DCT

1:23-cv-00373

Azurity Pharma Inc v. Accord Healthcare Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00373, D. Del., 03/31/2023
  • Venue Allegations: Venue is asserted based on Defendant Accord Healthcare, Inc.'s specific consent to jurisdiction and venue in Delaware prior to the suit.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiffs' Thyquidity® oral solution constitutes an act of infringement of a patent covering a method for preparing a stable levothyroxine solution.
  • Technical Context: The technology concerns pharmaceutical formulation methods for levothyroxine, a synthetic thyroid hormone used to treat hypothyroidism, which is known to be unstable in liquid solutions.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's February 14, 2023 notification letter regarding its ANDA filing. The complaint was filed within the 45-day statutory window, triggering an automatic 30-month stay on the FDA’s approval of the Defendant’s generic product. Plaintiffs note that confidential access to the ANDA, granted on March 16, 2023, did not confirm certain statements made in the notice letter.

Case Timeline

Date Event
2011-03-10 ’307 Patent Priority Date
2015-06-09 ’307 Patent Issue Date
2023-02-14 Defendant sends Notice Letter of ANDA filing to Plaintiffs
2023-03-16 Plaintiffs receive confidential access to Defendant's ANDA
2023-03-31 Complaint Filing Date

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

  • Patent Identification: U.S. Patent No. 9,050,307, "Method for the Preparation of a Levothyroxine Solution", issued June 9, 2015 (the "’307 Patent").

The Invention Explained

  • Problem Addressed: The patent’s background section states that while oral solutions of levothyroxine are useful for patients who cannot swallow tablets, such solutions are "less stable compared to tablets during storage" and are "prone to decomposition" (’307 Patent, col. 2:7-12). This instability can lead to the formation of liothyronine, an impurity believed to cause side effects (’307 Patent, col. 2:9-11).
  • The Patented Solution: The patent discloses a specific multi-step method for preparing a more stable oral levothyroxine solution. The core of the method involves first mixing a salt of levothyroxine with an aqueous solvent and adjusting the pH to a basic level (at least 8) to facilitate dissolution, yielding a clear solution. Subsequently, the pH of this clear solution is lowered to a final, acidic range (between 5 and 6) for storage (’307 Patent, col. 2:32-41).
  • Technical Importance: This two-step pH adjustment process is asserted to produce a liquid formulation with improved storage stability and fewer impurities compared to previously known liquid formulations, thereby providing a safer and more reliable therapeutic option (’307 Patent, col. 2:42-43).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’307 Patent (Compl. ¶27). Independent claim 1 is central to the invention.
  • Independent Claim 1 of the ’307 Patent recites the following essential method steps:
    • providing a salt of levothyroxine,
    • mixing levothyroxine with an aqueous solvent,
    • adjusting the pH to a pH of at least 8 to yield a basic aqueous solvent,
    • dissolving the levothyroxine in the basic aqueous solvent to yield a levothyroxine solution, and
    • lowering the pH of the clear levothyroxine solution to between 5-6.
  • The complaint does not specify any dependent claims but reserves the right to assert them.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant's proposed generic version of Plaintiffs' Thyquidity® product, referred to as the "Accord ANDA Product" (Compl. ¶16).

Functionality and Market Context

  • The complaint alleges that the Accord ANDA Product is a generic oral solution of levothyroxine sodium (Compl. ¶10, ¶16). By virtue of its ANDA submission, the Defendant has represented to the FDA that its product has the same active ingredients, route of administration, dosage form, and strength as Plaintiffs' Thyquidity® and is bioequivalent to it (Compl. ¶20).
  • The complaint does not provide sufficient detail for analysis of the specific manufacturing process used for the Accord ANDA Product. The infringement allegation rests on the premise that the future manufacture of the product described in the ANDA will practice the claimed method.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or provide specific factual allegations detailing how the Defendant's manufacturing process maps to the elements of the asserted claims. The infringement allegation is statutory, based on the act of submitting an ANDA under 35 U.S.C. § 271(e)(2) for a drug product whose manufacture will allegedly infringe the ’307 Patent (Compl. ¶27). The core of the infringement theory, which will require development through discovery, is that the confidential process described in Accord's ANDA includes the specific steps recited in the patent's claims.

No probative visual evidence provided in complaint.

Identified Points of Contention

  • Evidentiary Question: The central issue will be factual and evidentiary: does the confidential manufacturing process for the Accord ANDA Product, as described in its ANDA filing, include every step of an asserted claim of the ’307 Patent? Specifically, discovery will focus on whether Accord’s process involves the sequential pH adjustment of first raising the pH to 8 or higher to dissolve the levothyroxine, followed by lowering the pH to a final range of 5-6.
  • Technical Question: A potential dispute may arise over the definition of "dissolving" and the state of the solution. The patent claims and describes obtaining a "clear levothyroxine solution" or "clear homogeneous solution" at the intermediate basic pH step (’307 Patent, col. 10:9; col. 4:37-38). The degree and timing of dissolution in Accord's process compared to this requirement will be a likely point of contention.

V. Key Claim Terms for Construction

  • The Term: ‘aqueous solvent’ (Claim 1)

  • Context and Importance: This term defines the medium in which the levothyroxine is mixed and dissolved. The composition of this "solvent" is fundamental to the claimed process. Practitioners may focus on this term because its scope will determine whether a formulation containing co-solvents, such as the glycerol mentioned in the specification, falls within the claim.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification explicitly states that the "aqueous solvent was a mixture of water and a water-miscible organic solvent or solubilizer" and that the preferred organic solvent "comprises glycol" (’307 Patent, col. 3:18-22). This language supports a construction that is not limited to pure water but extends to aqueous systems containing other components.
    • Evidence for a Narrower Interpretation: A party seeking a narrower construction might argue that the term should be limited by the specific examples provided, such as a water/glycerol mixture in a particular ratio range (e.g., 10:1 to 1:10) (’307 Patent, col. 3:28-30).

  • The Term: ‘dissolving the levothyroxine in the basic aqueous solvent to yield a levothyroxine solution’ (Claim 1)

  • Context and Importance: This term defines a critical step that occurs after the pH is raised but before it is lowered. The interpretation of what constitutes "dissolving" to "yield a levothyroxine solution" is crucial, as it sets a condition that must be met mid-process.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party could argue that any process where the solid levothyroxine enters the solution phase meets this limitation, without requiring 100% dissolution or perfect clarity at this stage.
    • Evidence for a Narrower Interpretation: The claim language itself, in the subsequent step, refers to the "clear levothyroxine solution" (’307 Patent, col. 10:10). Furthermore, the specification's process description notes stirring "until a clear homogeneous solution was obtained" after making the solution basic (’307 Patent, col. 4:36-38). This suggests that "dissolving" requires achieving a complete, clear solution before proceeding to the final pH-lowering step, potentially narrowing the claim's scope.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Accord has specific intent to infringe and that there are "no substantial non-infringing uses for the Accord ANDA Product" other than the use claimed in the patent (Compl. ¶29). This language tracks the requirements for pleading induced infringement.
  • Willful Infringement: The complaint alleges that Accord had "actual and constructive knowledge" of the ’307 Patent at the time it filed its ANDA, and that this filing constituted an act of infringement (Compl. ¶29). This forms the basis for a claim of willfulness, predicated on knowledge of the patent prior to the infringing act.

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

  • A primary issue will be one of factual proof: As the complaint lacks specific details about the accused manufacturing method, the case will depend on whether discovery reveals that Accord's confidential process for making its generic product practices the precise, two-stage pH manipulation recited in Claim 1—first alkalizing to at least pH 8 to achieve dissolution, and then acidifying to a final pH between 5 and 6.
  • The secondary, and potentially dispositive, issue will be one of claim construction: The dispute may turn on the definition of "dissolving." The case will explore whether this term requires the achievement of a "clear homogeneous solution" before the final pH adjustment step, a requirement that could create a critical distinction between the patented method and the accused process.