Bio Rad Laboratories Inc v. 10X Genomics Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bio-Rad Laboratories, Inc. (Delaware)
  • Defendant: 10X Genomics, Inc. (Delaware)
  • Plaintiff’s Counsel: Farnan LLP; Weil, Gotshal & Manges LLP
• Case Identification: 1:19-cv-01699, D. Del., 09/11/2019
• Venue Allegations: Venue is alleged to be proper as both Plaintiff and Defendant are incorporated in Delaware.
• Core Dispute: Plaintiff alleges that Defendant’s Next GEM platform for genetic analysis infringes a patent related to methods for performing and detecting enzymatic reactions within microfluidic droplets.
• Technical Context: The technology concerns high-throughput biological analysis using droplet microfluidics, a method for partitioning samples into millions of tiny, discrete volumes (droplets) to perform individual reactions, which is significant for single-cell genomics and diagnostics.
• Key Procedural History: The complaint notes that the parties have a history of litigation, referencing a November 2018 jury verdict finding that 10X Genomics willfully infringed different patents (licensed by Bio-Rad) and a subsequent permanent injunction. Plaintiff also alleges that Defendant has been aware of the patent-in-suit’s technology since at least 2014, when it cited the patent’s priority application during the prosecution of its own patents.

Case Timeline

Date	Event
2004-10-08	U.S. Patent No. 8,871,444 Priority Date
2014-04-04	Defendant allegedly cites priority application of patent-in-suit during its own patent prosecution
2014-10-28	U.S. Patent No. 8,871,444 Issues
2015-02-01	Prior litigation initiated by Plaintiff's predecessor against Defendant
2015-01-01	Defendant launches its GemCode droplet-based emulsion system (approximate date)
2016-01-01	Defendant launches its Chromium droplet-based emulsion system (approximate date)
2018-11-01	Jury finds Defendant willfully infringed in prior litigation
2019-08-01	Plaintiff obtains permanent injunction against Defendant in prior litigation
2019-09-11	Complaint Filed

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

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.

The Invention Explained

• Problem Addressed: The patent's background describes the limitations of existing techniques for in vitro molecular evolution, such as phage display or SELEX. These methods were often restricted to selecting for simple binding activities, could not easily evolve proteins for catalytic functions, and were limited in the size and diversity of molecular libraries that could be practically screened ('444 Patent, col. 1:10-col. 2:62).
• The Patented Solution: The invention provides a method to overcome these limitations by using microcapsules, or droplets, to create a physical link between a genetic element (the "genotype," e.g., a gene) and the protein it encodes (the "phenotype"). By compartmentalizing each gene and its corresponding protein in a discrete droplet, the protein's specific activity (e.g., an enzymatic reaction) can be assayed within that droplet. The entire droplet can then be sorted based on the outcome of that reaction, allowing for the selection of genes that encode for highly active or desirable proteins ('444 Patent, Abstract; col. 5:1-14). The method specifies that at least one step, such as forming or sorting the droplets, must be performed using microfluidic control ('444 Patent, col. 4:1-6).
• Technical Importance: This approach enables the high-throughput screening of massive libraries of molecules for complex functional activities, not just binding, thereby mimicking and accelerating evolutionary processes in a laboratory setting ('444 Patent, col. 2:50-62).

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 2, 4, and 8 (Compl. ¶29).
• Independent Claim 1 includes the following essential elements:
  • A method for detecting an enzymatic reaction product.
  • Providing a droplet generator to produce, under microfluidic control, a plurality of aqueous microcapsules.
  • The microcapsules are surrounded by an immiscible continuous phase comprising a fluorinated oil with a fluorinated polymer surfactant.
  • Each microcapsule comprises an enzyme, a genetic element, and reagents.
  • Pooling the microcapsules in common compartments where they contact but do not fuse.
  • Conducting the enzymatic reaction on the genetic element of at least one microcapsule.
  • Detecting the product of the enzymatic reaction.

III. The Accused Instrumentality

Product Identification

• The "Next GEM" platform, which consists of an instrument known as the Chromium Controller along with associated reagent kits (Compl. ¶22).

Functionality and Market Context

• The complaint alleges the Next GEM platform is a droplet-based emulsion system used to perform genetic analyses, such as single-cell gene expression and immune profiling (Compl. ¶22). The complaint further alleges that the platform is central to Defendant's business and that Defendant expected all of its Chromium instruments sold by the end of Q3 2019 to operate exclusively with the accused Next GEM products (Compl. ¶23, 32). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint references an exemplary claim chart in Exhibit 5, which is not provided with the filed document (Compl. ¶29). The narrative infringement theory alleges that when customers use the Next GEM platform—which consists of a "specialized microfluidic device along with specialized reagents for conducting reactions in microfluidic droplets"—they perform the method claimed in the ’444 Patent (Compl. ¶¶39-40). The complaint alleges that the use of Defendant’s instrument and reagent kits for their intended purpose of genetic analysis directly infringes the asserted method claims (Compl. ¶¶29, 34).

• Identified Points of Contention:
  • Scope Questions: A central question may be the interpretation of "pooling the microcapsules into one or more common compartments." The parties may dispute whether a continuous-flow delay line or collection area within the accused microfluidic chip meets this "common compartments" limitation, or if the claim requires a more distinct pooling or collection step. A second question relates to the scope of "conducting the enzymatic reaction on the genetic element." It is unclear whether this requires the reaction product to physically or chemically modify the genetic element itself—a potentially narrow construction—or if it merely requires the reaction to occur in the same droplet as the genetic element.
  • Technical Questions: The infringement analysis may turn on a factual comparison of the materials used in the accused system with the claim’s specific requirement for an immiscible phase comprising "a fluorinated oil that comprises a fluorinated polymer surfactant." The precise chemical composition of the reagents in Defendant's kits will be a key area of discovery.

V. Key Claim Terms for Construction

• The Term: "pooling the microcapsules into one or more common compartments such that a portion of the plurality of microcapsules contact each other but do not fuse"

  • Context and Importance: The meaning of "pooling" and "common compartments" is critical, as it describes a specific state or arrangement of the microcapsules after their formation. Practitioners may focus on this term because its definition will determine whether a standard microfluidic channel, where droplets flow in sequence, can be considered a "common compartment" where they are "pooled."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes creating a "large cross-sectional area" channel to provide "extremely long time delays," which could be argued to constitute a "common compartment" where droplets are effectively pooled ('444 Patent, col. 11:23-28).
    • Evidence for a Narrower Interpretation: Elsewhere, the specification describes a process where "the microcapsules are then broken so that all the contents of the individual microcapsules are pooled," suggesting that "pooling" might refer to the mixing of contents after breaking the droplets, a different concept from what is recited in claim 1 ('444 Patent, col. 6:13-16).

• The Term: "conducting the enzymatic reaction on the genetic element"

  • Context and Importance: This phrase is ambiguous and central to the scope of infringement. Its construction will determine the required relationship between the enzymatic reaction and the genetic element within the droplet.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself does not explicitly require modification. A broad reading could suggest the reaction merely needs to happen in the presence of the genetic element within the same confined microcapsule.
    • Evidence for a Narrower Interpretation: The detailed description repeatedly discusses embodiments where the gene product "modifies the genetic element which encoded it" to make it selectable ('444 Patent, col. 5:10-14). This suggests the phrase could be interpreted more narrowly to require that the reaction's output directly or indirectly acts upon the genetic element, a much higher bar for infringement.

VI. Other Allegations

• Indirect Infringement: The complaint alleges induced infringement, stating that Defendant controls the design and sale of the Next GEM platform with the specific intent that its customers will use it to perform the patented method. This is allegedly supported by Defendant's promotional materials, product manuals, and other instructional materials (Compl. ¶¶34-37). The complaint also alleges contributory infringement, asserting the Next GEM platform's components constitute a material part of the invention and are not staple articles suitable for substantial non-infringing use (Compl. ¶¶39-40).
• Willful Infringement: Willfulness is alleged based on Defendant’s purported knowledge of the ’444 Patent and its infringement. This knowledge is allegedly derived from several sources: (1) the November 2018 trial in a related case involving Bio-Rad; (2) Defendant's licensing of other patents from Harvard University's droplet patent portfolio; and (3) Defendant's citation of the priority application for the ’444 Patent in its own patent prosecution filings as early as April 2014 (Compl. ¶¶30-32).

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

The resolution of this dispute will likely depend on the court's determination of several key issues, framed here as open questions:

• A core issue will be one of definitional scope: How will the court construe "pooling the microcapsules into one or more common compartments"? Does this language read on the architecture of a continuous-flow microfluidic device, or does it require a distinct physical chamber or state that the accused products may not possess?
• A second critical issue will be one of functional scope: Does the claim limitation "conducting the enzymatic reaction on the genetic element" require that the reaction's product physically or chemically alters the genetic element itself, as described in certain patent embodiments, or does it merely require co-location of the reaction and the genetic element within the same droplet?
• A key evidentiary question will be one of factual correspondence: Do the specific oils and surfactants used in Defendant’s Next GEM reagent kits fall within the literal scope of the claim’s requirement for a "fluorinated oil that comprises a fluorinated polymer surfactant"?