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.
• Case Identification: 1:23-cv-01303, D. Del., 04/02/2026
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because the Defendant, Alamar Biosciences, Inc., is a Delaware corporation and thus resides in the judicial district.
• Core Dispute: Plaintiff alleges that Defendant’s Nucleic Acid Linked Immuno-Sandwich Assay (NULISA) platform and associated ARGO system infringe a patent related to methods for detecting molecular interactions.
• Technical Context: The lawsuit concerns technology in the field of proteomics, specifically high-sensitivity immunoassays used to detect and quantify proteins, which serve as crucial biomarkers for disease research and diagnostics.
• Key Procedural History: The complaint notes that after the original complaint was filed, Defendant Alamar challenged the validity of the patent-in-suit in an inter partes review (IPR) proceeding at the Patent Trial and Appeal Board (PTAB). In a Final Written Decision, the PTAB determined that Alamar failed to prove that the asserted patent claims were unpatentable.

Case Timeline

Date	Event
2005-07-08	U.S. Patent No. 7,883,848 Priority Date
2011-02-08	U.S. Patent No. 7,883,848 Issue Date
2023-04-13	Alamar announces unveiling of NULISA platform
2023-08-11	Olink sends letter to Alamar notifying it of the ’848 patent
2023-11-09	Alamar announces first early access installation of its ARGO HT System
2023-11-15	Original complaint filed in D. Del.
2024-01-04	Alamar commercially launches the ARGO system
2026-03-04	PTAB issues Final Written Decision in IPR2024-01353
2026-04-02	Amended 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 (“the ’848 patent”), Regulation Analysis by Cis Reactivity, RACR, issued February 8, 2011.

The Invention Explained

• Problem Addressed: The patent’s background section describes the limitations of then-current high-throughput techniques for analyzing molecular interactions. Methods like protein microarrays were costly and labor-intensive, while genetic systems like the yeast two-hybrid system suffered from high rates of false positives and were not easily adaptable to molecules other than proteins (’848 Patent, col. 1:23-2:67).
• The Patented Solution: The invention proposes a method to discover new molecular interactions in a high-throughput manner. The core idea is to attach a unique nucleic acid "tag" or moiety (NAM) to each molecule of interest (MOI) in a library (’848 Patent, col. 5:14-19). When two MOIs interact, their attached NAMs are brought into proximity, allowing them to be joined together to form a new, combined oligonucleotide (’848 Patent, col. 5:32-46). This combined oligonucleotide serves as a unique signature for that specific molecular interaction. The patent further describes that this interaction can be a "functional interaction" (e.g., an enzyme acting on a substrate) that leaves a "detectable trace" on the complex, which can then be selected for analysis (’848 Patent, col. 6:4-23). By analyzing the nucleic acid signatures of the selected complexes, the specific molecules that functionally interacted can be identified.
• Technical Importance: The technology provided a method for combinatorial screening of molecular interactions in a solution-based format, which avoids potential issues caused by immobilizing one of the interaction partners on a solid surface (’848 Patent, col. 2:19-22).

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 2–8, 11, 12, 14, and 15 (Compl. ¶22; Compl. ¶34).
• Independent claim 1 of the ’848 patent recites a method with the following essential elements:
  • 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;
  • 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, wherein the associated oligonucleotide comprises at least two identification elements derived from the at least two nucleic acid moieties;
  • subjecting the plurality of cis-reactive cells to conditions which stimulate a desired functional interaction having a detectable trace;
  • selecting all cis-reactive cells exhibiting the detectable trace; and
  • 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 also asserts dependent claims related to selective separation, PCR amplification, and the nature of the molecules being analyzed (Compl. ¶34).

III. The Accused Instrumentality

Product Identification

• Defendant Alamar’s Nucleic Acid Linked Immuno-Sandwich Assay (“NULISA”) platform, including the NULISAseq and NULISA qPCR assays, and the associated ARGO system (Compl. ¶1).

Functionality and Market Context

• The NULISA platform is described as a biomarker detection and quantification assay for proteins (Compl. ¶19). The system uses matched pairs of antibodies, each conjugated to a specific oligonucleotide probe (Compl. ¶25). When this pair of antibodies binds to a target protein in a sample, the associated oligonucleotides are brought into proximity, allowing them to be joined together (ligated) via a "specific DNA ligator sequence" (Compl. ¶28; Compl. ¶29). This creates a new, unique DNA reporter molecule whose sequence identifies the original target protein (Compl. ¶¶28-29). This reporter molecule can then be detected and quantified using methods like qPCR or Next Generation Sequencing (NGS) (Compl. ¶32).
• A diagram from the infringement claim chart illustrates Alamar's NULISA probes, which consist of a "Biotinylated oligo" and a "polyA-tailed oligo" each conjugated to an antibody, and shows how "Bridging oligos" ensure "specific ligation" to form a "Verified antigen-specific antibody pair" (Compl. Ex. O, p. 2).
• The complaint alleges that Alamar markets the NULISA platform as achieving “superior sensitivity” for detecting low-abundance biomarkers (Compl. ¶21) and acknowledges that the technology is based on the Proximity Ligation Assay (PLA) originally commercialized by Olink's forerunner (Compl. ¶21). The ARGO system is described as a "fully automated, high-throughput" instrument for running the NULISA assays (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;	Alamar's NULISA platform uses probes consisting of an antibody (the "molecule of interest") coupled to a nucleic acid moiety. The moiety contains a "target-specific molecular identifier" (the "identification sequence element") and a sequence that facilitates ligation (the "association element").	¶¶24-27	col. 5:14-19
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...	When two NULISA probes bind to a target protein, they are brought into close proximity. A "specific DNA ligator sequence" then hybridizes to both nucleic acid moieties, forming what the complaint alleges is a "cis-reactive cell" containing an "associated oligonucleotide."	¶¶28-29	col. 6:4-13
c. subjecting the plurality of cis-reactive cells to conditions which stimulate a desired functional interaction having a detectable trace;	The introduction of a ligation mix containing T4 DNA ligase stimulates the ligation of the nucleic acid moieties, producing a ligated nucleic acid that serves as a "detectable trace."	¶30	col. 6:14-17
d. selecting all cis-reactive cells exhibiting the detectable trace;	Alamar's "dual capture and release mechanism" is alleged to select the complexes that have undergone the functional interaction (ligation). The process results in an "eluate" containing the "reporter molecules."	¶31	col. 6:18-19
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 resulting reporter molecules are analyzed by qPCR or NGS to detect the "target-specific (TMI) barcodes," which are alleged to be the claimed "identification sequence elements."	¶32	col. 6:20-23

Identified Points of Contention

• Scope Questions: The patent is titled "Regulation Analysis by Cis Reactivity" and is framed as a method for discovering functional interactions between molecules (’848 Patent, col. 5:14-25). The accused NULISA platform, however, uses known antibody-antigen binding to detect the presence of the antigen. This raises the question of whether a method that uses a known interaction to detect an analyte can infringe a patent directed to discovering unknown interactions between the assay components themselves.
• Technical Questions: A key technical question will be what the "selecting" step of claim 1(d) requires. The complaint alleges Alamar's "dual capture and release mechanism" meets this limitation (Compl. ¶31). However, the parallel PTAB proceeding highlighted a distinction between selecting the entire "cis-reactive cell" (the full antibody-DNA complex) versus selecting only the resulting "associated oligonucleotide" (the DNA reporter molecule) (Compl. Ex. B, p. 19). The court will need to determine whether Alamar's process, which involves eluting the reporter molecules for analysis (Compl. Ex. O, p. 6), selects the "cell" as a whole, or just a piece of it, and whether that distinction matters for infringement.

V. Key Claim Terms for Construction

• The Term: "cis-reactive cell"

• Context and Importance: This term defines the fundamental complex that is the subject of the claimed method. The infringement case depends on whether Alamar's immunocomplex, formed when its antibody probes bind to a target protein, qualifies as a "cis-reactive cell." Practitioners may focus on this term because its construction will determine if the patent's scope, seemingly aimed at discovering interactions, can cover a product designed for analyte detection.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification provides a structural definition: "an association of at least two interactor moieties, joined by an associated oligonucleotide" (’848 Patent, col. 9:35-37). This language does not explicitly limit the purpose for which the cell is formed, potentially supporting the view that any structure meeting these physical criteria is a "cis-reactive cell."
  • Evidence for a Narrower Interpretation: The patent's primary embodiment for functional interactions describes discovering interactions between MOIs, such as a kinase and its substrate (’848 Patent, Fig. 4B; ’848 Patent, col. 15:1-7). This context, focused on studying the interaction between the interactors themselves rather than using them to find a third molecule, suggests a narrower, purpose-driven interpretation.

• The Term: "selecting all cis-reactive cells exhibiting the detectable trace"

• Context and Importance: This step is critical because the PTAB found that prior art failed to teach it, leading to the confirmation of the patent's validity (Compl. ¶13; Compl. Ex. B, p. 35). The infringement analysis will turn on whether Alamar's purification process constitutes "selecting" the "cis-reactive cell" itself.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent's dependent claims suggest "selecting" can be accomplished via "selective separation or selective detection" (’848 Patent, col. 43:25-31), which could be argued to encompass a process that ultimately detects the signature of the correct cells, even if the cell is disassembled.
  • Evidence for a Narrower Interpretation: The specification distinguishes between the embodiment for detecting affinity interactions, which involves "selecting the plurality of associated oligonucleotides," and the claimed method for detecting functional interactions, which requires "selecting all cis-reactive cells" (’848 Patent, col. 13:30-46; ’848 Patent, col. 15:18-20). This explicit distinction suggests the claimed method requires the selection of the entire complex (the cell), not just the resulting DNA reporter molecule. The PTAB adopted this narrower view in its Final Written Decision (Compl. Ex. B, p. 17).

VI. Other Allegations

• Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b), stating that Alamar's advertising, promotional materials, and publications encourage and instruct customers to use the NULISA platform in a manner that directly infringes the ’848 patent (Compl. ¶43). The complaint also alleges contributory infringement under 35 U.S.C. § 271(c), asserting that the NULISA platform and ARGO system are especially made for use in an infringing manner and have no substantial non-infringing uses (Compl. ¶44).
• Willful Infringement: Willfulness is alleged based on both pre-suit and post-suit knowledge. The complaint cites a letter sent by Olink to Alamar's CEO on August 11, 2023, as evidence of pre-suit knowledge (Compl. ¶42). Post-suit knowledge is based on the filing of the lawsuit itself and Alamar's subsequent loss in the IPR proceeding before the PTAB (Compl. ¶42).

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

• A core issue will be one of definitional scope: can the term "cis-reactive cell", which the patent describes in the context of discovering unknown functional interactions between molecules (e.g., enzyme-substrate pairs), be construed to cover the NULISA immunocomplex, a structure that uses known antibody affinities for the fundamentally different purpose of detecting a third-party analyte?
• A key evidentiary question, mirroring the dispositive issue in the parallel IPR proceeding, will be one of operational identity: does Alamar’s “dual capture and release mechanism” perform the claimed step of "selecting all cis-reactive cells" by isolating the entire antibody-DNA complex for analysis, or does it effectively select only the resulting DNA reporter molecule, creating a potential mismatch with the claim language as construed by the PTAB?
• The case will also present a significant procedural question regarding the persuasive weight of the PTAB’s Final Written Decision. How the court treats the Board's claim construction and findings—particularly regarding the "selecting" limitation that was central to upholding the patent's validity against prior art—will heavily influence its analysis of infringement by Alamar’s accused system.