Element Biosciences Inc v. Illumina Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Element Biosciences, Inc. (Delaware)
  • Defendant: Illumina, Inc. (Delaware)
  • Plaintiff's Counsel: Young Conaway Stargatt & Taylor, LLP
• Case Identification: 1:25-cv-01175, D. Del., 07/08/2026
• Venue Allegations: Venue is alleged to be proper in the District of Delaware as Defendant Illumina, Inc. is a Delaware corporation and therefore resides in the district.
• Core Dispute: Plaintiff alleges that Defendant's DNA sequencing systems, which utilize sequencing-by-synthesis (SBS) chemistry, infringe five patents related to methods for improving the accuracy, chemistry, and efficiency of DNA sequencing.
• Technical Context: The lawsuit concerns next-generation sequencing (NGS), a foundational technology for modern genomics research, clinical diagnostics, and personalized medicine.
• Key Procedural History: The complaint notes that during the prosecution of the '161 patent, the U.S. Patent and Trademark Office (USPTO) initially rejected claims as abstract but later allowed them after amendments, which Plaintiff frames as confirmation of a non-obvious technical improvement. Plaintiff also alleges that Defendant's own patents, listed on its virtual patent marking website for the accused products, describe methods similar to those claimed in the patents-in-suit.

Case Timeline

Date	Event
2007-02-05	Priority Date for '313 Patent
2008-03-19	Priority Date for '161, '174, and '887 Patents
2012-08-21	'161 Patent Office Action mentioned in complaint
2012-11-21	'161 Patent Response to Final Rejection mentioned in complaint
2013-12-17	'161 Patent Issue Date
2017-03-28	'301 Patent Issue Date
2018-03-06	'174 Patent Issue Date
2021-05-11	'887 Patent Issue Date
2022-01-01	Illumina launches XLEAP-SBS chemistry
2023-03-31	Element and PhenomeX Inc. license agreement date
2024-03-31	Discontinuation of reagent sales for HiSeq Systems
2025-09-30	Last order date for MiSeq and MiniSeq systems
2026-06-16	'313 Patent Issue Date
2026-07-08	Complaint Filing Date
2029-12-31	End of system support for MiSeq and MiniSeq systems

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

U.S. Patent No. 8,612,161 - "Methods and Compositions for Base Calling Nucleic Acids"

The Invention Explained

• Problem Addressed: The patent addresses the problem of "dephasing" in sequencing-by-synthesis (SBS), where errors in nucleotide incorporation cause some DNA template strands to fall behind ("sequence lag") or jump ahead ("sequence lead") of the main sequencing cycle Compl. ¶¶106-108 This cumulative effect reduces the primary signal, spreads it across cycles, and ultimately limits the effective read length and accuracy of the sequencing run Compl. ¶109
• The Patented Solution: The invention provides a mathematical method to correct for dephasing by computationally "rephasing" the sequencing data Compl. ¶110 It discloses using a matrix equation to model the signal-reducing effects of lead and lag Compl. ¶111 By determining the "ratio contribution" to the dye intensity at a given position (the "interrogation position") from the dye intensities of subsequent and/or preceding positions, the system can correct for the phasing artifacts and arrive at a more accurate identification of the nucleotide Compl. ¶112 Compl. ¶118
• Technical Importance: This data-correction approach aimed to increase both the fidelity and achievable read lengths of SBS technologies, overcoming a key technical bottleneck that limited their utility Compl. ¶112

Key Claims at a Glance

• The complaint asserts infringement of at least Claim 1 and makes reference to independent claim 26 (Compl. ¶¶60; Compl. ¶124).
• Independent Claim 1 contains the following essential elements:
  • A method for determining the identity of a nucleic acid at an interrogation position from data acquired from one or more channels in parallel, comprising:
  • sequencing a nucleic acid by DNA sequencing by synthesis utilizing nucleotides with fluorescent dyes which are incorporated into a complementary strand;
  • obtaining a data set for one or more dye intensities at one or more nucleic acid positions in said complementary sequence, wherein each dye corresponds to a nucleotide;
  • determining the ratio contribution to dye intensity at said interrogation position from dye intensities at the interrogation position and at one or both of i) at least one subsequent nucleic acid positions and ii) at least one preceding nucleic acid positions; and
  • applying said ratio contribution to said data set to arrive at an identity for a nucleotide at said interrogation position. Compl. ¶74
• The complaint also notes that dependent claims further recite methods for correcting for signal noise and spectral crosstalk Compl. ¶113

U.S. Patent No. 9,605,301 - "Methods and Solutions for Inhibiting Undesired Cleaving of Labels"

The Invention Explained

• Problem Addressed: The complaint does not explicitly state the problem addressed by the '301 patent, but the infringement allegations imply a problem related to residual chemicals in the SBS process. Specifically, after the cleavage step that removes the fluorescent label and the 3'-OH blocking group, leftover "cleaving agent" could prematurely act on the next nucleotide to be incorporated, disrupting the subsequent cycle.
• The Patented Solution: The patent claims a method of incorporating labeled nucleotides that involves providing and introducing a "cleaving agent scavenger" into the reaction chamber Compl. ¶162 This scavenger is introduced to neutralize or "scavenge" the cleaving agent from the previous step, thereby preventing its undesired activity in the next incorporation cycle (Compl. ¶¶162; Compl. ¶198). The complaint alleges that in Illumina's accused process, this scavenger is part of a "post-cleave wash" step (Compl. ¶¶182; Compl. ¶198).
• Technical Importance: This method provides a chemical solution to improve the fidelity of the iterative SBS process by isolating the chemical reactions of each cycle from one another.

Key Claims at a Glance

• The complaint asserts infringement of at least Claim 1 Compl. ¶155
• Independent Claim 1 contains the following essential elements:
  • A method of incorporating labeled nucleotides into nucleic acid, comprising:
  • providing a reaction chamber, a first solution (with polymerase and labeled, capped nucleotide analogues), a second solution (with a cleaving agent), and a cleaving agent scavenger;
  • introducing the first solution to incorporate a first nucleotide analogue;
  • detecting the label of the incorporated analogue;
  • introducing the second solution to remove the capping group and cleave the linker with the cleaving agent; and
  • introducing the cleaving agent scavenger to scavenge the cleaving agent Compl. ¶162

Multi-Patent Capsule: U.S. Patent No. 9,909,174

• Patent Identification: U.S. Patent No. 9,909,174, "Methods and Compositions for Incorporating Nucleotides," issued March 6, 2018.
• Technology Synopsis: The patent describes a method for determining the identity of a nucleotide at a position using a sequencing device configured for measuring color in more than one detector channel. The method involves using a mixture of both labeled and non-labeled reversible terminators, detecting the label of an incorporated nucleotide in two channels, and determining the nucleotide's identity from that two-channel detection Compl. ¶230
• Asserted Claims: At least Claim 1 Compl. ¶218
• Accused Features: The complaint alleges that Illumina's "two-channel" sequencing systems (e.g., MiniSeq, MiSeq i100, NextSeq, NovaSeq) infringe the '174 patent. Specifically, these systems are alleged to use a mixture of labeled (A, C, T) and non-labeled/dark (G) terminators and determine base identity by detecting signals in two color channels (e.g., blue and green) (Compl. ¶219; Compl. ¶220; Compl. ¶221; Compl. ¶222; Compl. ¶223; Compl. ¶224; Compl. ¶225; Compl. ¶226; Compl. ¶227; Compl. ¶228; Compl. ¶229; Compl. ¶230; Compl. ¶231; Compl. ¶232; Compl. ¶233; Compl. ¶234; Compl. ¶235; Compl. ¶236; Compl. ¶237; Compl. ¶238; Compl. ¶239; Compl. ¶240; Compl. ¶241; Compl. ¶242; Compl. ¶243).

Multi-Patent Capsule: U.S. Patent No. 11,001,887

• Patent Identification: U.S. Patent No. 11,001,887, "Methods and Compositions for Incorporating Nucleotides," issued May 11, 2021.
• Technology Synopsis: The patent describes a method of incorporating labeled nucleotides into a nucleic acid. The method involves providing a mixture of labeled and non-labeled terminators, where the labeled terminators are labeled with at least one type of fluorescent dye. The process includes incorporating a nucleotide, detecting its color in two channels, and then removing the label and the reversible blocking group with a cleaving agent before incorporating a second nucleotide Compl. ¶284
• Asserted Claims: At least Claim 1 Compl. ¶272
• Accused Features: The complaint accuses Illumina's "two-channel" sequencing systems of infringement. The allegations focus on systems that use a mixture of labeled and non-labeled ("dark") nucleotides, detect the incorporated base using two fluorescent dyes and two images per cycle, and then use a cleaving agent to remove the label and blocking group to proceed to the next cycle (Compl. ¶273; Compl. ¶274; Compl. ¶275; Compl. ¶276; Compl. ¶277; Compl. ¶278; Compl. ¶279; Compl. ¶280; Compl. ¶281; Compl. ¶282; Compl. ¶283; Compl. ¶284; Compl. ¶285; Compl. ¶286; Compl. ¶287; Compl. ¶288; Compl. ¶289; Compl. ¶290; Compl. ¶291; Compl. ¶292; Compl. ¶293; Compl. ¶294; Compl. ¶295; Compl. ¶296; Compl. ¶297; Compl. ¶298; Compl. ¶299; Compl. ¶300; Compl. ¶301; Compl. ¶302; Compl. ¶303; Compl. ¶304; Compl. ¶305; Compl. ¶306; Compl. ¶307).

Multi-Patent Capsule: U.S. Patent No. 12,656,313

• Patent Identification: U.S. Patent No. 12,656,313, "Methods and Devices for Sequencing Nucleic Acids in Smaller Batches," issued June 16, 2026.
• Technology Synopsis: The patent describes a method and device for sequencing that uses at least one moveable flow cell. The flow cell is moved between an initial position and an imaging position, and cycles of nucleotide incorporation are performed. An individual cycle includes incorporating a nucleotide, washing, detecting first and second fluorescence intensities from the spot, and identifying the nucleotide using those two intensities Compl. ¶349
• Asserted Claims: At least Claim 1 Compl. ¶339
• Accused Features: The complaint accuses Illumina's MiSeq i100, NextSeq 1000/2000, and NovaSeq systems of infringement. These systems are alleged to use a moveable flow cell stage that positions the flow cell relative to imaging optics, a reagent delivery mechanism, and a two-channel imaging platform to identify nucleotides based on two detected fluorescence intensities per cycle Compl. ¶¶359-360 Compl. ¶¶374-378

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are Illumina's DNA sequencing systems, including the iSeq, MiniSeq, MiSeq, NextSeq, NovaSeq, and legacy HiSeq series systems, when used in combination with Illumina's corresponding Library Preparation Kits and Sequencing Reagent Kits Compl. ¶¶16-17 Compl. ¶60

Functionality and Market Context

• The complaint describes Illumina's platforms as operating on the principle of sequencing-by-synthesis (SBS). The process involves cyclic steps of incorporating fluorescently-labeled reversible terminators one base at a time onto DNA templates that are immobilized in clusters on a glass substrate, or "flow cell" Compl. ¶¶18-19 Compl. ¶¶21-22
• After each incorporation, the clusters are imaged to detect which nucleotide was added, and then a chemical cleavage step removes both the fluorescent label and the reversible terminator, preparing the strand for the next cycle (Compl. ¶¶24; Compl. ¶28). The complaint provides a graphic from an Illumina video showing the structure of a modified nucleotide with a dye, a cleavable linker, and a removable blocking group Compl. p. 7
• A key distinction drawn in the complaint is the evolution of Illumina's detection chemistry from four-channel systems (e.g., HiSeq), which use a different colored dye for each of the four bases, to two-channel systems (e.g., NovaSeq X Series), which use combinations of two colors to identify all four bases Compl. ¶¶31-33 The complaint includes a diagram from an Illumina technical note illustrating how four-channel and two-channel imaging works Compl. p. 10
• The complaint also identifies Illumina's new XLEAP-SBS chemistry, launched in 2022 and used in systems like the NovaSeq X, as an "update" featuring a novel blocking group, linker, and polymerase for faster sequencing Compl. ¶¶34-36

IV. Analysis of Infringement Allegations

U.S. Patent No. 8,612,161 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method for determining an identity of a nucleic acid...from data acquired from one or more channels in parallel	The accused NextSeq 550 system is a two-channel system that uses SBS in a massively parallel fashion to determine nucleotide identity.	¶¶75-78	col. 40:1-8
a) sequencing a nucleic acid by DNA sequencing by synthesis utilizing nucleotides with fluorescent dyes which are incorporated into a complementary strand	The NextSeq 550 system uses Illumina's SBS, a reversible-terminator method with fluorescently labeled nucleotides that are incorporated into growing DNA strands.	¶¶79-81	col. 28:27-30
b) obtaining a data set for one or more dye intensities at one or more nucleic acid positions in said complementary sequence...	During sequencing, the NextSeq 550's software (RTA) obtains a data set by imaging clusters of nucleic acids to detect dye intensities at each position (cycle).	¶¶82-85	col. 44:30-45
c) determining the ratio contribution to dye intensity at said interrogation position from dye intensities at...i) at least one subsequent nucleic acid positions...and ii) at least one preceding nucleic acid positions	The complaint alleges on information and belief that the NextSeq 550 practices the methods of Illumina's '275 patent, which describes estimating phasing and pre-phasing parameters based on dye intensities at the interrogation position as well as preceding and subsequent positions.	¶¶86-92	col. 44:30-45:41
d) applying said ratio contribution to said data set to arrive at an identity for a nucleotide at said interrogation position	The NextSeq 550 allegedly uses its RTA software to apply the determined ratio contribution to correct for phasing and prephasing, thereby arriving at the final nucleotide identity.	¶¶93-95	col. 52:7-13

• Identified Points of Contention:
  • Technical Question: A central point of dispute will likely be whether the algorithms in Illumina's RTA software actually perform the step of "determining the ratio contribution" from both subsequent and preceding positions, as required by claim 1(c). The complaint relies heavily on Illumina's separate '275 patent to allege what the accused software does Compl. ¶¶86-93, which raises the evidentiary question of whether the accused products actually practice the methods of the '275 patent and whether those methods, in turn, meet the limitations of the '161 patent.
  • Scope Question: The analysis may focus on how the term "ratio contribution" is defined and calculated. The court will need to determine if the error-correction calculations performed by Illumina's RTA software fall within the scope of this claim term as it is defined and used in the '161 patent's specification.

U.S. Patent No. 9,605,301 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of incorporating labeled nucleotides into nucleic acid, comprising: (a) providing i) a reaction chamber comprising plurality of nucleic acid template molecules bound to a solid support	The accused NovaSeq X systems use a flow cell, which is a glass-based substrate with nanowells containing nucleic acid template molecules bound to its surface.	¶¶166-169	col. 5:10-18
ii) a first solution comprising polymerase and a plurality of nucleotide analogues...each...comprises a unique label attached through a cleavable linker, and...contains a removable chemical moiety capping the 3'-OH group	The NovaSeq X systems use XLEAP-SBS chemistry, which includes a mix of fluorescently tagged, reversibly terminating nucleotides that have a unique label (dye), a cleavable linker, and a removable 3'-OH blocking group.	¶¶170-175	col. 3:6-14
iii) a second solution comprising a cleaving agent	Following imaging, a "deblocking composition comprising a cleavage agent" is used to cleave the fluorescent label and blocking group. This is alleged to be a separate, second solution.	¶¶176-181	col. 7:45-53
and iv) a cleaving agent scavenger	After the cleavage step, a "post-cleave wash" step occurs using a "universal wash composition" which allegedly contains lipoic acid as a scavenger.	¶¶182-184	col. 8:36-41
b) introducing said first solution into said reaction chamber under conditions wherein a first nucleotide analogue is incorporated	A sequencing run on the NovaSeq X begins with introducing the first solution (containing polymerase and nucleotides) into the flow cell to incorporate a nucleotide.	¶¶185-188	col. 6:15-18
c) detecting the label of the incorporated nucleotide analogue	After incorporation, clusters are excited and the fluorescent signal is detected by a camera using two-channel imaging.	¶¶189-191	col. 6:23-28
d) introducing said second solution...such that the chemical moiety...capping the 3'-OH group is removed and said cleavable linker is cleaved	A second solution ("deblocking composition") is introduced to cleave the 3'-OH blocking group and the label's linker, allowing for the next incorporation.	¶¶192-197	col. 6:29-37
e) introducing said cleaving agent scavenger...so as to scavenge said cleaving agent.	A post-cleave wash solution containing a scavenger is introduced into the chamber, which allegedly scavenges the cleaving agent.	¶¶198-200	col. 8:36-41

• Identified Points of Contention:
  • Technical/Functional Question: A key issue will be whether the "universal wash composition" used in the accused systems' "post-cleave wash" step Compl. ¶198 functions as a "cleaving agent scavenger" as claimed. The defense may argue that this wash step is merely for rinsing and that its components do not perform the specific scavenging function required by the patent.
  • Definitional Scope: The dispute may turn on whether providing the required components in different commercial kits (e.g., a sequencing reagent kit and a library preparation kit) and introducing them at different times in a multi-step workflow constitutes "providing" them as part of a single claimed "method."

V. Key Claim Terms for Construction

• '161 Patent

  • The Term: "determining the ratio contribution"
  • Context and Importance: This term is the core of the inventive method described in Claim 1(c) for correcting phasing errors. The entire infringement allegation hinges on whether Illumina's RTA software performs an operation that meets this definition. Practitioners may focus on this term because it appears to describe a specific mathematical operation, and the case will depend on whether the accused software's algorithm is functionally and structurally equivalent to the claimed determination.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent describes the invention as providing "specific methods to account for incorporation errors and correct this dephasing" Compl. ¶110, suggesting the term could encompass various mathematical approaches to error correction.
    • Evidence for a Narrower Interpretation: The patent discloses a specific "matrix equation that describes a model for the reduced measured signal resulting from lead and lag effect" (Compl. ¶111, citing '161 Patent, at 44:30-45:41). This could support a narrower construction limited to methods that employ a similar matrix-based calculation.

• '301 Patent

  • The Term: "cleaving agent scavenger"
  • Context and Importance: This term, recited in claim elements 1(a)(iv) and 1(e), is central to the patent's proposed solution for improving SBS chemistry fidelity. The infringement case depends on proving that a component in Illumina's wash solution (e.g., lipoic acid) not only has the properties of a scavenger but is introduced for the purpose of scavenging the cleaving agent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language requires "introducing said cleaving agent scavenger... under conditions so as to scavenge said cleaving agent" Compl. ¶162, which might be argued to cover any compound that has the effect of neutralizing the cleaving agent, regardless of its primary purpose.
    • Evidence for a Narrower Interpretation: The complaint alleges the '301 patent's associated patent family describes using scavenger compounds like lipoic acid in a "post-cleavage wash composition" (Compl. ¶182; Compl. ¶183). This specific embodiment could be used to argue for a narrower definition, potentially limited to compounds explicitly identified as scavengers and used in a distinct post-cleavage step.

VI. Other Allegations

• Indirect Infringement: Plaintiff alleges both induced and contributory infringement for all five patents-in-suit. Inducement is primarily based on allegations that Illumina provides its customers with user guides, manuals, and educational materials that instruct them to operate the accused sequencing systems in an infringing manner Compl. ¶¶96-97 Compl. ¶¶201-202 Contributory infringement is based on the allegation that the accused systems and kits are especially designed to practice the patented methods and are not staple articles of commerce suitable for substantial non-infringing use Compl. ¶¶98-99 Compl. ¶¶203-204
• Willful Infringement: The complaint alleges that Illumina's infringement has been willful and deliberate since at least the date of service of the original complaint in the action Compl. ¶100 Compl. ¶151 This suggests the willfulness claim is based on post-suit knowledge rather than pre-suit notice.

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

1. A central issue will be one of algorithmic equivalence: does the proprietary algorithm in Illumina's Real-Time Analysis (RTA) software perform the specific mathematical steps of "determining the ratio contribution" from both preceding and subsequent positions, as required by Claim 1 of the '161 patent, or does it use a fundamentally different, non-infringing method to correct for phasing errors?
2. The case may also turn on a question of chemical functionality: does a component of Illumina's wash solution, such as lipoic acid, function as a "cleaving agent scavenger" as claimed in the '301 patent, or does it primarily serve a general-purpose washing or rinsing function that falls outside the claim scope?
3. A key evidentiary question will be one of proof through proxy: to what extent can Plaintiff rely on technical disclosures in Illumina's own patents (e.g., the '275 and '831 patents) as evidence for how the accused products actually operate, and will the court find that this proxy evidence is sufficient to demonstrate that the accused systems practice the specific limitations of the patents-in-suit?