DCT

4:18-cv-00525

NuGen Tech Inc v. Keygene NV

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 4:18-cv-00525, N.D. Cal., 01/24/2018
  • Venue Allegations: Plaintiff alleges venue is proper because Defendants are subject to personal jurisdiction in the district, having directed enforcement efforts at Plaintiff, a resident of the district, through written correspondence and in-person meetings.
  • Core Dispute: Plaintiff seeks a declaratory judgment that its next-generation sequencing products do not infringe two of Defendants' patents related to high-throughput genetic polymorphism detection and that those patents are invalid.
  • Technical Context: The technology at issue involves methods for identifying genetic variations (polymorphisms) in DNA by combining complexity reduction techniques with high-throughput sequencing, a foundational process in modern genomics, plant breeding, and medical diagnostics.
  • Key Procedural History: The action was filed after Defendants sent letters to Plaintiff in December 2017 and January 2018, accusing Plaintiff's products of infringement, providing exemplary claim charts, and proposing a meeting to resolve the allegations. The complaint notes that Defendants have previously initiated separate patent litigation in the District of Oregon.

Case Timeline

Date Event
2005-09-29 U.S. Patent 9,745,627 Priority Date
2005-12-22 U.S. Patent 9,702,004 Priority Date
2017-07-11 U.S. Patent 9,702,004 Issues
2017-08-14 KeyGene representatives meet with NuGEN in San Carlos, CA
2017-08-29 U.S. Patent 9,745,627 Issues
2017-12-13 KeyGene sends letter alleging infringement to NuGEN
2018-01-09 KeyGene's counsel sends letter with claim charts to NuGEN
2018-01-24 Complaint for Declaratory Judgment Filed

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

U.S. Patent No. 9,702,004 - Method for high-throughput AFLP-based polymorphism detection, Issued July 11, 2017

The Invention Explained

  • Problem Addressed: The patent describes that conventional methods for detecting genetic markers, such as Amplified Fragment Length Polymorphism (AFLP), are limited by the resolving power of electrophoresis and the high cost of traditional Sanger sequencing, which restricts throughput and the ability to capture all polymorphisms in a sample (’004 Patent, col. 2:34-58).
  • The Patented Solution: The invention claims a method that combines the AFLP technique—which reduces the complexity of a genomic sample by digesting DNA and selectively amplifying a subset of the resulting fragments—with modern high-throughput sequencing (’004 Patent, col. 3:12-24). By sequencing the AFLP fragments instead of just measuring their size, the method professes to increase the number of detectable markers and enable more accurate "co-dominant" genotyping, where both alleles in a heterozygous individual can be identified (’004 Patent, Abstract; col. 2:51-53).
  • Technical Importance: This approach sought to provide a more economically feasible and comprehensive platform for large-scale polymorphism discovery, a critical need for applications like plant breeding and genetic mapping (’004 Patent, col. 1:47-54).

Key Claims at a Glance

  • The complaint refers to allegations against the "independent claims" without specifying claim numbers (Compl. ¶11). Claim 1 is the first independent claim.
  • Essential elements of Independent Claim 1 include:
    • Ligating an adaptor to a nucleic acid fragment.
    • Amplifying the adaptor-ligated fragment to produce a library where the fragments comprise an identifier tag.
    • Sequencing a pool of two or more such libraries using high-throughput sequencing, where each library has a unique identifier tag.
    • Clustering the sequences per library and determining the genotypes of polymorphisms.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,745,627 - High Throughput Screening of Populations Carrying Naturally Occurring Mutations, Issued August 29, 2017

The Invention Explained

  • Problem Addressed: The patent identifies shortcomings in prior art mutation screening techniques, such as TILLING, which rely on enzymes like CEL I. These methods are described as cumbersome, unreliable, insensitive to mutations near the ends of DNA fragments, and unable to distinguish between functionally significant (non-sense) and insignificant (missense) mutations without follow-up sequencing (’627 Patent, col. 3:1-14).
  • The Patented Solution: The invention discloses a method to screen large populations for mutations by pooling DNA samples, amplifying a target sequence using primers that incorporate unique "tags" for different sample pools, and then using high-throughput sequencing on the combined products (’627 Patent, Abstract). By clustering the resulting sequences and using the tags to trace a mutation back to its original sample pool, the method aims to provide a more direct and efficient way to identify individuals carrying specific genetic variations (’627 Patent, col. 6:18-40).
  • Technical Importance: The claimed method aimed to replace indirect, enzyme-based mutation detection with a direct sequencing-based approach, thereby increasing the efficiency, sensitivity, and scale of genetic screening in research and development (’627 Patent, col. 2:56-62).

Key Claims at a Glance

  • The complaint refers to allegations against the "independent claims" without specifying claim numbers (Compl. ¶11). Claim 1 is the first independent claim.
  • Essential elements of Independent Claim 1 include:
    • Tagging each of a plurality of nucleic acid molecules with a plurality of tags to create a set of tagged molecules.
    • Amplifying the set of tagged molecules.
    • Sequencing the amplification products with multi-fold redundancy.
    • Aligning the sequence reads to identify the genetic variation.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

  • Product Identification: The accused products are Plaintiff’s "next-generation sequencing products," specifically identified as the "Ovation® Target Enrichment System and Allegro Targeted Genotyping" (Compl. ¶¶10, 13, 16).
  • Functionality and Market Context: The complaint characterizes the accused products as "biological science reagents" for use in next-generation sequencing (Compl. ¶¶2, 11). The infringement allegations from Defendants, as cited in the complaint, are based on the theory that the "product manuals... instruct users to perform steps that fall squarely within the scope of each step of at least the independent claims of the KeyGene patents" (Compl. ¶11). This suggests the products are kits or systems used to prepare DNA libraries for sequencing, and the core of the dispute centers on the methods that these products enable or instruct users to perform. The complaint does not provide further technical detail on the operation of the products.

IV. Analysis of Infringement Allegations

The complaint references "exemplary claim charts" provided by Defendants' counsel, but these charts are not included as exhibits with the complaint (Compl. ¶11). Therefore, a detailed element-by-element analysis is not possible from the provided documents.

No probative visual evidence provided in complaint.

  • Summary of Alleged Infringement:
    • ’004 Patent: Defendants allege that Plaintiff indirectly infringes the ’004 Patent (Compl. ¶11). The theory of infringement appears to be that the product manuals for the Ovation® Target Enrichment System and Allegro Targeted Genotyping products instruct customers to perform a method of preparing and sequencing tagged DNA libraries that meets all the limitations of the patent's method claims (Compl. ¶¶10-11, 16-18).
    • ’627 Patent: Defendants likewise allege indirect infringement of the ’627 Patent (Compl. ¶11). The alleged basis is that Plaintiff’s product manuals instruct users to prepare and sequence tagged DNA from various samples in a manner that constitutes performance of the patented method for high-throughput mutation screening (Compl. ¶¶10-11, 30).
  • Identified Points of Contention:
    • Technical Questions: A primary technical question for the ’004 patent is whether the accused Ovation® and Allegro products, which are described as "Target Enrichment" and "Targeted Genotyping" systems, practice the specific "AFLP-based" polymorphism detection method claimed in the patent. The court may need to determine if there is a fundamental mismatch between the AFLP technique (requiring restriction enzymes) and the technology employed by Plaintiff’s products.
    • Scope Questions: The infringement analysis for both patents will likely depend on the construction of key method steps. For the ’627 Patent, a central question is whether the claimed step of "tagging each of a plurality of nucleic acid molecules" is limited to the primer-based tagging shown in the embodiments or if it can be construed more broadly to cover other forms of sample indexing potentially used in Plaintiff’s systems.

V. Key Claim Terms for Construction

  • For the ’004 Patent:

    • The Term: "amplifying the ... restriction fragments ... to produce a library of ... fragments, wherein the amplified ... fragments comprise an identifier tag" (derived from claim 1).
    • Context and Importance: This limitation is central because the dispute involves kits that instruct users on preparing DNA libraries. The definition of how fragments are amplified and how they come to "comprise an identifier tag" will be critical to the infringement analysis, particularly for the indirect infringement claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification describes a tag generally as "a short sequence that can be added to a primer ... to provide a unique identifier" (’004 Patent, col. 5:6-9). This could support a reading that covers various forms of sequence-based identifiers.
      • Evidence for a Narrower Interpretation: The patent is titled "AFLP-based" and its background and embodiments are grounded in the AFLP technique. A party could argue the claims should be limited to that context, where tags are incorporated into primers used for selective amplification of restriction fragments, as depicted in Figure 1B (’004 Patent, Fig. 1B; col. 13:10-15).

  • For the ’627 Patent:

    • The Term: "tagging each of a plurality of nucleic acid molecules using a plurality of tags" (from claim 1).
    • Context and Importance: As the first step of the method, the construction of "tagging" is foundational. Whether this term is construed broadly to cover any method of affixing a unique sequence to a sample, or narrowly to the specific primer-based approach in the embodiments, could determine the outcome of the infringement question. Practitioners may focus on this term because different library preparation kits use distinct molecular strategies for sample indexing.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent provides a broad definition: "'Tagging' refers to the addition of a tag or label to a nucleic acid in order to be able to distinguish it from a second or further nucleic acid" (’627 Patent, col. 5:1-4). This language may support an interpretation covering various molecular tagging strategies.
      • Evidence for a Narrower Interpretation: The embodiments appear to implement tagging in a specific manner: "By using primers ... containing a tag sequence that is unique for each of the primers representing all pool dimensions, the specific plant origin of each tag sequence is known" (’627 Patent, col. 9:28-33). This could be used to argue that "tagging" in the context of the invention requires incorporation via amplification primers.

VI. Other Allegations

  • Indirect Infringement: The complaint states that Defendants' allegations expose Plaintiff to claims of "indirect (e.g., induced) infringement" (Compl. ¶11). The factual basis alleged by Defendants is that Plaintiff's "product manuals available for each of the NuGEN products instruct users to perform steps that fall squarely within the scope of each step of at least the independent claims" (Compl. ¶11).
  • Willful Infringement: The complaint, being a declaratory judgment action by the accused infringer, does not allege willfulness. However, it documents pre-suit communications from Defendants on December 13, 2017, and January 9, 2018, which provided notice of the patents-in-suit and the specific allegations of infringement (Compl. ¶¶10-11). These facts could form the basis for a willfulness counterclaim by Defendants based on alleged pre-suit and ongoing post-suit knowledge of infringement.

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

  1. A central issue will be one of technical application: Do Plaintiff’s "Target Enrichment" and "Targeted Genotyping" products, when used as instructed, practice the specific "AFLP-based" methodology that is a cornerstone of the ’004 patent, or do they rely on a distinct, non-infringing technology for reducing sample complexity?
  2. A key legal question will be one of claim scope: Can the terms "tagging" (’627 patent) and "comprise an identifier tag" (’004 patent) be construed broadly enough to read on the sample indexing methods instructed by Plaintiff’s kits, or are they implicitly limited by the patent specifications to the specific primer-based amplification context described in the embodiments?
  3. A critical evidentiary question for the indirect infringement claims will be one of instruction and intent: Do Plaintiff's product manuals affirmatively instruct users to perform every limitation of the asserted method claims, and did Plaintiff distribute its products with the specific intent to encourage its customers to infringe Defendants' patents?