Olink Proteomics Ab v. Alamar Biosciences Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Olink Proteomics AB (Sweden) and Olink Proteomics Inc. (Delaware)
  • Defendant: Alamar Biosciences, Inc. (Delaware)
  • Plaintiff’s Counsel: Richards, Layton & Finger, P.A.; Goodwin Procter LLP
• Case Identification: 1:23-cv-01303, D. Del., 11/15/2023
• Venue Allegations: Venue is alleged to be proper because Defendant Alamar Biosciences, Inc. is a Delaware corporation and therefore resides in the judicial district.
• Core Dispute: Plaintiff alleges that Defendant’s Nucleic acid Linked Immuno-Sandwich Assay (NULISA) platform infringes a patent related to methods for detecting molecular interactions.
• Technical Context: The technology relates to high-sensitivity immunoassays used for proteomic analysis and biomarker discovery, a field critical for life sciences research and diagnostics.
• Key Procedural History: The complaint alleges that Plaintiff provided Defendant with pre-suit notice of the patent-in-suit via a letter dated August 11, 2023, which may be relevant to the allegation of willful infringement.

Case Timeline

Date	Event
2005-07-08	’848 Patent Priority Date
2011-02-08	’848 Patent Issue Date
2023-04-13	Defendant announces unveiling of NULISA platform
2023-08-11	Plaintiff sends pre-suit notice letter to Defendant regarding '848 Patent
2023-11-09	Defendant announces installation of ARGO HT System at first customer site
2023-11-15	Complaint Filing Date

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

U.S. Patent No. 7,883,848 - “Regulation Analysis by Cis Reactivity, RACR”

• Patent Identification: U.S. Patent No. 7,883,848, “Regulation Analysis by Cis Reactivity, RACR,” issued February 8, 2011.

The Invention Explained

• Problem Addressed: The patent addresses the limitations of then-current high-throughput techniques for identifying molecular interactions, such as protein microarrays and yeast two-hybrid systems. These methods are described as being limited by cost, labor, a high frequency of false positives, and the difficulty of screening large libraries of molecules against each other in a combinatorial fashion (’848 Patent, col. 1:21 - col. 3:3).
• The Patented Solution: The invention proposes a method where each "molecule of interest" (MOI), such as a protein, is coupled to a unique nucleic acid tag, or "nucleic acid moiety" (NAM), to form an "interactor." When two MOIs interact due to affinity or function, their corresponding NAMs are brought into close physical proximity. This proximity enables the NAMs to be joined together (e.g., by ligation), forming a new, unique "associated oligonucleotide" that contains the identification sequences from both original interactors. This new DNA molecule serves as a reporter, converting the molecular interaction event into a quantifiable nucleic acid signal (’848 Patent, Abstract; col. 5:21-40). The process is illustrated conceptually in Figure 1 of the patent.
• Technical Importance: This technology enables the simultaneous screening of many-against-many molecular interactions within a single experiment, a significant advance over methods that typically analyze one interaction partner against a limited set of others (’848 Patent, col. 3:56-62).

Key Claims at a Glance

• The complaint recites independent claim 1 as being infringed (Compl. ¶12).
• Essential elements of independent claim 1 include:
  • a. forming a plurality of interactors by coupling each molecule of interest with a nucleic acid moiety that comprises an identification sequence element and an association element;
  • b. forming a plurality of "cis-reactive cells," each comprising at least two interactors bound in proximity by an associated oligonucleotide formed from the association of their nucleic acid moieties;
  • c. subjecting the cis-reactive cells to conditions that stimulate a desired functional interaction having a detectable trace;
  • d. selecting all cis-reactive cells that exhibit the detectable trace; and
  • e. subjecting the associated oligonucleotides from the selected cells to an analysis to detect the identification sequence elements.
• The complaint does not explicitly reserve the right to assert dependent claims but makes a general allegation of infringement of the ’848 patent (Compl. ¶35).

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are Defendant's Nucleic acid Linked Immuno-Sandwich Assay (“NULISA”) platform and its associated ARGO system (Compl. ¶1).

Functionality and Market Context

• The NULISA platform is described as a biomarker detection and quantification assay for proteins (Compl. ¶18). The platform allegedly uses probes made of an antibody conjugated to a nucleic acid oligonucleotide; these are referred to as "interactors" (Compl. ¶¶21-22). When a pair of these antibody probes binds to a target protein in a sample, they form an "immunocomplex" (Compl. ¶25). This binding event brings the attached oligonucleotides into proximity, allowing them to be joined via ligation to form a new "DNA reporter molecule" (Compl. ¶¶24, 26). The quantity of this reporter molecule, which corresponds to the amount of target protein, is then measured using methods like quantitative PCR or Next Generation Sequencing (Compl. ¶27). The complaint references a commercial video from the defendant that provides a general overview of the NULISA platform's operation (Compl. ¶20). The complaint alleges that Defendant has acknowledged that the NULISA technology is based on the Proximity Ligation Assay (PLA) technology originally commercialized by a forerunner of the Plaintiff (Compl. ¶19).

IV. Analysis of Infringement Allegations

'848 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a. forming a plurality of interactors by coupling each molecule of interest with at least one nucleic acid moiety, the nucleic acid moiety comprising an identification sequence element and an association element;	The NULISA platform allegedly uses probes consisting of an antibody ("molecule of interest") and a nucleic acid. The complaint alleges these form "a plurality of interactors" and that the oligonucleotides contain an "identification sequence element" (e.g., a barcode) and an "association element" (a ligatable end) (Compl. ¶¶21-24).	¶¶21, 23, 24	col. 5:41-55
b. forming a plurality of cis-reactive cells wherein a cis-reactive cell comprises at least two interactors bound in proximity to one another by an associated oligonucleotide formed from the association between at least two nucleic acid moieties...	When two NULISA probes bind to a target protein, an "immunocomplex" is formed. The complaint alleges this structure is a "cis-reactive cell" and that the ligation of the probe arms forms an "associated oligonucleotide" that connects the interactors (Compl. ¶¶25-26).	¶¶25, 26	col. 6:11-19
c. subjecting the plurality of cis-reactive cells to conditions which stimulate a desired functional interaction having a detectable trace;	The complaint does not specify a separate stimulation step but appears to allege that the formation of the "highly specific immunocomplex" itself constitutes the stimulated functional interaction, and the resulting ligated DNA reporter molecule is the detectable trace (Compl. ¶¶12, 27).	¶27	col. 6:19-21
d. selecting all cis-reactive cells exhibiting the detectable trace; and	The complaint alleges this step is practiced as a result of the NULISA platform’s "dual capture and release mechanism" and the formation of the "highly specific immunocomplex" when the target protein is present, which is what is ultimately detected (Compl. ¶27).	¶27	col. 6:19-21
e. subjecting the associated oligonucleotides from the cis-reactive cells selected in step (d) to an analysis that permits detection of the at least two identification sequence elements.	The complaint alleges that "the levels of the DNA reporter can be quantified by quantitative PCR or NGS," which constitutes the analysis of the associated oligonucleotides to detect the interaction event (Compl. ¶27).	¶27	col. 6:21-24

• Identified Points of Contention:
  • Scope Questions: Claim 1 is directed to a method of detecting "functional interactions." A central question will be whether the affinity-based binding of antibodies to a target protein, as allegedly performed by the accused NULISA platform, falls within the patent’s definition of a "functional interaction." The complaint’s theory appears to equate the binding event with the claimed "functional interaction," which may become a point of dispute.
  • Technical Questions: What evidence does the complaint provide that the accused NULISA platform performs the distinct sequential steps of (b) forming a "cis-reactive cell," (c) then subjecting it to conditions to stimulate a functional interaction, and (d) then selecting the cells with a detectable trace? The infringement theory seems to conflate the formation of the immunocomplex with the functional interaction and its detection, which may not map precisely to the claim's multi-step structure.

V. Key Claim Terms for Construction

• The Term: "functional interaction"

• Context and Importance: This term is the central limitation of claim 1. The viability of the infringement case hinges on whether the accused NULISA platform, which detects proteins based on antibody-antigen affinity, performs a "functional interaction." Practitioners may focus on this term because its construction will determine whether the patent covers standard proximity ligation assays or is limited to more complex assays (e.g., those measuring enzymatic activity).

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification states that "Functional interactions may include an affinity interaction" (’848 Patent, col. 15:37-38). This language could support a construction where simple binding falls within the scope of the term.
  • Evidence for a Narrower Interpretation: The patent provides numerous examples of functional interactions that imply an active process beyond simple binding, such as "kinase, phosphatase, glycosylation, deglycosylation, ubiqutinylation," and "cleavage" (’848 Patent, col. 15:40-45). The description of the embodiment for detecting functional interactions suggests a process where proximity is first established to form a "cis reactive cell," which is then subjected to conditions to stimulate the function (’848 Patent, col. 6:11-21). This could support a narrower construction requiring an active function beyond the initial affinity binding.

• The Term: "cis-reactive cell"

• Context and Importance: The definition and method of forming this structure are critical to claim 1(b). The infringement allegation equates the NULISA "immunocomplex" with a "cis-reactive cell" (Compl. ¶25). Whether this mapping is correct will depend on the construction of this term.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent defines the term broadly as "an association of at least two interactor moieties, joined by an associated oligonucleotide" (’848 Patent, col. 10:35-38). This general definition could plausibly read on the ligated immunocomplex alleged to be formed by the NULISA platform.
  • Evidence for a Narrower Interpretation: Claim 1(b) recites "forming a plurality of cis-reactive cells... by an associated oligonucleotide," which suggests the oligonucleotide is the agent that forms the cell. However, the patent's description suggests the cell is formed first by bringing interactors into proximity, which then allows the associated oligonucleotide to be formed (’848 Patent, col. 6:11-19). This potential tension between the claim language and the specification may raise questions about the precise structure and timing of the "cis-reactive cell" formation.

VI. Other Allegations

• Indirect Infringement: The complaint alleges inducement of infringement under 35 U.S.C. § 271(b), asserting that Defendant knowingly encourages its customers to use the NULISA platform in an infringing manner (Compl. ¶36). It also alleges contributory infringement under § 271(c), stating the NULISA platform is not a staple article of commerce suitable for substantial noninfringing use (Compl. ¶37).
• Willful Infringement: The complaint alleges willful infringement based on Defendant's alleged knowledge of the ’848 patent. The specific basis for this knowledge is an alleged pre-suit notification letter sent by Plaintiff to Defendant's CEO on August 11, 2023 (Compl. ¶¶33, 40).

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

• A core issue will be one of definitional scope: Can the claim term "functional interaction" be construed to cover the affinity binding of an antibody to its target protein, as allegedly performed by the accused NULISA assay? Or does the patent’s text and structure require a more active process, such as enzymatic activity, that is stimulated after the initial binding event?
• A key question of claim interpretation will be whether the accused NULISA process, where binding and ligation appear to be part of a continuous detection mechanism, can be mapped onto the specific, sequential steps of claim 1, particularly the distinct formation of a "cis-reactive cell" (step b) followed by a "stimulation" of a functional interaction (step c).