DCT

5:23-cv-06360

ChromaCode Inc v. Bio Rad Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 5:23-cv-06360, N.D. Cal., 03/27/2024
  • Venue Allegations: Venue is alleged to be proper in the Northern District of California because Defendant Bio-Rad maintains its corporate headquarters and regular, established places of business within the district, and offers for sale and sells the accused products there.
  • Core Dispute: Plaintiffs allege that Defendant’s Droplet Digital PCR systems, which are capable of detecting more biological targets than available fluorescent colors, infringe patents related to signal encoding and decoding for multiplexed biochemical assays.
  • Technical Context: The technology addresses limitations in molecular diagnostics, where the number of fluorescent dyes limits how many distinct targets (e.g., DNA sequences) can be simultaneously detected in a single sample.
  • Key Procedural History: The complaint alleges that Plaintiff ChromaCode is the exclusive licensee of the patents-in-suit from Plaintiff California Institute of Technology. It further alleges that Bio-Rad had pre-suit knowledge of the patented technology and ChromaCode's exclusive rights through a series of fundraising and technical discussions between the parties beginning in 2014.

Case Timeline

Date Event
2012-02-03 Priority Date for ’051, ’170, and ’921 Patents
2018-09-04 U.S. Patent No. 10,068,051 Issues
2020-09-08 U.S. Patent No. 10,770,170 Issues
2022-12-14 Accused QX600 System Offered for Sale (at least as of)
2023-11-28 U.S. Patent No. 11,827,921 Issues
2024-03-27 Complaint Filing Date

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

U.S. Patent No. 10,068,051

  • Patent Identification: U.S. Patent No. 10068051, "Signal Encoding and Decoding in Multiplexed Biochemical Assays," issued September 4, 2018 (the "’051 Patent").
  • The Invention Explained:
    • Problem Addressed: The patent's background section notes that traditional multiplexed assays, such as those using fluorescence, are limited because they "generally require complex reporting mechanisms" and can only use a small number of colors simultaneously before signals begin to overlap spectrally (Compl. ¶¶13-14; ’051 Patent, col. 1:35-44, col. 7:35-40). This restricts the number of unique biological targets that can be detected in a single reaction (Compl. ¶14).
    • The Patented Solution: The invention provides a method to detect a large number of analytes (M) using a smaller number of fluorescent colors (F), where M > F (Compl. ¶34). It achieves this by encoding each analyte not just with a single color, but with a unique combination of signal intensities across multiple color channels. A "cumulative intensity signal" is then measured, and a "non-degenerate" coding scheme allows for the unambiguous identification of which combination of analytes is present in the sample ('051 Patent, Abstract; col. 4:20-44).
    • Technical Importance: This approach allows for a significant increase in the multiplexing capability of established technologies like PCR without requiring new, complex, or expensive optical hardware (Compl. ¶35).
  • Key Claims at a Glance:
    • The complaint asserts independent claim 1 (Compl. ¶51).
    • Essential elements of claim 1 include:
      • A method of detecting the presence or absence of at least seven polynucleotide analytes in a single sample solution volume.
      • Providing at least seven hybridization probes, each corresponding to one of the analytes.
      • Each probe comprises at least one fluorophore selected from four fluorophores.
      • When excited, each probe generates a cumulative intensity signal.
      • Measuring the cumulative intensity signal(s) to generate a measurement.
      • The cumulative signal measurement "non-degenerately indicates" the presence or absence of the analytes.
      • The method does not require immobilization, physical separation, or mass spectrometry.
    • The complaint alleges infringement of "at least claim 1," thereby reserving the right to assert other claims (Compl. ¶51).

U.S. Patent No. 10,770,170

  • Patent Identification: U.S. Patent No. 10770170, "Signal Encoding and Decoding in Multiplexed Biochemical Assays," issued September 8, 2020 (the "’170 Patent").
  • The Invention Explained:
    • Problem Addressed: The patent addresses the same limitations in multiplexing as the ’051 Patent, as it shares the same specification (Compl. ¶31).
    • The Patented Solution: The ’170 Patent claims a method that applies the core signal encoding technology to a specific technical environment: detecting analytes within "a plurality of droplets" ('170 Patent, claim 1). The method involves partitioning a sample mixture into droplets and then measuring the cumulative intensity from signals generated within those droplets to unambiguously determine which of at least five analytes are present (Compl. ¶31; ’170 Patent, col. 65:66-67:13).
    • Technical Importance: This solution is specifically adapted for droplet digital PCR (ddPCR) platforms, aiming to increase their multiplexing capacity beyond the traditional one-color-per-target limit (Compl. ¶35).
  • Key Claims at a Glance:
    • The complaint asserts independent claim 1 (Compl. ¶62).
    • Essential elements of claim 1 include:
      • A method of unambiguously detecting any unique combination of at least five polynucleotide analytes in a plurality of droplets.
      • Forming a mixture of the sample and at least five hybridization probes, each with at least one fluorophore from at most four fluorophores.
      • Partitioning the mixture into the plurality of droplets.
      • Exciting the fluorophores to generate signals and measuring them to create a cumulative intensity measurement.
      • Determining the presence or absence of each analyte based on the cumulative intensity measurement.
      • The method does not require immobilization or mass spectrometry.
    • The complaint alleges infringement of "at least claim 1," reserving the right to assert other claims (Compl. ¶62).

U.S. Patent No. 11,827,921 (Multi-Patent Capsule)

  • Patent Identification: U.S. Patent No. 11827921, "Signal Encoding and Decoding in Multiplexed Biochemical Assays," issued November 28, 2023 (the "’921 Patent").
  • Technology Synopsis: The ’921 Patent, which shares a specification with the ’051 and ’170 patents, claims an "assay" rather than a "method" (Compl. ¶¶33, 73). The claimed assay is capable of unambiguously detecting at least M analytes using F wavelength components where M is greater than F. This is achieved by encoding each analyte as a value of one component of a fluorescent signal, which generates a coding scheme for detection ('921 Patent, claim 1).
  • Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶73).
  • Accused Features: The accused feature is the "amplitude-based PCR multiplexing" capability of the QX600 System, which allegedly constitutes an assay that detects more analytes than available fluorescent colors (M > F) (Compl. ¶73).

III. The Accused Instrumentality

  • Product Identification: The accused products are Bio-Rad’s QX600 Droplet Digital PCR System and related systems, components, and assays, including the QX600 Auto DG Droplet Digital System (Compl. ¶39, n.6).
  • Functionality and Market Context: The QX600 System is advertised as a digital PCR instrument with "advanced six-color multiplexing" capable of "quantifying 12 targets per well" (Compl. ¶¶39, 41). The complaint alleges the system achieves this by using a technique Bio-Rad terms "Amplitude multiplex," which it describes as a "Method to increase multiplexing up to twelve targets per well, with one or two targets detected per [color]" (Compl. ¶43). The complaint includes a figure from Bio-Rad's marketing materials showing 2-D fluorescence amplitude plots from a single well detecting 12 different gene targets across six fluorescence channels (Compl. p. 17). This figure, labeled "Detection of 12 copy number targets in a single well," visually depicts distinct data clusters corresponding to different targets within the same color channels, illustrating the alleged amplitude multiplexing functionality (Compl. p. 17). Bio-Rad's press releases allegedly tout these as "advanced multiplexing capabilities" (Compl. ¶39).

IV. Analysis of Infringement Allegations

’051 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of detecting the presence or absence of at least seven polynucleotide analytes... in a single sample solution volume... The QX600 system is marketed for quantifying up to 12 targets in a single well. ¶41 col. 69:8-12
...comprising at least seven hybridization probes, each hybridization probe corresponding to one of the at least seven polynucleotide analytes... The QX600 system uses assays with probes to detect specific polynucleotide targets. The complaint alleges that assays with at least seven probes are used. ¶¶43, 51 col. 69:14-17
...wherein each hybridization probe comprises at least one fluorophore selected from four fluorophores... The complaint alleges infringement via assays that use probes comprising at least one fluorophore selected from four of the six available fluorophores in the QX600 system. ¶¶41, 51 col. 69:18-20
...when excited and when contacted with its corresponding polynucleotide analyte, generates a cumulative intensity signal... Bio-Rad's user guide allegedly describes an "encoding scheme based on the cumulative signal from each fluorophore." The system uses "Amplitude multiplex" to detect multiple targets per color. ¶43 col. 69:21-24
...measuring the cumulative intensity signal(s), thereby generating a cumulative signal measurement... The QX600 Droplet Reader and QX Manager Software measure the fluorescent signals from the assay to quantify the targets. ¶41 col. 69:34-36
...wherein the cumulative signal measurement non-degenerately indicates the presence or absence of the at least seven polynucleotide analytes... Bio-Rad's materials claim "unambiguously identifying 12 targets" and "clear discrimination of multiple targets," which allegedly relies on the patented non-degenerate encoding scheme. ¶¶39, 41 col. 69:37-40
...without requiring any step of immobilization of said polynucleotide analytes, physical separation... or mass spectrometry. The accused QX600 system is a liquid-phase, in-solution PCR system that does not rely on these separation or immobilization techniques. ¶¶41, 43 col. 69:44-48
  • Identified Points of Contention:
    • Scope Questions: A central question may be whether Bio-Rad's "Amplitude multiplex" technology, which relies on different signal strengths, meets the claim limitation of a "cumulative intensity signal" that "non-degenerately indicates" the presence of analytes as those terms are construed in light of the patent's specification.
    • Technical Questions: What evidence does the complaint provide that the accused system's signal processing for combinations of analytes results in a "non-degenerate" output as required by the claim? The complaint relies on marketing claims of "unambiguous" detection, but technical data showing the separation between all possible signal combinations will be critical.

’170 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of unambiguously detecting any unique combination of presence or absence of at least five polynucleotide analytes in a plurality of droplets... The accused product is the "QX600 Droplet Digital PCR System," which by its name and function operates on a plurality of droplets and is advertised for detecting up to 12 analytes. ¶¶39, 41 col. 65:66-67:1
...forming a mixture of said sample and at least five hybridization probes... at most four fluorophores; The system utilizes assays with fluorescent probes to detect targets; the complaint alleges use of assays with at least five probes and up to four fluorophores. ¶62 col. 66:2-6
...partitioning said mixture into said plurality of droplets; The QX600 System is a "Droplet Digital PCR" system which inherently performs this function as part of its workflow. ¶39 col. 66:7-8
...measuring said one or more signals to generate a cumulative intensity measurement... The system's "Amplitude multiplex" functionality allegedly relies on measuring cumulative signals based on fluorescence intensity to distinguish targets. ¶¶43, 62 col. 66:15-18
...determining whether each of said least five polynucleotide analytes is present... based on said cumulative intensity measurement... The QX Manager software analyzes the measured signals to determine the presence and quantity of each target based on the intensity data from the droplets. ¶¶41, 62 col. 66:21-25
  • Identified Points of Contention:
    • Scope Questions: The points of contention are similar to those for the ’051 Patent, focusing on whether "amplitude multiplexing" constitutes a "cumulative intensity measurement" for "unambiguously detecting" analytes.
    • Technical Questions: The dispute will likely center on how Bio-Rad's system technically performs the claimed steps within its droplet-based architecture and whether the results are truly "unambiguous" for every unique combination of analytes as required by the claim.

V. Key Claim Terms for Construction

  • The Term: "cumulative intensity signal" / "cumulative intensity measurement"

  • Context and Importance: This is the central concept of the patented invention. The outcome of the case may depend on whether Bio-Rad's "amplitude multiplexing"—which uses varying signal strengths to identify multiple targets within a single color channel—is encompassed by this term. Practitioners may focus on this term because it defines the core technical mechanism of infringement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes generating a "cumulative measurement" on a solution, which could be argued to cover any method where signals from multiple sources are measured together to produce a combined value ('051 Patent, col. 2:50-52).
    • Evidence for a Narrower Interpretation: The patent's detailed examples and figures describe a specific, structured "non-degenerate" coding scheme where intensity levels are assigned in a tiered or binary-like fashion (e.g., intensities of 1, 2, 4) ('051 Patent, Table 3, col. 13:5-16). A defendant might argue the term is limited to such structured, predefined coding schemes rather than any general variation in signal amplitude.

  • The Term: "non-degenerately indicates" ('051 Patent) / "unambiguously detecting" ('170 Patent)

  • Context and Importance: These terms define the required level of accuracy and certainty for the detection method. The dispute will likely focus on the degree of signal separation and statistical confidence needed to meet this standard. If Bio-Rad's system produces overlapping or difficult-to-distinguish signals for certain analyte combinations, it may not meet this limitation.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides "decoding matrices" that map every possible legitimate signal combination to a unique analyte combination, suggesting that any system providing such a unique mapping is non-degenerate ('051 Patent, Table 4, col. 14:48-55).
    • Evidence for a Narrower Interpretation: The patent explicitly discusses a method for generating a non-degenerate coding scheme by identifying and "eliminating at least one potential analyte code" that would otherwise cause ambiguity ('051 Patent, col. 5:6-14). This suggests a deliberate design process to ensure non-degeneracy, which a plaintiff would argue Bio-Rad copied and a defendant might argue its own system does not use.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement based on Bio-Rad's distribution of materials such as the "QX600 System User Guide," which allegedly instruct and encourage end-users to perform the patented methods of multiplexed detection (Compl. ¶¶52, 63). Contributory infringement is also alleged, based on the assertion that the assays are especially adapted for infringing use (Compl. ¶¶53-54, 64-65).
  • Willful Infringement: Willfulness is alleged based on Bio-Rad's purported pre-suit knowledge of the patents and ChromaCode's exclusive rights. The complaint alleges this knowledge was obtained through fundraising and technical discussions between the parties in 2014, 2017, and 2018, and also from the publication of the '051 patent application in 2015 and its issuance in 2018, all prior to the launch of the accused QX600 system (Compl. ¶¶37-38, 55-56).

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

  • A core issue will be one of definitional scope: can the patents' claim terms "cumulative intensity signal" and "non-degenerately indicates," which are described in the context of a specific mathematical coding scheme, be construed to cover Bio-Rad's commercially branded "Amplitude multiplex" technology? The case will likely feature a significant claim construction dispute over the breadth of these foundational terms.
  • A second central issue will be one of pre-suit knowledge and intent: what was the nature and extent of the technical information allegedly disclosed to Bio-Rad during the multi-year fundraising discussions, and does that information establish that Bio-Rad's subsequent development and launch of the QX600 system constituted willful infringement?
  • A key evidentiary question will be one of technical implementation: beyond marketing claims of "unambiguous" detection, what technical evidence will demonstrate that the accused QX600 system actually performs the claimed methods—particularly by generating distinct, separable signals for every possible combination of analytes required by the claims?