DCT

2:23-cv-08417

ChromaCode Inc v. Bio Rad Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-08417, C.D. Cal., 10/05/2023
  • Venue Allegations: Plaintiff alleges venue is proper in the Central District of California because Defendant maintains regular and established places of business in the district and offers for sale and sells the accused products within the district.
  • Core Dispute: Plaintiff alleges that Defendant’s Droplet Digital Polymerase Chain Reaction (PCR) systems infringe patents related to methods for detecting multiple biological targets in a single sample by using a limited number of fluorescent signals.
  • Technical Context: The technology addresses a key limitation in biochemical diagnostics, enabling the simultaneous identification of more biological targets (e.g., DNA sequences) than the number of available fluorescent colors, which is significant for advanced diagnostic assays and life science research.
  • Key Procedural History: Plaintiff ChromaCode asserts it is the exclusive licensee of the patents-in-suit from the California Institute of Technology (Caltech). The complaint alleges that Defendant Bio-Rad had pre-suit knowledge of ChromaCode's patented technology through fundraising discussions that began in 2014 and continued through 2018, during which ChromaCode allegedly shared information about its intellectual property portfolio.

Case Timeline

Date Event
2012-02-03 Priority date for U.S. Patent Nos. 10,068,051 and 10,770,170
2018-09-04 U.S. Patent No. 10,068,051 issues
2020-09-08 U.S. Patent No. 10,770,170 issues
Late 2022 Defendant Bio-Rad announces the accused QX600 System
2023-10-05 Complaint filed

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

U.S. Patent No. 10,068,051 - "Signal Encoding and Decoding in Multiplexed Biochemical Assays"

  • Patent Identification: U.S. Patent No. 10,068,051, "Signal Encoding and Decoding in Multiplexed Biochemical Assays," issued September 4, 2018 (the "’051 Patent").

The Invention Explained

  • Problem Addressed: Traditional methods for detecting multiple biological targets ("multiplexing") are limited by the small number of fluorescent colors that can be distinguished without "spectral overlap" (Compl. ¶13). This "one-target-one-color" approach typically restricts assays to identifying only 4 to 6 targets simultaneously, and overcoming this limitation often requires complex and expensive processing steps ('051 Patent, col. 7:35-57; Compl. ¶13-14).
  • The Patented Solution: The invention provides a method to detect numerous analytes using a limited number of fluorophores by creating a coding scheme based on the cumulative intensity of the fluorescent signals ('051 Patent, Abstract). Instead of assigning one unique color to each target, targets are assigned a "code" based on a unique combination of colors and/or signal intensity levels. By measuring the total, or cumulative, intensity in each color channel, the system can decode the signal to determine which combination of targets is present, thereby breaking the one-to-one color-to-target limitation ('051 Patent, Fig. 1; col. 4:20-40).
  • Technical Importance: The technology enables "high definition multiplexing," a method critical to developing efficient, affordable, and widely available PCR assays for detecting diseases and other medical conditions (Compl. ¶9).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶47).
  • The essential elements of claim 1 include:
    • A method for detecting the presence or absence of at least seven polynucleotide analytes in a single sample solution.
    • Providing a sample solution containing the analytes and at least seven corresponding hybridization probes.
    • Each probe comprises at least one fluorophore selected from a set of four fluorophores.
    • When a probe contacts its corresponding analyte and is excited, it generates a cumulative intensity signal.
    • Contacting the sample with the probes and exciting them to generate cumulative intensity signal(s).
    • Measuring the cumulative signal(s) to generate a measurement that "non-degenerately indicates" the presence or absence of the analytes.
    • The method avoids any requirement for immobilization, physical separation, or mass spectrometry of the analytes.

U.S. Patent No. 10,770,170 - "Signal Encoding and Decoding in Multiplexed Biochemical Assays"

  • Patent Identification: U.S. Patent No. 10,770,170, "Signal Encoding and Decoding in Multiplexed Biochemical Assays," issued September 8, 2020 (the "’170 Patent").

The Invention Explained

  • Problem Addressed: The '170 Patent shares the same specification as the '051 Patent and addresses the same fundamental problem of overcoming the color limitations in multiplexed biochemical assays (Compl. ¶29).
  • The Patented Solution: This patent adapts the core signal encoding and decoding technology specifically for use in droplet-based digital PCR (dPCR) systems ('170 Patent, col. 47:13-15). The claimed method involves forming a mixture of a sample and hybridization probes, partitioning that mixture into a plurality of droplets, exciting the fluorophores within the droplets to generate signals, and then measuring the cumulative intensity of those signals to unambiguously determine which of at least five analytes are present using at most four fluorophores ('170 Patent, Abstract; col. 47:11-48:9).
  • Technical Importance: The invention provides a solution that improves upon existing dPCR technology, enabling the development of commercially viable advanced PCR assays for complex applications, such as cancer detection (Compl. ¶31).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶59).
  • The essential elements of claim 1 include:
    • A method for "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, where each probe has at least one fluorophore and at most four fluorophores.
    • "Partitioning said mixture into said plurality of droplets."
    • Exciting the fluorophore(s) to generate signals.
    • Measuring the signals to create a "cumulative intensity measurement."
    • Determining the presence or absence of each of the analytes based on this cumulative measurement.
    • The method avoids any requirement for immobilization or mass spectrometry.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are Defendant’s QX600 Droplet Digital PCR System and QX ONE Droplet Digital PCR System, along with associated components, assays, and software (Compl. ¶35, 41).

Functionality and Market Context

  • The QX600 System is advertised as enabling "advanced six-color multiplexing" and is capable of "quantifying 12 targets per well" (Compl. ¶35, 36).
  • The QX ONE System is described as offering "four color channels" and enabling the detection of "as many as eight targets" in a single reaction (Compl. ¶42).
  • The complaint alleges that both systems achieve this higher level of multiplexing through a strategy called "amplitude multiplexing," which relies on measuring the "cumulative signal" from fluorophores to distinguish targets (Compl. ¶38, 42). A Bio-Rad technical bulletin for the QX600 System displays 2-D plots showing distinct clusters of signals at varying amplitude levels, which the complaint presents as evidence of the accused method (Compl. p. 17, referencing Ex. F). A similar bulletin for the QX ONE system also illustrates "8-plex amplitude multiplexing" with 2-D plots showing signal clusters based on amplitude (Compl. p. 18, referencing Ex. G).
  • The complaint positions these products within the "immense" global PCR market, which it values at over $7.10 billion in the U.S. alone as of 2020 (Compl. ¶24).

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... Defendant's QX600 and QX ONE systems are advertised as quantifying up to 12 and 8 targets, respectively. ¶35, ¶42 col. 2:48-49
...each hybridization probe comprises at least one fluorophore selected from four fluorophores... The QX ONE system is advertised as using four color channels (FAM, HEX, Cy5, and Cy5.5). The QX600 system uses six colors, which inherently includes the capability of using four. ¶36, ¶42, ¶47 col. 47:19-21
...measuring the cumulative intensity signal(s), thereby generating a cumulative signal measurement... Defendant's user guides and marketing materials for the accused systems describe using "amplitude multiplexing" and an encoding scheme based on the "cumulative signal from each fluorophore." ¶38, ¶39, ¶42 col. 47:29-31
...wherein the cumulative signal measurement non-degenerately indicates the presence or absence of the at least seven polynucleotide analytes... Defendant's press releases and product pages state that its systems are capable of "unambiguously identifying" and enabling "clear discrimination" of multiple targets. ¶35, ¶36 col. 47:32-35

’170 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of unambiguously detecting...at least five polynucleotide analytes in a plurality of droplets... Defendant's products are identified as "Droplet Digital PCR" systems and are advertised as detecting more than five targets (up to 12 for the QX600 and 8 for the QX ONE). ¶35, ¶41, ¶59 col. 47:11-15
...partitioning said mixture into said plurality of droplets... The accused products are marketed as Droplet Digital PCR Systems and are described as utilizing "droplet generation." ¶35 col. 47:29-30
...wherein each of said at least five hybridization probes further comprises at least one fluorophore and at most four fluorophores... The QX ONE system uses four color channels. The complaint alleges the QX600 system, which has six channels, infringes when running assays that use four or fewer fluorophores. ¶42, ¶59 col. 47:25-28
...measuring said one or more signals to generate a cumulative intensity measurement... Defendant's marketing materials describe using "amplitude multiplexing" based on the "cumulative signal" from fluorescent probes to identify multiple targets. ¶38, ¶39, ¶42 col. 47:38-40

Identified Points of Contention

  • Scope Questions: A central question for the '170 Patent may be whether assays run on the six-color QX600 System meet the "at most four fluorophores" limitation of claim 1. The infringement case may depend on evidence that Defendant provides or instructs users to run specific assays that use four or fewer of the available color channels. For the '051 Patent, a similar question arises as to whether the QX600 System practices the claimed method using only four of its six available colors to detect at least seven targets.
  • Technical Questions: The case may raise the question of what technical evidence demonstrates that Defendant's "amplitude multiplexing" is functionally the same as the "cumulative intensity signal measurement" recited in the claims. Further, the terms "non-degenerately" ('051 Patent) and "unambiguously" ('170 Patent) may be contested, raising the question of whether the accused systems achieve the level of decoding precision required by the claims or if operational ambiguities place them outside the claim scope.

V. Key Claim Terms for Construction

  • The Term: "non-degenerately" (’051 Patent) and "unambiguously" (’170 Patent)

    • Context and Importance: These terms define the invention's core functional advantage over prior art methods, which suffered from ambiguity or "degeneracy" when signals could correspond to multiple target combinations. The dispute may turn on whether the accused systems achieve the required level of decoding certainty. Practitioners may focus on these terms because they are qualitative and central to the infringement analysis.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification describes the goal of "unambiguously detecting the presence or absence of M analytes" ('051 Patent, col. 2:11-12). It also describes a method for generating a non-degenerate coding scheme by "eliminating at least one potential analyte code...to eliminate degeneracy," which could suggest that any intentional design choice to resolve ambiguity meets the definition ('051 Patent, col. 5:12-14).
      • Evidence for a Narrower Interpretation: The specification provides detailed mathematical frameworks and decoding matrices (e.g., Table 4) for creating perfectly non-degenerate schemes ('051 Patent, col. 14:38-18:44). A defendant might argue the terms should be limited to systems that employ these specific mathematical constructs or achieve the perfect one-to-one mapping shown in the patent's examples.

  • The Term: "cumulative intensity signal" (’051 Patent) and "cumulative intensity measurement" (’170 Patent)

    • Context and Importance: These terms describe the physical mechanism used to encode multiple targets. The infringement analysis will depend on whether Defendant's "amplitude multiplexing" technology operates in a way that falls within this definition.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification describes a system where "the intensity of the blue color reports the number of analytes that are present" and provides examples where signal intensities are additive ('051 Patent, col. 13:21-23; col. 19:22-30). This could support a reading that covers any system where signal strengths from multiple probes combine in a measurable way.
      • Evidence for a Narrower Interpretation: The specification notes that for a fluorescent signal, "the intensity need only be approximately additive and digital" ('051 Patent, col. 17:15-16). A defendant may argue that its signal processing algorithm is more complex than a simple summation of intensities and therefore does not generate a "cumulative" signal as taught by the patent.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. Inducement is based on allegations that Defendant's user guides and instructions encourage customers to perform the patented methods (Compl. ¶48, 60). Contributory infringement is based on allegations that the assays Defendant provides are especially made for an infringing use (Compl. ¶50, 62).
  • Willful Infringement: The willfulness claim is based on alleged pre-suit knowledge. The complaint alleges that Plaintiff disclosed its patented technology to Defendant during fundraising discussions between 2014 and 2018, prior to the launch of the accused products (Compl. ¶33-34, 51, 63).

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

  • A core issue will be one of definitional scope: can the terms "non-degenerately" and "unambiguously," which are defined in the patent through specific mathematical examples of eliminating ambiguity, be construed to cover the operational performance of Defendant's commercial "amplitude multiplexing" systems?
  • A key evidentiary question will be one of operational mode: for the accused QX600 system, which operates with six color channels, what evidence will demonstrate that it performs assays meeting the "four fluorophores" limitation of the '051 Patent or the "at most four fluorophores" limitation of the '170 Patent?
  • A central technical question will be one of functional operation: does the signal processing in Defendant's accused systems result in a "cumulative intensity measurement" as described in the patents, or do the underlying algorithms differ sufficiently to create a non-infringing distinction?