DCT

3:19-cv-05639

Fluidigm Corp A Delaware Corp v. Ionpath Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:19-cv-05639, N.D. Cal., 03/30/2020
  • Venue Allegations: Venue is alleged to be proper as Defendant IONpath has its principal place of business, resides, conducts substantial business, and has committed the alleged acts of patent infringement within the Northern District of California.
  • Core Dispute: Plaintiff alleges that Defendant’s MIBIscope mass cytometry systems, associated reagents, and analytical services infringe patents related to methods and systems for high-parameter analysis of single cells.
  • Technical Context: The technology at issue is mass cytometry, a technique that uses antibodies tagged with stable heavy metal isotopes to simultaneously measure dozens of proteins and other biomarkers on individual cells, enabling deep biological insights in fields like immunology and oncology.
  • Key Procedural History: The complaint alleges that Plaintiff provided Defendant with notice of one of the patents-in-suit in September 2018. The original complaint in this action was filed in September 2019, with this Second Amended Complaint filed in March 2020. Plaintiff also alleges that Defendant was formed by former consultants to Plaintiff who were subject to consulting and confidentiality agreements related to the technology at issue.

Case Timeline

Date Event
2004-03-25 Priority Date for ’386 and ’698 Patents
2006-05-27 Priority Date for ’104 Patent
2014-09-16 Defendant IONpath, Inc. founded
2017-12 Defendant first offered MIBIscope product for sale
2018-09-11 ’104 Patent Issued
2018-09-24 Plaintiff allegedly provided Defendant notice of ’104 Patent
2019-01-15 ’386 Patent Issued
2019-09-06 Original Complaint filed
2019-09-23 Original Complaint served on Defendant
2019-10-08 ’698 Patent Issued
2019-10-11 First Amended Complaint served on Defendant
2019-11-05 Defendant announced commercial launch of MIBIscope
2020-03-30 Second Amended Complaint filed

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

U.S. Patent No. 10,180,386 - “Mass Spectrometry Based Multi-Parametric Particle Analyzer”

  • Patent Identification: U.S. Patent No. 10,180,386 (“Mass Spectrometry Based Multi-Parametric Particle Analyzer”), issued January 15, 2019.

The Invention Explained

  • Problem Addressed: The patent’s background section describes limitations of prior art cell analysis techniques, such as fluorescence-based flow cytometry, which are constrained by the spectral overlap of fluorophores, limiting the number of parameters that can be measured simultaneously (’386 Patent, col. 2:11-45).
  • The Patented Solution: The invention provides a method for analyzing single cells using mass spectrometry. Cells are labeled with antibodies attached to elemental tags, specifically lanthanide or noble metals, which have distinct masses (’386 Patent, col. 19:1-12). The cells are then introduced sequentially into a device that vaporizes, atomizes, and ionizes them, and a mass spectrometer detects the resulting elemental tags as a transient signal, allowing for the elemental composition of each individual cell to be determined (’386 Patent, Abstract; col. 4:1-15).
  • Technical Importance: This approach allows for highly multiplexed analysis, enabling researchers to quantify dozens of biomarkers on thousands of individual cells simultaneously, far exceeding the capabilities of fluorescence-based methods (Compl. ¶¶18, 20).

Key Claims at a Glance

  • The complaint asserts independent method claim 1 and at least dependent claim 9 (Compl. ¶¶33, 135).
  • The essential elements of independent claim 1 include:
    • Providing a sample of cells tagged with antibodies, where each antibody is specific for a different analyte and is tagged with an elemental tag comprising a lanthanide or noble metal.
    • Vaporizing, atomizing, and ionizing the elemental tags from a single first cell.
    • Detecting the elemental composition of the first cell using mass spectroscopy by detecting a transient signal from the ionized tags.
    • Repeating the vaporizing, atomizing, ionizing, and detecting steps for a single second cell.
    • Detecting the transient signals from the first and second cells sequentially.
  • The complaint does not explicitly reserve the right to assert other dependent claims.

U.S. Patent No. 10,072,104 - “Polymer Backbone Element Tags”

  • Patent Identification: U.S. Patent No. 10,072,104 (“Polymer Backbone Element Tags”), issued September 11, 2018.

The Invention Explained

  • Problem Addressed: The patent describes a need for improved methods of protein quantitation that offer greater sensitivity, selectivity, and multiplexing capability than prior methods like flow cytometry and ligand binding assays (’104 Patent, col. 1:35-60).
  • The Patented Solution: The invention is a method for analyzing an analyte using a novel type of elemental tag. This tag consists of a linear or branched polymer backbone with multiple "pendant groups" that can bind metal atoms (’104 Patent, Abstract). An affinity reagent, such as an antibody, is attached to this polymer tag. After incubation with a sample, the tag bound to the analyte on an intact cell is analyzed using atomic spectroscopy without a prior step of acidifying the sample to release the ions (’104 Patent, col. 32:8-24).
  • Technical Importance: The polymer backbone structure allows for the attachment of many copies of a metal isotope to a single affinity reagent, which can significantly amplify the detection signal and improve assay sensitivity (Compl. ¶¶72-73; ’104 Patent, Abstract).

Key Claims at a Glance

  • The complaint asserts independent method claim 1 and at least dependent claim 14 (Compl. ¶¶41, 173).
  • The essential elements of independent claim 1 include:
    • Incubating an analyte on an intact cell with an "element tagged affinity reagent," where the element tag is a polymer with multiple metal-binding pendant groups.
    • Separating the unbound reagent from the bound reagent.
    • Analyzing the element tag bound to the analyte on the intact cell via atomic spectroscopy.
    • Performing the analysis "without prior acidification of the sample."
  • The complaint does not explicitly reserve the right to assert other dependent claims.

U.S. Patent No. 10,436,698 - “Mass Spectrometry Based Multi-Parametric Particle Analyzer”

  • Patent Identification: U.S. Patent No. 10,436,698 (“Mass Spectrometry Based Multi-Parametric Particle Analyzer”), issued October 8, 2019.
  • Technology Synopsis: Belonging to the same family as the ’386 Patent, this patent addresses the limitations of fluorescence-based cell analysis by claiming a system for performing mass cytometry (Compl. ¶¶48, 51). The claimed system comprises a first device to vaporize, atomize, and ionize elemental tags from single cells and a second device to sequentially detect the transient signals from those tags using mass spectrometry (Compl. ¶49).
  • Asserted Claims: Independent claim 1 and at least dependent claim 6 (Compl. ¶¶49, 207).
  • Accused Features: The IONpath MIBIscope system is accused of infringing the ’698 Patent (Compl. ¶¶72, 94).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendant’s MIBIscope system (also referred to as the MIBI-TOF system), its associated MIBItag reagents and conjugation kits, and an in-house "Pharma Partnership service" that uses the system to perform analysis for customers (Compl. ¶¶72, 96, 97, 101).

Functionality and Market Context

The complaint alleges the MIBIscope is a mass cytometry system designed to analyze and image biomarkers in tissue samples (Compl. ¶72). The system's alleged method of operation involves staining a tissue sample with antibodies conjugated to metal isotopes, then using a primary ion beam to raster-scan the tissue, which generates secondary elemental ions from the tags (Compl. ¶92). These secondary ions are then analyzed using time-of-flight mass spectrometry to create a high-dimensional image of the tissue (Compl. ¶¶92, 94). The complaint positions the MIBIscope as a direct competitor to Plaintiff’s own mass cytometry systems and alleges it is sold for over $1,000,000 (Compl. ¶¶4, 74, 87). A diagram from a 2018 article illustrates the alleged MIBI-TOF workflow, showing tissue staining with isotope-labeled antibodies, measurement by time-of-flight mass spectrometry, and generation of an N-dimensional image (Compl. ¶92).

IV. Analysis of Infringement Allegations

’386 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
providing a sample containing a plurality of tagged cells tagged with a plurality of tagged antibodies... wherein each of the tagged antibodies is tagged with an elemental tag comprising a lanthanide or noble metal; The accused MIBI System is used with either Defendant's MIBItags or Plaintiff's Maxpar reagents, both of which are antibodies conjugated with elemental reporters, to stain tissue samples for analysis. ¶141 col. 17:55-67
vaporizing, atomizing, and ionizing multiple elemental tags from a single first cell of the plurality of tagged cells; The MIBIscope system uses a primary ion gun that raster-scans a tissue sample, which is alleged to vaporize, atomize, and ionize the elemental tags on individual cells within the tissue. ¶141 col. 17:49-54
detecting, using mass spectroscopy, the elemental composition of the first cell by detecting a transient signal of the multiple vaporized, atomized, and ionized elemental tags of the first cell; The MIBIscope uses time-of-flight mass spectrometry to detect the secondary ions generated from the elemental tags of a single cell, creating a transient signal corresponding to that cell's elemental composition. ¶141 col. 18:1-14
vaporizing, atomizing, and ionizing multiple elemental tags from a single second cell...and detecting...the elemental composition of the second cell...wherein the transient signal associated with the first cell and the transient signal associated with the second cell are detected sequentially. The system allegedly raster-scans across the tissue sample, thereby analyzing cells sequentially, one after another, and generating distinct transient signals for each cell. ¶141 col. 15:35-39

’104 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
incubating an element tagged affinity reagent with an analyte, the element tagged affinity reagent comprising an affinity reagent tagged with an element tag, the element tag comprising a linear or branched polymer having multiple metal-binding pendant groups... The accused method uses MIBItags or Maxpar reagents, which are alleged to be element-tagged antibodies. The complaint alleges these tags comprise a polymer with metal-binding components, used to incubate with and bind to analytes in a tissue sample. ¶178 col. 3:40-50
separating unbound element tagged affinity reagent from bound element tagged affinity reagent; Defendant allegedly provides and instructs users to employ a wash buffer (MIBI 20x TBS-T) to remove unbound reagents after the staining step. ¶178 col. 25:13-16
analyzing the element tag bound to the affinity reagent attached to the analyte of the intact cell by atomic spectroscopy, wherein analyzing occurs without prior acidification of the sample. The MIBIscope analyzes the stained tissue directly using secondary ion mass spectrometry, a process that the complaint alleges does not require prior acidification to release the metal tags. ¶178 col. 32:20-24
  • Identified Points of Contention:
    • Scope Questions: A central question for the ’386 and ’698 Patents may be whether the term "sequentially analyzing single cells," which is often associated in the patent specification with flow cytometry of suspended particles, can be construed to read on the accused method of raster-scanning cells fixed in a stationary tissue sample. A related question concerns whether the term "particle" as used in the patent can be construed to read on a cell fixed within a larger tissue sample.
    • Technical Questions: A key technical dispute may arise over whether the accused system's use of a primary ion beam to generate secondary ions (Secondary Ion Mass Spectrometry, or SIMS) constitutes "vaporizing, atomizing, and ionizing" as those terms are used in the claims of the ’386 and ’698 Patents. The specifications of those patents describe this process primarily in the context of an Inductively Coupled Plasma (ICP) source, and the defense may argue that the SIMS mechanism is technically distinct from the claimed process. An image from a brochure for the MIBIscope I depicts the alleged infringing system workflow, showing a "Primary Ion Gun" generating "Secondary Elemental Ions" for detection (Compl. ¶94).

V. Key Claim Terms for Construction

The Term: "sequentially analyzing single cells" (from claim 1 of the ’386 Patent)

  • Context and Importance: This term's construction may be determinative of infringement. The dispute may focus on whether the claim requires cells to be analyzed in a fluid stream, as in traditional flow cytometry, or if it is broad enough to cover the cell-by-cell raster-scanning of a stationary tissue slide as allegedly performed by the MIBIscope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself does not explicitly require the cells to be in motion or in a fluid stream. The patent also refers to analyzing "particles" generally, which could support a construction not limited to a specific physical state (’386 Patent, col. 15:35-39).
    • Evidence for a Narrower Interpretation: The patent specification repeatedly references "flow cytometers" and describes the invention as an "elemental-flow cytometer" (’386 Patent, col. 15:34-35). The background section is framed as an improvement over Fluorescence Activated Cell Sorters (FACS), which operate on suspended cells, suggesting the invention was conceived in that context (’386 Patent, col. 2:1-10).

The Term: "vaporizing, atomizing, and ionizing" (from claim 1 of the ’386 Patent)

  • Context and Importance: Practitioners may focus on this term because the accused MIBIscope allegedly uses a different physical mechanism (SIMS) than the one primarily disclosed in the patent (ICP) to generate detectable ions. The infringement analysis will turn on whether the accused process performs these three claimed functions, either literally or under the doctrine of equivalents.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claims do not limit the method to any specific device. The specification states that the means to perform these steps "may include glow discharge, graphite furnace, and capacitively coupled plasma devices, or other suitable devices," which suggests the inventors did not intend to limit the claims to the preferred ICP embodiment (’386 Patent, col. 17:60-63).
    • Evidence for a Narrower Interpretation: The specification's detailed explanation and preference for an Inductively Coupled Plasma (ICP) device could be used to argue that the terms should be understood in the specific context of how an ICP operates, potentially narrowing the claim scope to exclude the different sputtering mechanism of SIMS (’386 Patent, col. 17:63-65).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all three patents. Inducement allegations are based on Defendant’s marketing materials, published articles, press releases, and technical support, which allegedly instruct and encourage customers to use the MIBIscope system and MIBItag reagents in an infringing manner (Compl. ¶¶146-157, 183-191, 218-229). Contributory infringement is alleged on the basis that the MIBIscope and MIBItags are "purpose-built" for infringement and have no substantial non-infringing uses (Compl. ¶¶162, 165, 199).
  • Willful Infringement: Willfulness is alleged based on both pre-suit and post-suit knowledge. The complaint alleges Plaintiff sent a letter providing notice of the ’104 patent on September 24, 2018 (Compl. ¶100). For all patents, willfulness is alleged based on Defendant’s continued marketing, sales, and commercial launch of the MIBIscope system after being served with the original and first amended complaints in September and October 2019, respectively (Compl. ¶¶142, 179, 214).

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

  • A core issue will be one of definitional scope: can the claim term “sequentially analyzing single cells,” which the patent specification links to the field of flow cytometry for suspended particles, be construed to cover the raster-scanning of cells fixed within a stationary tissue sample?
  • A second central issue will be one of technical operation and equivalence: does the accused MIBIscope’s process of using a primary ion beam to generate secondary ions from elemental tags (SIMS) meet the claim limitations of “vaporizing, atomizing, and ionizing,” particularly when the patents-in-suit heavily emphasize Inductively Coupled Plasma (ICP) technology as the means for achieving this result?
  • A key factual question will concern knowledge and intent: given the allegations that Defendant was founded by Plaintiff's former consultants and received explicit pre-suit and post-suit notice, the litigation will likely focus intensely on the evidence supporting Defendant’s state of mind for the purposes of indirect and willful infringement.