DCT

1:22-cv-01375

Bruker Spatial Biology Inc v. 10X Genomics Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-01375, D. Del., 01/27/2023
  • Venue Allegations: Venue is asserted in the District of Delaware on the basis that Defendant is a Delaware corporation and therefore resides in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s Visium spatial profiling product line infringes patents related to methods for spatially detecting and quantifying multiple target analytes, such as RNA and proteins, within a biological tissue sample.
  • Technical Context: The lawsuit concerns technology in the field of spatial biology, which enables researchers to analyze the spatial organization of molecular activity within tissues, a critical capability for understanding complex biological systems in fields like oncology and immunology.
  • Key Procedural History: The complaint alleges that Defendant had pre-suit knowledge of both asserted patents due to related litigation between the parties (Case No. 1:22-cv-00261-MFK). Specifically, it alleges Defendant was notified of an intent to assert the ’689 Patent in July 2022 and had knowledge of the application leading to the ’142 Patent as of October 2022, which may be relevant to the allegations of willful infringement.

Case Timeline

Date Event
2018-02-12 Earliest Priority Date for ’142 and ’689 Patents
2019-11-26 Launch of Defendant's Visium Spatial Gene Expression Solution
2022-07-05 U.S. Patent No. 11,377,689 Issued
2022-07-11 Defendant allegedly notified of intent to assert ’689 Patent in prior litigation
2022-07-19 Defendant allegedly received proposed counterclaim and chart for ’689 Patent
2022-10-18 U.S. Patent No. 11,473,142 Issued
2022-10-20 Defendant allegedly served with complaint and chart for ’142 Patent
2023-01-27 First Amended Complaint Filed

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

U.S. Patent No. 11,473,142, "Chemical Compositions and Uses Thereof," Issued October 18, 2022

The Invention Explained

  • Problem Addressed: The patent describes prior art methods for detecting biological molecules in tissue, such as immunohistochemistry and in situ hybridization, as being severely limited in the number of targets (e.g., proteins or nucleic acids) that can be analyzed simultaneously, typically less than ten (Compl. ¶15; ’142 Patent, col. 16:30-36). This low "plex" level prevents comprehensive analysis of complex biological processes within a single sample.
  • The Patented Solution: The invention claims methods for simultaneous, multiplexed spatial detection of numerous analytes. The core concept involves using probes that bind to specific targets in a tissue sample. Each probe is attached to a unique identifier oligonucleotide via a cleavable linker. A force, such as UV light, is applied to a user-defined region of interest (ROI), which cleaves the linkers and releases the identifier oligonucleotides only from that specific location. The released identifiers are then collected and analyzed (e.g., via sequencing) to determine the identity and quantity of the target analytes present in the selected ROI, all while preserving the original spatial context of the tissue ('142 Patent, Abstract; col. 1:43-61).
  • Technical Importance: This technology allows for highly multiplexed (e.g., over 1000 targets) spatial profiling, which provides a detailed molecular map of a tissue sample by combining the spatial information of imaging with the quantitative power of high-throughput sequencing (Compl. ¶15; ’142 Patent, col. 16:37-43).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶24).
  • The essential elements of independent claim 1 are:
    • A method for spatially detecting oligonucleotides from at least a first and a second location of a tissue sample.
    • Collecting oligonucleotides from the first location under conditions that release them.
    • Collecting oligonucleotides from the second location under conditions that release them.
    • Synthesizing a first plurality of DNA products from the oligonucleotides from the first location, where the DNA products identify that first location.
    • Synthesizing a second plurality of DNA products from the oligonucleotides from the second location, where the DNA products identify that second location.
    • Sequencing both pluralities of DNA products to spatially detect the oligonucleotides from both locations.
  • The complaint also asserts dependent claims 2-13 (Compl. ¶24).

U.S. Patent No. 11,377,689, "Chemical Compositions and Uses Thereof," Issued July 5, 2022

The Invention Explained

  • Problem Addressed: The patent addresses the same fundamental problem as the ’142 Patent: the inability of conventional methods to perform high-plex spatial analysis of analytes within a tissue sample, thereby limiting researchers' understanding of biological heterogeneity (Compl. ¶15; ’689 Patent, col. 16:30-36).
  • The Patented Solution: The ’689 Patent claims methods for spatially detecting analytes specifically within a formalin-fixed paraffin-embedded (FFPE) tissue sample, a common type of preserved tissue. The method involves contacting the FFPE sample with nucleic acid probes that bind to targets, collecting the probes from different locations, and performing extension and ligation reactions to generate products for sequencing. The resulting sequence data reveals both the identity of the target analyte and the specific location within the FFPE sample from which it was collected (’689 Patent, Abstract; col. 148:16-19).
  • Technical Importance: The claimed methods are significant for their applicability to FFPE samples, which are a vast and critical resource for clinical pathology and retrospective research studies, enabling high-plex spatial analysis on widely available archived tissues (’689 Patent, Claim 16).

Key Claims at a Glance

  • The complaint asserts independent claims 16, 21, 24, 27, and 30 (Compl. ¶32).
  • The essential elements of lead independent claim 16 are:
    • A method for spatially detecting a target analyte in at least two locations of an FFPE tissue sample.
    • Contacting the sample with pluralities of nucleic acid probes that bind to the target analyte.
    • Collecting ligated probes from a first location under conditions that release them.
    • Collecting ligated probes from a second location under conditions that release them.
    • Performing a first extension reaction on probes from the first location to incorporate a sequence identifying that first location.
    • Performing a second extension reaction on probes from the second location to incorporate a sequence identifying that second location.
    • Identifying the resulting extension products by sequencing to spatially detect the analyte.

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendant's "Visium Spatial system ('Visium')" and its related products, which include the Visium CytAssist instrument, Visium Spatial Gene Expression slides and reagents, and analysis software such as Space Ranger and Loupe Browser (Compl. ¶16-17).
  • Functionality and Market Context: The complaint alleges the Visium system is a commercial product line launched in November 2019 that provides spatial profiling of RNA and/or protein in tissue samples (Compl. ¶16, ¶18). It is marketed as a system to "map the whole transcriptome within the tissue context" and to "discover and reveal the spatial organization of cell types, states, and biomarkers" (Compl. ¶17-18). The system allegedly allows users to profile RNA expression for over 18,000 genes in human and mouse FFPE samples and is designed for use with standard next-generation sequencing (NGS) applications (Compl. ¶18).

IV. Analysis of Infringement Allegations

The complaint states that preliminary infringement claim charts are attached as exhibits (Ex. 3 and Ex. 4) but does not include them in the filing (Compl. ¶25, ¶33). Therefore, a tabular analysis is not possible.

The complaint's narrative theory alleges that Defendant directly infringes by using the Visium system for its own research and development, and indirectly infringes by selling the Visium system to customers and providing support through Certified Service Providers (CSPs) (Compl. ¶19-22). The infringement allegations center on the use of the Visium system to perform the steps of the asserted method claims. For the ’142 Patent, this involves the alleged collection of oligonucleotides from distinct spatial locations for sequencing (Compl. ¶24). For the ’689 Patent, the allegations focus on the use of the Visium system with FFPE samples to perform the claimed steps of probe collection, extension reactions to add location identifiers, and subsequent sequencing (Compl. ¶32).

No probative visual evidence provided in complaint.

  • Identified Points of Contention:
    • Scope Questions: A central question for the ’142 Patent will be whether the accused Visium process involves "releasing" oligonucleotides from a specific location in a manner that falls within the scope of the claims. For the ’689 Patent, a key question will be whether the accused process performs an "extension reaction that incorporates" a location-identifying sequence as specifically required by the claims.
    • Technical Questions: The complaint relies on marketing statements to describe the functionality of the accused products (Compl. ¶18). A point of contention may arise if the actual technical operation of the Visium system differs from the methods described in the patents. The court will need to examine evidence on how the Visium slides, reagents, and software work together and whether that process maps onto each element of the asserted claims.

V. Key Claim Terms for Construction

  • Term ('142 Patent): "collecting a plurality of oligonucleotides ... under conditions that release the plurality of oligonucleotides" (Claim 1)

    • Context and Importance: This term is central to the claimed method. Practitioners may focus on this term because the mechanism of "release" defines how spatial information is preserved. The infringement analysis will depend on whether the accused Visium process, which makes location-specific oligonucleotides available for analysis, constitutes a "release" as contemplated by the patent.
    • Intrinsic Evidence for a Broader Interpretation: The claim language itself is general and does not specify a particular release mechanism. A party could argue that any method that frees oligonucleotides from one location for collection, while leaving others in place, satisfies this limitation.
    • Intrinsic Evidence for a Narrower Interpretation: The specification repeatedly describes the release mechanism in the context of "providing a force" to cleave a linker, with a "photo-cleavable linker" and UV light being the primary example ('142 Patent, Abstract; col. 17:3-7; Fig. 1). A party could argue that the term "release" should be construed more narrowly in light of these specific embodiments.

  • Term ('689 Patent): "formalin-fixed paraffin-embedded (FFPE) tissue sample" (Claim 16)

    • Context and Importance: This term strictly defines the type of sample to which independent claim 16 applies. Its construction is important because it cabins the entire infringement analysis for this claim to a specific, albeit common, context in pathology.
    • Intrinsic Evidence for Interpretation: This is a standard term of art. The patent does not appear to offer a special definition, simply stating that the claimed method is for an "FFPE" sample ('689 Patent, col. 148:17-19). The dispute is less likely to be about the term's meaning and more about the factual question of whether Defendant's accused activities involve the use of FFPE samples, which the complaint alleges based on Defendant's marketing materials (Compl. ¶18).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement, stating that Defendant intentionally encourages infringement through its marketing, user manuals, and support for its Visium products (Compl. ¶26, ¶34). It also alleges contributory infringement, asserting that Defendant supplies material components of the invention (e.g., Visium slides and reagents) that are not staple articles of commerce and are specifically designed for practicing the patented methods (Compl. ¶27, ¶35).
  • Willful Infringement: Willfulness is alleged for both patents. For the ’142 Patent, the claim is based on Defendant’s alleged knowledge of the underlying patent application from prior litigation since at least October 12, 2022, and its alleged decision to continue infringing after the patent issued and after being served with a complaint on October 20, 2022 (Compl. ¶28). For the ’689 Patent, willfulness is based on alleged notice as of July 11, 2022, and receipt of a claim chart on July 19, 2022, in connection with the separate litigation (Compl. ¶36).

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

  • A core issue will be one of claim construction and technical scope: Do the specific biochemical steps performed by the accused Visium system—particularly how it encodes spatial information onto nucleic acid tags for sequencing—fall within the scope of the patent claims, which recite steps like "releasing" oligonucleotides ('142 Patent) and performing an "extension reaction that incorporates" a location identifier ('689 Patent)?
  • A second key question will be one of infringement liability: Given that the asserted claims are for multi-step methods, the case may turn on whether 10x Genomics is a direct infringer performing all steps itself, or whether its liability depends on proving induced or contributory infringement based on the actions of its customers.
  • Finally, a central evidentiary question will concern willfulness: The complaint alleges specific dates of notice related to prior litigation. The court will have to weigh the evidence surrounding this alleged pre-suit knowledge to determine whether any infringement, if found, was sufficiently egregious to justify enhanced damages.