DCT
1:24-cv-00300
Agilent Tech Inc v. Axion Biosystems Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Agilent Technologies, Inc. (Delaware)
- Defendant: Axion BioSystems, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:24-cv-00300, D. Del., 03/06/2024
- Venue Allegations: Venue is asserted based on Defendant’s incorporation in the State of Delaware.
- Core Dispute: Plaintiff alleges that Defendant’s impedance-based cell analysis systems infringe a patent related to the label-free, real-time monitoring of excitable cells.
- Technical Context: The technology concerns the field of bioelectronics, where microelectrodes are used to measure the electrical impedance of cells in culture, providing a way to monitor cellular health, growth, and activity for applications such as drug discovery and safety screening.
- Key Procedural History: The complaint notes that on February 23, 2023, Plaintiff Agilent filed a separate lawsuit against Defendant Axion in the same court (the "'198 Case") for infringement of three other patents related to impedance-based analysis. Plaintiff alleges that the patent-in-suit here and the patents in the '198 Case share overlapping technology and inventorship, and that this history supports Defendant’s knowledge of the asserted patent. Post-filing, the assignee filed a disclaimer for several claims of the asserted patent, which will narrow the scope of the patent for this litigation.
Case Timeline
| Date | Event |
|---|---|
| 2008-05-05 | '508 Patent Priority Date |
| 2019-01-01 | Alleged Launch of Accused Products (stated as "at least as early as 2019") |
| 2023-02-23 | Prior Litigation ('198 Case) Filed |
| 2024-02-20 | '508 Patent Issue Date |
| 2024-03-06 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
- Patent Identification: U.S. Patent No. 11,906,508, "Label-Free Monitoring of Excitation-Contraction Coupling and Excitable Cells Using Impedance Based Systems with Millisecond Time Resolution," issued February 20, 2024 (the “’508 Patent”).
The Invention Explained
- Problem Addressed: The patent’s background section identifies significant drawbacks in prior art methods for assessing the cardiotoxicity of drugs (’508 Patent, col. 1:47-52). Traditional methods are described as either too labor-intensive and costly (e.g., isolating primary heart cells) or too narrowly focused on specific molecular targets (e.g., cell lines expressing a single ion channel), potentially missing other toxicity mechanisms (’508 Patent, col. 2:1-6). Furthermore, existing systems are characterized as having very limited throughput, often capable of monitoring only a single cell at a time (’508 Patent, col. 2:48-54).
- The Patented Solution: The invention is a system for high-throughput, real-time, label-free monitoring of "excitable cells" like cardiomyocytes using impedance measurements with "millisecond time resolution" (’508 Patent, col. 2:55-64). This high-speed measurement capability allows the system to resolve the rapid, rhythmic beating of heart cells (a short-term effect), while also being capable of monitoring long-term cell health, growth, and morphology over hours or days on the same multi-well platform (’508 Patent, col. 4:9-19). The system achieves this by integrating a multi-well plate, where each well contains an electrode array, with an impedance analyzer featuring multiple parallel analog-to-digital conversion channels and analytical software (’508 Patent, Abstract).
- Technical Importance: This approach allows for more comprehensive and efficient drug safety screening by enabling the simultaneous evaluation of both acute (e.g., arrhythmia) and chronic (e.g., cytotoxicity) effects of a compound on a physiologically relevant cell model (’508 Patent, col. 2:31-54).
Key Claims at a Glance
- The complaint asserts independent claim 16 (Compl. ¶29).
- The essential elements of Claim 16 are:
- A system for continuously monitoring cells in real time, label free, with impedance-based analysis, the system comprising:
- (a) a plurality of analog-to-digital (A2D) signal converters electrically arranged in parallel to one another;
- (b) a well plate comprising a plurality of wells on a nonconductive substrate, wherein each well comprises one electrode array of a plurality of electrode arrays disposed on the nonconductive substrate that is connected to the plurality of A2D signal converters;
- (c) an impedance analyzer connected to or including the plurality of A2D signal converters, wherein the impedance analyzer measures, via digitally converted signals from the A2D signal converters, a first plurality of cell-substrate impedances at a first time and a second plurality of cell-substrate impedances at a second time, the impedances being measured between a first and second electrode structure in each electrode array; and
- (d) a software program that analyzes the first and second pluralities of cell-substrate impedances to produce a plurality of time period analyses of the cell samples, wherein individual time period analyses are associated with individual wells.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are the Axion Maestro Platforms (including the Maestro Z, ZHT, Pro, Edge, and TrayZ models), the CytoView-Z Plates, and the AxIS Z software (Compl. ¶2, ¶29).
Functionality and Market Context
- The complaint alleges the accused products combine to form a system that provides "continuous, label-free, impedance-based monitoring of [] cells" (Compl. ¶19). The CytoView-Z Plates are multi-well plates with embedded electrodes on the culture surface of each well (Compl. ¶19.a). The Maestro platform is described as using impedance measurements to quantify the presence of cells on these electrodes by measuring how much an electrical signal is blocked by the cell-electrode interface (Compl. ¶19.b-c). The complaint provides a schematic from Axion's materials showing the interdigitated electrode structure within a well (Compl. ¶34; Compl. Ex. G). The AxIS Z software is alleged to analyze these impedance measurements to report on "changes in cell proliferation, morphology, and viability" in real time (Compl. ¶20).
- The complaint positions the parties as direct competitors in the market for real-time, live-cell assay systems, citing an Axion news release that acknowledges Agilent as another key player in the field (Compl. ¶23).
IV. Analysis of Infringement Allegations
'508 Patent Infringement Allegations
| Claim Element (from Independent Claim 16) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A system for continuously monitoring cells in real time, label free, with impedance-based analysis... | Axion's Maestro Z platform in combination with other accused products "offers continuous, label-free, impedance-based monitoring of your cells." | ¶30 | col. 2:55-64 |
| a) a plurality of analog-to-digital (A2D) signal converters electrically arranged in parallel to one another; | On information and belief, the Maestro Z and/or CytoView-Z Plates comprise a plurality of A2D converters arranged in parallel to convert analog signals to digital signals, inferred from the system's ability to monitor impedance from each individual well. | ¶31 | col. 24:60-66 |
| b) a well plate comprising a plurality of wells on a nonconductive substrate, wherein each well...comprises one electrode array...that is connected to the plurality of A2D signal converters; | The CytoView-Z Plates are alleged to be multi-well plates on a nonconductive PET substrate, with each well comprising an electrode array connected to the A2D converters. | ¶32-36 | col. 23:1-14 |
| c) an impedance analyzer...that measures...a first plurality of cell-substrate impedances at a first time and a second plurality of cell-substrate impedances at a second time... | The Maestro Z platform is alleged to function as an impedance analyzer that measures cell-substrate impedance across multiple wells at different times, as shown in an Axion chart depicting impedance curves over a 40-hour period. | ¶37 | col. 4:9-19 |
| d) a software program that analyzes the first plurality of cell-substrate impedances...and the second...to produce a plurality of time period analyses...wherein individual time period analyses...are associated with individual wells... | The AxIS Z software allegedly analyzes impedance from each well to produce analyses associated with individual wells. The complaint provides a visual from an Axion video showing impedance heatmaps of a 96-well plate at a first time point and a second time point. | ¶40 | col. 2:4-6 |
Identified Points of Contention
- Scope Questions: The complaint alleges the presence of "a plurality of analog-to-digital (A2D) signal converters electrically arranged in parallel to one another" based on "information and belief" (Compl. ¶31). This suggests a potential dispute over whether the internal hardware architecture of the Maestro platform meets this specific structural limitation, raising the question of what evidence Plaintiff can produce to substantiate this claim.
- Technical Questions: A key question concerns the functional software limitation requiring a program that produces "a plurality of time period analyses." What evidence will be presented to show that the outputs of the AxIS Z software, such as the visualized heatmaps (Compl. p. 16), constitute the specific "analyses" required by the claim, as opposed to merely a display of raw or minimally processed data?
V. Key Claim Terms for Construction
The Term: "plurality of analog-to-digital (A2D) signal converters electrically arranged in parallel to one another"
Context and Importance: This term is central because it defines a specific hardware architecture that enables the patent's high-throughput, high-speed measurement capability. Practitioners may focus on this term because the infringement allegation is pleaded on "information and belief" (Compl. ¶31), indicating the accused system's internal configuration is not publicly documented and will be a key point of discovery and dispute.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party seeking a broader construction may point to the patent’s overall objective of high-throughput monitoring and argue that "arranged in parallel" should be interpreted functionally to cover any architecture achieving rapid measurement across multiple wells. The specification’s reference to using "multiple analogue-to-digital (AD) conversion channels so that analog electronic signals from multiple channels can be converted to digital signals simultaneously" could support this view (’508 Patent, col. 24:62-66).
- Evidence for a Narrower Interpretation: A party seeking a narrower construction may argue that the claim language requires a specific physical structure of distinct A2D converters wired in parallel. The patent's emphasis on achieving "millisecond time resolution" for "each and every well of the system" could be used to argue that only a truly parallel hardware architecture, not a single fast A2D converter that is multiplexed across wells, can meet this demanding performance requirement (’508 Patent, col. 4:1-4).
The Term: "time period analyses"
Context and Importance: The definition of this term is critical for determining whether the accused AxIS Z software performs the function required by the final limitation of Claim 16. The dispute will likely center on what level of data processing qualifies as an "analysis."
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Plaintiff may argue that any processed output showing cellular status over time, such as the impedance growth curves or heatmaps depicted in the complaint (Compl. pp. 14, 16), qualifies as a "time period analysis." The patent describes monitoring cell characteristics like "cell attachment, cell growth and cell viability" over time, which may support a broad, functional interpretation of the term (’508 Patent, col. 4:26-30).
- Evidence for a Narrower Interpretation: Defendant may argue that the term requires more than simple data visualization. The claim specifies the software produces analyses "of the plurality of cell samples" where "individual...analyses...are associated with individual wells" (’508 Patent, col. 46:1-5). This could be interpreted to require a discrete, calculated output for each well (e.g., a specific rate or value), rather than a graphical representation of the underlying data.
VI. Other Allegations
Indirect Infringement
- The complaint alleges induced infringement, stating that Axion provides materials like brochures, application notes, and protocols that instruct and encourage customers to use the accused products in a manner that directly infringes Claim 16 (Compl. ¶42). This includes specific instructions to "Culture your cells in an Axion multiwell CytoView-Z plate" and "Analyze changes...with AxIS Z software" (Compl. ¶17).
Willful Infringement
- Willfulness is alleged based on both pre- and post-suit knowledge. The complaint asserts Axion had knowledge of the patent application upon its publication in April 2023 and of the issued patent itself as of its February 2024 issue date (Compl. ¶22). This allegation is supported by claims of direct competition between the parties and the existence of a prior patent lawsuit filed in 2023 over similar impedance-based technology (Compl. ¶23-26).
VII. Analyst’s Conclusion: Key Questions for the Case
- A key evidentiary question will be one of architectural proof: can Agilent, through discovery, produce evidence to overcome its "information and belief" pleading and demonstrate that the accused Maestro system's internal hardware contains the "plurality of analog-to-digital (A2D) signal converters electrically arranged in parallel to one another," as structurally mandated by Claim 16?
- A core issue will be one of functional scope: does the term "time period analyses" require a specific, calculated output for each well (e.g., a growth rate or IC50 value), or can it be construed more broadly to cover the graphical visualizations of impedance data over time that the accused AxIS Z software allegedly provides? The outcome of this claim construction dispute will be critical to the infringement analysis.