DCT
2:16-cv-00430
Biofire Defense v. Fluidigm Corp
Key Events
Amended Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: BioFire Defense, LLC (Delaware) and University of Utah Research Foundation (Utah)
- Defendant: Fluidigm Corporation (Delaware)
- Plaintiff’s Counsel: Thorpe, North & Western, LLP
- Case Identification: 2:16-cv-00430, D. Utah, 11/17/2016
- Venue Allegations: Venue is alleged to be proper in the District of Utah because Defendant conducts business in the district, is subject to personal jurisdiction, and because a substantial part of the alleged infringing activity occurred in the district.
- Core Dispute: Plaintiffs allege that Defendant’s BioMark genetic analysis system, including its associated assays and integrated fluidic circuits, infringes two patents related to methods and systems for monitoring DNA amplification during Polymerase Chain Reaction (PCR) in real-time.
- Technical Context: The technology at issue is real-time PCR, a foundational technique in molecular biology for amplifying and quantifying DNA, with significant applications in diagnostics, life sciences research, and genetic testing.
- Key Procedural History: The complaint notes that U.S. Patent No. 7,670,832 was the subject of a reexamination, with a certificate issued on September 21, 2015, which may have implications for the scope and interpretation of its claims.
Case Timeline
| Date | Event |
|---|---|
| 1996-06-04 | Earliest Priority Date for ’670 Patent |
| 1996-06-04 | Earliest Priority Date for ’832 Patent |
| 2001-01-16 | U.S. Patent No. 6,174,670 Issued |
| 2010-03-02 | U.S. Patent No. 7,670,832 Issued |
| 2015-09-21 | Reexamination Certificate Issued for ’832 Patent |
| 2016-11-17 | First Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,174,670 - "Monitoring Amplification of DNA During PCR"
- Patent Identification: U.S. Patent No. 6,174,670, "Monitoring Amplification of DNA During PCR," issued January 16, 2001.
The Invention Explained
- Problem Addressed: The patent's background describes conventional PCR as a process requiring lengthy, multi-hour amplification cycles, followed by separate, time-consuming post-reaction analysis steps (such as gel electrophoresis) to identify and quantify the resulting DNA products (’670 Patent, col. 1:36-41; col. 3:9-12).
- The Patented Solution: The invention discloses methods for monitoring the PCR process in real-time by observing fluorescence signals during the amplification cycles. This is achieved by using either double-strand-specific DNA binding dyes or sequence-specific fluorescent probes, enabling the simultaneous amplification and analysis of DNA within a single instrument without post-PCR processing (’670 Patent, Abstract; col. 3:19-27). This allows for the generation of melting curves by monitoring fluorescence as temperature changes, which can be used to identify and quantify the PCR products (’670 Patent, col. 5:1-9).
- Technical Importance: This integration of amplification and analysis into a single, rapid process represented a significant advance by reducing total time and enabling real-time quantification of DNA (’670 Patent, col. 3:28-32).
Key Claims at a Glance
- The complaint asserts independent claim 76 (’670 Patent, col. 74:1-6).
- The essential elements of claim 76 are:
- A method of analyzing nucleic acid hybridization comprising the steps of:
- providing a mixture comprising a nucleic acid sample to be analyzed and a nucleic acid binding fluorescent entity; and
- monitoring fluorescence while changing temperature at a rate of ≥0.1° C./second.
U.S. Patent No. 7,670,832 - "System For Fluorescence Monitoring"
- Patent Identification: U.S. Patent No. 7,670,832, "System For Fluorescence Monitoring," issued March 2, 2010.
The Invention Explained
- Problem Addressed: The patent, which shares a specification with the ’670 Patent, addresses the same need for a faster and more integrated approach to PCR by describing the apparatus required to perform real-time monitoring (’832 Patent, col. 1:21-30).
- The Patented Solution: The invention is a device that integrates the necessary components for real-time PCR into a single system. This system includes a heat exchange component for rapid thermal cycling, a control device to manage the temperature cycles, an optical excitation source (e.g., a lamp), a photodetector to measure fluorescence, and a processor programmed to generate a melting curve from the collected fluorescence data (’832 Patent, Abstract; col. 2:48-56).
- Technical Importance: This claimed system provides the physical hardware that enables the real-time, quantitative PCR methods, combining thermal control and optical detection to create a cohesive analytical instrument (’832 Patent, col. 2:48-56).
Key Claims at a Glance
- The complaint asserts independent claim 1 (’832 Patent, col. 63:46-64:18).
- The essential elements of claim 1 are:
- A device for performing PCR and monitoring the reaction of a sample comprising a nucleic acid and a fluorescent dye, comprising:
- a reaction vessel with the sample therein;
- a heat exchange component for heating and cooling the sample;
- a control device programmed for repeatedly operating the heat exchange component to subject the sample to thermal cycling to generate an amplification product;
- an excitation source for optically exciting the sample to cause the sample to fluoresce;
- a photodetector for detecting temperature-dependent fluorescence levels from the sample; and
- a processor programmed to generate a melting curve of the amplification product contained within the reaction vessel during or subsequent to amplification.
- The complaint alleges infringement of "at least independent claim 1," suggesting a reservation of the right to assert dependent claims (Compl. ¶30).
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is Fluidigm's "Infringing System," which is identified as the combination of the BioMark analytical instrument, associated assays (e.g., Delta Gene assays), and integrated fluidic circuits ("IFCs") which function as reaction vessels (Compl. ¶¶17-19).
- Functionality and Market Context: The complaint alleges the BioMark instrument includes a temperature control module for thermal cycling, a light source for sample excitation, a photodetector for detecting fluorescent emissions, and a data collection module for processing data points (Compl. ¶17). The system is allegedly designed to be used with IFCs containing a nucleic acid sample, primers for amplification, and a fluorescent binding dye (Compl. ¶¶18, 32). The combination is allegedly used to perform PCR and monitor the reaction to generate a melting curve for genetic analysis (Compl. ¶¶31, 35). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
6,174,670 Infringement Allegations
| Claim Element (from Independent Claim 76) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| providing a mixture comprising a nucleic acid sample to be analyzed and a nucleic acid binding fluorescent entity | Defendant's Infringing System is allegedly used by mixing a nucleic acid sample with a fluorescent binding dye and an assay within an IFC. | ¶26 | col. 22:28-44 |
| monitoring fluorescence while changing temperature at a rate of ≥0.1° C./second | The BioMark instrument is allegedly used to monitor fluorescence from the mixture while changing its temperature at a rate equal to or greater than 0.1° C. per second to generate a melting curve. | ¶26 | col. 38:23-29 |
- Identified Points of Contention:
- Evidentiary Question: A primary factual question for the court will be whether the accused BioMark system, when operated as instructed, monitors fluorescence while changing temperature at the specific rate of ≥0.1° C./second as required by the claim. The complaint makes this allegation, but it remains a technical point to be proven.
7,670,832 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a reaction vessel with the sample therein, wherein the sample further comprises a polymerase and a pair of primers... | The accused IFC allegedly serves as the reaction vessel containing the sample, polymerase, and primers. | ¶32 | col. 57:3-6 |
| a heat exchange component for heating and cooling the sample | The accused BioMark instrument allegedly comprises a thermal cycler that includes a heat exchange component. | ¶33 | col. 57:51-54 |
| a control device programmed for repeatedly operating the heat exchange component to subject the sample to thermal cycling... | The BioMark allegedly includes a control device programmed to operate the heat exchange component for thermal cycling. | ¶33 | col. 57:51-54 |
| an excitation source for optically exciting the sample... | The BioMark allegedly comprises a lamp or other excitation source. | ¶34 | col. 57:55-58 |
| a photodetector for detecting temperature-dependent fluorescence levels from the sample | The BioMark allegedly comprises a camera or other photodetector. | ¶34 | col. 57:55-58 |
| a processor programmed to generate a melting curve... during or subsequent to amplification | The BioMark allegedly comprises a processor programmed to generate a melting curve of the amplification product subsequent to amplification. | ¶35 | col. 57:58-61 |
- Identified Points of Contention:
- Scope Questions: A potential dispute may arise over the construction of "processor programmed to generate a melting curve... subsequent to amplification." The question for the court will be whether this language requires the melting curve generation to be part of the same, integrated automated protocol as the amplification, or if it can read on a system where generating the curve is a distinct post-processing step initiated by the user after amplification is complete.
V. Key Claim Terms for Construction
The Term: "monitoring fluorescence while changing temperature" (from ’670 Patent, Claim 76)
Context and Importance: This phrase defines the core action of the asserted method claim. The interpretation of "while changing" is critical to determining infringement. Practitioners may focus on this term because its construction will determine whether performing a series of discrete fluorescence measurements during a temperature ramp meets the limitation, or if a more continuous mode of data acquisition is required.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification discusses acquiring fluorescence "once each cycle," which may support an interpretation that does not require continuous monitoring within a cycle (’670 Patent, col. 4:55-58). The claim language itself does not include the word "continuously."
- Evidence for a Narrower Interpretation: The patent’s detailed description of generating melting curves by heating a sample through its dissociation temperature while observing fluorescence suggests a need for data acquisition during the temperature ramp itself to capture the melting event accurately (’670 Patent, col. 5:1-9, col. 36:3-14).
The Term: "subsequent to amplification" (from ’832 Patent, Claim 1)
Context and Importance: This term establishes the timing of the "generate a melting curve" step relative to the amplification step. Its construction is central because if it is construed to require a tightly integrated, automatic sequence, systems that perform these as separate user-initiated steps may not infringe.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: In its plain meaning, "subsequent" simply means "after." This could support a reading where the processor is programmed with the capability to generate the curve at any time after amplification has concluded, without a requirement for immediate, automated execution.
- Evidence for a Narrower Interpretation: The patent’s overall focus on creating a rapid, integrated system that combines amplification and analysis in one instrument could support a narrower construction where "subsequent to" implies the next step in a single, pre-programmed workflow (’832 Patent, Abstract; col. 2:48-56).
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. It asserts that Defendant's product literature and software (e.g., Melting Temperature Analysis software) instruct and encourage users to perform the patented methods (Compl. ¶¶42, 54, 64, 72). The complaint further alleges the accused system is especially adapted for infringement and lacks substantial non-infringing uses (Compl. ¶¶68, 78).
- Willful Infringement: Willfulness is alleged for all causes of action based on the assertion that Defendant acted in an "objectively reckless manner" with knowledge that its acts were highly likely to infringe Plaintiffs' patent rights (Compl. ¶¶29, 38, 50, 62, 70, 80).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary issue will be one of technical operation: what factual evidence exists to demonstrate that the accused BioMark system, as operated by users, actually monitors fluorescence while changing temperature at a rate of at least 0.1° C. per second, as required by the method claim of the ’670 Patent?
- A key legal issue will be one of definitional scope: can the term "subsequent to amplification" in the system claim of the ’832 Patent be construed to cover a device where melting curve generation is a distinct, user-initiated software function performed after the thermal cycling protocol has finished, or does it require a more integrated, automated process?
- A third core issue will relate to knowledge and intent: for the claims of indirect and willful infringement, the case may turn on what evidence Plaintiffs can produce to establish that Defendant had pre-suit knowledge of the specific patents-in-suit and possessed the specific intent to encourage infringing acts by its customers.