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; Quinn Emanuel Urquhart & Sullivan, LLP
• Case Identification: 1:25-cv-01175, D. Del., 09/22/2025
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Illumina, Inc. is a Delaware corporation and therefore resides in the district.
• Core Dispute: Plaintiff alleges that Defendant’s DNA sequencing systems, along with associated reagent and library preparation kits, infringe four patents related to sequencing-by-synthesis (SBS) methods, including base calling algorithms and the chemical compositions used in the process.
• Technical Context: The lawsuit concerns technology in the field of next-generation sequencing (NGS), a foundational tool for modern genomics research, clinical diagnostics, and personalized medicine.
• Key Procedural History: Plaintiff Element Biosciences, Inc. identifies itself as the exclusive licensee of the Patents-in-Suit. The complaint repeatedly cites other U.S. patents listed on Defendant Illumina’s virtual patent marking website as evidence for how the accused products allegedly operate, a tactic which may suggest that Plaintiff's infringement theories are based, in part, on Defendant's own public-facing technical assertions.

Case Timeline

Date	Event
2008-03-19	Priority Date for ’161, ’301, ’174, and ’887 Patents
2013-12-17	U.S. Patent No. 8,612,161 Issues
2017-03-28	U.S. Patent No. 9,605,301 Issues
2018-03-06	U.S. Patent No. 9,909,174 Issues
2021-05-11	U.S. Patent No. 11,001,887 Issues
2022-01-01	Illumina launches XLEAP-SBS chemistry (approx. date)
2023-03-31	Element becomes exclusive licensee of Patents-in-Suit
2025-09-22	Complaint Filed

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’s background section describes that in sequencing-by-synthesis methods, phenomena such as "sequence lead" (where a strand gets ahead of the current cycle) and "sequence lag" (where a strand falls behind) can introduce errors, or "noise," that corrupt the signal data used to identify nucleotides (’161 Patent, col. 1:55-67).
• The Patented Solution: The invention claims a computational method to correct for these lead and lag errors, also known as phasing and prephasing. The method analyzes the fluorescent dye intensity not just at the current position being sequenced (the "interrogation position") but also at preceding and subsequent positions to calculate a "ratio contribution" that is then used to correct the data set and arrive at a more accurate identity for the nucleotide at the interrogation position (’161 Patent, col. 2:1-33).
• Technical Importance: This data correction approach was designed to increase the accuracy and achievable read length of sequencing-by-synthesis systems by computationally filtering out the cumulative signal noise caused by phasing errors (’161 Patent, col. 40:22-40).

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶ 59).
• The essential elements of Claim 1 are:
  • 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 the complementary sequence.
  • Determining the ratio contribution to dye intensity at an interrogation position from dye intensities at that position and at one or both of at least one subsequent and at least one preceding nucleic acid position.
  • Applying the ratio contribution to the data set to arrive at an identity for a nucleotide at the interrogation position.
• The complaint does not explicitly reserve the right to assert dependent claims for this patent.

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

The Invention Explained

• Problem Addressed: In cyclic sequencing-by-synthesis, a "cleaving agent" is used to remove a fluorescent label and a terminating moiety from an incorporated nucleotide to allow the next cycle to begin. The patent addresses the technical problem of residual cleaving agent from one cycle prematurely acting on the reagents of the subsequent cycle, which can cause errors (’301 Patent, col. 12:20-24).
• The Patented Solution: The invention provides a method that introduces a "cleaving agent scavenger" into the reaction. After the cleaving agent has performed its function, the scavenger is introduced to react with and neutralize any leftover cleaving agent, thereby preventing it from interfering with the next round of nucleotide incorporation (’301 Patent, col. 2:25-33).
• Technical Importance: This use of a scavenger provides a chemical control mechanism to improve the fidelity of each sequencing cycle, thereby increasing the overall accuracy and reliability of the sequencing process.

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶ 110).
• The essential elements of Claim 1 are:
  • Providing a reaction chamber, a first solution with polymerase and labeled 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 nucleotide.
  • Introducing the second solution to cleave the label and a removable moiety from the incorporated nucleotide.
  • Introducing the cleaving agent scavenger into the reaction chamber to scavenge the cleaving agent.
• The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 9,909,174 - "Methods and Compositions for Incorporating Nucleotides"

• Technology Synopsis: The ’174 patent relates to a method for identifying a nucleotide using a device with more than one detector channel. The method provides a mixture of both labeled and non-labeled "reversible terminators" (nucleotides that temporarily halt synthesis). A nucleotide from this mixture is incorporated, and its label is detected in two channels to determine its identity (Compl. ¶ 185; ’174 Patent, Abstract).
• Asserted Claims: Claim 1 (Compl. ¶ 173).
• Accused Features: The complaint alleges that Illumina’s two-channel sequencing systems (e.g., NovaSeq X Series) infringe by using a "two-color chemistry" that employs a mixture of fluorescently labeled nucleotides and unlabeled or "dark" nucleotides (for the 'G' base) and determines the identity of all four bases by detecting signals in two different color channels (Compl. ¶¶ 184, 189, 198).

U.S. Patent No. 11,001,887 - "Methods and Compositions for Incorporating Nucleotides"

• Technology Synopsis: The ’887 patent claims a method of incorporating nucleotides into a nucleic acid that also uses a mixture of labeled and non-labeled terminators. The claimed process involves a sequence of steps: providing the mixture, incorporating a first labeled nucleotide, detecting its color in two channels, and then removing both the label and the terminating chemical moiety with a cleaving agent before incorporating a second nucleotide (Compl. ¶ 239; ’887 Patent, Abstract).
• Asserted Claims: Claim 1 (Compl. ¶ 227).
• Accused Features: The complaint accuses Illumina's two-channel systems of infringing by providing a mixture of labeled and "dark" (unlabeled) nucleotides, incorporating one, detecting its color signature across two fluorescent channels, and then using a cleaving agent to remove the label and blocking group to prepare for the next cycle (Compl. ¶¶ 261, 268, 271, 277).

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are Defendant Illumina's DNA sequencing systems, including the iSeq, MiniSeq, MiSeq, MiSeq i100, NextSeq, NovaSeq, and legacy HiSeq series systems, when used in combination with Illumina's compatible Library Preparation Kits and Sequencing Reagent Kits (Compl. ¶¶ 15-16, 36-38, 59).

Functionality and Market Context

• The complaint alleges that all accused systems operate using Illumina's "proven sequencing by synthesis (SBS) technology" (Compl. ¶ 17). This process involves cyclically adding one nucleotide at a time to a growing DNA strand immobilized on a "flow cell." In each cycle, a fluorescently labeled "reversible terminator" nucleotide is incorporated, its signal is detected by a camera, and then the label and terminator are chemically cleaved to allow the next cycle to begin (Compl. ¶¶ 23-27).
• The complaint describes Illumina's transition from older four-channel chemistry (four unique dyes for four bases) to a more rapid two-channel chemistry (using two dyes in combination to encode the four bases) (Compl. ¶¶ 30-32). A graphic included in the complaint illustrates the two-channel detection scheme (Compl. ¶ 31). The complaint also identifies a newer "XLEAP-SBS" chemistry, launched in 2022, as an "update to Illumina's sequencing by synthesis (SBS) chemistry" (Compl. ¶¶ 33-34).
• The products are positioned as Illumina's current and legacy commercial sequencing platforms, suggesting they represent a significant portion of the NGS market (Compl. ¶¶ 36, 38).

IV. Analysis of Infringement Allegations

8,612,161 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a) sequencing a nucleic acid by DNA sequencing by synthesis utilizing nucleotides with fluorescent dyes which are incorporated into a complementary strand,	The accused NextSeq 550 system uses Illumina’s proven SBS chemistry, a reversible terminator-based method using fluorescently labeled nucleotides.	¶78-80	col. 1:25-30
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 accused system images clusters of nucleic acids using two-channel chemistry, and its RTA software obtains dye intensity data for each cycle.	¶81, ¶83	col. 2:6-8
c) 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...	The accused system's RTA software corrects for "phasing" (lag from preceding positions) and "prephasing" (lead from subsequent positions), which allegedly involves determining a contribution from intensities at neighboring positions. The complaint uses Illumina's '275 patent to describe this process.	¶82, ¶87-91	col. 2:15-24
d) applying said ratio contribution to said data set to arrive at an identity for a nucleotide at said interrogation position in said nucleotide sequence.	The accused RTA software applies the phasing and prephasing corrections to the dye intensity data to maximize data quality and determine the final base call for the nucleotide at the interrogation position.	¶92-94	col. 2:25-33

• Identified Points of Contention:
  • Algorithmic Equivalence: The complaint alleges that the accused system's "RTA software," which "corrects the effects of phasing and prephasing," meets the claim limitations (Compl. ¶ 93). A central question for the court will be whether this general correction function performs the specific steps of "determining the ratio contribution" and "applying said ratio contribution" as required by the claim language.
  • Evidentiary Basis: The complaint relies heavily on descriptions from a different Illumina patent (the '275 patent) to explain the functionality of the accused RTA software (Compl. ¶¶ 85-92). This raises the question of what evidence will be required to prove that the accused products actually practice the methods described in the '275 patent and that those methods fall within the scope of the ’161 patent’s claims. The complaint's visual of phasing and prephasing illustrates the problem the patent purports to solve (Compl. ¶ 82).

9,605,301 Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a) providing i) a reaction chamber... ii) a first solution comprising polymerase and a plurality of nucleotide analogues...	The accused NovaSeq X Series system uses a flow cell (reaction chamber) and provides a first solution containing polymerase and fluorescently labeled nucleotide analogues as part of its XLEAP-SBS chemistry. A complaint graphic shows the labeled nucleotide components (Compl. ¶ 127).	¶121-130	col. 16:16-32
...iii) a second solution comprising a cleaving agent...	The accused process provides a "deblocking composition" which is alleged to be a second solution containing a cleaving agent (e.g., a palladium catalyst as described in Illumina's '831 patent).	¶131-136	col. 16:33-35
...and iv) a cleaving agent scavenger;	The accused process provides a "universal wash composition" used in a "post-cleave wash" step, which is alleged to contain a scavenger (e.g., lipoic acid or Pd scavengers as described in Illumina's '962 and '831 patents).	¶137-139	col. 12:21-24
d) introducing said second solution into said reaction chamber under conditions such that the chemical moiety... and said cleavable linker is cleaved by said cleaving agent; and	Following imaging, the accused process introduces the deblocking composition (second solution) to cleave the fluorescent label and the 3'-OH blocking group from the incorporated nucleotide.	¶147-152	col. 16:42-49
e) introducing said cleaving agent scavenger into said reaction chamber under conditions so as to scavenge said cleaving agent.	Following cleavage, the accused process performs a post-cleave wash step with the wash solution, which is alleged to introduce the scavenger to neutralize any residual cleaving agent.	¶153-155	col. 16:50-54

• Identified Points of Contention:
  • Chemical Identity: The infringement theory relies on mapping components described in other Illumina patents (the '831 and '962 patents) to the "cleaving agent" and "cleaving agent scavenger" limitations of the ’301 patent (Compl. ¶¶ 132, 137). A key technical question will be whether the chemical compositions used in Illumina's accused XLEAP-SBS process (e.g., the "deblocking composition" and "universal wash composition") contain the specific chemical agents and function in the specific manner required by the claims.
  • Scope Questions: The case may turn on whether providing separate "deblocking" and "wash" solutions meets the claim requirements of providing a "second solution comprising a cleaving agent" and separately providing a "cleaving agent scavenger." The sequence and purpose of introducing these components will be a focus of analysis.

V. Key Claim Terms for Construction

Patent: U.S. 8,612,161

• The Term: "determining the ratio contribution"
• Context and Importance: This term defines the core computational step of the invention. Its construction will be critical to determining whether Illumina's general-purpose "phasing and prephasing correction" software performs the specific mathematical operation claimed by the patent. Practitioners may focus on this term because it is the central point of novelty for the claimed method.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The Summary of the Invention describes the step more generally as "applying the ratio contribution to probe intensity to the data set to arrive at an identity for a nucleic acid" (’161 Patent, col. 2:25-28), which may support an interpretation covering various mathematical approaches that use signal ratios from adjacent cycles.
  • Evidence for a Narrower Interpretation: The detailed description provides a specific mathematical framework using a "lead-lag matrix" (K_Lead/Lag) to model and calculate these contributions (’161 Patent, col. 3:15-25, FIG. 8). A defendant may argue this specific matrix-based calculation defines the scope of "determining the ratio contribution."

Patent: U.S. 9,605,301

• The Term: "cleaving agent scavenger"
• Context and Importance: The presence and function of a "scavenger" is a key limitation of the asserted claim. Infringement hinges on whether a substance used in Illumina's SBS workflow meets this definition. Practitioners may focus on this term because it appears to be a primary point of distinction over prior art sequencing chemistries.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification describes the scavenger's function as addressing "leftover cleaving agent which might prematurely cleave in the next cycle" and lists multiple chemical classes that could serve this purpose, such as compounds with disulfide bonds (e.g., cystamine) or azido groups (’301 Patent, col. 12:21-24; col. 13:15-25). This suggests a functional definition.
  • Evidence for a Narrower Interpretation: The claim requires "introducing said cleaving agent scavenger... so as to scavenge said cleaving agent," which implies intent and primary purpose. A defendant might argue that a compound used in the accused process that has a different primary function but an incidental scavenging effect does not meet this limitation.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Illumina induces infringement by providing customers with its sequencing systems along with "user guides and manuals and educational materials" that instruct them to operate the systems in a manner that directly infringes the patents-in-suit (Compl. ¶¶ 95, 156, 212, 279). Contributory infringement is alleged on the basis that Illumina sells systems and reagent kits that are especially designed to practice the patented methods and are not staple articles of commerce with substantial non-infringing uses (Compl. ¶¶ 97, 158, 214, 281).
• Willful Infringement: Willfulness is alleged based on Illumina's continued infringement after having notice of the patents, with such notice occurring "at least as of the date of service of this complaint" (Compl. ¶¶ 106, 167, 223, 290).

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

• A central evidentiary issue for all asserted patents will be one of technical substantiation: The complaint consistently uses technical descriptions from other patents on Illumina’s virtual marking list to define the functionality of the accused systems. A key question for the court will be whether discovery confirms that the accused products actually operate as described in these other patents and, if so, whether that operation falls within the distinct claim scope of each of the four patents-in-suit.
• The case will likely turn on questions of chemical and algorithmic equivalence. For the chemistry-focused patents (’301, ’174, ’887), the dispute will likely involve a granular analysis of whether the specific molecules and compositions in Illumina's SBS and XLEAP-SBS processes meet the claimed definitions of, for example, a "cleaving agent scavenger" or a "mixture of labeled and non-labeled... terminators." For the data processing patent (’161), the question will be whether Illumina's proprietary "RTA" software performs the specific mathematical steps of the claims or achieves a similar result through a non-infringing algorithm.