DCT

1:21-cv-01707

Azurity Pharma Inc v. Aurobindo Pharma Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-01707, D. Del., 12/02/2021
  • Venue Allegations: Venue is alleged to be proper as Defendant Aurobindo Pharma USA, Inc. is a Delaware corporation, and the district is a likely destination for the accused product.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration for a generic version of Plaintiff's Epaned® oral solution constitutes an act of infringement of three patents related to stable liquid enalapril formulations.
  • Technical Context: The technology concerns ready-to-use, stable oral liquid formulations of enalapril, an ACE inhibitor used for treating hypertension, which is of particular market significance for pediatric and geriatric patients who may have difficulty swallowing solid tablets.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notification letter from Aurobindo to Azurity regarding the filing of ANDA No. 216458. The patents-in-suit are listed in the FDA's Orange Book in connection with Azurity's New Drug Application (NDA) No. 208686 for its Epaned® product.

Case Timeline

Date Event
2016-03-18 Earliest Priority Date for all Patents-in-Suit
2020-09-29 U.S. Patent No. 10,786,482 Issues
2021-02-16 U.S. Patent No. 10,918,621 Issues
2021-06-22 U.S. Patent No. 11,040,023 Issues
2021-12-02 Complaint Filed

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

U.S. Patent No. 10,786,482 - “Enalapril Formulations”

The Invention Explained

  • Problem Addressed: The patent describes the difficulty certain patient populations, such as children and the elderly, have with swallowing solid dosage forms like tablets (ʼ482 Patent, col. 5:25-29). It notes that creating liquid versions by crushing tablets in a pharmacy can lead to inaccurate dosing, rapid instability of the active ingredient, and potential contamination (ʼ482 Patent, col. 5:42-53).
  • The Patented Solution: The patent discloses a stable, ready-to-use oral liquid formulation of enalapril. The solution to the stability problem is described as a specific combination of components: enalapril, a citrate buffer (comprising citric acid and sodium citrate), and the preservative sodium benzoate, all maintained at a pH below 3.5 (ʼ482 Patent, Abstract; col. 2:21-29). This formulation is designed to be stable for at least 12 months under refrigerated conditions (5±3° C) (ʼ482 Patent, col. 2:27-29).
  • Technical Importance: This technology provided the first FDA-approved ready-to-use oral liquid formulation of enalapril, enhancing safety and dosing accuracy for patient populations unable to use solid tablets (Compl. ¶15).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" of the ’482 Patent without specifying which claims are asserted (Compl. ¶33). Independent claim 1 is representative.
  • Independent Claim 1 requires:
    • An oral liquid formulation comprising:
    • (i) about 0.6 to about 1.2 mg/ml enalapril or a pharmaceutically acceptable salt or solvate thereof;
    • (ii) a buffer comprising a mixture of citric acid and sodium citrate, present at a concentration between about 5 mM and about 20 mM;
    • (iii) about 1 mg/ml sodium benzoate; and
    • (iv) water;
    • The formulation must maintain about 95% w/w or greater of its initial enalapril amount after at least 12 months of storage at about 5±3° C.

U.S. Patent No. 10,918,621 - “Enalapril Formulations”

The Invention Explained

  • Problem Addressed: As a continuation of the same patent family, the ’621 Patent addresses the same technical problem: the lack of a stable, accurately-dosable, ready-to-use liquid form of enalapril suitable for patients who cannot swallow tablets (ʼ621 Patent, col. 1:24-28; col. 5:20-28).
  • The Patented Solution: The ’621 Patent similarly describes a stable oral liquid formulation. The key inventive concept is a specific combination of enalapril, the sweetener sucralose, a buffer containing citric acid, and the preservative sodium benzoate, maintained at a pH below 3.5 to achieve long-term stability (ʼ621 Patent, Abstract; col. 2:23-31).
  • Technical Importance: This formulation provides a commercially viable liquid alternative to solid enalapril tablets, expanding therapeutic access to pediatric and other specific patient populations (Compl. ¶15).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" (Compl. ¶38). Independent claim 1 is representative.
  • Independent Claim 1 requires:
    • An oral liquid formulation comprising:
    • (i) enalapril or a pharmaceutically acceptable salt or solvate thereof;
    • (ii) a sweetener that is sucralose;
    • (iii) a buffer comprising citric acid;
    • (iv) a preservative that is sodium benzoate; and
    • (v) water;
    • The formulation must have a pH less than about 3.5.
    • The formulation must be stable at about 5±3° C. for at least 12 months.

U.S. Patent No. 11,040,023 - “Enalapril Formulations”

Technology Synopsis

  • The ’023 Patent, part of the same family, also discloses stable, ready-to-use liquid oral formulations of enalapril. It addresses the need for an alternative to solid tablets by teaching a specific formulation that combines enalapril, the sweetener sucralose, a citrate buffer, and a sodium benzoate preservative at a controlled low pH to ensure stability over time ('023 Patent, Abstract; col. 1:29-33).

Asserted Claims & Accused Features

  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶55). Independent claims 1 and 13 are available for assertion.
  • Accused Features: The complaint alleges that Defendant’s proposed generic product, designed to be a bioequivalent copy of Epaned®, will contain the claimed formulation (Compl. ¶¶31, 55).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "Aurobindo ANDA Product," a proposed generic version of Azurity's Epaned® Product, for which Aurobindo submitted Abbreviated New Drug Application (ANDA) No. 216458 to the FDA for marketing approval (Compl. ¶¶1, 27).

Functionality and Market Context

  • The complaint alleges that Aurobindo's ANDA represents that its proposed product has the same active ingredients, dosage form, strength, and route of administration as Azurity’s Epaned® Product and is bioequivalent to it (Compl. ¶31). Epaned® is identified in the complaint as the only FDA-approved, ready-to-use enalapril oral solution for treating hypertension in children, and is also indicated for adults (Compl. ¶15). The act of infringement alleged is the submission of the ANDA itself, which seeks approval to market the generic drug before the expiration of the patents-in-suit (Compl. ¶¶33, 38, 55).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or detailed technical specifications of the accused product. Instead, it advances an infringement theory under 35 U.S.C. § 271(e)(2), where the submission of an ANDA seeking approval to market a patented drug prior to patent expiration is itself an act of infringement. The core allegation is that because Aurobindo's ANDA product is represented to the FDA as a bioequivalent generic of Epaned® with the same active ingredient, dosage form, and strength, the formulation described in the ANDA will necessarily meet the limitations of one or more claims of the patents-in-suit, which are listed in the Orange Book as covering Epaned® (Compl. ¶¶19, 25, 31, 33). The complaint does not contain sufficient detail to construct a claim-by-claim infringement chart.

  • Identified Points of Contention:
    • Compositional Scope: A central issue may be whether the precise formulation disclosed in Aurobindo's confidential ANDA filing falls within the scope of the asserted claims. This raises the question of whether Aurobindo's formulation uses the exact same excipients (e.g., sucralose, sodium benzoate, citrate buffer), concentrations, and final pH as claimed in the patents.
    • Functional Scope: The claims include functional limitations regarding stability (e.g., "stable at about 5±3° C. for at least 12 months"). This suggests a possible point of contention over whether Aurobindo's product will meet this requirement, and what evidence is necessary to demonstrate that it does or does not.

V. Key Claim Terms for Construction

  • The Term: "stable at about 5±3° C. for at least 12 months" (ʼ482 Patent, cl. 1; ʼ621 Patent, cl. 1).

    • Context and Importance: This functional limitation is a cornerstone of the claimed invention. The dispute will likely focus on whether Aurobindo's product can be proven to meet this stability requirement. Practitioners may focus on this term because demonstrating that the ANDA product will exhibit this specific long-term stability profile is crucial for proving infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification provides an explicit definition: "Stable as used herein refers to enalapril oral liquid formulations having about 95% or greater of the initial enalapril amount and about 5% w/w or less total impurities or related substances at the end of a given storage period" (ʼ482 Patent, col. 18:40-45). This could support an interpretation where any formulation meeting this objective chemical standard infringes, regardless of the precise mechanism of stability.
      • Evidence for a Narrower Interpretation: The patent includes detailed examples with specific stability data (e.g., ʼ482 Patent, Table E-2). A party might argue that the term should be understood in the context of the specific formulations and conditions tested in the patent’s examples, potentially limiting its scope.

  • The Term: "buffer comprising a mixture of citric acid and sodium citrate" (ʼ482 Patent, cl. 1).

    • Context and Importance: The specific composition of the buffer is a key limitation differentiating this claim. Whether Aurobindo's formulation contains this exact "mixture" will be critical to the infringement analysis for the ʼ482 patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The term "comprising" is typically interpreted as open-ended, suggesting that other components could be present in the buffer as long as citric acid and sodium citrate are included. The specification describes the buffer as comprising these two components, without explicitly excluding others (ʼ482 Patent, col. 2:24-25).
      • Evidence for a Narrower Interpretation: The claim requires a "mixture of" these two components, and the specification consistently describes embodiments using both (e.g., ʼ482 Patent, col. 2:36-37). A party could argue that this requires both components to be actively added to form the primary buffering system, rather than, for example, being formed in situ or being present with other primary buffering agents.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Aurobindo's future commercial activity will induce and contribute to infringement by third parties (e.g., patients) (Compl. ¶¶34, 47, 48, 56). The basis for these allegations is Aurobindo's alleged knowledge of the patents-in-suit and its intent to market a product with instructions for an infringing use, for which there are allegedly no substantial non-infringing uses (Compl. ¶¶35, 40, 57).
  • Willful Infringement: While the complaint does not use the term "willful," it lays a foundation for such a claim by alleging that Aurobindo has "actual and constructive knowledge" of the patents and a "specific intent to infringe" (Compl. ¶¶35, 40, 57). This knowledge is predicated on the patents' listing in the FDA Orange Book and Aurobindo’s notification of its ANDA filing to Azurity.

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

  • A core issue will be one of compositional identity: does the specific formulation detailed in Aurobindo's confidential ANDA submission—including the identity and concentration of its sweetener, preservative, and buffer components, as well as its final pH—fall within the literal scope of the asserted patent claims?
  • A second central question will concern validity, an issue that will likely be raised in Defendant's response: are the claimed formulations, defined by specific combinations of well-known pharmaceutical excipients and pH ranges, non-obvious improvements over the prior art, or do they represent predictable solutions to the known problem of enalapril instability in liquid?
  • A key evidentiary question for infringement will be one of predictive stability: what evidence, based on the data submitted in the ANDA, demonstrates that Aurobindo's proposed product will meet the long-term stability requirements recited as functional limitations in the claims?