DCT

3:20-cv-03207

Bio Rad Laboratories Inc v. 10X Genomics Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: Bio-Rad Laboratories, Inc. v. 10X Genomics, Inc., 3:20-cv-03207, D. Mass., 12/18/2019
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Massachusetts because Defendant 10X Genomics consented to jurisdiction and venue in a forum selection clause contained within a prior license agreement with Harvard University. Plaintiffs further allege 10X Genomics is judicially estopped from contesting venue due to its arguments in a prior litigation in Delaware. Pendent venue is asserted for one of the patents-in-suit based on a common nucleus of operative fact with the other asserted patents.
  • Core Dispute: Plaintiffs allege that Defendant’s Next GEM platform for genetic analysis infringes three patents related to methods and systems for partitioning biological samples into microfluidic droplets for high-throughput analysis.
  • Technical Context: The technology at issue involves using microfluidic devices to create vast numbers of picoliter-volume aqueous droplets within an oil emulsion, enabling the isolation and analysis of individual cells or molecules for applications such as single-cell sequencing.
  • Key Procedural History: The complaint notes that in a prior litigation, a jury found Defendant 10X Genomics willfully infringed patents related to its older "GemCode" and "Chromium" platforms, resulting in a permanent injunction. The complaint alleges that the currently accused "Next GEM" platform was launched following that verdict. The complaint also references a separate "Delaware Litigation" concerning a license agreement, which is the source of the forum selection clause relied upon for venue.

Case Timeline

Date Event
2004-10-08 Priority Date for ’444 and ’277 Patents
2011-04-25 Priority Date for ’115 Patent
2014-04-04 10X Genomics cites priority application for ’444 Patent during its own prosecution
2014-10-28 U.S. Patent No. 8,871,444 Issues
2015-02-01 Prior lawsuit filed by RainDance (later Bio-Rad) against 10X Genomics
2015-01-01 10X Genomics launches its "GemCode" platform
2015-12-04 10X Genomics cites application for ’115 Patent during its own prosecution
2018-03-20 U.S. Patent No. 9,919,277 Issues
2018-11-01 Jury verdict of willful infringement against 10X Genomics in prior litigation
2019-01-29 U.S. Patent No. 10,190,115 Issues
2019-08-01 Permanent injunction entered against 10X Genomics in prior litigation
2019-09-12 10X Genomics launches its Initial Public Offering, featuring the Next GEM platform
2019-12-18 Complaint Filed

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

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 section describes the limitations of existing in vitro molecular evolution techniques like phage display, which are restricted in library size and are not well-suited for selecting molecules based on catalytic or regulatory functions beyond simple binding affinity (’444 Patent, col. 1:12-2:52).
  • The Patented Solution: The invention provides a method using microfluidic systems to generate vast numbers of microcapsules, or droplets, which act as miniature test tubes (’444 Patent, col. 3:4-15). By encapsulating individual "genetic elements" (e.g., a single gene) along with the necessary reagents for expression, the gene’s product (e.g., a protein) is physically confined in the same droplet as the gene that coded for it. This physical linkage of genotype to phenotype allows for the high-throughput sorting of the droplets based on the functional activity of the expressed protein, enabling the selection of molecules with desired catalytic properties from massive libraries (’444 Patent, Abstract; col. 5:1-6).
  • Technical Importance: This approach provided a platform for screening molecular libraries orders of magnitude larger than previously possible and enabled selection based on functional activity, a significant advance for directed evolution and enzyme engineering (’444 Patent, col. 45:50-62).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 and dependent claims 2, 4, and 8 (Compl. ¶32).
  • Independent Claim 1 requires:
    • A method for detecting a product of an enzymatic reaction.
    • Providing a droplet generator to produce a plurality of aqueous microcapsules surrounded by an immiscible continuous phase comprising a fluorinated oil with a fluorinated polymer surfactant.
    • Each microcapsule comprising an enzyme, a genetic element, and reagents for the enzymatic reaction.
    • Pooling the microcapsules such that 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.
  • The complaint reserves the right to assert other claims (Compl. ¶32).

U.S. Patent No. 9,919,277 - In vitro evolution in microfluidic systems

Issued March 20, 2018

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’444 Patent, this patent addresses the same technical problem: the limitations of prior art in vitro evolution systems in both library size and the types of functional activities that can be selected for (’277 Patent, col. 1:12-2:52).
  • The Patented Solution: The invention claims methods for conducting enzymatic reactions within microfluidic droplets, where a genetic element is linked to a bead inside the droplet (’277 Patent, Claim 1). This bead-based linkage provides a physical anchor within the micro-compartment, ensuring the gene remains associated with its expressed product and any subsequent reactions, thereby facilitating the sorting of the gene based on the product's activity (’277 Patent, col. 21:58-22:4).
  • Technical Importance: The use of a solid support like a bead within the droplet provides a specific mechanism for ensuring the linkage between genotype and phenotype, adding a degree of physical stability and control to the high-throughput screening process.

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 and dependent claims 2-6, 8-9, 11, and 13-14 (Compl. ¶49).
  • Independent Claim 1 requires:
    • A method for conducting an enzymatic reaction.
    • Providing a droplet generator to produce a plurality of aqueous microcapsules surrounded by an immiscible continuous phase comprising a fluorinated oil with a fluorinated polymer surfactant.
    • Each microcapsule comprising an enzyme, a genetic element linked covalently or non-covalently to a bead, and reagents.
    • Pooling the microcapsules.
    • Conducting the enzymatic reaction on the genetic element.
  • The complaint reserves the right to assert other claims (Compl. ¶49).

U.S. Patent No. 10,190,115 - Methods and Compositions For Nucleic Acid Analysis

Issued January 29, 2019

  • Technology Synopsis: The patent describes methods for analyzing nucleic acids by partitioning samples and barcoded adaptors into separate sets of droplets, which may be of different sizes, and then merging the droplets (’115 Patent, Abstract). This process allows for the unique barcoding of nucleic acids from discrete partitions, such as single cells, which is a foundational step for applications like single-cell sequencing (’115 Patent, col. 1:36-54).
  • Asserted Claims: At least claims 1, 4-15, and 18-26 are asserted (Compl. ¶64).
  • Accused Features: The complaint alleges that 10X Genomics' Next GEM products, which are used for single-cell analysis, infringe by employing the claimed methods of partitioning and merging droplets containing samples and barcoded adaptors (Compl. ¶¶64, 69).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the 10X Genomics "Next GEM" platform (Compl. ¶25). This platform includes the "Chromium Controller" instrument and associated reagent kits, such as the "Chromium Single Cell Gene Expression Solution," "Chromium Single Cell Immune Profiling Solution," and "Chromium Single Cell ATAC Solution" (Compl. ¶25).

Functionality and Market Context

The Next GEM platform utilizes microfluidic chips to partition biological samples, such as single cells, into discrete aqueous microdroplets within an oil emulsion (Compl. ¶¶13, 15). These droplets serve as individual reaction chambers for various genetic analyses, including next-generation sequencing (NGS) and single-cell analysis (Compl. ¶¶15, 25). The complaint alleges that the Next GEM platform was the centerpiece of 10X Genomics' $362 million IPO and that the company projected that Next GEM-based products would constitute "substantially all" of its Chromium sales by the end of 2020 (Compl. ¶¶26, 35). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint incorporates by reference preliminary claim charts as exhibits but does not attach them to the filing (Compl. ¶¶32, 49, 64). Accordingly, the narrative infringement theories are summarized below.

’444 Patent Infringement Allegations

The complaint alleges that 10X Genomics infringes, both directly and indirectly, by making, using, and selling the Next GEM platform (Compl. ¶32). The core of the infringement theory is that customers use the Next GEM platform to practice the patented method. Specifically, the complaint alleges that the platform, which includes a microfluidic device and specialized reagents, is used to conduct enzymatic reactions within microfluidic droplets as claimed, thereby detecting a product of that reaction for genetic analysis (Compl. ¶¶37-38, 42-43).

’277 Patent Infringement Allegations

Similar to the '444 Patent, the complaint alleges that use of the Next GEM platform by 10X Genomics' customers constitutes infringement of the claimed method (Compl. ¶49). The narrative alleges that the platform is used to perform the claimed method for conducting an enzymatic reaction within microfluidic droplets (Compl. ¶¶53-54). The allegations for the ’277 Patent are substantially similar to those for the ’444 Patent, focusing on the use of droplet-based emulsions for genetic analysis (Compl. ¶¶58-59).

Identified Points of Contention

  • Scope Questions: For the ’444 Patent, a potential point of contention is the claim limitation "conducting the enzymatic reaction on the genetic element." The dispute may center on whether this requires the enzymatic reaction to directly modify the genetic element (e.g., a nucleic acid), or if it can be construed more broadly to cover a reaction whose product serves as a reporter for the genetic element within the same droplet. For the ’277 Patent, a central issue will be the interpretation of "a genetic element linked... to a bead." The infringement analysis will depend on whether the accused Next GEM platform uses beads to physically tether the genetic material within the droplets as required by the claim.
  • Technical Questions: A key evidentiary question for the ’277 Patent is what evidence shows that the Next GEM platform actually links genetic elements to beads inside its microfluidic droplets. The complaint does not provide specific technical facts or diagrams to support this claimed element of the infringement allegation.

V. Key Claim Terms for Construction

"conducting the enzymatic reaction on the genetic element" (’444 Patent, Claim 1)

  • Context and Importance: This term's construction is critical because it defines the necessary relationship between the enzymatic activity and the gene being analyzed. The outcome of the infringement analysis may depend on whether the accused product's process of generating a detectable signal is considered a reaction "on" the genetic element itself.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes the invention’s goal as establishing a "physical link" between a gene product and the "genetic element which encoded it" by co-encapsulation, which could support a functional interpretation where the reaction simply needs to occur in the same compartment to report on the element's properties (’444 Patent, col. 45:34-40).
    • Evidence for a Narrower Interpretation: The specification also describes embodiments where the "gene product... results in a modification of the genetic element which encoded it," suggesting a direct chemical alteration (’444 Patent, col. 5:2-6). This language may support an argument that the reaction must act upon the nucleic acid itself.

"a genetic element linked covalently or non-covalently to a bead" (’277 Patent, Claim 1)

  • Context and Importance: This limitation is a specific structural requirement of the claimed method. Infringement hinges on whether the accused Next GEM platform utilizes a bead as a solid support for the genetic element within the droplet. Practitioners may focus on this term because it presents a clear factual question for the infringement analysis.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term "linked" is not explicitly defined, which may allow for arguments that any functional association with a bead, even if transient or part of a larger complex, satisfies the limitation.
    • Evidence for a Narrower Interpretation: The specification describes embodiments where genes are attached to microbeads, which are then encapsulated. For example, it states "genetic elements can comprise genes attached to microbeads" (’277 Patent, col. 21:65-22:4). This may support a narrower construction requiring a direct and stable attachment of the genetic element to the bead itself.

VI. Other Allegations

Indirect Infringement

The complaint alleges induced infringement across all three patents. The basis for this allegation is that 10X Genomics controls the design and manufacture of the Next GEM platform and provides customers with promotional materials, product manuals, and technical instructions that allegedly encourage and facilitate use of the platform in an infringing manner (Compl. ¶¶37-40, 53-56, 69-72). The complaint also alleges contributory infringement, stating the Next GEM platform is a specialized apparatus with no substantial non-infringing uses (Compl. ¶¶42-43, 58-59, 74-75).

Willful Infringement

The complaint alleges willful infringement based on pre-suit knowledge of the patents and the infringing nature of its activities. For the ’444 and ’277 Patents, this is based on 10X Genomics' alleged familiarity with the Harvard patent portfolio from a prior litigation, the trial testimony of its executives, and its citation of the ’444 patent’s priority application during its own patent prosecution (Compl. ¶¶33-35, 50-51). For the ’115 Patent, willfulness is alleged based on the fact that the sole inventor is a co-founder of 10X Genomics and a former Bio-Rad employee, and that 10X Genomics cited the application for the ’115 patent in its own prosecution history (Compl. ¶¶65-66).

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

  • A core issue will be one of claim scope and technical evidence: For the ’444 Patent, the dispute will likely focus on whether generating a detectable signal within a droplet constitutes an enzymatic reaction "on the genetic element." For the ’277 Patent, a central evidentiary question will be whether the accused Next GEM platform uses a "bead" to link the genetic element as explicitly required by the claim, a technical detail not substantiated in the complaint.
  • A second key issue will be the impact of prior litigation and relationships: The case will test how 10X Genomics' history—including a prior willful infringement verdict on related technology and its employment of the ’115 patent’s inventor—influences the determination of knowledge and intent for the current willfulness allegations. This history may create a high bar for the defendant to argue lack of knowledge.