DCT

1:19-cv-00862

10X Genomics Inc v. Celsee Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00862, D. Del., 05/08/2019
  • Venue Allegations: Venue is asserted in the District of Delaware on the basis that Defendant Celsee, Inc. is a Delaware corporation and therefore resides in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s Genesis System for single-cell analysis infringes five patents related to methods for preparing and analyzing nucleic acids from single cells using a two-level barcoding system.
  • Technical Context: The technology is single-cell genomics, a field that enables researchers to analyze the genetic material of individual cells, which provides a higher resolution of biological information compared to older "bulk" methods that average data across many cells.
  • Key Procedural History: The complaint alleges that Defendant was "built to copy 10x's technology," has monitored Plaintiff's patent filings, and has copied Plaintiff's job postings verbatim. These allegations, if substantiated, may be relevant to the claims of willful infringement.

Case Timeline

Date Event
2009-08-20 Earliest Priority Date for ’981, ’197, and ’459 Patents
2012-01-01 Plaintiff 10x Genomics, Inc. founded
2012-12-14 Earliest Priority Date for ’648 Patent
2013-03-15 Earliest Priority Date for ’541 Patent
2015-02-01 Plaintiff launches GemCode product
2016-01-01 Plaintiff launches successor Chromium product line
2018-06-15 Accused Product (Genesis System) launched (approx. mid-2018)
2018-12-18 ’981 Patent Issues
2019-03-12 ’648 Patent Issues
2019-03-26 ’197 Patent Issues
2019-04-30 ’541 Patent Issues
2019-05-07 ’459 Patent Issues
2019-05-08 Complaint Filed

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

U.S. Patent No. 10,155,981 - "Methods for analyzing nucleic acids from single cells" (Issued Dec. 18, 2018)

The Invention Explained

  • Problem Addressed: The patent's background section describes limitations of prior art DNA sequencing technologies where fragmentation of a genome prevents the ability to link sequence changes that are physically distant from each other on the same chromosome (e.g., haplotyping) ('981 Patent, col. 1:39-44).
  • The Patented Solution: The invention provides methods for analyzing nucleic acids from single cells by generating "tagged polynucleotides" that contain a "multiplex identifier" (MID) ('981 Patent, Abstract). This MID comprises two distinct tag sequences: a first tag to identify the cell of origin, and a second tag to uniquely identify the original molecule within that cell ('981 Patent, Claims 1(b)(ii)(I-II)). This dual-barcoding system allows for pooling nucleic acids from many cells while retaining the ability to trace each resulting sequence read back to both its cell of origin and its molecule of origin, thereby preserving linkage information ('981 Patent, col. 2:25-39; FIG. 5).
  • Technical Importance: This approach enables large-scale, high-throughput single-cell analysis, allowing researchers to maintain critical linkage information (e.g., for determining haplotypes) that is lost with conventional bulk sequencing methods ('981 Patent, FIG. 5).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶39).
  • The essential elements of claim 1 include:
    • Providing a sample comprising a plurality of single cells.
    • Generating tagged polynucleotides from the sample polynucleotides of the single cells.
    • Each tagged polynucleotide comprises a sequence from a sample polynucleotide and a multiplex identifier (MID).
    • The MID itself comprises two distinct parts: (1) a "first tag sequence" associated with the single cell of origin, and (2) a "second tag sequence" to distinguish the sample polynucleotide from other polynucleotides derived from the same cell.
    • Sequencing the tagged polynucleotides.
    • Using the first tag to correlate the sequence to the cell and the second tag to correlate the sequence to the original sample polynucleotide.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 10,240,197 - "Methods for analyzing nucleic acids from single cells" (Issued Mar. 26, 2019)

The Invention Explained

  • Problem Addressed: The ’197 Patent shares a specification with the ’981 Patent and addresses the same technical problem: the loss of linkage information between different parts of a single chromosome when using conventional sequencing methods that rely on fragmentation (’197 Patent, col. 1:39-44).
  • The Patented Solution: The patented solution is functionally identical to that of the ’981 Patent, employing a dual-level tagging system to label nucleic acids from single cells (’197 Patent, Abstract). The first tag identifies the cell of origin, while the second tag uniquely identifies the original nucleic acid molecule from within that cell. This allows for massive pooling and sequencing while preserving the data's original context (’197 Patent, col. 2:25-39; FIG. 5).
  • Technical Importance: As with the ’981 Patent, this method is significant for enabling high-throughput single-cell genomics and preserving long-range genetic information, which is critical for applications like haplotyping (’197 Patent, FIG. 5).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶47).
  • The essential elements of claim 1 include:
    • Providing a sample with a plurality of cells.
    • Generating tagged polynucleotides where each tag has two parts: (1) a "first tag sequence" distinguishing the polynucleotide from those from other cells, and (2) a "second tag sequence" distinguishing it from other polynucleotides from the same cell.
    • Sequencing the tagged polynucleotides.
    • Using both tag sequences to "count a number of sample polynucleotides."
  • The complaint does not explicitly reserve the right to assert dependent claims.

Multi-Patent Capsule: U.S. Patent No. 10,227,648

  • Patent Identification: U.S. Patent No. 10,227,648, "Methods and systems for processing polynucleotides," issued March 12, 2019.
  • Technology Synopsis: The patent addresses the need for improved control over polynucleotide fragmentation for sequencing. It discloses methods that generate non-overlapping fragments of a target polynucleotide, which can be barcoded, pooled, and sequenced (’648 Patent, Abstract; col. 2:28-46).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶56).
  • Accused Features: The complaint alleges that the Celsee Genesis System and its associated accessories and reagents infringe the ’648 Patent (Compl. ¶56).

Multi-Patent Capsule: U.S. Patent No. 10,273,541

  • Patent Identification: U.S. Patent No. 10,273,541, "Methods and systems for processing polynucleotides," issued April 30, 2019.
  • Technology Synopsis: The patent describes methods and systems for analyzing nucleic acids from individual cells by generating nucleic acid sequences attached to oligonucleotides that comprise a common barcode. This allows for the characterization and identification of nucleic acid sequences as being derived from an individual cell (’541 Patent, col. 2:10-31).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶65).
  • Accused Features: The complaint alleges that the Celsee Genesis System and its associated accessories and reagents infringe the ’541 Patent (Compl. ¶65).

Multi-Patent Capsule: U.S. Patent No. 10,280,459

  • Patent Identification: U.S. Patent No. 10,280,459, "Methods for analyzing nucleic acids from single cells," issued May 7, 2019.
  • Technology Synopsis: This patent is in the same family as the ’981 and ’197 patents. It describes methods for analyzing nucleic acids from single cells using a two-level tagging system, comprising a first tag to identify the cell and a second tag to identify the molecule within that cell, to preserve linkage information during sequencing (’459 Patent, Abstract; col. 2:25-39).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶74).
  • Accused Features: The complaint alleges that the Celsee Genesis System and its associated accessories and reagents infringe the ’459 Patent (Compl. ¶74).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the Celsee Genesis System and its associated accessories and reagents, including its Celsingle Technology and Celsingle Slides (Compl. ¶12, ¶17, ¶18). A photograph of the instrument is provided in the complaint (Compl. p. 4).

Functionality and Market Context

  • The Genesis System is designed to "capture and isolate single cells" for molecular analysis (Compl. ¶14). The system allegedly pairs isolated cells with a "unique cellular barcode and unique molecular indices" (Compl. ¶14). The complaint refers to this as "dual tagging," which allows a user to track both a molecule of interest and its cell of origin (Compl. ¶15). A workflow diagram in the complaint illustrates a four-step process of Sample Prep, Isolation, Detection, and Analysis, with the Analysis step including "Cell Barcode Counting" and "UMI Counting" (unique molecular indices) (Compl. p. 5).
  • The product is positioned to compete directly with Plaintiff's Chromium product line (Compl. ¶12). Celsee allegedly markets the Genesis System as having superior performance, including a cell capture rate of over 70% (Compl. ¶28), a claim Plaintiff alleges is false and misleading (Compl. ¶30).

IV. Analysis of Infringement Allegations

The complaint references, but does not include, claim chart attachments detailing the infringement allegations (Compl. ¶39, ¶47). In the absence of these exhibits, the infringement theory is summarized based on the complaint's narrative allegations.

Plaintiff's core infringement theory appears to center on the Genesis System's "dual tagging" functionality (Compl. ¶15). The complaint alleges the system pairs single cells with a "unique cellular barcode" to identify the cell of origin, and also with "unique molecular indices" to identify individual molecules within that cell (Compl. ¶14). This alleged two-level barcoding system maps conceptually to the key limitations of the asserted independent claims of the ’981 and ’197 patents, which require a "first tag sequence" associated with the single cell and a "second tag sequence" for distinguishing polynucleotides from within that same cell. The infringement allegation is that Celsee's "cellular barcode" meets the "first tag sequence" limitation, and its "unique molecular indices" meet the "second tag sequence" limitation.

  • Identified Points of Contention:
    • Scope Questions: A primary question for claim construction may be whether the term "multiplex identifier (MID) sequence" as defined and used in the patents-in-suit encompasses the combination of a "cellular barcode" and "unique molecular indices" as allegedly used in the Genesis System. The court will need to determine the scope of the two-part tag structure required by the claims.
    • Technical Questions: The complaint does not describe the specific technical mechanism by which the Genesis System pairs cells with barcodes and molecular indices. A key factual question for the litigation will be what evidence demonstrates that the accused system's actual method of operation—allegedly using "Celsingle Slides" (Compl. ¶17)—performs the steps of "generating a plurality of tagged polynucleotides" as recited in the asserted method claims.

V. Key Claim Terms for Construction

  • The Term: "multiplex identifier (MID) sequence" (appearing in, e.g., '981 Patent, Claim 1)

  • Context and Importance: This term is central to the claimed invention, as it defines the dual-barcoding structure. Practitioners may focus on this term because the defendant will likely argue that its two separate tags ("cellular barcode" and "unique molecular indices") do not constitute a single "multiplex identifier sequence" as contemplated by the patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification defines a MID broadly as a "tag or combination of tags associated with a polynucleotide whose identity... can be used to differentiate polynucleotides in a sample" ('981 Patent, col. 6:33-36). This language suggests a functional definition that could encompass a combination of two distinct tags.
    • Evidence for a Narrower Interpretation: The patent's detailed description illustrates the MID as part of a unitary oligonucleotide structure used in a specific "reflex process" ('981 Patent, Fig. 1A-B, Fig. 3). A defendant may argue that the term's meaning should be narrowed by these embodiments to a single, pre-fabricated oligonucleotide containing both tags.

  • The Term: "a first tag sequence associated with the single cell" and "a second tag sequence distinguishing the sample polynucleotide from other sample polynucleotides derived from the same single cell" (appearing in, e.g., '981 Patent, Claim 1)

  • Context and Importance: The definition of these two parallel limitations will determine whether the accused product's two-tag system performs the distinct functions required by the claim. The dispute will likely focus on whether Celsee's tags truly perform these separate roles as claimed.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim language is functional, describing what the tags do (associate with a cell vs. distinguish molecules within a cell). This could support a reading that covers any two tags that achieve these distinct results, regardless of their specific chemical structure or method of attachment.
    • Evidence for a Narrower Interpretation: The specification provides examples where MIDs are employed to "uniquely tag each individual polynucleotide in a sample" ('981 Patent, col. 6:45-53). A defendant might argue that the term "associated with the single cell" implies a more direct and specific form of association than what is practiced by the accused system.

VI. Other Allegations

  • Indirect Infringement: The complaint includes a general allegation of direct, contributory, and induced infringement (Compl. ¶35). However, the specific facts alleged in the body of the complaint and the individual causes of action focus on direct infringement and do not provide sufficient detail for analysis of knowledge or specific intent required for indirect infringement claims.
  • Willful Infringement: The complaint alleges willful infringement for all five patents based on Defendant’s alleged regular monitoring of Plaintiff’s patent portfolio (Compl. ¶41, ¶50, ¶59, ¶68, ¶77). The complaint specifically alleges Defendant knew or should have known of each patent at least as of its issue date (e.g., Compl. ¶42). This allegation is further supported by broader claims that Defendant was "built to copy 10x's technology" (Compl. ¶19).

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

  • A core issue will be one of definitional scope: can the claimed two-part "multiplex identifier" be construed to read on the accused system's use of a "cellular barcode" in combination with "unique molecular indices"? This will likely be a central focus of claim construction.
  • A key evidentiary question will be one of operational equivalence: what evidence will show that the accused Genesis System's method of isolating cells and pairing them with tags on "Celsingle Slides" performs the specific method steps of "generating a plurality of tagged polynucleotides" as required by the asserted claims?
  • A central question for damages will be willfulness: given the complaint's allegations of intentional copying that extend beyond the accused technology to ancillary business materials like job postings, the court will likely need to evaluate whether any infringement was egregious enough to warrant enhanced damages.