DCT
1:19-cv-12533
Bio Rad Laboratories Inc v. 10X Genomics Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bio-Rad Laboratories, Inc. (Delaware) and President and Fellows of Harvard College (Massachusetts)
- Defendant: 10X Genomics, Inc. (Delaware)
- Plaintiff’s Counsel: Weil, Gotshal & Manges LLP
- Case Identification: 1:19-cv-12533, D. Mass., 12/18/2019
- Venue Allegations: Plaintiff alleges venue is proper because Defendant consented to jurisdiction in Massachusetts via a forum selection clause contained in a license agreement, which Defendant itself invoked in a prior litigation between the parties. Plaintiff further alleges pendent venue for one of the asserted patents due to the overlap in accused products and underlying technology.
- Core Dispute: Plaintiffs allege that Defendant’s Next GEM platform for genetic analysis infringes three U.S. patents related to the use of droplet-based microfluidics for partitioning and analyzing biological samples.
- Technical Context: The technology involves using microfluidic devices to create massive numbers of discrete droplets (microcapsules), each acting as a separate reaction vessel for high-throughput biochemical applications like single-cell analysis and next-generation sequencing.
- Key Procedural History: The complaint notes that the parties have a significant litigation history. In a prior case involving different patents, a jury found in November 2018 that 10X Genomics willfully infringed, leading to a permanent injunction against 10X's older products in August 2019. The complaint alleges that the currently accused Next GEM platform was launched by 10X following that jury verdict.
Case Timeline
| Date | Event |
|---|---|
| 2004-10-08 | Earliest Priority Date for ’444 and ’277 Patents |
| 2011-04-25 | Priority Date for ’115 Patent |
| 2014-10-28 | U.S. Patent No. 8,871,444 Issues |
| 2015-02-01 | Prior litigation initiated by Plaintiff's predecessor-in-interest |
| 2018-03-20 | U.S. Patent No. 9,919,277 Issues |
| 2018-11-01 | Jury verdict of willful infringement against Defendant in prior litigation |
| 2019-01-29 | U.S. Patent No. 10,190,115 Issues |
| 2019-08-01 | Permanent injunction granted against Defendant in prior litigation |
| 2019-09-12 | Defendant 10X Genomics launches its Initial Public Offering |
| 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 high-throughput screening technologies like phage display, which are primarily suited for selecting molecules based on binding affinity rather than more complex functions like catalytic or regulatory activity (’444 Patent, col. 1:10-2:10).
- The Patented Solution: The invention provides a method to physically link a gene (the "genotype") with the protein it produces and that protein's function (the "phenotype") by compartmentalizing them within microfluidic droplets. Each droplet acts as a self-contained micro-reactor where a gene can be expressed and the resulting protein's activity can be assayed. Droplets containing proteins with the desired activity can then be sorted, enabling the selection and evolution of genes that encode for specific functions (’444 Patent, Abstract; col. 3:4-11; Fig. 15A).
- Technical Importance: This method allows for the ultra-high-throughput screening and directed evolution of proteins for specific catalytic and regulatory functions, a capability that was difficult to achieve with prior art systems (Compl. ¶ 17).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2, 4, and 8 (Compl. ¶ 32).
- Claim 1 recites a method with the essential elements of:
- Providing a droplet generator to produce aqueous microcapsules in an immiscible continuous phase comprising a fluorinated oil and a fluorinated polymer surfactant.
- The microcapsules contain an enzyme, a genetic element, and reagents.
- Pooling the microcapsules into a common compartment where they contact but do not fuse.
- Conducting an enzymatic reaction on the genetic element within at least one microcapsule.
- Detecting the product of the enzymatic reaction.
U.S. Patent No. 9,919,277 - "In vitro Evolution in Microfluidic Systems," issued March 20, 2018
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the parent ’444 Patent: the need for a robust, high-throughput system to link a gene's function to its sequence for selection and evolution (’277 Patent, col. 1:10-2:65).
- The Patented Solution: The claimed solution is also centered on using microfluidic droplets to compartmentalize reactions. This patent’s claims add the specific requirement that the genetic element within the droplet be linked to a bead, providing a solid support for the genetic material during the process (’277 Patent, col. 72:50-57). This can facilitate handling and retention of the genetic element.
- Technical Importance: As with the ’444 Patent, this technology enables functional screening at a massive scale, with the bead linkage potentially offering process advantages (Compl. ¶ 17).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2-6, 8-9, 11, and 13-14 (Compl. ¶ 49).
- Claim 1 recites a method with the essential elements of:
- Providing a droplet generator to produce aqueous microcapsules in an immiscible continuous phase comprising a fluorinated oil and a fluorinated polymer surfactant.
- The microcapsules contain an enzyme, reagents, and a genetic element linked covalently or non-covalently to a bead.
- Pooling the microcapsules into a common compartment.
- Conducting the enzymatic reaction on the genetic element.
U.S. Patent No. 10,190,115 - "Methods and Compositions For Nucleic Acid Analysis," issued January 29, 2019
Technology Synopsis
The patent addresses the need for improved methods of multiplexing and analyzing nucleic acid samples using partitioned droplets (’115 Patent, col. 1:18-28). The invention describes methods and compositions where a first set of droplets containing barcoded adaptors is merged with a second set of droplets containing sample polynucleotides, thereby allowing the polynucleotides to be tagged with unique barcodes inside the newly formed merged droplet for downstream analysis (’115 Patent, Abstract; col. 1:30-48).
Asserted Claims
Claims 1, 4-15, and 18-26 (Compl. ¶ 64). Independent claims appear to be 1 (a composition) and 14 (a device).
Accused Features
The complaint alleges that Defendant's "Next GEM products" constitute or are used in a manner that infringes the claimed composition and device (Compl. ¶¶ 64, 69).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendant's "Next GEM" platform (Compl. ¶ 25). This platform includes the "Chromium Controller" instrument along with various associated reagent kits, such as the "Chromium Single Cell Gene Expression Solution" (Compl. ¶ 25).
Functionality and Market Context
The complaint alleges the Next GEM platform uses "droplet-based emulsions for next generation sequencing and single-cell analysis" (Compl. ¶ 13). It is designed to partition biological samples into individual microdroplets using microfluidic chips to perform genetic analyses (Compl. ¶¶ 15, 26). The complaint asserts that this platform is central to Defendant's business, forming the basis of a $362 million IPO and projected to constitute "substantially all" of its sales by the end of 2020 (Compl. ¶ 26).
IV. Analysis of Infringement Allegations
The complaint incorporates by reference external claim chart exhibits which were not filed with the complaint itself (Compl. ¶¶ 32, 49). The following charts summarize the infringement theory based on the complaint's narrative allegations regarding the function of the accused platform.
U.S. Patent No. 8,871,444 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for detecting a product of an enzymatic reaction... | The Next GEM platform is used for genetic analyses such as single-cell gene expression and NGS library preparation, processes that rely on enzymatic reactions like reverse transcription and PCR. | ¶¶13, 15, 25 | col. 72:8-9 |
| providing a droplet generator to produce, under microfluidic control, a plurality of aqueous microcapsules surrounded by an immiscible continuous phase that comprises a fluorinated oil that comprises a fluorinated polymer surfactant... | The Next GEM platform allegedly utilizes microfluidic chips to generate droplet-based emulsions for partitioning biological samples. | ¶¶13, 26 | col. 72:10-18 |
| each of the plurality of microcapsules comprising an enzyme, a genetic element, and reagents for the enzymatic reaction; | The platform is sold with reagent kits that allegedly provide the necessary components for conducting genetic analyses within the microcapsules. | ¶25 | col. 72:19-22 |
| conducting the enzymatic reaction on the genetic element... | The platform is allegedly used by customers to perform enzymatic reactions, such as reverse transcription or amplification, using the partitioned sample as a template. | ¶¶25, 42 | col. 72:28-30 |
| detecting the product of the enzymatic reaction. | The output of the platform is a library prepared for next-generation sequencing, which is a method of detecting the products of the enzymatic reactions. | ¶15 | col. 72:31-32 |
U.S. Patent No. 9,919,277 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for conducting an enzymatic reaction... | The Next GEM platform is used for genetic analyses such as single-cell gene expression and NGS library preparation, which involve enzymatic reactions. | ¶¶13, 15, 25 | col. 72:48-49 |
| providing a droplet generator to produce... a plurality of aqueous microcapsules surrounded by an immiscible continuous phase that comprises a fluorinated oil that comprises a fluorinated polymer surfactant... | The Next GEM platform allegedly utilizes microfluidic chips to generate droplet-based emulsions. | ¶¶13, 26 | col. 72:50-57 |
| each of the plurality of microcapsules comprising an enzyme, a genetic element linked covalently or non-covalently to a bead, and reagents for the enzymatic reaction; | The complaint does not provide sufficient detail for analysis of whether the accused Next GEM platform utilizes a bead to which a genetic element is linked. | ¶¶25, 58 | col. 72:54-57 |
| conducting the enzymatic reaction on the genetic element... | The platform is allegedly used by customers to perform enzymatic reactions using the partitioned sample as a template. | ¶¶25, 58 | col. 72:62-63 |
No probative visual evidence provided in complaint.
Identified Points of Contention
- Scope Questions: A potential area of dispute may be whether the asserted method claims, which derive from a specification heavily focused on "in vitro evolution," can be construed to cover the accused platform's use in commercial-scale single-cell analysis and NGS library preparation. This raises the question of whether the context of the specification limits the scope of otherwise broad claim terms like "genetic element" and "enzymatic reaction."
- Technical Questions: For the ’277 Patent, a central factual question will be whether the Next GEM platform's technology involves linking a "genetic element" to a "bead" as required by claim 1. The complaint does not contain specific allegations on this technical point.
V. Key Claim Terms for Construction
The Term: "genetic element" (’444 Claim 1; ’277 Claim 1)
Context and Importance
This term's definition is critical for determining the scope of infringement. A broad construction covering any nucleic acid (e.g., mRNA from a single cell) would favor the plaintiff's theory that the accused commercial platform infringes. A narrower construction, potentially limited by the specification's focus on libraries of gene variants for directed evolution, could support a non-infringement argument. Practitioners may focus on this term because its interpretation could determine whether the patents apply beyond the research context of "in vitro evolution."
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The claims themselves do not explicitly limit the term to a specific type of nucleic acid, only that it is present in the microcapsule (’444 Patent, col. 72:20).
- Evidence for a Narrower Interpretation: The patent title, "In vitro Evolution in Microfluidic Systems," and the abstract's description of evolving nucleic acids and proteins could be cited to argue that "genetic element" should be understood in the context of a library of variants undergoing selection, not a general biological sample (’444 Patent, Title; Abstract).
The Term: "conducting the enzymatic reaction on the genetic element" (’444 Claim 1)
Context and Importance
The construction of this phrase may determine whether standard biochemical processes like reverse transcription or PCR meet this limitation. The dispute may center on whether the reaction must physically or chemically alter the "genetic element" itself for sorting purposes, as described in the specification, or whether merely using the genetic element as a template is sufficient.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: In a general sense, an enzymatic reaction like PCR uses the genetic element as a template and thus could be described as being conducted "on" it.
- Evidence for a Narrower Interpretation: The specification describes modifying the genetic element to create a physical link between genotype and phenotype, stating "the desired activity of a gene product results in a modification of the genetic element which encoded it" (’444 Patent, col. 3:1-3). This could support an argument that the claim requires a reaction that modifies the genetic element for subsequent selection, not just amplification.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement. Inducement is alleged based on Defendant’s sale of the Next GEM platform with the specific intent that its customers will use it to perform the claimed methods, allegedly supported by instructional materials, product manuals, and marketing (Compl. ¶¶ 37-41, 53-57). Contributory infringement is alleged on the basis that the platform's components are a material part of the invention and are not staple articles of commerce suitable for substantial non-infringing use (Compl. ¶¶ 42-43, 58-59).
- Willful Infringement: The complaint alleges willful infringement based on extensive pre-suit knowledge of the patents and technology. Allegations include: (1) Defendant's knowledge of the asserted patents and portfolio from prior litigation where it was found to have willfully infringed other Bio-Rad patents (Compl. ¶¶ 33, 50); (2) Defendant citing the priority application for the ’444 Patent in its own patent prosecution filings years before the suit (Compl. ¶ 34); and (3) for the ’115 Patent, the named inventor is a co-founder of Defendant 10X and a former employee of Plaintiff Bio-Rad who allegedly worked on the patented invention (Compl. ¶ 65).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim scope: can method claims from patents titled and described in the context of "in vitro evolution" be interpreted broadly enough to cover the defendant's commercial platform, which performs related but distinct applications like single-cell gene expression analysis?
- A key evidentiary question for the ’277 patent will be one of technical implementation: what evidence will be presented to establish whether the accused Next GEM platform's process involves linking the sample nucleic acid to a "bead," a specific limitation required by the asserted claim?
- A significant focus of the litigation will likely be on willfulness: given the extensive litigation history between the parties and the alleged direct connection between a 10X co-founder and the ’115 patent, the central question for willfulness will be what the defendant knew about the patents-in-suit and when, and what, if any, good-faith basis it had for believing its Next GEM platform did not infringe.