DCT

1:24-cv-00911

Illumina Inc v. Molecular Loop Biosciences Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: Illumina, Inc. v. Molecular Loop Biosciences, Inc., No. 1:24-cv-00911, D. Mass., 06/09/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Massachusetts because Defendant Molecular Loop Biosciences, Inc. is headquartered in the district and maintains its principal place of business there.
  • Core Dispute: Plaintiffs seek a declaratory judgment that their DNA sequencing products and services do not infringe five of Defendant’s patents, and further allege that one of the patents-in-suit is unenforceable due to prosecution laches and inequitable conduct.
  • Technical Context: The dispute centers on methods for improving the accuracy of next-generation DNA sequencing by using unique nucleic acid identifiers, or "barcodes," to track individual DNA molecules in a multiplex reaction.
  • Key Procedural History: The complaint alleges that after initial communications in June 2023 regarding a potential commercial opportunity, Molecular Loop changed its position in December 2023 and accused Illumina of infringement. Subsequently, Molecular Loop allegedly sent letters to several of Illumina's customers, including ARUP Laboratories and Tempus Labs, accusing them of infringing the patents-in-suit. The complaint also raises significant allegations of unenforceability against U.S. Patent No. 11,840,730, asserting that Molecular Loop unreasonably delayed prosecution for over 12 years and filed false "Request Not to Publish" documents with the U.S. Patent and Trademark Office to conceal the patent application while amending its claims to cover Illumina’s existing products.

Case Timeline

Date Event
2009-04-30 Earliest Priority Date ('730 Patent)
2010-12-23 Earliest Priority Date ('281, '851, '852, '200 Patents)
2015-10-22 U.S. Patent No. 9,163,281 ('281 Patent) Issued
2018-10-30 Illumina's TruSight Oncology 500 (TSO500) Assay Publicly Released
2021-06-22 U.S. Patent No. 11,041,851 ('851 Patent) Issued
2021-06-22 U.S. Patent No. 11,041,852 ('852 Patent) Issued
2023-06-26 Molecular Loop representative contacts Illumina for a "Possible IP Discussion"
2023-09-26 U.S. Patent No. 11,768,200 ('200 Patent) Issued
2023-12-01 Molecular Loop accuses Illumina of infringing the Patents-in-Suit during a meeting
2023-12-12 U.S. Patent No. 11,840,730 ('730 Patent) Issued
2024-01-19 Illumina's customer ARUP receives letter from Molecular Loop alleging infringement
2024-06-09 Complaint for Declaratory Judgment Filed

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

U.S. Patent No. 9,163,281 - Methods for Maintaining the Integrity and Identification of a Nucleic Acid Template in a Multiplex Sequencing Reaction (Issued Oct. 22, 2015)

The Invention Explained

  • Problem Addressed: In high-throughput, multiplex DNA sequencing, where samples from multiple sources (e.g., patients) are pooled and analyzed simultaneously, errors can arise that cause a DNA sequence from one sample to be incorrectly attributed to another ('9163281 Patent, col. 1:32-55). This can occur through the formation of "heteroduplexes" or "chimeric molecules" during the sample preparation and amplification steps, compromising the accuracy of the results ('9163281 Patent, col. 1:45-53, Fig. 1).
  • The Patented Solution: The invention proposes a method to validate the integrity of a DNA sample by incorporating a unique pair of identifiers (e.g., barcodes) into each template nucleic acid, with one identifier at each end flanking the sequence of interest ('9163281 Patent, Abstract). A sequence read is considered valid only if both correct identifiers from the unique pair are detected ('9163281 Patent, col. 2:15-24). Templates that contain only one identifier or an incorrect pair—a potential sign of a chimeric molecule—are excluded from the final analysis, thereby reducing errors.
  • Technical Importance: This approach provided a method for error-checking and data validation directly within the sequencing workflow, addressing a critical need for high accuracy in applications like clinical diagnostics and research genomics ('9163281 Patent, col. 1:40-44).

Key Claims at a Glance

  • The complaint asserts non-infringement of independent claims 1, 16, and 29 (Compl. ¶¶46-48).
  • Claim 1 (Independent): A method for validating the integrity of a template, including the steps of:
    • obtaining a template nucleic acid;
    • incorporating at least two of the same sequence identifiers into the template;
    • sequencing the template to generate sequence reads; and
    • analyzing the sequence reads to determine if the two incorporated sequence identifiers remain associated with the template.
  • Claim 16 (Independent): A method for analyzing a nucleic acid, including attaching a pair of the same barcode sequences to the template.
  • Claim 29 (Independent): A method for analyzing a nucleic acid, including attaching a first barcode sequence and a second barcode sequence to the template, "wherein the first and second barcode sequences are the same."

U.S. Patent No. 11,041,851 - Methods for Maintaining the Integrity and Identification of a Nucleic Acid Template in a Multiplex Sequencing Reaction (Issued Jun. 22, 2021)

The Invention Explained

  • Problem Addressed: The patent addresses the general problem of ensuring the accuracy of molecular detection assays by validating results and detecting errors introduced during sample preparation ('851 Patent, col. 2:1-7).
  • The Patented Solution: The invention describes a method for validating the detection of an "analyte of interest" by using "two or more identifier sequences that are uniquely associated" with it ('851 Patent, Abstract). The method requires excluding templates that contain only one identifier or an incorrect pair from the final analysis ('851 Patent, col. 21:3-4). The independent claim specifies that the two or more identifier sequences associated with each analyte "are the same" ('851 Patent, col. 21:1-2).
  • Technical Importance: The method offers a generalizable error-correction framework applicable not only to nucleic acid sequencing but also to other detection assays, such as protein detection, where sample integrity is paramount ('851 Patent, col. 2:8-11).

Key Claims at a Glance

  • The complaint asserts non-infringement of independent claim 1 (Compl. ¶54).
  • Claim 1 (Independent): A method for validating detection of an analyte of interest, comprising:
    • detecting the presence of two or more identifier sequences that are uniquely associated with an analyte of interest;
    • wherein the two or more identifier sequences associated with each analyte of interest have four or more nucleotides and are the same; and
    • excluding templates containing only one identifier or an incorrect pair from analysis.

U.S. Patent No. 11,041,852 - Methods for Maintaining the Integrity and Identification of a Nucleic Acid Template in a Multiplex Sequencing Reaction (Issued June 22, 2021)

  • Technology Synopsis: The patent describes a method to reduce "cross-over error" in multiplex sequencing by tagging nucleic acid templates from different samples with distinct pairs of identifiers. Sequence reads that contain combinations of identifiers different from the predefined pairs are discarded (Compl. ¶60).
  • Asserted Claims: Independent claim 1 (Compl. ¶¶60-61).
  • Accused Features: Plaintiffs' VeriSeq NIPT Solution v2 and TruSight Oncology 500 ctDNA v2 products are accused of infringement (Compl. ¶¶60-61).

U.S. Patent No. 11,768,200 - Methods for Maintaining the Integrity and Identification of a Nucleic Acid Template in a Multiplex Sequencing Reaction (Issued Sep. 26, 2023)

  • Technology Synopsis: The patent discloses a method for validating a sequencing reaction by using a pair of identifiers associated with a nucleic acid analyte. The method involves excluding sequences that contain only one identifier or an incorrect pair of identifiers from the analysis (Compl. ¶67).
  • Asserted Claims: Independent claim 1 (Compl. ¶¶67-68).
  • Accused Features: Plaintiffs' VeriSeq NIPT Solution v2 and TruSight Oncology 500 ctDNA v2 products are accused of infringement (Compl. ¶¶67-68).

U.S. Patent No. 11,840,730 - Methods and Compositions for Evaluating Genetic Markers (Issued Dec. 12, 2023)

  • Technology Synopsis: The patent relates to methods for evaluating genetic markers using "differentiator tags." During prosecution, the inventor allegedly distinguished the invention from prior art by stating that a "distinguishing feature" is that "each individual nucleic acid molecule is tagged with a unique differentiator tag" (Compl. ¶73).
  • Asserted Claims: Independent claims 1 and 9 (Compl. ¶¶77-79).
  • Accused Features: Illumina's TruSight Oncology 500 ctDNA and UMI plate products are accused of infringement (Compl. ¶¶77-79).

III. The Accused Instrumentality

Product Identification

  • The complaint identifies Plaintiffs' "VeriSeq NIPT Solution v2 assay products" and "TruSight Oncology 500 ctDNA v2 products" as accused instrumentalities (Compl. ¶¶46-48, 54, 60-61, 67-68). More broadly, the dispute involves products and services that utilize "Unique Molecular Identifiers (UMIs)" and/or "Unique Dual Indices (UDIs)" (Compl. ¶¶28-29, 36).

Functionality and Market Context

  • These products are tools used in next-generation sequencing workflows for genetic analysis, including noninvasive prenatal testing (NIPT) and oncology assays (Compl. ¶¶24, 33). The complaint positions Illumina as a "global leader and pioneer" whose innovations have substantially advanced genetic research by dramatically lowering the cost of sequencing the human genome (Compl. ¶23). The complaint alleges that Molecular Loop has contacted Illumina's customers, who use these products to provide genetic testing services, and accused them of infringement (Compl. ¶¶37-42).

IV. Analysis of Infringement Allegations

'281 Patent Infringement Allegations

Claim Element (from Independent Claim 29) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for analyzing a nucleic acid, the method comprising: Plaintiffs' accused products and services are used in next-generation sequencing workflows. ¶29 col. 1:22-24
attaching a first barcode sequence to the template; The accused products utilize kits containing Unique Dual Indices (UDIs), which are tags attached to nucleic acid sequences. ¶28 col. 1:45-50
attaching a second barcode sequence to the template; UDIs are attached to both ends of a nucleic acid template for use during sequencing analysis. ¶29 col. 1:45-50
wherein the first and second barcode sequences are the same, Plaintiffs allege their accused products do not practice this limitation. ¶48 col. 4:10-14
  • Identified Points of Contention:
    • Scope Questions: A central dispute concerns the claim limitation "the same," which appears in independent claims 1, 16, and 29 of the '281 Patent. The complaint alleges that Plaintiffs' products utilizing UDIs do not meet this requirement (Compl. ¶¶46-48). This raises the question of whether the term "the same" requires the two barcode sequences to be identical in their nucleotide sequence, or if it could be construed more broadly to mean they are drawn from the same set or class of barcodes for a given sample.
    • Technical Questions: What evidence does the complaint provide that the accused products use barcode sequences that are not "the same"? The complaint alleges that Molecular Loop has accused Illumina's products using "Unique Dual Indexes" of infringement (Compl. ¶28), a technology that often involves using two different indices to mitigate "index hopping" errors in sequencing. This suggests a potential technical mismatch between the operation of the accused products and the literal claim language.

'851 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for validating detection of an analyte of interest, the method comprising: detecting the presence of two or more identifier sequences that are uniquely associated with an analyte of interest, Plaintiffs' products use UMIs and/or UDIs, which are types of identifier tags attached to nucleic acid sequences during sequencing analysis. ¶¶28-29 col. 2:3-7
wherein the two or more identifier sequences associated with each analyte of interest have four or more nucleotides and are the same; Plaintiffs allege that their accused products do not practice this limitation. ¶54 col. 21:1-2
and excluding templates containing only one identifier or an incorrect pair from analysis. The complaint does not provide sufficient detail for analysis of this element. col. 2:21-24
  • Identified Points of Contention:
    • Scope Questions: As with the '281 Patent, the core of the non-infringement argument centers on the claim phrase "and are the same" (Compl. ¶54). The case may turn on the construction of this term.
    • Technical Questions: The complaint's non-infringement argument suggests that the identifier sequences used in the accused products are, in fact, not identical. The court will need to examine the technical operation of the accused products to determine if they practice this specific claim limitation.

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

  • The Term: "the same"
  • Context and Importance: This term appears in the independent claims of both the '281 and '851 patents and is the primary basis for Plaintiffs' non-infringement allegations (Compl. ¶¶46-48, 54). The resolution of whether Plaintiffs' use of Unique Dual Indices—which are often intentionally different—infringes claims requiring "the same" barcode sequences will be critical. Practitioners may focus on this term because modern sequencing protocols frequently use distinct dual indices to prevent "index hopping," a source of error the patents-in-suit purport to solve.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification of the '851 Patent states that in a preferred configuration, "each template from a particular sample is associated with the same unique pair of barcode sequences" ('851 Patent, col. 2:55-58). This language could be argued to mean that all templates within one sample get the same pair of barcodes, but does not explicitly state that the two barcodes within that pair must be identical to each other.
    • Evidence for a Narrower Interpretation: The plain language of the claims, such as "wherein the first and second barcode sequences are the same" ('281 Patent, claim 29) and "wherein the two or more identifier sequences ... are the same" ('851 Patent, claim 1), may strongly support an interpretation requiring sequence identity. The specification does not appear to provide an explicit definition of "the same" that contradicts this plain meaning.

VI. Other Allegations

  • Indirect Infringement: The complaint seeks a declaration of non-infringement for indirect infringement, stating that the "normal, advertised and expected use" of its products does not infringe (Compl. ¶3). The basis for the controversy is Defendant’s alleged communication with Plaintiffs’ customers, accusing them of infringement based on their use of Plaintiffs’ products (Compl. ¶¶36-37).
  • Willful Infringement: While not alleged by Plaintiffs, the complaint details pre-suit communications starting in June 2023, where Illumina was made aware of the patents-in-suit (Compl. ¶¶30-31). This timeline of alleged notice could form the basis for a future claim of willful infringement by Molecular Loop.
  • Unenforceability of the '730 Patent: Plaintiffs allege that the '730 Patent is unenforceable under the doctrines of prosecution laches and inequitable conduct (Compl. ¶¶83-150). The complaint alleges that Molecular Loop and its counsel:
    1. Unreasonably delayed prosecution for over 14 years from the earliest priority date (Compl. ¶93).
    2. Amended the patent's claims in October 2020, years after Illumina's TSO 500 product was released, to "capture products brought to market by Illumina" (Compl. ¶¶3, 89).
    3. Filed false "Request Not to Publish" certifications with the USPTO in 2016 and 2020, stating the invention had not been and would not be the subject of a foreign application requiring publication, despite a prior PCT application having been filed in 2010 (Compl. ¶¶95-96, 115). This allegedly concealed the pending application from public view (Compl. ¶101).

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

  • A core issue will be one of definitional scope: can the claim term "the same," when applied to barcode sequences, be construed to cover products that utilize pairs of different unique dual indices, a common practice in modern next-generation sequencing to enhance accuracy?
  • A dispositive issue for the '730 patent will be one of enforceability: did the patentee's alleged 14-year prosecution delay, coupled with the filing of allegedly false non-publication requests that concealed the application from public view while claims were amended to target existing products, constitute prosecution laches and inequitable conduct sufficient to render the patent unenforceable?