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., 12/08/2025
• 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, which utilize sequencing-by-synthesis (SBS) chemistry, infringe four patents related to methods for improving the accuracy and efficiency of the sequencing process.
• Technical Context: The lawsuit concerns next-generation DNA sequencing (NGS), a foundational technology in genomics, personalized medicine, and biological research that allows for rapid and large-scale sequencing of DNA and RNA.
• Key Procedural History: The complaint is a First Amended Complaint. Plaintiff Element is the exclusive licensee of the patents-in-suit. The complaint alleges that Defendant Illumina marks several of its own patents on the accused products, and Plaintiff leverages the disclosures in those Illumina-owned patents to support its infringement allegations.

Case Timeline

Date	Event
2008-03-19	Earliest Priority Date for Patents-in-Suit
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)
2025-12-08	Complaint Filing Date

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

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

• Issued: December 17, 2013

The Invention Explained

• Problem Addressed: In sequencing-by-synthesis (SBS), millions of DNA strands are sequenced in parallel, one base at a time per cycle. However, errors can occur where some strands fall behind a cycle ("sequence lag") or jump ahead ("sequence lead"). This phenomenon, called "dephasing," causes the fluorescent signal from a cluster of DNA strands to become mixed and degraded over successive cycles, limiting the accuracy and achievable read length of the sequencing run. (’161 Patent, col. 40:1-8, col. 44:9-15; Compl. ¶¶105-108).
• The Patented Solution: The patent discloses a data processing method to computationally correct for dephasing. Instead of taking the signal from a given cycle at face value, the method mathematically determines how the signal intensities from preceding and subsequent cycles contribute to the signal at the current position being interrogated. By applying this "ratio contribution" to the raw data set, the method aims to reconstruct the "true" signal for each position, thereby correcting the errors caused by lead and lag. (’161 Patent, Abstract; col. 44:30-45:41).
• Technical Importance: This data correction approach allows for increased fidelity and longer read lengths in SBS sequencing, which are critical metrics for the utility and commercial value of sequencing platforms. (Compl. ¶109).

Key Claims at a Glance

• The complaint asserts at least independent claim 1. (Compl. ¶73).
• Claim 1 of the ’161 patent recites a method with the following essential elements:
  • sequencing a nucleic acid by DNA sequencing by synthesis utilizing nucleotides with fluorescent dyes;
  • obtaining a data set for one or more dye intensities at one or more nucleic acid positions;
  • 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 nucleic acid position and at least one preceding nucleic acid position; and
  • applying said 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, but the infringement counts are for the patent generally. (Compl. ¶¶100-152).

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

• Issued: March 28, 2017

The Invention Explained

• Problem Addressed: SBS chemistry involves cycles of adding a labeled nucleotide and then using a "cleaving agent" to remove the label and a blocking group to prepare for the next cycle. The patent addresses the problem of residual cleaving agent from one cycle carrying over into the next, where it can prematurely cleave the newly added nucleotide's label before it can be detected, leading to signal loss and sequencing errors. (’301 Patent, col. 12:20-24).
• The Patented Solution: The invention introduces the use of a "cleaving agent scavenger." This is a chemical compound introduced into the reaction chamber to react with and neutralize any residual cleaving agent. The method described in the claims involves providing separate solutions for incorporation (nucleotides and polymerase), cleaving (cleaving agent), and scavenging (scavenger), and introducing them sequentially to ensure undesired cleavage is inhibited. (’301 Patent, Abstract; Compl. ¶161).
• Technical Importance: This method aims to improve sequencing accuracy by chemically isolating the discrete steps of the SBS cycle, preventing cross-contamination of reagents between cycles.

Key Claims at a Glance

• The complaint asserts at least independent claim 1. (Compl. ¶161).
• Claim 1 of the ’301 patent recites a method with the following essential elements:
  • providing a reaction chamber, a first solution (with polymerase and nucleotide analogues), a second solution (with a cleaving agent), and a cleaving agent scavenger;
  • introducing the first solution to incorporate a nucleotide;
  • detecting the label of the incorporated nucleotide;
  • introducing the second solution to cleave the label and blocking moiety; and
  • introducing the cleaving agent scavenger to scavenge the cleaving agent.
• The complaint does not explicitly reserve the right to assert dependent claims. (Compl. ¶¶205-213).

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

• Issued: March 6, 2018
• Technology Synopsis: The patent addresses methods for identifying nucleotides in a "two-channel" or "two-color" sequencing context. The invention involves providing a mixture of both labeled and non-labeled reversible terminators, incorporating a nucleotide, and detecting its label in two detector channels to determine its identity. This approach allows four different bases to be distinguished using only two distinct fluorescent signals. (Compl. ¶¶215, 229).
• Asserted Claims: At least Claim 1. (Compl. ¶229).
• Accused Features: Illumina’s two-channel sequencing systems, including the MiniSeq, MiSeq i100, NextSeq series, NovaSeq 6000, and NovaSeq X Series systems. (Compl. ¶218).

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

• Issued: May 11, 2021
• Technology Synopsis: This patent also relates to two-channel sequencing chemistry. The claimed method involves providing a mixture of labeled and non-labeled terminators, incorporating a first nucleotide, detecting its color in two channels, removing the label and blocking group with a cleaving agent, and then incorporating a second nucleotide. The invention appears directed to the cyclical process of two-color sequencing. (Compl. ¶283).
• Asserted Claims: At least Claim 1. (Compl. ¶283).
• Accused Features: Illumina’s two-channel sequencing systems, including the MiniSeq, MiSeq i100, NextSeq series, NovaSeq 6000, and NovaSeq X Series systems. (Compl. ¶272).

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are Defendant Illumina’s DNA sequencing systems, including the HiSeq, iSeq 100, MiniSeq, MiSeq/MiSeqDx, MiSeq i100, NextSeq 500/550/550Dx, NextSeq 1000/2000, NovaSeq 6000/6000Dx, and NovaSeq X Series. The infringement allegations also extend to the use of these systems in combination with Illumina’s corresponding Library Preparation Kits and Sequencing Reagent Kits. (Compl. ¶¶15-16, 36-38, 59).

Functionality and Market Context

• The complaint alleges all accused systems operate using Illumina’s proprietary sequencing-by-synthesis (SBS) technology. (Compl. ¶17). This process involves immobilizing DNA fragments on a glass substrate ("flow cell"), amplifying them into clusters, and then iteratively determining the DNA sequence. (Compl. ¶¶18-21). Each sequencing cycle consists of incorporating a fluorescently labeled nucleotide with a reversible terminator, imaging the flow cell to identify the incorporated base, and then chemically cleaving the fluorescent label and terminator to prepare for the next cycle. (Compl. ¶23). An image from an Illumina video illustrates many identical single-stranded DNA molecules bound inside a nanowell on a flow cell surface. (Compl. ¶22, p. 5). The systems vary in their detection chemistry, using one, two, or four color channels to identify the four DNA bases. (Compl. ¶¶30-32, 40).

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) 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, which involves detecting fluorescently labeled nucleotides as they are incorporated into growing DNA strands.	¶¶78-80	col. 40:1-8
b) 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,	During sequencing, the NextSeq 550 system images clusters of nucleic acids using two-channel chemistry after each incorporation cycle. The system’s Real-Time Analysis (RTA) software extracts dye intensity data from these images for each cycle and nucleic acid position.	¶¶81, 83-84	col. 52:1-5
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 in said complementary sequence, and ii) at least one preceding nucleic acid positions in said complementary sequence, and	The complaint alleges that the NextSeq 550 system’s RTA software performs "Phasing Correction" to correct for errors where DNA strands fall behind (phasing) or jump ahead (prephasing). A diagram in an Illumina document illustrates 'Phasing and Prephasing,' where a DNA strand becomes out of phase with the current incorporation cycle. (Compl. ¶82, p. 22). The complaint alleges, based on an Illumina patent marked on the product, that this correction involves calculating phasing and pre-phasing parameters based on dye intensities at the current, preceding, and subsequent positions.	¶¶82, 85-91	col. 44:30-45:13
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 RTA software allegedly applies the calculated phasing corrections to the observed intensity data to reduce noise, maximize data quality, and determine the identity of the nucleotide (base call) at each position.	¶¶92-94	col. 52:6-13

Identified Points of Contention

• Scope Questions: A primary question will be whether the algorithm used in Illumina’s RTA software for "Phasing Correction" meets the specific claim limitation of "determining the ratio contribution." The infringement theory relies heavily on mapping the functionality described in Illumina's own patent ('275 patent) onto the claim language of the '161 patent, raising the question of whether this mapping is technically and legally correct.
• Technical Questions: The complaint alleges "on information and belief" that the accused systems practice the methods of the '275 patent. This suggests that a key factual dispute will be the precise mathematical operations performed by the proprietary RTA software and whether those operations are equivalent to calculating a "ratio contribution" from adjacent cycle data as claimed.

U.S. Patent No. 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... iii) a second solution comprising a cleaving agent, and iv) a cleaving agent scavenger;	The accused NovaSeq X system requires a flow cell (reaction chamber). The complaint alleges it uses reagent kits that provide separate solutions: a first solution for incorporation (containing polymerase and labeled nucleotides), a second "deblocking composition" (containing a cleaving agent), and a "universal wash composition" used post-cleavage that allegedly contains a cleaving agent scavenger. A graphic from Illumina's website depicts the structure of its modified nucleotides, identifying a dye, a cleavable linker, and a removable blocking group. (Compl. ¶171, p. 43).	¶¶165-183	col. 16:21-34
b) introducing said first solution into said reaction chamber under conditions wherein a first nucleotide analogue is incorporated by said polymerase;	In each SBS cycle, the first solution containing polymerase and nucleotide analogues is introduced into the flow cell, where the polymerase incorporates the complementary nucleotide into the growing DNA strands.	¶¶184-187	col. 16:35-37
c) detecting the label of the incorporated nucleotide analogue;	After incorporation, the clusters on the flow cell are excited with light and a fluorescent signal is emitted. The NovaSeq X system detects this signal with a camera using two channels (green and blue) to determine the identity of the incorporated base. A scatter plot from an Illumina document illustrates how base calls are made in its two-channel chemistry by plotting blue versus green intensity. (Compl. ¶189, p. 48).	¶¶188-190	col. 16:38-39
d) introducing said second solution into said reaction chamber under conditions such that the chemical moiety of the incorporated nucleotide analogue capping the 3'-OH group is removed and said cleavable linker is cleaved by said cleaving agent; and	After imaging, the second solution ("deblocking composition"), containing a cleaving agent, is introduced into the flow cell. This solution allegedly cleaves the fluorescent label and removes the 3'-OH blocking group to prepare the strand for the next cycle.	¶¶191-196	col. 16:40-45
e) introducing said cleaving agent scavenger into said reaction chamber under conditions so as to scavenge said cleaving agent.	Following the cleavage step, a "post-cleave wash" occurs using a "universal wash composition." Citing another Illumina patent, the complaint alleges this wash solution contains a scavenger (lipoic acid) that is introduced into the flow cell and scavenges the cleaving agent.	¶¶197-199	col. 16:46-49

Identified Points of Contention

• Scope Questions: A central issue may be whether a compound included in a "universal wash composition" meets the claim definition of a "cleaving agent scavenger" that is introduced "so as to scavenge said cleaving agent." A court may need to decide if this requires the compound's primary purpose to be scavenging, or if a secondary or inherent property of a wash buffer component is sufficient.
• Technical Questions: The infringement theory relies on disclosures in other Illumina patents ('831 and '962) to identify the specific chemicals used as the "cleaving agent" and "scavenger." A key factual question will be whether the accused reagent kits actually contain the alleged palladium catalysts and lipoic acid, and whether those compounds function as claimed under the accused systems' operating conditions.

V. Key Claim Terms for Construction

From the ’161 Patent

• The Term: "determining the ratio contribution"
• Context and Importance: This term defines the core mathematical correction step of the invention. The scope of "ratio contribution" will be critical to determining if Illumina's proprietary "Phasing Correction" algorithm, which the complaint alleges is based on Illumina's own '275 patent, performs the claimed step.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: Practitioners may argue that the claim language does not limit the term to a specific formula. The specification's disclosure of a matrix equation (’161 Patent, col. 44:30-45:41) could be presented as one exemplary, but not exclusive, way of determining this contribution, allowing for other algorithmic implementations that achieve the same result.
  • Evidence for a Narrower Interpretation: Practitioners may focus on the detailed matrix equations and definitions of the ratio terms (e.g., R+1Lead,1, R-1Lag,2) provided in the specification (’161 Patent, col. 3-4, 7-8). This could support an argument that "determining the ratio contribution" is not a generic concept but is limited to the specific mathematical framework disclosed.

From the ’301 Patent

• The Term: "cleaving agent scavenger"
• Context and Importance: Infringement of the '301 patent hinges on whether the accused process uses a "scavenger." The complaint identifies a component of a general wash buffer as the scavenger, making the definition of this term pivotal.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent states the scavenger is "employed to address leftover cleaving agent" and is "designed to react with any leftover cleaving reagent." (’301 Patent, col. 12:20-24). This functional language may support a broader definition where any compound added that performs this function qualifies, regardless of its other roles.
  • Evidence for a Narrower Interpretation: The patent provides specific examples of scavengers, such as cystamine, and describes them as a distinct component of the claimed method alongside the cleaving agent. (’301 Patent, col. 13:10-21). This may support an argument that a "scavenger" must be a compound provided for the specific and primary purpose of scavenging, not a general-purpose chemical in a wash buffer that might have incidental scavenging properties.

VI. Other Allegations

Indirect Infringement

For all four patents-in-suit, the complaint alleges both induced and contributory infringement. The inducement theory is based on Illumina allegedly instructing and encouraging its customers to use the accused sequencing systems and reagent kits in their normal, infringing manner via user guides, manuals, and other educational materials. (Compl. ¶¶95-96, 200-201). The contributory infringement allegation is based on the assertion that the accused systems and kits are especially designed for practicing the patented methods and are not staple articles of commerce suitable for substantial noninfringing use. (Compl. ¶¶97-98, 202-203).

Willful Infringement

Willfulness is alleged for all four patents based on Illumina's continued infringement after having been put on notice of the patents via the original complaint in the action. (Compl. ¶¶99, 150, 204).

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

• A central issue will be one of algorithmic equivalence: Does the proprietary "Phasing Correction" algorithm in Illumina's RTA software perform the same or an equivalent function as the '161 patent's claimed step of "determining the ratio contribution" from adjacent sequencing cycles? The outcome may depend on whether the court views the claim as requiring a specific mathematical model or covering the general concept of using data from neighboring cycles to correct dephasing errors.
• A key question will be one of functional purpose: Does a chemical compound within Illumina's "universal wash composition" function as a "cleaving agent scavenger" as claimed by the '301 patent, or is its role merely incidental to a general-purpose wash step? This dispute may turn on whether the claim requires a component to be included for the specific, intended purpose of scavenging, or if performing the function is sufficient for infringement.
• A recurring evidentiary question will be one of reverse engineering and inference: The complaint repeatedly relies on disclosures from Illumina's own patents (which are marked on accused products) to allege the specific chemical compositions and software functions that infringe. This raises the question of whether Plaintiff can produce sufficient evidence to prove that the accused products actually practice the methods described in those patents, or if there are material differences in implementation.