DCT

1:24-cv-01398

Advanced Accelerator Applications USA Inc v. Curium US LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01398, D. Del., 12/20/2024
  • Venue Allegations: Venue is alleged to be proper as two defendants are incorporated in Delaware, and the other two are foreign corporations that may be sued in any district. The complaint also alleges that Defendants committed an act of infringement in the district by filing their New Drug Application and have stipulated to jurisdiction in a related case.
  • Core Dispute: Plaintiff alleges that Defendants' filing of a New Drug Application for a generic version of Plaintiff's LUTATHERA® radiopharmaceutical constitutes an act of infringement of a patent covering stable, concentrated drug formulations.
  • Technical Context: The technology concerns formulations for targeted radioligand therapies, which use radioactive isotopes to treat cancer, and addresses the technical challenge of preventing the drug's degradation from its own radiation.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act following Defendants' submission of a New Drug Application (No. 218525) and a corresponding Paragraph IV certification notice letter. The action follows a related, ongoing lawsuit between the parties (C.A. No. 24-1161-MN) concerning other patents covering LUTATHERA®. The patent-in-suit in this case, U.S. Patent No. 12,168,063, issued just three days prior to the filing of this complaint.

Case Timeline

Date Event
2018-07-25 '063 Patent Priority Date
2024-09-05 Curium sends Paragraph IV Notice Letter to Plaintiff
2024-10-17 Plaintiff files initial related lawsuit (C.A. No. 24-1161-MN)
2024-12-13 Plaintiff files First Amended Complaint in related lawsuit
2024-12-17 '063 Patent Issues
2024-12-20 Complaint Filed

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

U.S. Patent No. 12,168,063 - Stable, Concentrated Radionuclide Complex Solutions (Issued Dec. 17, 2024)

The Invention Explained

  • Problem Addressed: The patent describes a fundamental challenge with radiopharmaceutical drugs: the high-energy emissions from the radioactive component constantly degrade the drug's other molecules, a process called "radiolysis" (’063 Patent, col. 1:52-60). A standard solution, producing the drug in a highly diluted form, is undesirable because it requires administering large, inconvenient, and potentially poorly tolerated infusion volumes to patients (’063 Patent, col. 2:31-41).
  • The Patented Solution: The invention is a pharmaceutical formulation that is both highly concentrated and stable against radiolysis, allowing it to be produced as a "ready-to-use" product (’063 Patent, col. 4:50-56). The solution is achieved by using at least one, and preferably two, different chemical stabilizers (’063 Patent, Abstract). The patent describes a particularly advantageous method where a first stabilizer is present during the initial high-temperature reaction that forms the drug complex, and a second stabilizer is added afterward to enhance the stability of the final product for storage and shipping (’063 Patent, col. 4:5-21).
  • Technical Importance: This formulation technology enables centralized, commercial-scale manufacturing of radiopharmaceuticals, which can then be shipped to clinical centers, eliminating the need for complex, last-minute preparation in hospital labs and improving quality control (’063 Patent, col. 4:36-49).

Key Claims at a Glance

  • The complaint does not identify specific claims but alleges infringement of "one or more claims" of the ’063 patent (Compl. ¶¶ 39, 42). Embodiment 23, presented in the patent specification, is representative of the core invention.
  • The essential elements of this representative embodiment are:
    • A pharmaceutical aqueous solution comprising a complex formed by the radionuclide ¹⁷⁷Lutetium and the somatostatin receptor binding moiety DOTA-TATE or DOTA-TOC.
    • The radionuclide is present in a high concentration, providing a volumetric radioactivity of 250 to 500 MBq/mL.
    • The solution contains a first stabilizer, gentisic acid, at a concentration of 0.5 to 1 mg/mL.
    • The solution contains a second stabilizer, ascorbic acid, at a concentration of 2.0 to 5.0 mg/mL.
  • The complaint reserves the right to assert infringement of other claims (Compl. ¶53).

III. The Accused Instrumentality

Product Identification

  • Defendants' "505(b)(2) Product," identified as a "Lutetium Lu-177 Dotatate injection solution" (Compl. ¶15).

Functionality and Market Context

  • The accused product is a generic version of Plaintiff's LUTATHERA® drug (Compl. ¶¶ 1, 38). The complaint alleges that, based on Defendants' New Drug Application, the product will have the same active ingredient, method of administration, dosage form, and strength as LUTATHERA®, and will be bioequivalent to it (Compl. ¶37, ¶51).
  • LUTATHERA® is a targeted radioligand therapy indicated for the treatment of certain neuroendocrine tumors in adults (Compl. ¶33). The complaint alleges that Defendants are preparing for commercial-scale production and have opened a new Lutetium-177 production facility (Compl. ¶17).

IV. Analysis of Infringement Allegations

The complaint bases its infringement allegations on the statutory act of filing a New Drug Application under 35 U.S.C. § 271(e)(2), rather than on a direct technical analysis of the accused product's formulation, details of which are not public (Compl. ¶39). The central theory is that because the accused product is intended to be a bioequivalent version of LUTATHERA®, which is covered by the ’063 patent, the accused product will necessarily meet the limitations of the patent's claims (Compl. ¶¶ 34, 37). No probative visual evidence provided in complaint.

’063 Patent Infringement Allegations

Claim Element (from Representative Embodiment 23) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical aqueous solution, comprising (a) a complex formed by (ai) the radionuclide ¹⁷⁷Lutetium (Lu-177) The accused product is identified as a "Lutetium Lu-177 Dotatate injection solution" and is alleged to have the same active ingredient as LUTATHERA®. ¶1, ¶37 col. 8:28-29
... and (aii) the chelating agent linked somatostatin receptor binging organic moiety DOTA-TATE (oxodotreotide) or DOTA-TOC (edotreotide) The accused product is identified as a "Lutetium Lu-177 Dotatate injection solution," where "Dotatate" is another name for DOTA-TATE. ¶1, ¶15 col. 8:32-35
... present in a concentration that it provides a volumetric radioactivity of from 250 to 500 MBq/mL The accused product is alleged to have the same strength as LUTATHERA®, whose commercial embodiment has a volumetric activity of 370 MBq/mL, falling within the claimed range. ¶37 col. 8:29-31
(bi) gentisic acid or a salt thereof as the first stabilizer... and (bii) ascorbic acid or a salt thereof as the second stabilizer against radiolytic degradation... The complaint does not specify the stabilizers in the accused product. It alleges that because the product is a bioequivalent version of the patented LUTATHERA® product, it will infringe the formulation claims. ¶34, ¶37 col. 8:36-42

Identified Points of Contention

  • Technical Question: A primary issue for discovery will be determining the actual chemical composition of the accused product. What specific stabilizers does it contain, in what amounts, and does its manufacturing process involve the sequential addition of stabilizers as described in the patent? The complaint provides no direct evidence on these points.
  • Scope Questions: The dispute may raise the question of whether "bioequivalence" to LUTATHERA® necessarily requires infringement of the patent's specific formulation claims. The parties may contest whether the excipients in the accused product function as a "stabilizer against radiolytic degradation" as that term is used and defined in the patent.

V. Key Claim Terms for Construction

  • The Term: "stabilizer against radiolytic degradation"

  • Context and Importance: This term is the functional heart of the invention. The infringement analysis will depend on whether the excipients used in the accused product fall within the scope of this term. Practitioners may focus on this term because the case could turn on whether Defendants' formulation, even if using different chemicals, performs the same stabilizing function claimed in the patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification provides a non-exhaustive list of potential stabilizers, including "gentisic acid...ascorbic acid...methionine, histidine, melatonin, ethanol, and Se-methionine" (’063 Patent, col. 5:10-15). It also defines the term functionally as "free radical scavengers" or "quenchers" (’063 Patent, col. 30:10-19), which could support a construction that is not limited to the specific examples.
    • Evidence for a Narrower Interpretation: The specification repeatedly describes the combination of gentisic acid and ascorbic acid as being of "particular suitability" and "particular advantage" (’063 Patent, Abstract; col. 4:5-10). A party could argue that the claims should be construed more narrowly in light of these heavily emphasized embodiments.

  • The Term: "a first stabilizer" / "a second stabilizer"

  • Context and Importance: The patent's description of a sequential addition process, where one stabilizer is present during complex formation and another is added later, is presented as a key inventive feature (’063 Patent, col. 4:14-21). Whether the accused manufacturing process meets this limitation will be a critical infringement question.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The process described in the patent involves a "Forming a complex" step followed by a "Diluting the complex solution" step, where the second stabilizer may be added in the dilution solution (’063 Patent, col. 8:52-66). This could be interpreted as covering any multi-stage process where stabilizers are introduced at different points.
    • Evidence for a Narrower Interpretation: A party may argue that the terms require two chemically distinct stabilizers added at functionally distinct stages of manufacturing (one for the high-temperature reaction, the other for shelf-life). If the accused process involves adding all excipients simultaneously, it could be argued that it does not meet this limitation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement, stating that Defendants know of the ’063 patent and intend for their product to be used in an infringing manner upon FDA approval (Compl. ¶44, ¶55). It also pleads contributory infringement, alleging the accused product is especially made for infringing the patent and has no substantial non-infringing use (Compl. ¶45, ¶56).
  • Willful Infringement: The complaint alleges that Defendants had "actual and constructive knowledge" of the ’063 patent at least as of December 13, 2024 (from filings in the related case), prior to the filing of this lawsuit, and that their continued pursuit of FDA approval constitutes an ongoing act of infringement (Compl. ¶40).

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

  • A central issue will be one of undisclosed composition: What is the actual chemical formulation of the accused product? The case will likely turn on facts obtained through discovery regarding the specific stabilizers, their concentrations, and the manufacturing process used by Defendants, as the complaint currently relies on an inference of infringement from bioequivalence.
  • A key legal question will be one of definitional scope: How will the term "stabilizer against radiolytic degradation" be construed? The outcome may depend on whether the court adopts a broad, functional definition that could cover a range of chemical agents, or a narrower one tethered to the specific embodiments (gentisic and ascorbic acid) emphasized in the patent specification.