DCT
1:17-cv-00275
Pacific Biosciences Of California Inc v. Oxford Nanopore Tech Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Pacific Biosciences of California, Inc. (Delaware Corp.; California PPoB)
- Defendant: Oxford Nanopore Technologies, Inc. (Delaware Corp.; Massachusetts PPoB)
- Plaintiff’s Counsel: Farnan LLP; Weil, Gotshal & Manges LLP
- Case Identification: 1:17-cv-00275, D. Del., 03/15/2017
- Venue Allegations: Venue is based on Defendant being a Delaware corporation.
- Core Dispute: Plaintiff alleges that Defendant’s nanopore-based single-molecule sequencing products infringe a patent related to methods for sequencing a nucleic acid template using N-mer analysis.
- Technical Context: The dispute is situated in the competitive market for single-molecule DNA sequencing, a technology that enables the determination of long stretches of a DNA sequence in a single pass.
- Key Procedural History: The complaint alleges that Defendant had pre-suit knowledge of the technology, citing a PacBio parent application during the prosecution of its own patent application in March 2016. The complaint also notes the existence of an ongoing International Trade Commission (ITC) investigation involving the parties.
Case Timeline
| Date | Event |
|---|---|
| 2009-04-10 | '400 Patent Priority Date |
| 2015 | Oxford begins commercializing single-molecule sequencing products |
| 2016-03-21 | Oxford cites parent application of '400 Patent in its own prosecution |
| 2017-01-17 | '400 Patent Issue Date |
| 2017-03-15 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,546,400 - "Nanopore Sequencing Using N-mers"
- Patent Identification: U.S. Patent No. 9,546,400, "Nanopore Sequencing Using N-mers," issued January 17, 2017.
The Invention Explained
- Problem Addressed: The patent describes that prior nanopore sequencing devices were generally not capable of achieving single-nucleotide resolution, making it difficult to accurately determine a DNA sequence. (’400 Patent, col. 1:50-53).
- The Patented Solution: The invention proposes a method that does not require single-base resolution. Instead of analyzing one nucleotide at a time, it measures an electrical property (e.g., current) that is influenced by a group of multiple ("N-mer") nucleotides simultaneously present in the nanopore. This measured signal is then compared against "calibration information"—a pre-established set of signal data for known N-mer combinations—to determine the DNA sequence. (’400 Patent, Abstract; col. 5:4-16). Figure 29 of the patent illustrates an algorithm for using a lookup table of voltage levels for possible sequence contexts to determine the correct sequence. (’400 Patent, Fig. 29).
- Technical Importance: This N-mer analysis approach provides a method for obtaining sequence information even when the underlying measurement system cannot distinguish between individual adjacent nucleotides. (’400 Patent, Abstract).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2-8, 10, 14, and 15 (Compl. ¶22).
- Independent Claim 1 recites a method with the following essential elements:
- Providing a substrate with a nanopore containing a template nucleic acid.
- Providing a voltage across the nanopore.
- Measuring a property (e.g., current) that varies based on N monomeric units (where N is three or greater) as the nucleic acid translocates through the pore.
- Determining the sequence by comparing the measured property to calibration information that was produced by measuring that same property for known sequence combinations.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Defendant’s MinION and PromethION single-molecule sequencing instruments, along with their associated reagents, consumables, and software (Compl. ¶13). The complaint provides a photograph of a representative MinION device and its flow cell component (Compl. ¶13, Figure 4).
Functionality and Market Context
- The complaint alleges that the accused products operate by passing a strand of DNA through a protein nanopore embedded in a membrane (Compl. ¶¶ 13-15). As the DNA translocates, it disrupts an electrical current, producing a signal. Crucially, the complaint alleges this signal arises not from a single DNA base, but from a "contiguous group of DNA bases" that interacts with the nanopore at a given time (Compl. ¶16). The complaint includes a diagram illustrating a strand of DNA being drawn through a nanopore, disrupting an electrical current (Compl. ¶15, Exhibit 7). To determine the sequence, the system allegedly "uses calibration information produced by measuring the signals from the different combinations of bases that may interact with the nanopore at a given time" (Compl. ¶16). The products are positioned as competitors to PacBio in the market for "long read" single-molecule sequencing (Compl. ¶12).
IV. Analysis of Infringement Allegations
'400 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a) providing a substrate comprising a nanopore in contact with a solution, the solution comprising a template nucleic acid above the nanopore; | Oxford's products include a sequencing instrument with a nanopore-containing membrane in contact with a solution containing the nucleic acid to be sequenced. | ¶18 | col. 2:1-5 |
| b) providing a voltage across the nanopore; | A voltage is applied across the membrane to drive an electrical current. | ¶18 | col. 3:25-29 |
| c) measuring a property which has a value that varies for N monomeric units of the template nucleic acid in the pore...wherein N is three or greater... | As a nucleic acid is drawn through the pore, the electrical current is disrupted in a manner that varies based on a group of N monomeric units (where N ≥ 3) interacting with the pore. | ¶18 | col. 5:32-34 |
| d) determining the sequence...by performing a process including comparing the measured property from step (c) to calibration information produced by measuring such property for 4 to the N sequence combinations. | An artificial neural network compares the measured signal to calibration information derived from signals of known base combinations to determine the nucleic acid sequence. | ¶18 | col. 5:20-28 |
- Identified Points of Contention:
- Scope Questions: A central issue may be the construction of "calibration information." The question for the court will be whether the training process and resulting model of Oxford’s alleged "artificial neural network" (Compl. ¶18) falls within the scope of the patent's term, which is described as being "produced by measuring" the property for known sequence combinations (’400 Patent, cl. 1).
- Technical Questions: A key factual dispute will likely concern whether Oxford's products actually perform the method recited in step (c). Specifically, what evidence does the complaint provide that the signal measured by the accused products "varies for N monomeric units... wherein N is three or greater"? While the complaint alleges this (Compl. ¶18), proof will require technical evidence from discovery regarding the operation of Oxford's signal processing algorithms.
V. Key Claim Terms for Construction
- The Term: "calibration information"
- Context and Importance: This term is the crux of the inventive method. The infringement case depends on whether the data and models used by Oxford's accused sequencers meet this definition. Practitioners may focus on this term because the allegation of an "artificial neural network" (Compl. ¶18) may not map directly onto the patent's exemplary disclosure of a "lookup table" (’400 Patent, Fig. 29).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language broadly defines the information as being "produced by measuring such property for 4 to the N sequence combinations" (’400 Patent, cl. 1), which could be argued to encompass any data set derived from known sequences used to train a predictive model.
- Evidence for a Narrower Interpretation: The specification provides an exemplary algorithm in Figure 29 that uses an explicit "lookup table of voltage levels for each possible sequence context." A party could argue this embodiment suggests "calibration information" refers to a pre-compiled, discrete data table, rather than the distributed weights of a trained neural network.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement, stating that Oxford knows and intends for its customers to infringe by using the MinION and PromethION instruments as instructed (Compl. ¶24). The allegations are supported by references to Oxford’s "promotional and marketing materials," "distribution channels," customer "starter packs," and "instructional materials" (Compl. ¶¶ 25-27).
- Willful Infringement: Willfulness is alleged based on pre-suit knowledge. The complaint asserts that Oxford cited the parent application of the ’400 Patent during its own patent prosecution on March 21, 2016, nearly a year before the suit was filed, and that Oxford has monitored PacBio's patent filings (Compl. ¶23).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim construction: can the term "calibration information," which the patent illustrates with an exemplary "lookup table," be construed broadly enough to read on the trained "artificial neural network" that Oxford allegedly uses to interpret sequencing data?
- A key evidentiary question will be one of technical proof: what evidence will discovery yield about the internal workings of Oxford’s accused software, and will that evidence demonstrate that the system’s signal analysis is in fact based on a "contiguous group" of three or more DNA bases, as required by the patent and alleged in the complaint?