DCT

1:25-cv-01287

10X Genomics Inc v. Illumina Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-01287, D. Del., 10/21/2025
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware as Defendant Illumina, Inc. is a Delaware corporation and therefore resides in the district.
  • Core Dispute: Plaintiffs allege that Defendant’s Single Cell 3' RNA Prep Kits and associated workflows infringe five patents related to foundational single-cell genomic analysis technologies, including methods for creating barcoded beads via split-pool synthesis and for processing samples in droplet-based systems.
  • Technical Context: The lawsuit concerns the field of single-cell transcriptomics, which enables the analysis of gene expression on a cell-by-cell basis, providing high-resolution insights critical for research in areas such as oncology, immunology, and neuroscience.
  • Key Procedural History: The complaint alleges that Defendant was aware of the asserted patent families prior to the lawsuit, citing Defendant's interactions with a licensee of the "Nolan Patents," Defendant's citation of the Nolan patent family during its own patent prosecution, and an ancestor publication of the "10x Patents" appearing on the face of a patent co-owned by Defendant. Plaintiffs also provided Defendant with written notice of infringement for all five asserted patents on October 20, 2025, one day prior to filing the complaint.

Case Timeline

Date Event
2011-01-31 Priority Date for '214 Patent and '902 Patent
2019-02-12 Priority Date for '993 Patent, '239 Patent, and '102 Patent
2023-03-01 Fluent BioSciences began marketing accused single-cell technology (at least as of this date)
2023-07-04 '214 Patent Issued
2024-03-19 '902 Patent Issued
2024-07-09 Illumina acquired Fluent BioSciences
2025-04-15 '993 Patent Issued
2025-05-20 '239 Patent Issued
2025-09-16 '102 Patent Issued
2025-10-20 10x Genomics, Inc. sent notice letter to Illumina regarding infringement of all five Asserted Patents
2025-10-21 Complaint Filed

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

U.S. Patent No. 11,692,214 - "Barcoded beads and method for making the same by split-pool synthesis"

  • Patent Identification: U.S. Patent No. 11,692,214, "Barcoded beads and method for making the same by split-pool synthesis," issued July 4, 2023 (Compl. ¶21).

The Invention Explained

  • Problem Addressed: The patent addresses the insufficiency of prior methods for analyzing biological samples, which either required significant sample amounts or failed to provide cell-specific information, particularly for multiplexed protein measurements (Compl. ¶25; ’214 Patent, col. 1:47-52).
  • The Patented Solution: The invention provides a population of beads, each carrying a nucleic acid tag. This tag uniquely combines a "cell origination barcode" with a "degenerate sequence" (Compl. ¶23). This combination allows a user to simultaneously determine the identity of a biological target (e.g., a protein or gene) and the specific cell from which it originated (Compl. ¶25; ’214 Patent, col. 1:40-45). The patent also claims the "split-pool barcoding process" used to manufacture these beads, an iterative method of splitting beads into groups, adding barcode fragments, and pooling them back together to create a vast number of unique combinations (’214 Patent, abstract; ’214 Patent, fig. 4).
  • Technical Importance: This method provides a "method for simultaneously determining (i) the identity of the bound target and (ii) the unique cell from which that target originated," enabling highly multiplexed, high-throughput single-cell analysis (Compl. ¶25).

Key Claims at a Glance

  • The complaint asserts independent claims 1 (a composition of matter) and 11 (a method of manufacturing) (Compl. ¶23).
  • Claim 1 (Composition): A population of beads comprising:
    • A first bead with a first nucleic acid tag (comprising a first cell origination barcode and a degenerate sequence).
    • A second bead with a second nucleic acid tag (comprising a second cell origination barcode and a degenerate sequence).
    • Wherein the first and second cell origination barcodes are different.
  • Claim 11 (Method): A method for making a population of barcoded beads, comprising:
    • Adding nucleic acid tags that comprise a cell origination barcode and a degenerate sequence onto beads by a split-pool barcoding process.
  • The complaint reserves the right to assert dependent claims (Compl. ¶27).

U.S. Patent No. 11,932,902 - "Barcoded beads and method for making the same by split-pool synthesis"

  • Patent Identification: U.S. Patent No. 11,932,902, "Barcoded beads and method for making the same by split-pool synthesis," issued March 19, 2024 (Compl. ¶22).

The Invention Explained

  • Problem Addressed: The '902 Patent addresses the same problem as the '214 Patent: prior methods required large biological samples and could not provide cell-specific information for multiplexed analysis (’902 Patent, col. 1:51-56; Compl. ¶30).
  • The Patented Solution: The invention describes an iterative "split-pool synthesis" method for creating uniquely barcoded beads. The process involves repeatedly splitting a pool of beads into separate reaction volumes, appending distinct pre-made oligonucleotide sequences in each volume, and then pooling the beads back together (’902 Patent, abstract; Compl. ¶28). This builds a unique "cell origination barcode" on each bead, composed of a specific sequence of the appended oligonucleotides, enabling high-throughput single-cell analysis (’902 Patent, col. 1:44-49; Compl. ¶30).
  • Technical Importance: This iterative synthesis process allows for the creation of a massive number of unique barcodes, making it possible to individually track molecules from a large population of single cells (Compl. ¶30).

Key Claims at a Glance

  • The complaint asserts independent claims 1 (method), 17 (method), and 23 (composition) (Compl. ¶28).
  • Claim 1 (Method): A method for adding cell origination barcodes onto beads, comprising:
    • (a) splitting a pool of beads into a plurality of reaction volumes;
    • (b) appending different pre-made oligonucleotides onto the beads in the different volumes;
    • (c) pooling the beads; and
    • (d) repeating steps (a)-(c) one or more times, where subsequently appended oligonucleotides are added to previously appended ones to form the barcodes.
  • Claim 17 (Method): A method of adding barcodes to beads via a split-pool process comprising multiple rounds of (i) splitting, (ii) adding pre-made oligonucleotides, and (iii) pooling the beads (Compl. ¶28).
  • Claim 23 (Composition): A population of beads comprising:
    • A first bead with a barcode comprising a first plurality of ordered oligonucleotides.
    • A second bead with a barcode comprising a second plurality of ordered oligonucleotides.
    • Wherein the barcode sequences are different.
  • The complaint reserves the right to assert dependent claims (Compl. ¶32).

U.S. Patent No. 12,275,993 - "Analysis of nucleic acid sequences"

  • Patent Identification: U.S. Patent No. 12,275,993, "Analysis of nucleic acid sequences," issued April 15, 2025 (Compl. ¶33).
  • Technology Synopsis: The patent addresses the challenge of modifying reagent concentrations within already-formed droplets (’993 Patent, col. 1:41-43). The claimed solution is a method involving two separate emulsions: a first containing a lysis reagent and a second containing droplets with a cell and nucleic acid barcode molecules. The lysis reagent is transferred from the first emulsion to the second via micelles to lyse the cell (’993 Patent, abstract; Compl. ¶¶36-37).
  • Asserted Claims: Independent claims 1 and 25 (Compl. ¶36).
  • Accused Features: The accused workflow is alleged to use a first emulsion with a lysis reagent and a second emulsion with cells and barcoded beads, and to transfer the lysis reagent between them via micelles (Compl. ¶16; Attachment C, pp. 5, 24).

U.S. Patent No. 12,305,239 - "Analysis of nucleic acid sequences"

  • Patent Identification: U.S. Patent No. 12,305,239, "Analysis of nucleic acid sequences," issued May 20, 2025 (Compl. ¶34).
  • Technology Synopsis: Like the '993 patent, this patent addresses reagent transfer between droplets (’239 Patent, col. 1:41-43). The claimed method involves generating a first set of droplets containing a lysis agent, partitioning cells and barcoded particles into a second set of droplets, generating a "micellized lysis agent" from the first set, and delivering it to the second set to lyse the cells and enable mRNA capture (’239 Patent, abstract; Compl. ¶41).
  • Asserted Claims: Independent claims 1 and 29 (Compl. ¶41).
  • Accused Features: The accused workflow is alleged to generate and deliver a micellized lysis agent between droplet populations to lyse cells, release mRNA, and generate barcoded nucleic acid molecules (Compl. ¶16; Attachment D, pp. 21, 24).

U.S. Patent No. 12,416,102 - "Systems and methods for transfer of reagents between droplets"

  • Patent Identification: U.S. Patent No. 12,416,102, "Systems and methods for transfer of reagents between droplets," issued September 16, 2025 (Compl. ¶35).
  • Technology Synopsis: This patent also addresses the challenge of altering reagents in existing droplets (’102 Patent, col. 1:41-43). The claimed method involves generating droplets by agitating immiscible fluids, where a first droplet contains a barcoded bead and an analyte carrier (e.g., a cell). A reagent from a second droplet is transferred to the first via a "mediator" (e.g., a surfactant aggregate) to release nucleic acids for barcoding (’102 Patent, abstract; Compl. ¶46).
  • Asserted Claims: Independent claim 1 (Compl. ¶46).
  • Accused Features: The accused workflow is alleged to use agitation to generate droplets and a mediator to transfer a reagent between droplets to release nucleic acids from an analyte carrier for barcoding (Compl. ¶16; Attachment E, p. 9).

III. The Accused Instrumentality

Product Identification

  • The "Accused Instrumentalities" are identified as the "Illumina Single Cell 3' RNA Kits" and all associated products, components, reagents, and services, which were previously marketed by Fluent BioSciences as "Fluent PIPseq V 3' Single Cell RNA Kits" (Compl. ¶19).

Functionality and Market Context

  • The complaint alleges the accused kits use a "microfluidics-free" workflow called "PIPseq" chemistry to perform single-cell mRNA capture and barcoding (Compl. ¶16). This process involves creating emulsions of cells and barcoded hydrogel beads by vortexing, a process the complaint refers to as creating "particle-templated instant partitions (PIPs)" (Compl. ¶16).
  • A key part of the accused workflow is the use of a separate emulsion containing lysis reagents. This lysis reagent is allegedly transferred to the cell-containing droplets via "micellar transport" to lyse the cells and release mRNA for capture on the barcoded beads (Compl. ¶16). The complaint provides a diagram from an Illumina data sheet illustrating this multi-step workflow. (Compl. p. 8, Figure 2).
  • The complaint alleges the barcoded beads themselves are synthesized using a "split-pooling method" described in scientific publications by Clark and Delley (Compl. ¶17). It further alleges that Illumina's product documentation for its DRAGEN data analysis pipeline indicates the use of a "tiered barcode system" with four separate barcode segments (Compl. ¶18). The kits are marketed as providing a "high-resolution view of complex tissues" through an "easy and scalable workflow" (Compl. ¶16).

IV. Analysis of Infringement Allegations

'214 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A population of beads, comprising: The Accused Instrumentalities contain a population of barcoded hydrogel beads used for single-cell mRNA capture and barcoding. ¶53; Attachment A, p. 2 col. 1:23-26
(a) a first bead associated with a first nucleic acid tag that comprises: (i) a first cell origination barcode; and (ii) a degenerate sequence; and The barcoded beads contain a nucleic acid tag with a "cellular barcode" (the claimed cell origination barcode) and a "3N base binning index" and/or an "ACG spacer" (the claimed degenerate sequence). ¶17; Attachment A, p. 6 col. 2:1-12
(b) a second bead associated with a second nucleic acid tag that comprises: (i) a second cell origination barcode, and (ii) a degenerate sequence; wherein the first and second cell origination barcodes are different. The population of beads contains beads with different cellular barcodes, created by a split-pool synthesis method that generates a diverse library of barcodes. ¶17; Attachment A, p. 14 col. 2:1-12
  • Identified Points of Contention:
    • Scope Question: A central question will be whether the components of the oligonucleotide tags on the accused beads meet the definitions of "cell origination barcode" and "degenerate sequence" as construed from the patent. Practitioners may focus on whether the "3-base binning index" or "ACG spacer" alleged in the complaint performs the function of or has the structure of a "degenerate sequence" as required by the claim.
    • Technical Question: The infringement analysis may turn on the evidence presented regarding the specific structure and function of the different sequence elements on the accused barcoded oligonucleotides and how they correspond to the elements recited in the claim.

'902 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for adding cell origination barcodes onto beads, comprising: The barcoded beads in the Accused Instrumentalities are allegedly synthesized using a method of adding cell origination barcodes. ¶17; Attachment B, p. 2 col. 1:23-26
(a) splitting a pool of beads into a plurality of reaction volumes; The synthesis method for the accused beads allegedly uses a "split-pool approach" which involves "repeatedly partitioning the beads into random fractions." ¶17; Attachment B, p. 5 col. 2:1-17
(b) appending pre-made oligonucleotides onto the beads in the plurality of reaction volumes, wherein at least some of the plurality of reaction volumes each receive a pre-made oligonucleotide that contains a sequence that is different from the other pre-made oligonucleotides added to the plurality of reaction volumes; The split-pool synthesis allegedly involves modifying the beads in the partitioned fractions with a "specific barcode fragment," where different fragments are used in different fractions. ¶17; Attachment B, p. 8 col. 2:1-17
(c) pooling the beads; and After modification, the beads are allegedly pooled back together. ¶17; Attachment B, p. 16 col. 2:1-17
(d) repeating steps (a)-(c) one or more times to produce a pool of beads that comprise the cell origination barcodes, wherein in step (d) the oligonucleotides that are appended in the one or more repeats of step (b) are added to previously appended oligonucleotides to form the cell origination barcodes. The synthesis process allegedly repeats these steps for multiple rounds to build the final barcodes, with new barcode fragments being added to previously appended fragments. ¶17; Attachment B, p. 18 col. 2:1-17
  • Identified Points of Contention:
    • Scope Question: The dispute may center on the definition of "appending pre-made oligonucleotides." The complaint alleges the accused synthesis method uses enzymatic reactions to concatenate pre-synthesized oligos (Attachment B, p. 2). The court may need to determine if this specific chemical process falls within the scope of the claimed "appending" step.
    • Technical Question: A key factual question will be what specific chemical and physical steps are used in the manufacture of the accused beads and whether those steps map onto the elements of the claimed method, particularly the iterative nature of splitting, appending, and pooling.

V. Key Claim Terms for Construction

The Term: "split-pool barcoding process" / "split-pool process" ('214 and '902 Patents)

  • Context and Importance: This term describes the core manufacturing method for creating the barcoded beads. As infringement of method claims in both patents and composition claims that depend on this process is alleged, its construction will be central to determining whether the accused synthesis method infringes.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patents describe the process generally as one that "works by repeatedly partitioning the beads into random fractions, modifying the beads with a specific barcode fragment and pooling the beads," which "results in a barcode set which grows exponentially" (’902 Patent, abstract; ’902 Patent, col. 2:1-17). This language may support an interpretation that covers any iterative partitioning and tagging process, regardless of the specific chemistry.
    • Evidence for a Narrower Interpretation: The detailed description and figures illustrate a specific embodiment involving enzymatic ligation to "concatenate pre-synthesized oligos" (’902 Patent, col. 2:13-17; ’902 Patent, fig. 4). A defendant may argue that the claims should be limited to this specific type of chemical "appending" and does not cover other methods of building barcodes.

The Term: "degenerate sequence" ('214 Patent)

  • Context and Importance: This is a required element of the claimed bead composition in Claim 1 of the ’214 Patent. Infringement hinges on whether a corresponding feature exists on the accused beads and meets the construed definition of this term.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term is not explicitly defined, leaving it open to its plain and ordinary meaning. The specification describes its use in a nucleic acid tag alongside a cell origination barcode, which could suggest it encompasses any non-barcode sequence, such as a spacer or a sequence for technical variability (’214 Patent, claim 1).
    • Evidence for a Narrower Interpretation: The term "degenerate" in genetics often refers to randomness or redundancy (e.g., a degenerate primer). The patent discusses its use in a method for "simultaneously determining (i) the identity of the bound target and (ii) the unique cell" (’214 Patent, col. 1:40-42). A defendant may argue that this implies a functional requirement, such as enabling molecular counting or error correction, which may not be met by a simple fixed spacer or binning index as alleged in the complaint.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all five patents. Inducement is based on allegations that Illumina provides extensive instructional materials, including User Guides, Training Packets, and protocols, that intentionally encourage and instruct customers to use the Accused Instrumentalities in a manner that directly infringes the asserted claims (Compl. ¶¶55; Compl. ¶65; Compl. ¶73; Compl. ¶81; Compl. ¶89). Contributory infringement is based on allegations that the accused kits are especially made and adapted for infringing use and are not staple articles of commerce suitable for substantial non-infringing use (Compl. ¶¶56; Compl. ¶66; Compl. ¶74; Compl. ¶82; Compl. ¶90).
  • Willful Infringement: The complaint alleges willful and deliberate infringement for all five patents. The basis for willfulness includes alleged pre-suit knowledge through multiple avenues: (1) a notice letter sent by 10x on October 20, 2025; (2) Illumina's alleged awareness of the Nolan patent family ('214 and '902 patents) through its interactions with licensee Scale Biosciences and its own citation of the family during patent prosecution; and (3) Illumina's alleged awareness of the 10x patent family ('993, '239, '102 patents) because an ancestor publication appears on a patent co-owned by Illumina (Compl. ¶¶54; Compl. ¶58; Compl. ¶64; Compl. ¶68; Compl. ¶72; Compl. ¶76; Compl. ¶80; Compl. ¶84; Compl. ¶88; Compl. ¶92).

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

  • A primary issue will be one of claim scope and manufacturing equivalence: does the specific "split-pool" synthesis method allegedly used by Illumina to create its barcoded beads, which reportedly involves enzymatic ligation (Compl. ¶17; Attachment B, p. 2), fall within the scope of the "split-pool barcoding process" and "appending pre-made oligonucleotides" steps as claimed in the '214 and '902 patents?
  • A second core issue will be one of functional and structural equivalence for the patents covering the workflow: does the accused "PIPseq" workflow—which involves creating two separate emulsions (one with cells and beads, one with a lysis agent) and allegedly transferring the agent via "micellar transport" (Compl. ¶16)—operate in a manner that meets the specific, multi-step limitations for reagent transfer between droplets as claimed in the '993, '239, and '102 patents?
  • A significant evidentiary question for damages will be the extent of pre-suit knowledge and willfulness: what evidence will emerge to support the allegations that Illumina was aware of the asserted patent families through its own patent prosecution activities and competitive monitoring, and if so, whether its conduct rises to the level of willful infringement?