DCT

1:24-cv-11501

Illumina Inc v. Molecular Loop Biosciences Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-11501, D. Mass., 06/09/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Massachusetts as Defendant Molecular Loop Biosciences, Inc. is headquartered there and its principal place of business is located in the district.
  • Core Dispute: Plaintiffs seek a declaratory judgment that their genetic sequencing products do not infringe five patents owned by Defendant, and further allege that one of the patents is unenforceable due to prosecution laches and inequitable conduct during its prosecution.
  • Technical Context: The dispute centers on next-generation DNA sequencing technology, specifically methods using molecular "barcodes" or "tags" to identify and ensure the integrity of individual DNA samples when multiple samples are processed together in a single reaction.
  • Key Procedural History: The complaint details a series of communications between the parties beginning in June 2023, initially framed as a commercial opportunity, which escalated to accusations of infringement against Plaintiffs and their customers. The complaint also contains detailed allegations that the most recently issued patent, U.S. Patent No. 11,840,730, is unenforceable due to unreasonable prosecution delays of over 12 years and inequitable conduct, specifically the filing of false "Request Not to Publish" documents with the U.S. Patent and Trademark Office to conceal the patent application from the public.

Case Timeline

Date Event
2009-04-30 Earliest Priority Date for ’730 Patent
2010-12-23 Earliest Priority Date for ’281, ’851, ’852, and ’200 Patents
2015-10-20 ’281 Patent Issued
2018-10-30 Public Release of Illumina's TSO 500 Assay Products
2021-06-22 ’851 Patent Issued
2021-06-22 ’852 Patent Issued
2023-06-26 Molecular Loop first contacts Illumina regarding "Possible IP Discussion"
2023-09-26 ’200 Patent Issued
2023-12-01 Molecular Loop accuses Illumina of infringing the Patents-in-Suit
2023-12-12 ’730 Patent Issued
2024-01-19 Molecular Loop sends infringement allegation letter to Illumina customer ARUP
2024-06-09 Complaint for Declaratory Judgment Filed

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

This report provides a full analysis of U.S. Patent Nos. 11,041,851 and 11,041,852. The remaining patents are summarized in Multi-Patent Capsules.

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: June 22, 2021

The Invention Explained

  • Problem Addressed: In multiplex sequencing, where DNA from multiple sources (e.g., patients) is pooled and analyzed simultaneously, errors can be introduced during sample preparation. These errors, such as "molecular overlap," can lead to the incorrect assignment of a DNA sequence to the wrong patient sample, compromising the accuracy of the results (’851 Patent, col. 1:29-54).
  • The Patented Solution: The invention proposes using "two or more identifiers," such as nucleic acid barcodes, that are uniquely associated with each DNA sample. By requiring the detection of both identifiers (e.g., by placing them on opposite ends of the DNA fragment to be sequenced), the system can validate that the sequence data is correct and has not been compromised. Templates with only one identifier or an incorrect pair of identifiers are excluded from analysis, preventing false results (’851 Patent, col. 2:3-24; Fig. 2).
  • Technical Importance: This approach provided a method to increase the fidelity of high-throughput sequencing by creating an internal control system to detect and discard data corrupted by common sample preparation artifacts (’851 Patent, col. 2:25-28).

Key Claims at a Glance

  • Independent Claim 1 is asserted (Compl. ¶54).
  • Essential elements of Claim 1:
    • A method for validating detection of an analyte of interest.
    • 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.
    • Excluding templates containing only one identifier or an incorrect pair from analysis.
  • The complaint states that all claims dependent on Claim 1 are also not infringed (Compl. ¶54).

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

The Invention Explained

  • Problem Addressed: The patent addresses the problem of "cross-over error" in multiplex sequencing, where a DNA fragment from one sample incorrectly combines with a barcode or identifier from a different sample during the amplification process, leading to a "chimeric molecule" (’852 Patent, col. 3:52-62; Fig. 1).
  • The Patented Solution: The invention describes a method where nucleic acids from different samples are tagged with "distinct pairs" of identifiers. After sequencing, any resulting sequence read that contains a combination of identifiers different from the pre-defined "distinct pairs" is identified as a chimeric product of cross-over error and is discarded. This filtering step is claimed to reduce cross-over error (’852 Patent, Abstract; col. 5:45-53).
  • Technical Importance: The method provides a computational means to identify and remove specific types of artifacts generated during multiplex amplification, thereby improving the reliability of the final sequencing data set (’852 Patent, col. 6:1-6).

Key Claims at a Glance

  • Independent Claim 1 is asserted (Compl. ¶¶60-61).
  • Essential elements of Claim 1:
    • A method for reducing template cross-over error.
    • Incorporating at least two members of a plurality of identifier sequences into template nucleic acids from at least two different samples, wherein the two members constitute a distinct pair associated with the template.
    • Combining the templates into a single sample.
    • Amplifying the templates on a flow cell surface to form clusters, where at least one cluster has a chimeric sequence with a combination of identifiers different from any distinct pair.
    • Sequencing the amplicons.
    • Discarding sequence reads that contain a combination of identifiers different than any of said distinct pairs, thereby to reduce cross-over error.
  • The complaint states that all claims dependent on Claim 1 are also not infringed (Compl. ¶¶60-61).

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: October 20, 2015
  • Technology Synopsis: This patent, from the same family as the '851 and '852 patents, addresses errors in multiplex sequencing. The solution involves incorporating multiple of the same barcode sequence into a single DNA template to validate its integrity.
  • Asserted Claims: Independent Claims 1, 16, and 29 (Compl. ¶¶46-48).
  • Accused Features: The complaint alleges that Plaintiffs' VeriSeq NIPT Solution v2 and TruSight Oncology 500 ctDNA v2 products are accused of infringement (Compl. ¶46).

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: September 26, 2023
  • Technology Synopsis: This patent also addresses maintaining sample integrity in multiplex sequencing. The claimed solution involves validating the sequence of an analyte by analyzing for the presence of both identifiers in a pair and excluding sequences that contain only one identifier or an incorrect pair.
  • Asserted Claims: Independent Claim 1 (Compl. ¶¶67-68).
  • Accused Features: The complaint alleges that 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: December 12, 2023
  • Technology Synopsis: This patent describes methods for evaluating genetic markers using "differentiator tags" to uniquely label individual nucleic acid molecules before amplification. The tags are used to correct for errors or bias by "collapsing" reads that share both a target sequence and a differentiator tag into a single count, ensuring that each original molecule is counted only once.
  • Asserted Claims: Independent Claims 1 and 9 (Compl. ¶¶77-79).
  • Accused Features: The complaint alleges that Illumina's TruSight Oncology 500 ctDNA and UMI plate products are accused of infringement (Compl. ¶¶77-78).

III. The Accused Instrumentality

Product Identification

The complaint identifies Plaintiffs' "VeriSeq NIPT Solution v2 assay products and TruSight Oncology 500 ctDNA v2 products" as the primary accused instrumentalities (Compl. ¶46). It also mentions Illumina's "UMI plate products" in relation to the '730 Patent (Compl. ¶77).

Functionality and Market Context

These products are described as assays and tools used in next-generation sequencing workflows (Compl. ¶24). The complaint states they are used for applications such as noninvasive prenatal testing (NIPT) and oncology testing (Compl. ¶¶6-7, 24). The functionality at issue involves the use of "Unique Molecular Identifiers (UMIs)" and/or "Unique Dual Indices (UDIs)," which are types of molecular tags attached to nucleic acid sequences to allow for identification and error correction during sequencing analysis (Compl. ¶29). Illumina is positioned as a "global leader and pioneer" in DNA sequencing technology (Compl. ¶23).

IV. Analysis of Infringement Allegations

As this is a complaint for declaratory judgment of non-infringement, the following charts summarize Plaintiffs' arguments for why their products do not meet the specified claim limitations.

No probative visual evidence provided in complaint.

U.S. Patent No. 11,041,851 Non-Infringement Allegations

Claim Element (from Independent Claim 1) Plaintiff's Alleged Non-Infringing Functionality Complaint Citation Patent Citation
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 The accused products do not use two or more identifier sequences that "are the same." ¶54 col. 21:1-2

U.S. Patent No. 11,041,852 Non-Infringement Allegations

Claim Element (from Independent Claim 1) Plaintiff's Alleged Non-Infringing Functionality Complaint Citation Patent Citation
incorporating at least two members of a plurality of identifier sequences into template nucleic acids obtained from at least two different samples, wherein said two members constitute a distinct pair associated with said template The complaint alleges the accused products do not practice this limitation. ¶61 col. 21:1-6
discarding sequence reads obtained in said sequencing step that contain said combination of identifier sequences that are different than any of said distinct pairs, thereby to reduce cross-over error The accused products do not perform the claimed step of discarding sequence reads containing identifier combinations that are different from the pre-defined distinct pairs. ¶60 col. 21:16-21
  • Identified Points of Contention:
    • Scope Questions: The non-infringement arguments for the '851 Patent, as well as for the related '281 Patent, hinge on the interpretation of "the same." The central question will be whether the accused products, which allegedly use unique or different identifiers, fall outside the scope of claims requiring "the same" identifier or barcode.
    • Technical Questions: For the '852 Patent, the dispute raises a functional question: do the accused products perform the specific claimed step of "discarding" sequence reads based on identifier pairs to reduce cross-over error? Plaintiffs' position suggests their products either do not generate such combinations or do not use the claimed discarding method to filter them.

V. Key Claim Terms for Construction

  • The Term: "are the same" (’851 Patent, Claim 1) and "the same barcode sequences" (’281 Patent, Claims 16, 29).
  • Context and Importance: The construction of this term is central to Plaintiffs' non-infringement defense for at least two of the patents. Plaintiffs' argument is that their products do not use identical identifiers as required by the claims. The case may turn on whether "the same" is limited to sequences that are 100% identical, or if it could be construed more broadly.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The complaint does not provide specific detail for analysis of this element.
    • Evidence for a Narrower Interpretation: The specification of the '851 Patent distinguishes between identifiers that "may be the same or different, so long as the combination is unique" generally, but Claim 1 specifically requires that the "two or more identifier sequences... are the same" (’851 Patent, col. 3:19-21, col. 21:2). This explicit claiming of "the same" may support a narrow construction limited to identical sequences.

VI. Other Allegations

  • Indirect Infringement: Plaintiffs seek a declaratory judgment that they have not induced or contributed to the infringement of any claim of the Patents-in-Suit (Compl. ¶3). The complaint does not provide specific facts regarding this count beyond a general denial of liability.
  • Willful Infringement: Willfulness is not explicitly alleged in the complaint. However, the complaint establishes a basis for potential future allegations of willfulness by detailing pre-suit knowledge, beginning with Molecular Loop's initial contact on June 26, 2023, and continuing through express accusations of infringement and letters to customers (Compl. ¶¶30, 35, 37-41).
  • Prosecution Laches and Inequitable Conduct (’730 Patent): Plaintiffs allege that the '730 Patent is unenforceable due to prosecution laches, asserting that Molecular Loop unreasonably delayed prosecution for over 12 years and amended the claims only after Illumina's products were on the market, causing prejudice (Compl. ¶¶85-104). Plaintiffs also allege inequitable conduct, asserting that Molecular Loop's attorney filed two separate "Request Not to Publish" declarations with the USPTO that contained "unmistakably false statements" by certifying that the invention had not been and would not be the subject of a foreign application requiring publication, when in fact it was the subject of a PCT application that had already been published years earlier (Compl. ¶¶108-109, 115-116, 136-137). These actions are alleged to have been a deliberate scheme to conceal the pending application from the public (Compl. ¶135).

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

  • A core issue will be one of definitional scope: does the claim term "the same," as applied to sequence identifiers or barcodes in the '281 and '851 patents, require absolute sequence identity? Plaintiffs' non-infringement defense for a significant portion of the asserted patent portfolio appears to rest on the argument that their products use different, rather than identical, tags.
  • A second central issue will be one of prosecutorial integrity: are the extensive allegations of unreasonable delay and false statements made to the U.S. Patent and Trademark Office sufficient to render the '730 Patent unenforceable due to prosecution laches or inequitable conduct? This question is independent of infringement and presents a significant validity challenge to the most recently issued patent in the dispute.
  • A key evidentiary question will be one of technical operation: for patents like the '852, do Plaintiffs' accused products actually perform the specific functional steps recited in the claims, such as the "discarding" of chimeric sequences based on identifier pairs? The dispute will require a detailed comparison of how the patented methods operate versus how the accused sequencing workflows function in practice.