DCT

1:24-cv-01161

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-01161, D. Del., 12/20/2024
  • Venue Allegations: Venue is alleged to be proper as two Curium defendants are Delaware corporations, and the defendants have stipulated to venue in the district for this action.
  • Core Dispute: Plaintiff alleges that Defendant’s proposed generic version of the cancer therapy Lutathera, for which it has filed an application with the FDA, will infringe six U.S. patents relating to stable, concentrated radiopharmaceutical solutions.
  • Technical Context: The technology involves radioligand therapies, which use radioactive isotopes attached to targeting molecules to deliver radiation directly to cancer cells, in this case for treating neuroendocrine tumors.
  • Key Procedural History: This Hatch-Waxman action is layered with allegations of trade secret misappropriation arising from a prior collaboration (2007-2010) between the parties' corporate predecessors, Mallinckrodt and BioSynthema. The complaint alleges Curium acquired Mallinckrodt and is using confidential information from that collaboration to develop its competing product. This First Amended Complaint was filed following the defendant's motion to dismiss the original complaint.

Case Timeline

Date Event
2018-07-25 Earliest Priority Date for all Patents-in-Suit
2020-03-24 U.S. Patent No. 10,596,276 Issues
2020-03-24 U.S. Patent No. 10,596,278 Issues
2024-02-20 U.S. Patent No. 11,904,027 Issues
2024-09-05 Defendant sends Paragraph IV notice letter to Plaintiff
2024-10-17 Plaintiff files original complaint
2024-11-13 Defendant files motion to dismiss original complaint
2024-11-19 U.S. Patent No. 12,144,873 Issues
2024-11-26 U.S. Patent No. 12,151,003 Issues
2024-12-10 U.S. Patent No. 12,161,732 Issues
2024-12-20 Plaintiff files First Amended Complaint

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

U.S. Patent No. 10,596,276, "Stable, Concentrated Radionuclide Complex Solutions," Issued March 24, 2020

The Invention Explained

  • Problem Addressed: Radiopharmaceutical drug products, which contain radioactive isotopes, are prone to "radiolysis," a process where the radiation emitted by the isotope degrades the drug molecules, reducing the product's stability and shelf-life (’276 Patent, col. 1:51-58). This problem is particularly acute in highly concentrated solutions, which are desirable for patient convenience but degrade more quickly ('276 Patent, col. 2:30-35).
  • The Patented Solution: The invention describes a manufacturing process for creating a highly concentrated, stable radiopharmaceutical solution that is ready for patient use. The solution involves a two-stage process: first, forming a complex of the radionuclide and a targeting molecule in the presence of a "first stabilizer" to protect it during heating, and second, diluting that complex with a solution containing another stabilizer to ensure stability during storage and transport ('276 Patent, col. 4:1-20). This sequential addition of stabilizers is described as a key aspect of achieving a stable, concentrated, ready-to-use product without relying on ethanol, which can cause tolerability issues for patients ('276 Patent, col. 4:28-33). The core chemical structure of the therapeutic compound is shown in the complaint's Figure 1, which depicts the radioactive isotope lutetium-177 bound to a chelator (DOTA) and a somatostatin analog (octreotate) (Compl. ¶36).
  • Technical Importance: This process enables the centralized, commercial-scale manufacturing of a ready-to-use radiopharmaceutical, which can then be shipped to clinical centers, overcoming the previous need for on-site, patient-specific preparation in hospital labs immediately before administration ('276 Patent, col. 4:35-47).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims (Compl. ¶111). Independent claim 1 is representative:
  • Claim 1 (Process Claim): A process for manufacturing a pharmaceutical aqueous solution, comprising:
    • Providing a solution comprising a complex of the radionuclide ¹⁷⁷Lu and a somatostatin receptor binding peptide linked to the chelating agent DOTA; a first stabilizer; and optionally a second stabilizer.
    • Diluting that solution with an aqueous dilution solution comprising at least one stabilizer.
    • A key conditional element: if the initial solution comprises only the first stabilizer, the dilution solution must comprise at least one stabilizer that is different from the first stabilizer.
    • The final solution must have a volumetric radioactivity of 250 to 500 MBq/mL and stabilizers in a total concentration of 1.0 to 5.0 mg/mL, and contain less than 1% ethanol.

U.S. Patent No. 10,596,278, "Stable, Concentrated Radionuclide Complex Solutions," Issued March 24, 2020

The Invention Explained

  • Problem Addressed: As with the ’276 Patent, this invention addresses the technical challenge of producing a stable, highly concentrated, ready-to-use radiopharmaceutical drug product that can withstand degradation from its own radioactivity (radiolysis) (’278 Patent, col. 1:51-58).
  • The Patented Solution: The invention is a pharmaceutical aqueous solution obtained by the specific manufacturing process detailed in the patent. This process involves the sequential addition of different stabilizers—one during the initial formation of the drug complex and a second added during a later dilution step—to achieve high stability in a concentrated form without the use of ethanol ('278 Patent, col. 4:1-20).
  • Technical Importance: By claiming the product resulting from this specific process, the patent seeks to protect the final stable and concentrated radiopharmaceutical formulation that enables centralized manufacturing and distribution to hospitals ('278 Patent, col. 4:35-47).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims (Compl. ¶136). Independent claim 1 is representative:
  • Claim 1 (Product-by-Process Claim): A pharmaceutical aqueous solution obtained by a process comprising:
    • Providing a solution containing the radionuclide-peptide complex, a first stabilizer, and optionally a second.
    • Diluting that solution with an aqueous solution containing at least one stabilizer.
    • A conditional element: if the initial solution has only the first stabilizer, the dilution solution must comprise a different stabilizer.
    • The final solution has a specific volumetric radioactivity (250 to 500 MBq/mL), total stabilizer concentration (1.0 to 5.0 mg/mL), and low ethanol content (<1%).

Multi-Patent Capsule: Additional Patents-in-Suit

  • U.S. Patent No. 11,904,027, "Stable, Concentrated Radionuclide Complex Solutions," Issued February 20, 2024

    • Technology Synopsis: This patent claims the final pharmaceutical product itself, defining it by its specific chemical components and their concentrations. The invention is a stable aqueous solution containing the ¹⁷⁷Lu-DOTA-peptide complex, a specific combination of two stabilizers (gentisic acid and ascorbic acid), a sequestering agent, and a buffer, all within specified concentration ranges (’027 Patent, col. 5:21-col. 6:8).
    • Asserted Claims: One or more claims (Compl. ¶161). Independent claim 1 is a representative product claim.
    • Accused Features: The composition of Defendant's proposed generic drug, which Plaintiff alleges will meet the claimed formulation requirements (Compl. ¶160).

  • U.S. Patent No. 12,144,873, "Stable, Concentrated Radionuclide Complex Solutions," Issued November 19, 2024

    • Technology Synopsis: This patent claims a method of treating a tumor by administering the specific pharmaceutical formulation. The claimed method requires administering a solution with the ¹⁷⁷Lu-DOTA-peptide complex and at least one stabilizer, where the final product has specific radioactivity and low ethanol content (’873 Patent, col. 41:42-col. 42:21).
    • Asserted Claims: One or more claims (Compl. ¶186). Independent claim 1 is a representative method-of-treatment claim.
    • Accused Features: The intended use of Defendant's proposed generic drug for treating tumors, as would be reflected in its FDA-approved labeling (Compl. ¶189).

  • U.S. Patent No. 12,151,003, "Stable, Concentrated Radionuclide Complex Solutions," Issued November 26, 2024

    • Technology Synopsis: This patent claims the final pharmaceutical product in a dose unit container. The claims define the product by its core components (¹⁷⁷Lu complex, stabilizers) and key properties (total stabilizer concentration, activity level, low ethanol content), as packaged for delivery and use (’003 Patent, col. 39:43-col. 40:11).
    • Asserted Claims: One or more claims (Compl. ¶213). Independent claim 1 is a representative product claim.
    • Accused Features: The final packaged drug product that Defendant will sell, which Plaintiff alleges will have the claimed composition and properties (Compl. ¶212).

  • U.S. Patent No. 12,161,732, "Stable, Concentrated Radionuclide Complex Solutions," Issued December 10, 2024

    • Technology Synopsis: This patent covers a process for manufacturing the pharmaceutical solution, focusing on the steps of diluting a concentrated complex and the characteristics of the resulting product. The claims specify the properties of the final solution, including its volumetric radioactivity and low ethanol content, resulting from a process that uses a sequence of stabilizers (’732 Patent, col. 37:48-col. 38:43).
    • Asserted Claims: One or more claims (Compl. ¶240). Independent claim 1 is a representative process claim.
    • Accused Features: The manufacturing process Defendant will use to produce its generic drug, which Plaintiff alleges will fall within the scope of the claimed process (Compl. ¶239, ¶244).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the Defendant's proposed generic version of Lutathera ([¹⁷⁷Lu]Lu-DOTA-TATE), which is the subject of Curium's 505(b)(2) New Drug Application No. 218525 submitted to the U.S. Food and Drug Administration (FDA) (Compl. ¶110).

Functionality and Market Context

  • The complaint alleges that by filing its 505(b)(2) application, Curium has necessarily represented to the FDA that its product will have the same active ingredient, method of administration, dosage form, and strength as Lutathera, and will be bioequivalent to it (Compl. ¶110). The product is a radioligand therapy for treating somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (Compl. ¶108). The complaint alleges that Curium's product was developed using confidential information and trade secrets misappropriated from Plaintiff's predecessor during a prior business collaboration (Compl. ¶2, ¶92).

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail to construct a claim chart. The infringement allegations are based on the act of filing the 505(b)(2) application under the Hatch-Waxman Act, which creates a statutory act of infringement (35 U.S.C. § 271(e)(2)) (Compl. ¶111). The complaint alleges that because Curium's product must be bioequivalent to Lutathera to gain FDA approval, it will necessarily practice the inventions claimed in the patents-in-suit upon commercial manufacture, use, or sale (Compl. ¶110, ¶114). The complaint contains heavily redacted sections that appear to describe specific features of Curium's proposed product, but this information is not public (Compl. ¶88).

  • Identified Points of Contention: The central infringement questions will depend on the actual formulation and manufacturing process detailed in Curium's confidential FDA application. Key points of contention may include:
    • Scope Questions: What is the precise chemical composition of Curium's formulation? Does it use the same stabilizers (e.g., gentisic acid, ascorbic acid) as specified in certain patent claims, and are they present in concentrations that fall within the claimed ranges?
    • Technical Questions: What manufacturing process does Curium employ? Does it involve the sequential addition of different stabilizers before and after the complexation step, as required by the asserted process claims?

V. Key Claim Terms for Construction

  • The Term: "stabilizer against radiolytic degradation" (from the claims of multiple patents, e.g., ’276 Patent, claim 1)

    • Context and Importance: The definition of this term is fundamental, as the patents are premised on using specific stabilizers or combinations thereof to achieve stability. The scope of this term will determine whether only the specific compounds disclosed in the patent (like gentisic acid and ascorbic acid) are covered, or if other chemical quenchers could also fall within the claims.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification provides a list of potential stabilizers, stating they "may be selected from" a group including gentisic acid, ascorbic acid, methionine, and others, which could suggest the listed chemicals are exemplary, not exhaustive ('276 Patent, col. 5:5-10).
      • Evidence for a Narrower Interpretation: The detailed examples and specific embodiments focus heavily on the combination of gentisic acid and ascorbic acid ('276 Patent, col. 35:9-25). A defendant may argue that the invention is limited to these specific, successfully tested compounds, especially given the unpredictability in the field of radiochemistry.

  • The Term: "diluting the solution comprising the complex with an aqueous dilution solution" (from ’276 Patent, claim 1)

    • Context and Importance: The process claims of the '276 and '732 patents require a specific sequence of steps, including a distinct "diluting" step where a second stabilizer is introduced. Whether Curium's manufacturing process includes a step that meets the legal definition of "diluting" as a separate process limitation will be a critical issue. Practitioners may focus on this term because if Curium combines all components in a single step or uses a process not fairly characterized as "diluting," it may argue non-infringement of the process claims.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent describes the overall process as forming a complex and then diluting it, suggesting two major stages ('276 Patent, col. 3:23-40). A plaintiff might argue that any process that starts with a more concentrated active mixture and ends with a less concentrated final product by adding a diluent meets this limitation.
      • Evidence for a Narrower Interpretation: The specific examples describe a discrete dilution step where a "mother solution" is mixed with a separate "solution containing a chelating agent" and other components ('276 Patent, col. 36:46-54). A defendant could argue this implies a distinct separation of steps, not a continuous or semi-continuous process.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will actively induce infringement by, among other things, proposing a product label that instructs users to administer the drug in a manner that infringes the method-of-treatment claims (Compl. ¶116, ¶192). It further alleges contributory infringement on the basis that the product is especially made for an infringing use and is not suitable for a substantial non-infringing use (Compl. ¶117, ¶193).
  • Willful Infringement: While the patent counts do not use the word "willful," the complaint alleges that Defendants have had actual knowledge of the patents since at least July 2024 and knew that filing the 505(b)(2) application constituted an act of infringement (Compl. ¶112, ¶137). The allegations of misappropriating trade secrets from a collaboration focused on the same technology may be used to argue that any infringement was deliberate and egregious.

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

  • A core issue will be one of factual comparison: once the details of Curium's confidential FDA filing are revealed in discovery, does the chemical formulation—specifically its choice of stabilizers and their concentrations—literally fall within the numerical ranges defined in the asserted product claims?
  • A second key issue will be one of process equivalence: does Curium's manufacturing method meet the sequential limitations of the asserted process claims, particularly the requirement of a distinct "diluting" step where a different stabilizer is introduced after the initial radiolabeling reaction?
  • A central theme of the litigation will be the interplay between patent infringement and trade secret misappropriation: how will Plaintiff's allegations that Defendant used stolen confidential information to "design around" the patents influence the court's interpretation of claim scope and its assessment of infringement?