DCT

3:19-cv-03770

Illumina Inc v. BGI Genomics Co Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:19-cv-03770, N.D. Cal., 09/18/2019
  • Venue Allegations: Plaintiff alleges venue is proper in the Northern District of California because several Defendant entities maintain principal places of business and established physical facilities in San Jose, California. For foreign-domiciled Defendants, venue is alleged as proper in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant’s MGISEQ and BGISEQ DNA sequencing systems, and associated reagents, infringe patents related to labeled nucleotides used in sequencing-by-synthesis chemistry.
  • Technical Context: The technology at issue is next-generation DNA sequencing (NGS), a foundational tool in modern genomics, clinical diagnostics, and biomedical research.
  • Key Procedural History: The complaint highlights that the ’537 Patent has been the subject of significant prior legal proceedings. It was previously enforced in an injunction against Qiagen, NV in the same district. Its validity was also upheld by the Patent Trial and Appeal Board (PTAB) and the U.S. Court of Appeals for the Federal Circuit in a challenge brought by Intelligent Bio-Systems. Further, the complaint notes that Defendant Complete Genomics Inc. (CGI) unsuccessfully challenged the ’537 Patent’s validity in two inter partes review (IPR) proceedings, which the PTAB rejected.

Case Timeline

Date Event
2001-12-04 Priority Date for ’537 and ’200 Patents
2009-07-28 ’537 Patent Issued
2015-10-01 Accused BGISEQ-500 Launched (approx.)
2016-05-24 Prior suit filed on ’537 Patent (Illumina v. Qiagen)
2016-08-09 ’200 Patent Issued
2016-11-01 Accused BGISEQ-50 Launched (approx.)
2017-10-01 Accused MGISEQ-200 / MGISEQ-2000 Launched (approx.)
2017-10-05 Alleged date of knowledge based on CGI IPR filings
2018-04-20 PTAB rejects CGI's IPR challenges to the ’537 Patent
2018-10-01 Accused MGISEQ-T7 Launched (approx.)
2019-09-18 Complaint Filed

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

U.S. Patent No. 7,566,537 - "Labelled Nucleotides"

The Invention Explained

  • Problem Addressed: The patent background describes methods for sequencing polynucleotides that are immobilized on a solid support. A key challenge was that modified nucleotides needed for sequencing (i.e., those carrying detectable labels and blocking groups) were often poor substrates for polymerase enzymes, making their incorporation into a growing DNA strand difficult and inefficient. (’537 Patent, col. 1:46-62).
  • The Patented Solution: The invention discloses modified nucleotides designed to overcome this problem. The solution involves attaching a detectable label (like a fluorophore) to the base of the nucleotide via a cleavable linker. The nucleotide also contains a removable blocking group at the 3'-hydroxyl position. This design permits a controlled, cyclical process: a polymerase adds one nucleotide to the DNA strand, its label is detected to identify the base, the label is chemically cleaved off, and the 3' blocking group is removed, preparing the strand for the next cycle. (’537 Patent, Abstract; col. 2:4-19).
  • Technical Importance: This "sequencing-by-synthesis" (SBS) chemistry enabled massively parallel sequencing, allowing millions of DNA fragments to be sequenced simultaneously on a solid surface, a foundational technology for the genomics revolution. (Compl. ¶1).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1. (Compl. ¶46).
  • Claim 1 of the ’537 Patent is a method claim with the following essential elements:
    • A method of labeling a nucleic acid molecule, comprising:
    • incorporating into the nucleic acid molecule a nucleotide or nucleoside molecule,
    • wherein the nucleotide has a base linked to a detectable label via a cleavable linker,
    • and has a ribose or deoxyribose sugar moiety with a protecting group attached via the 2' or 3' oxygen atom,
    • where the protecting group can be modified or removed to expose a 3' OH group,
    • and the protecting group comprises an azido group.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,410,200 - "Labelled Nucleotides"

The Invention Explained

  • Problem Addressed: As a continuation of the same patent family, the ’200 Patent addresses the same technical challenge as the ’537 Patent: enabling efficient and controllable polymerase-mediated, single-base incorporation for massively parallel DNA sequencing. (’200 Patent, col. 1:43-62).
  • The Patented Solution: The ’200 Patent also describes modified nucleotides with a label attached to the base via a cleavable linker and a removable 3'-hydroxyl blocking group. This allows for the same cyclical sequencing-by-synthesis process. (’200 Patent, Abstract; col. 2:21-41).
  • Technical Importance: This technology is a cornerstone of modern high-throughput DNA sequencing, enabling large-scale genomic analysis. (Compl. ¶1).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1. (Compl. ¶124).
  • Claim 1 of the ’200 Patent is a method claim with the following essential elements:
    • A method of labeling a nucleic acid molecule, comprising:
    • incorporating into the nucleic acid molecule a nucleotide molecule using a polymerase,
    • wherein the nucleotide has a base linked to a fluorophore via a cleavable linker,
    • and has a deoxyribose sugar moiety with a protecting group attached via the 3' oxygen atom,
    • where the protecting group can be modified or removed to expose a 3' OH group,
    • and the protecting group comprises an azido group.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants’ "MGISEQ" and "BGISEQ" DNA sequencing systems and related reagents. Specific models identified include the BGISEQ-500, BGISEQ-50, MGISEQ-200, MGISEQ-2000, and MGISEQ-T7. (Compl. ¶¶35, 37).

Functionality and Market Context

The complaint alleges these products are DNA sequencers that perform "stepwise sequencing-by-synthesis (SBS) where 3'-blocked nucleotides are labeled with cleavable fluorescent dyes, which leave behind a molecular ‘scar’ after they are removed." (Compl. ¶36). This description, which the complaint attributes to MGI’s Chief Scientific Officer, outlines a functionality that mirrors the patented methods. The complaint alleges that Defendants have imported, installed, and operated these systems in the United States at a facility in San Jose, California, for research, development, and promotional activities in preparation for entry into North American markets. (Compl. ¶¶7, 38). A map from BGI's website shows its global presence, including locations in San Jose, San Francisco, Los Angeles, and San Diego. (Compl. p. 6). A similar map from MGI Tech's website identifies a "Research Center" and "Commercial and After-Sales Service Center" in San Jose. (Compl. p. 9).

IV. Analysis of Infringement Allegations

’537 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of labeling a nucleic acid molecule, comprising: incorporating into the nucleic acid molecule a nucleotide... The accused MGISEQ and BGISEQ systems perform sequencing-by-synthesis (SBS), which incorporates nucleotides into DNA strands. ¶36, 38 col. 10:48-54
wherein the nucleotide has a base that is linked to a detectable label via a cleavable linker... The accused systems allegedly use nucleotides labeled with "cleavable fluorescent dyes" attached to the base. ¶36 col. 5:3-9
and has a ribose or deoxyribose sugar moiety with a protecting group attached via the... 3' oxygen atom... The accused systems allegedly use "3'-blocked nucleotides" to control stepwise incorporation. ¶36 col. 8:1-3
where the protecting group can be modified or removed to expose a 3' OH group, and the protecting group comprises an azido group. The complaint does not specify the chemical nature of the 3' blocking group but alleges the use of 3'-blocked nucleotides generally. Infringement of this element requires the specific blocking group to be an azido group. ¶36 col. 13:58-61

’200 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of labeling a nucleic acid molecule, comprising: incorporating into the nucleic acid molecule a nucleotide molecule using a polymerase... The accused MGISEQ and BGISEQ systems perform sequencing-by-synthesis (SBS), which uses a polymerase to incorporate nucleotides. ¶36, 42 col. 13:50-67
wherein the nucleotide has a base that is linked to a fluorophore via a cleavable linker... The accused systems allegedly use nucleotides labeled with "cleavable fluorescent dyes" (fluorophores) attached to the base. ¶36 col. 5:3-17
and has a deoxyribose sugar moiety with a protecting group attached via the 3' oxygen atom... The accused systems allegedly use "3'-blocked nucleotides" to control stepwise incorporation. ¶36 col. 8:1-3
where the protecting group can be modified or removed to expose a 3' OH group, the protecting group comprising an azido group. The complaint does not specify the chemical nature of the 3' blocking group but alleges the use of 3'-blocked nucleotides generally. Infringement of this element requires the specific blocking group to be an azido group. ¶36 col. 13:58-61

Identified Points of Contention

  • Technical Questions: A primary factual question will be the specific chemical structure of the reagents used in the accused systems. The complaint alleges the use of "3'-blocked nucleotides" generally (Compl. ¶36), but the asserted claims require that the blocking group specifically "comprises an azido group." The complaint does not provide evidence on this specific chemical point, which will be a focus of discovery.
  • Scope Questions: The complaint alleges the accused chemistry leaves behind a "molecular ‘scar’ after [the dyes] are removed." (Compl. ¶36). This raises the question of whether this process falls within the scope of the term "cleavable linker" as understood in the patents. A dispute may arise over whether the specific chemical cleavage mechanism used by Defendants is taught by or equivalent to the linkers disclosed in the patent specifications.

V. Key Claim Terms for Construction

  • The Term: "cleavable linker"

    • Context and Importance: This term is central to the patented method. The infringement analysis will depend on whether the chemical bond connecting the fluorescent dye to the nucleotide base in the accused products meets the definition of a "cleavable linker." Practitioners may focus on this term because the complaint's allegation of a residual "molecular scar" suggests the cleavage mechanism could be a point of technical dispute. (Compl. ¶36).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specifications of both the ’537 Patent and the ’200 Patent disclose a wide variety of chemical structures that can serve as cleavable linkers, including disulfide linkers, acid labile linkers (such as Sieber and dialkoxybenzyl linkers), and photocleavable linkers. (’537 Patent, col. 6:9-13, Fig. 2). This variety may support a construction not limited to any single chemical embodiment.
      • Evidence for a Narrower Interpretation: A defendant may argue that the term should be limited by the specific examples disclosed in the specification or by statements made during patent prosecution. The specific chemical properties of the linkers shown in the patents (e.g., those that cleave to leave no residual structure on the base) might be used to argue that linkers leaving a "scar" are outside the scope.

  • The Term: "protecting group comprises an azido group"

    • Context and Importance: This is a specific chemical limitation present in the asserted independent claims of both patents. A finding of literal infringement will require factual proof that the 3' blocking group used in Defendants’ reagents is, or contains, an azido group (–N₃).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specifications list the azido group as one of several suitable protecting groups. (’537 Patent, col. 8:1-3; col. 13:58-61). While its inclusion in the claim language is limiting, a plaintiff might argue for a broader interpretation under the doctrine of equivalents if the accused group performs the same function in substantially the same way to achieve the same result.
      • Evidence for a Narrower Interpretation: The plain language of the claim itself provides the strongest evidence for a narrow interpretation, as it explicitly recites this specific chemical moiety. Unlike more functional terms, "azido group" has a precise and well-understood chemical meaning, leaving little room for construction beyond its literal definition.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement against all Defendants. Inducement is alleged based on the promotion of the accused systems and the distribution of user manuals, reagent kit handbooks, and pre-programmed software protocols that instruct and encourage users to perform the patented methods. (Compl. ¶¶ 53-58, 131-136). Contributory infringement is alleged on the basis that the accused sequencers and specialized reagent kits are material components of the patented invention, are not staple articles of commerce, and have no substantial non-infringing uses. (Compl. ¶¶ 61-62, 139-140).
  • Willful Infringement: Willfulness is alleged based on Defendants’ purported knowledge of the patents-in-suit. This knowledge is alleged to arise from the patents' prominence in the field, prior successful litigation against a competitor (Qiagen), and specifically from Defendant CGI’s own failed inter partes review petitions filed against the ’537 Patent, which established knowledge as of at least October 5, 2017. (Compl. ¶¶ 63, 141).

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

  • A central issue will be one of chemical fact-finding: do the reagents used in the accused MGISEQ and BGISEQ systems utilize nucleotides with a 3'-hydroxyl protecting group that "comprises an azido group," as explicitly required by the asserted claims? The complaint alleges the use of "3'-blocked" nucleotides but does not provide specific evidence on the chemical identity of that blocking group.
  • A key question of claim scope and equivalence will be: does the accused method of removing the fluorescent dye, which the complaint states leaves a "molecular scar," fall within the literal or equivalent scope of the term "cleavable linker" as defined by the patents? The case may turn on whether this alleged technical difference is sufficient to place the accused systems outside the bounds of the claims.
  • Given the extensive litigation history of the ’537 Patent, including its survival of multiple PTAB challenges (one initiated by a Defendant), a core question for the willfulness and damages analysis will be whether Defendants’ continued activities in the U.S. market constitute egregious misconduct warranting enhanced damages.