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 under the laws of Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s genetic analysis platforms, which partition DNA samples into microfluidic droplets for barcoding and amplification, infringe six patents related to microfluidic droplet technology.
  • Technical Context: The lawsuit concerns microfluidics, a technology that enables high-throughput biological analysis by manipulating nanoliter-scale fluid volumes, which is significant for genetic sequencing and disease research.
  • Key Procedural History: The complaint alleges that Defendant had pre-suit knowledge of the asserted patents, citing them in its own patent prosecution filings. It also notes that Defendant made "failed efforts to invalidate" several of the patents-in-suit through inter partes review (IPR) proceedings, a detail that may be relevant to allegations of willful infringement. The University of Chicago is the owner of five of the patents-in-suit and has exclusively licensed them to RainDance in the relevant field.

Case Timeline

Date Event
2002-05-09 Priority Date for ’091, ’193, ’407, ’148, and ’083 Patents
2006-10-31 U.S. Patent No. 7,129,091 Issues
2011-07-20 Priority Date for ’430 Patent
2012-11-06 U.S. Patent No. 8,304,193 Issues
2012-12-11 U.S. Patent No. 8,329,407 Issues
2014-02-25 U.S. Patent No. 8,658,430 Issues
2014-09-02 U.S. Patent No. 8,822,148 Issues
2014-11-18 U.S. Patent No. 8,889,083 Issues
2015-01-14 Accused 10X Genomics platform presented at conference
2015-02-27 Accused GemCode platform presented at AGBT meeting
2015-06-30 10X Genomics announces commercial shipments of GemCode platform
2016-02-11 10X Genomics releases upgraded 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" (’091 Patent)

The Invention Explained

  • Problem Addressed: The patent’s background describes technical challenges in early microfluidic systems, including high dispersion and dilution of samples in pressure-driven flows and slow, diffusion-based mixing in laminar flows, both of which reduce the speed and control of chemical reactions (’091 Patent, col. 1:53-2:42).
  • The Patented Solution: The invention introduces a method of forming discrete sample droplets, or "plugs," within a continuous, immiscible carrier fluid (like oil) inside a microchannel (’091 Patent, Abstract). This compartmentalization prevents sample dispersion, and by passing these plugs through non-straight, winding channels, chaotic advection is induced within the droplets, leading to rapid mixing of reagents (’091 Patent, col. 3:6-12). This approach allows for precise control over reactions in small volumes.
  • Technical Importance: This technique of creating droplet-based microreactors enabled high-throughput screening and analysis by allowing thousands of independent reactions to be performed rapidly with minimal reagent consumption (Compl. ¶ 11).

Key Claims at a Glance

  • The complaint asserts infringement of multiple claims, including independent claim 1 (Compl. ¶ 31).
  • Essential elements of independent 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 so that at least one plug forms in the carrier-fluid;
    • wherein each plug-fluid is immiscible with the carrier-fluid;
    • wherein each plug comprises both the first and second plug-fluids so that the reaction of the reagents substantially occurs in the plug; and
    • wherein each plug is substantially surrounded by carrier.
  • The complaint also asserts dependent claims (Compl. ¶ 31).

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

The Invention Explained

  • Problem Addressed: The patent background identifies the challenge of controlling unstable chemical reactions, particularly autocatalytic reactions (where a product of the reaction also acts as a catalyst), which can be prone to unpredictable, runaway behavior in bulk solutions (’193 Patent, col. 12:41-44).
  • The Patented Solution: The invention proposes conducting such unstable reactions within discrete plugs in an immiscible carrier fluid. By isolating the reaction in nanoliter-scale droplets, any spontaneous or explosive decomposition is localized within a single plug, preventing a catastrophic reaction from propagating throughout the entire system and enabling better control and observation (’193 Patent, col. 12:50-58). The invention thereby provides a method to safely handle and analyze otherwise difficult-to-control chemical processes.
  • Technical Importance: This method provides a way to harness powerful but unstable autocatalytic reactions, such as the Polymerase Chain Reaction (PCR), for high-throughput biological applications where amplification is essential (Compl. ¶ 12).

Key Claims at a Glance

  • The complaint asserts infringement of multiple claims, including independent claim 1 (Compl. ¶ 45).
  • Essential elements of independent claim 1 include:
    • providing a microfluidic system comprising at least two channels having at least one junction;
    • flowing an aqueous fluid comprising at least one biological molecule and reagents for conducting an autocatalytic reaction through a first of the at least two channels;
    • flowing an oil through a second of the at least two channels;
    • forming at least one plug of the aqueous fluid; and
    • providing conditions suitable for the reaction in the at least one plug.
  • The complaint also asserts dependent claims (Compl. ¶ 45).

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

  • Technology Synopsis: This patent is directed to methods for performing reactions with biological molecules (e.g., DNA, RNA, proteins) inside microfluidic plugs. The invention focuses on providing conditions within the plugs suitable for these biological reactions to occur.
  • Asserted Claims: Claims 1-5, 8-11, and 13 are asserted (Compl. ¶ 59).
  • Accused Features: The complaint alleges that the use of the GemCode platform to partition and amplify nucleic acids infringes the ’407 Patent (Compl. ¶ 59).

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

  • Technology Synopsis: This patent specifically claims methods for performing the Polymerase Chain Reaction (PCR), a key DNA amplification technique, within continuously flowing microfluidic droplets. The claimed method involves providing the necessary conditions for PCR to occur within these plugs.
  • Asserted Claims: Claims 1-3 and 6-8 are asserted (Compl. ¶ 73).
  • Accused Features: The complaint alleges that the GemCode platform's use of thermal cycling to amplify DNA within droplets constitutes performance of the claimed PCR method (Compl. ¶¶ 19, 73).

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

  • Technology Synopsis: This patent, part of the same family as the ’091 patent, covers both the microfluidic device and the method for transporting and reacting materials within pressure-driven plugs. It claims both the apparatus for forming plugs and the method of using it.
  • Asserted Claims: Claims 1-2, 10-13, 20-22, 26, and 31 are asserted (Compl. ¶ 87).
  • Accused Features: The complaint alleges that Defendant makes, sells, and uses the GemCode platform, which is an apparatus that infringes the device claims, and that its customers' use infringes the method claims (Compl. ¶ 87).

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

  • Technology Synopsis: This patent is directed to methods for controlling the size of droplets formed in a microfluidic device. It describes techniques for manipulating droplet volume during formation, which is critical for ensuring uniformity in high-throughput applications.
  • Asserted Claims: Claims 1, 5, and 12-16 are asserted (Compl. ¶ 101).
  • Accused Features: The complaint alleges that the GemCode platform's operation necessarily involves manipulating droplet size in a manner that infringes the ’430 Patent (Compl. ¶ 101).

III. The Accused Instrumentality

Product Identification

  • The accused products are the "GemCode platform" and its upgraded version, the "Chromium Controller," along with their associated reagent kits (Compl. ¶¶ 15, 21, 23). The complaint defines the "GemCode platform" as the combination of either instrument with any of the reagent kits (Compl. ¶ 23).

Functionality and Market Context

  • The accused platform is a commercial genetic analysis tool that partitions nucleic acid samples into hundreds of thousands of microfluidic droplets, or "partitions" (Compl. ¶¶ 12, 13). According to the complaint, the system operates via a microfluidic chip with multiple input channels for introducing barcoded gel beads, a sample mixed with biochemical reagents, and an immiscible oil-surfactant solution (Compl. ¶¶ 18, 20). At a "double-cross" junction, the oil flow "pinches off" aqueous droplets, each encapsulating a portion of the sample and a gel bead containing a unique barcode (Compl. ¶¶ 18, 20). This process is depicted in a schematic from a 10X presentation. (Compl. at 4). After formation, these droplets are collected and subjected to thermal cycling, which releases the barcoded primers from the gel beads and initiates a DNA amplification reaction within each droplet (Compl. ¶¶ 19, 20). The resulting barcoded DNA molecules form a "sequencing library" for subsequent genetic analysis (Compl. ¶ 13).

IV. Analysis of Infringement Allegations

’091 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a method of conducting a reaction within at least one plug comprising the steps of: The accused GemCode platform is used by customers to conduct DNA amplification reactions within microfluidic droplets (Compl. ¶¶ 12, 19). ¶31 col. 2:51-54
introducing a carrier-fluid into a first microchannel of a device; The user introduces an oil-surfactant solution, which acts as the carrier-fluid, into an input well that feeds a microfluidic channel on the system's chip (Compl. ¶ 18). ¶18 col. 2:55-58
simultaneously introducing at least two streams of plug-fluids into a first inlet in fluid communication with the first microchannel The user introduces two separate aqueous streams: one containing barcoded gel beads, and another containing DNA mixed with biochemical reagents. These streams flow from separate input wells, mix, and then enter the main microchannel at an inlet junction (Compl. ¶ 18). ¶18 col. 4:14-17
so that at least one plug forms in the carrier-fluid; The oil flow intersects the combined aqueous stream and "pinches off droplets" (plugs) within the microchannel, as shown in a schematic from a 10X Genomics presentation (Compl. at 4). ¶18 col. 2:58-63
wherein each plug comprises both the first and second plug-fluids so that the reaction of the reagents substantially occurs in the plug The gel beads and DNA/reagents mix before being encapsulated, and a DNA amplification reaction subsequently occurs "inside of the droplets" during thermal cycling (Compl. ¶¶ 18, 19). ¶19 col. 3:20-31
and wherein each plug is substantially surrounded by carrier. Each aqueous droplet is fully encapsulated within the immiscible oil carrier fluid as it flows through the microchannel (Compl. ¶¶ 12, 18). ¶12 col. 2:58-60

’193 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for conducting an autocatalytic reaction in a plug in a microfluidic system, comprising: Customers use the accused platform to perform DNA amplification, an autocatalytic reaction, within microfluidic droplets (plugs) (Compl. ¶¶ 19, 45). ¶45 col. 12:41-44
providing a microfluidic system comprising at least two channels having at least one junction; The accused platform includes a microfluidic chip with multiple channels that intersect at a "double-cross" junction to form droplets (Compl. ¶¶ 16, 20). ¶20 col. 13:59-64
flowing an aqueous fluid comprising at least one biological molecule and reagents ... through a first of the at least two channels; An aqueous fluid containing DNA (a biological molecule) and biochemical reagents is flowed through channels on the chip (Compl. ¶ 18). ¶18 col. 14:1-5
flowing an oil through a second of the at least two channels; An oil-surfactant solution is flowed through a separate channel to the junction where droplets are formed (Compl. ¶ 18). ¶18 col. 17:59-62
forming at least one plug of the aqueous fluid The oil flow intersects the aqueous flow to "pinch off droplets" (plugs) (Compl. ¶ 18). This partitioning process is illustrated in a 10X brochure schematic (Compl. at 9). ¶18 col. 17:62-65
and providing conditions suitable for the reaction in the at least one plug such that the at least one substrate molecule is amplified. The collected droplets are placed on a thermal cycler to provide the temperature conditions suitable for amplifying the DNA (the substrate molecule) via PCR (Compl. ¶ 19). ¶19 col. 12:41-47

Identified Points of Contention

  • Scope Questions: A potential point of contention for the ’091 patent may be the construction of "introducing...two streams of plug-fluids into a first inlet." The complaint describes the accused system as having two aqueous streams that first combine and then enter the main channel to be partitioned by the oil flow (Compl. ¶ 18). The dispute may turn on whether introducing a pre-mixed fluid constitutes introducing "at least two streams" into the inlet where plugs are formed, or if the "inlet" is construed to be upstream where the two streams are still separate.
  • Technical Questions: For the ’193 patent, the core question is factual and definitional: does the DNA amplification performed by the accused platform meet the patent's definition of an "autocatalytic reaction"? While PCR is often described as such, the specific claim language and definitions in the patent specification will be central to this determination.

V. Key Claim Terms for Construction

The Term: "plug" (’091 Patent, Claim 1)

  • Context and Importance: This term defines the fundamental structure—the discrete droplet—at the heart of the invention. The infringement analysis depends on whether the "droplets" or "partitions" generated by the accused device (Compl. ¶¶ 12, 13) fall within the scope of a "plug" as claimed.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes plugs in various forms, including spherical or non-spherical, and notes that their shape may be independent of the channel shape, suggesting a broad definition not tied to a specific geometry (’193 Patent, col. 9:35-40).
    • Evidence for a Narrower Interpretation: The patent states that when plugs are formed, "their cross-section should be substantially similar to the cross-section of the channels in which they are formed," implying that a plug must generally fill the channel's cross-section (’193 Patent, col. 9:28-31). This could support a narrower definition that excludes fluid formations that do not substantially contact all channel walls.

The Term: "autocatalytic reaction" (’193 Patent, Claim 1)

  • Context and Importance: This term is the central limitation of the asserted method claim. Infringement hinges on whether the DNA amplification process performed in the accused system (Compl. ¶ 19) is properly characterized as "autocatalytic" in the context of the patent. Practitioners may focus on this term because its technical definition will control the outcome of the infringement analysis for this patent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification discusses a wide range of reactions, including PCR, and explicitly describes its use for handling "unstable mixtures" in systems that show "stochastic behavior," which is characteristic of autocatalytic processes like amplification from a single molecule (’193 Patent, col. 44:45-51, col. 46:1-5).
    • Evidence for a Narrower Interpretation: The specification provides a specific example of an inorganic autocatalytic reaction (chlorite-thiosulfate) in great detail (’193 Patent, col. 43:52-44:24). A defendant might argue that the term should be construed more narrowly in light of these specific, non-biological examples, or that the term implies a specific kinetic profile described therein.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges both induced and contributory infringement for all asserted patents. Inducement allegations are based on Defendant’s dissemination of promotional materials, product brochures, website content, user manuals, and open-source software, all of which allegedly instruct and encourage customers to use the GemCode platform in an infringing manner (Compl. ¶¶ 33-37, 47-51). Contributory infringement is alleged on the basis that Defendant sells the GemCode Instrument, Chromium Controller, and specialized reagent kits, which are alleged to be a material part of the patented invention, not staple articles of commerce, and to have no substantial non-infringing use (Compl. ¶¶ 38-39, 52-53).

Willful Infringement

  • Willfulness is alleged for all patents based on pre-suit knowledge. The complaint asserts that Defendant's top executives have acknowledged knowledge of the patents since at least April 18, 2013, and that Defendant cited several of the patents-in-suit in Information Disclosure Statements (IDSs) during the prosecution of its own patent applications, beginning in April 2014 (Compl. ¶¶ 32, 46, 60). The complaint further alleges that Defendant's continued infringement after the lawsuit was filed, and after its "failed efforts to invalidate" the patents in IPR proceedings, constitutes egregious misconduct supporting willfulness (Compl. ¶¶ 40, 54, 68).

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

  • A core issue will be one of claim construction: can the phrase "introducing...two streams of plug-fluids into a first inlet," as recited in the ’091 patent, be construed to read on the accused device's configuration, where two aqueous streams first merge and are then introduced into the main channel containing the immiscible carrier fluid? The case may turn on whether the "inlet" is defined as the point of plug formation or a structure further upstream.
  • A key evidentiary question will be one of procedural history and intent: what weight will be given to the complaint's allegations of pre-suit knowledge, Defendant's citation of the patents-in-suit during its own prosecution, and its unsuccessful IPR challenges? These facts raise the question of whether any infringement found would be deemed willful, which could expose the Defendant to enhanced damages.
  • A central technical question will be one of functional characterization: does the DNA amplification performed by the accused systems constitute an "autocatalytic reaction" as that term is used and defined within the context of the ’193 patent family? The answer will likely depend on expert testimony regarding the specific chemical kinetics of PCR and how they align with the patent's disclosure.