemCode platform to conduct reactions in plugs infringes method claims, and Defendant's sale of the platform infringes apparatus claims (Compl. ¶¶87; 89).

U.S. Patent No. 8,658,430 - "Manipulating Droplet Size"

• Technology Synopsis: The patent title suggests the invention relates to methods for controlling the size of droplets as they are formed in a microfluidic device. The complaint alleges infringement by using the GemCode platform to perform the claimed "method for droplet formation" (Compl. ¶¶101; 104).
• Asserted Claims: Claims 1, 5, and 12-16 Compl. ¶101
• Accused Features: The complaint alleges that the use of the GemCode platform to form droplets infringes the '430 patent Compl. ¶101

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 nucleic acid samples (such as DNA) or cells into hundreds of thousands to millions of microfluidic droplets, referred to as Gel-in-emulsions or "GEMs" (Compl. ¶¶12; 15; 21). The system uses a microfluidic chip with a 'double-cross' junction architecture Compl. ¶20 At this junction, a stream of gel beads loaded with barcoded oligonucleotides is mixed with a sample and enzyme mixture, and this combined stream is then intersected by an oil-surfactant solution, which "pinches off droplets" (Compl. ¶¶18; 21). A schematic provided in the complaint illustrates this process of solid-phase reagent delivery followed by fluid partitioning Compl. ¶16 Within each droplet, the gel bead dissolves, and a DNA amplification reaction occurs via thermal cycling, which attaches the unique barcode from the gel bead to the DNA fragments within that droplet (Compl. ¶¶7; 19). The complaint identifies Defendant as a "close competitor" to Plaintiff RainDance in this field Compl. ¶12 A figure from a 2016 Nature Biotechnology article included in the complaint shows a schematic of the accused process, from introducing barcoded primer gel beads to sequencing Compl. ¶20

IV. Analysis of Infringement Allegations

’091 Patent Infringement Allegations

’193 Patent Infringement Allegations

The complaint incorporates by reference an exemplary claim chart (Exhibit 18) that was not provided with the complaint document Compl. ¶45 Therefore, a claim chart summary cannot be created. The complaint’s narrative theory alleges that when customers use the GemCode platform for "partitioning a nucleic acid sample into droplets and then amplifying the nucleic acid in the droplets, the claimed method for conducting an autocatalytic reaction in plugs is performed" Compl. ¶52

Identified Points of Contention

• Scope Questions: A potential point of contention for the ’091 patent may be whether the accused device's architecture, which uses multiple distinct input wells that feed into a "double-cross" junction (Compl. ¶¶18, 20), meets the claim limitation of "introducing at least two streams of plug-fluids into a first inlet." The definition of "first inlet" could become a central issue of claim construction.
• Technical Questions: For the ’193 patent, a key question will be whether the DNA amplification performed in the accused system constitutes an "autocatalytic reaction" as that term is understood within the context of the patent. The complaint’s allegations suggest it does, but this will likely be a point of technical and legal dispute requiring claim construction (Compl. ¶¶48; 52). A schematic in the complaint describes the process in the accused device as including a "Cycle" step for "Molecular barcoding in GEMs," which is alleged to involve thermal cycling (Compl. ¶¶7; 19).

V. Key Claim Terms for Construction

’091 Patent

• The Term: "a first inlet"

  • Context and Importance: The infringement reading for claim 1 of the ’091 patent hinges on mapping the accused device's multi-well input structure to the claimed "first inlet." Defendant may argue its device, with separate wells for beads and reagents, lacks this claimed feature Compl. ¶18
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes embodiments where plug-fluids are "introduced either through a single inlet or from multiple inlets" '091 Patent, col. 3:15-17, which may support construing "a first inlet" as a general region encompassing multiple physical ports.
    • Evidence for a Narrower Interpretation: Figures in the patent, such as FIG. 4, depict multiple plug-fluid channels (401-405) converging at a single junction immediately before the main channel, which a party could argue defines the scope of "a first inlet" as a singular geometric feature '091 Patent, FIG. 4

• The Term: "plug"

  • Context and Importance: Practitioners may focus on this term because the accused system initially forms droplets containing a solid gel bead Compl. ¶18 The construction of "plug" will determine if such a structure, containing both liquid and a solid support that later dissolves, qualifies as a "plug" from the moment of formation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent defines plugs broadly as being formed when "a stream of at least one plug-fluid is introduced into the flow of a carrier-fluid" and can "vary in shape" '091 Patent, col. 9:20-22 '091 Patent, col. 9:34-35 This may support a broad reading that does not exclude plugs containing a dissolvable solid.
    • Evidence for a Narrower Interpretation: The patent consistently refers to the contents of plugs as "plug-fluids" '091 Patent, col. 2:57, which could support an argument that the plug's contents must be entirely fluid at the time of formation.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents. Inducement allegations are based on Defendant’s alleged knowledge and intent, supported by facts including the dissemination of promotional materials, brochures, user manuals, and technical materials that allegedly instruct and encourage customers to use the accused platforms in an infringing manner Compl. ¶¶33-37 Compl. ¶¶47-51 Contributory infringement is alleged on the basis that the GemCode platform and its components are a material part of the invention and are not staple articles of commerce suitable for substantial non-infringing use Compl. ¶¶38-39 Compl. ¶¶52-53
• Willful Infringement: The complaint alleges willful infringement for all asserted patents. The allegations are based on Defendant's alleged pre-suit knowledge, citing specific dates from discovery where Defendant's executives acknowledged awareness of the patents (e.g., since April 18, 2013 for the '091 patent) Compl. ¶32 The complaint further supports willfulness by alleging Defendant continued to infringe after the lawsuit was initiated and after its attempts to invalidate the '091 and '193 patents in inter partes review proceedings failed Compl. ¶40 Compl. ¶54

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

• A central issue will be one of structural and terminological scope: does the accused platform's microfluidic architecture, which utilizes separate input wells and a "double-cross" junction to combine gel beads, sample, and oil, fall within the scope of the patents' claims requiring, for example, introduction of fluids into "a first inlet" to form "plugs"? The construction of these terms will be critical.
• A second key question will be one of functional definition: does the enzymatic DNA amplification that occurs within the accused droplets meet the legal construction of an "autocatalytic reaction" as required by claim 1 of the '193 patent, or is there a definitional mismatch between the claim term and the accused process?
• A third area of focus will be willfulness and intent, given the complaint's detailed allegations of Defendant's pre-suit knowledge of the patents-in-suit. The evidentiary record concerning what Defendant knew, when it knew it, and what actions it took in light of that knowledge will be pivotal in determining whether any potential infringement was willful, which could expose the defendant to enhanced damages.