10X Genomics Inc v. Illumina Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: 10x Genomics, Inc. (Delaware) and Prognosys Biosciences, Inc. (Delaware)
  • Defendant: Illumina, Inc. (Delaware)
  • Plaintiff’s Counsel: Shaw Keller LLP; Tensegrity Law Group LLP
• Case Identification: 1:25-cv-01286, D. Del., 10/21/2025
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because the Defendant, Illumina, Inc., is a Delaware corporation and therefore resides in the district.
• Core Dispute: Plaintiff alleges that Defendant’s spatial transcriptomics technology platform infringes four patents related to methods and compositions for spatially encoded biological assays.
• Technical Context: The lawsuit concerns spatial transcriptomics, a genomics technology that maps gene activity within the spatial context of a tissue sample, which is significant for research in fields like oncology, neuroscience, and immunology.
• Key Procedural History: The complaint notes that patents from the asserted patent family have been the subject of prior litigation. Plaintiffs successfully asserted the ’607 Patent against NanoString Technologies and its successor. The Patent Trial and Appeal Board (PTAB) denied institution of an inter partes review challenging the validity of the ’138 Patent. The complaint also alleges that the parent application of the asserted patents was cited by the U.S. Patent and Trademark Office during the prosecution of an Illumina patent, which may be relevant to the question of pre-suit knowledge.

Case Timeline

Date	Event
2010-04-05	Priority Date for all Asserted Patents
2021-05-18	U.S. Patent No. 11,008,607 Issues
2023-01-10	U.S. Patent No. 11,549,138 Issues
2025-02-19	Illumina announces its "spatial technology program"
2025-02-25	U.S. Patent No. 12,234,505 Issues
2025-05-13	U.S. Patent No. 12,297,487 Issues
2025-05-21	PTAB denies institution of IPR on the ’138 Patent
2025-10-21	Complaint Filing Date

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

U.S. Patent No. 11,008,607 - "Spatially Encoded Biological Assays," issued May 18, 2021

The Invention Explained

• Problem Addressed: The patent describes a technical landscape where no practical method existed to simultaneously analyze the spatial expression patterns of a large number of genes or proteins at high resolution within a tissue sample (’607 Patent, col. 2:4-9). Existing techniques were either low-resolution, not scalable, or prohibitively expensive and laborious (’607 Patent, col. 1:58-2:3).
• The Patented Solution: The invention provides a method for creating high-resolution spatial maps of biological molecules (’607 Patent, col. 2:7-9). The method involves contacting a tissue sample with probes, where each probe has a capture agent to bind a target mRNA and an attached oligonucleotide with a unique sequence (’607 Patent, Claim 1). From this interaction, a new nucleic acid molecule is generated containing location-specific tags. By sequencing this new molecule, the original target mRNA can be identified and its precise location within the tissue sample can be determined (’607 Patent, Claim 1). This process provides "the resolution of in situ hybridization with the highly-parallel data analysis of sequencing" (’607 Patent, col. 2:31-34).
• Technical Importance: This approach provided a scalable method to generate digital, high-resolution spatial data for numerous biological targets simultaneously, addressing a significant unmet need in biological research (Compl. ¶39).

Key Claims at a Glance

• The complaint asserts independent claim 1 and reserves the right to assert other claims, including dependent claims (Compl. ¶¶ 30, 40, 69).
• Claim 1 (Method):
  • Contacting a tissue sample with a plurality of probes, where each probe comprises a capture agent that specifically binds a target mRNA and is coupled to an oligonucleotide comprising a sequence;
  • Generating a nucleic acid molecule comprising all or a portion of the oligonucleotide's sequence and one or more nucleic acid tags that can be used to determine the mRNA's location; and
  • Determining the sequence of the nucleic acid molecule to detect the target mRNA and determine its location.

U.S. Patent No. 11,549,138 - "Spatially Encoded Biological Assays," issued January 10, 2023

The Invention Explained

• Problem Addressed: As with the ’607 patent, the ’138 Patent addresses the need for reproducible, high-resolution spatial maps of biological molecules in tissues, which was not practically achievable with prior art methods (’138 Patent, col. 2:5-10).
• The Patented Solution: The invention is a physical composition designed for spatial analysis. It comprises an array, which includes a substrate and a plurality of capture probes immobilized on it in a "random pattern" (’138 Patent, Claim 1). Each probe contains three key parts: a domain to bind the target nucleic acid, a sequence that identifies a unique location on the substrate, and a primer binding site (’138 Patent, Claim 1). Claim 17 claims a similar composition that further includes a tissue section placed on the array (’138 Patent, Claim 17).
• Technical Importance: This composition provides a physical tool or apparatus that enables the spatial encoding and subsequent analysis of nucleic acids from a tissue sample in a highly multiplexed manner (Compl. ¶43).

Key Claims at a Glance

• The complaint asserts independent claims 1 and 17 and reserves the right to assert other claims, including dependent claims (Compl. ¶¶ 41, 49, 81).
• Claim 1 (Composition):
  • An array comprising a substrate and a plurality of capture probes, where each probe comprises: (i) a target-binding domain, (ii) a nucleic acid sequence identifying a unique location on the substrate, and (iii) a primer binding site.
  • The target-binding domain comprises a nucleic acid sequence complementary to at least a portion of the target.
  • The capture probes are immobilized on the substrate in a random pattern.
• Claim 17 (Composition):
  • An array as described above.
  • A tissue section disposed on the array.

U.S. Patent No. 12,234,505 - "Spatially Encoded Biological Assays," issued February 25, 2025

• Technology Synopsis: This patent claims a method for determining the spatial distribution of biological molecules in a tissue sample (’505 Patent, Claim 1). The method involves allowing target molecules to interact with nucleic acid probes and then coupling encoded oligonucleotides, which are arranged in a known spatial pattern, to those probes. The sequence of the encoded oligonucleotides is then determined and used to map the target molecules back to their original locations in the tissue (’505 Patent, col. 27:1-12).
• Asserted Claims: The complaint asserts independent claim 1 and reserves the right to assert other claims (Compl. ¶¶ 50, 57, 91).
• Accused Features: The complaint alleges that Illumina’s spatial technology workflow, which involves allowing target molecules to interact with probes and then determining their location via spatially arranged barcodes, infringes this method patent (Compl. ¶¶ 91-92).

U.S. Patent No. 12,297,487 - "Spatially Encoded Biological Assays," issued May 13, 2025

• Technology Synopsis: This patent claims a composition comprising a substrate, a plurality of capture probes, and a tissue section disposed on the substrate (’487 Patent, Claim 1). A second independent claim is directed to a composition for spatial analysis comprising a flow cell with a substrate having wells containing immobilized capture probes (’487 Patent, Claim 17). The core of the invention is the composition of the probes themselves, which include a target-binding domain, a location-identifying sequence, and a primer binding site (’487 Patent, col. 33:1-19).
• Asserted Claims: The complaint asserts independent claims 1 and 17 and reserves the right to assert other claims (Compl. ¶¶ 58, 65, 103).
• Accused Features: The complaint alleges that Illumina's spatial technology products, which include substrates with capture probes for analyzing tissue sections, constitute the claimed infringing compositions (Compl. ¶ 103).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendant’s "spatial technology program," also referred to as "Illumina spatial technology" (Compl. ¶¶ 20, 24). This includes the products, components, and methods that constitute Illumina's spatial transcriptomics workflow (Compl. ¶ 69).

Functionality and Market Context

The complaint alleges that Illumina’s technology provides for "whole-transcriptome profiling with cellular resolution and high sensitivity" (Compl. ¶ 20). Based on Illumina’s public disclosures, the workflow involves several steps: a tissue section is mounted on a "barcoded surface" or "decoded substrate"; mRNA from the tissue is captured by probes on the surface; the captured mRNA is converted to cDNA and tagged with a location-specific barcode; the spatially tagged cDNA is then released, prepared into a library, and sequenced. The resulting sequence data is analyzed to generate a "spatial transcriptomic map" or "unique transcript heatmap" of gene expression in the tissue (Compl. ¶¶ 9, 22, 24). The complaint provides a workflow diagram from an Illumina poster that outlines the steps as "Tissue permeabilization," "mRNA capture," "cDNA synthesis," "Elution off surface," "Library Prep," and "Sequencing" (Compl. ¶ 21, p. 9). Another visual from a presentation shows the process as capturing mRNA, converting it to cDNA tagged with a location barcode, releasing the tagged cDNA, and then sequencing to generate a spatial image (Compl. ¶ 22, p. 9). Illumina's website is cited as depicting a similar workflow that results in "Spatial analysis" (Compl. ¶ 24, p. 11).

IV. Analysis of Infringement Allegations

The complaint references exemplary claim charts in Attachments A and B but does not include these exhibits. Therefore, the narrative infringement theory is summarized below in prose.

U.S. Patent No. 11,008,607 Infringement Allegations

The complaint alleges that Illumina's spatial technology program, as practiced by Illumina and/or its customers, performs each step of method claim 1 (Compl. ¶¶ 69-70). The theory of infringement maps the accused workflow onto the claim elements. The step of "contacting a tissue sample with a plurality of probes" is allegedly met when a tissue section is placed on Illumina’s substrate containing capture probes (Compl. ¶¶ 22, 25). The step of "generating a nucleic acid molecule comprising... one or more nucleic acid tags that can be used to determine a location" is allegedly met when mRNA is captured and reverse transcribed into cDNA that is tagged with a "location barcode" from the substrate (Compl. ¶¶ 22, 25). Finally, the step of "determining... a sequence of the nucleic acid molecule... to detect the target mRNA and determine its location" is allegedly met by sequencing the barcoded cDNA library and analyzing the data to create a spatial map (Compl. ¶¶ 22, 25).

U.S. Patent No. 11,549,138 Infringement Allegations

The complaint alleges that Illumina infringes by making, using, selling, or importing its spatial technology products, which allegedly constitute the composition claimed in claims 1 and 17 (Compl. ¶ 81). The infringement theory posits that Illumina’s "barcoded surface" or "decoded substrate" is the claimed "array comprising a substrate and a plurality of capture probes" (Compl. ¶¶ 9, 22, 24). The complaint alleges these probes contain a target-binding domain (e.g., for polyA capture), a location-identifying sequence (the "location barcode"), and a primer binding site, as required by the claims (Compl. ¶¶ 25, 41). When a customer places a tissue section on this array, the composition allegedly meets all limitations of claim 17 (Compl. ¶ 41).

Identified Points of Contention

• Scope Questions: For the ’138 Patent, a central question will be whether Illumina's spatially organized array of barcodes meets the claim limitation requiring capture probes to be "immobilized on the substrate in a random pattern." The construction of "random pattern" will be critical, as Illumina’s product appears to rely on a spatially defined, rather than random, arrangement of probes to determine location.
• Technical Questions: For the ’607 Patent, a question may arise as to whether Illumina's use of a single oligonucleotide for both capture (via a poly(T) sequence) and as the backbone for tagging constitutes a "capture agent... coupled to an oligonucleotide" as recited in the claim, or if it is a single, unitary structure outside the claim's scope. The specifics of how Illumina's workflow "generat[es] a nucleic acid molecule" will also be a key factual question for the infringement analysis.

V. Key Claim Terms for Construction

The Term: "random pattern" (from ’138 Patent, Claim 1)

• Context and Importance: This term appears to be a crucial limitation for infringement of the ’138 Patent. Practitioners may focus on this term because Illumina’s accused technology is described as using a "decoded substrate" with barcodes at known locations, which suggests an ordered or defined pattern, not a random one (Compl. ¶¶ 9, 22). The outcome of the case could hinge on whether "random pattern" is construed broadly enough to read on Illumina's product, or if it is limited to specific embodiments like randomly deposited beads.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The complaint does not provide specific evidence from the patent for a broad interpretation. A party might argue that if the assignment of a specific barcode sequence to a specific physical location is random, the overall pattern could be considered "random" in an informational sense, even if the physical locations are ordered.
  • Evidence for a Narrower Interpretation: The specification of the ’138 patent (which is substantially similar to the ’607 patent) discusses embodiments using beads that are randomly deposited onto a substrate (’607 Patent, col. 19:24-33). This example of a physically random arrangement could be used to argue for a narrower construction that excludes spatially ordered arrays.

The Term: "capture agent ... coupled to an oligonucleotide" (from ’607 Patent, Claim 1)

• Context and Importance: The structure of the claimed "probe" is central to the infringement analysis. Practitioners may focus on this term because Illumina is alleged to use oligonucleotide probes that capture mRNA via poly(A) tails (Compl. ¶ 25). A dispute may arise over whether a single oligonucleotide containing both a poly(T) capture sequence and another functional sequence constitutes two separate components ("capture agent" and "oligonucleotide") that are "coupled," or a single, uncoupled component.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification discloses that a capture agent can itself be a nucleic acid (’607 Patent, col. 13:28-29). This may support an argument that one portion of an oligonucleotide (e.g., a poly(T) sequence) can serve as the "capture agent" while the remainder serves as the "oligonucleotide" to which it is "coupled" by the phosphodiester backbone.
  • Evidence for a Narrower Interpretation: The specification provides examples where the capture agent is a distinct molecule from the oligonucleotide, such as an antibody (’607 Patent, col. 10:55-61). This could support an argument that "coupled" requires two separate molecular species to be joined, rather than different domains of a single molecule.

VI. Other Allegations

Indirect Infringement

The complaint alleges induced infringement, stating that Illumina intentionally encourages infringement by providing customers and end users with its spatial products, along with instructions, marketing materials, and technical information on how to perform the allegedly infringing methods (Compl. ¶¶ 72, 83). The complaint also pleads contributory infringement, alleging the products are especially made for an infringing use and are not staple articles of commerce (Compl. ¶¶ 74, 84).

Willful Infringement

The complaint alleges willfulness based on both pre- and post-suit knowledge (Compl. ¶¶ 76, 86). Pre-suit knowledge is alleged based on several grounds: (1) Illumina's communications with patent owner Prognosys regarding a potential license starting in 2015; (2) public knowledge of Plaintiffs' successful litigation on the ’607 patent against NanoString; (3) the patent family being cited against Illumina during its own patent prosecution; and (4) a formal notice letter sent to Illumina on October 20, 2025 (Compl. ¶¶ 71, 82).

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

• A core issue will be one of definitional scope: can the term "random pattern," as used in the ’138 Patent, be construed to cover the spatially defined and ordered array of barcodes allegedly used in Illumina’s "decoded substrate"? The resolution of this claim construction issue may be dispositive for a significant portion of the case.
• A second key issue will be one of technical and factual infringement: for the asserted method claims, the central question will be whether the specific biochemical steps in Illumina's workflow for capturing, tagging, and releasing nucleic acids perform the functions required by the claim limitations, such as the "generating" of a new nucleic acid molecule from a "capture agent coupled to an oligonucleotide."
• A third area of focus will be the impact of prior legal proceedings: the complaint's emphasis on Plaintiffs' prior successful litigation involving the asserted patent family, including a victory against NanoString and the denial of an IPR petition filed by Curio Bioscience, raises the question of how this history will influence the court's view on issues of patent validity, claim construction, and potentially willfulness.