Azurity Pharma Inc v. Bionpharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Azurity Pharmaceuticals, Inc. (Delaware)
  • Defendant: Novitium Pharma, LLC (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnel LLP; Wilson Sonsini Goodrich & Rosati, P.C.
• Case Identification: 1:21-cv-01286, D. Del., 08/03/2023
• Venue Allegations: Venue is alleged to be proper in the District of Delaware as Defendant is a Delaware corporation.
• Core Dispute: Plaintiff alleges that Defendant’s generic enalapril maleate oral solution, the subject of ANDA No. 212408, infringes patents related to stable, ready-to-use liquid pharmaceutical formulations.
• Technical Context: The technology concerns pharmaceutical formulations designed to solve the problem of chemical instability in liquid versions of enalapril, an ACE inhibitor used to treat hypertension.
• Key Procedural History: The complaint alleges that Defendant was aware of the patents-in-suit due to prior infringement actions filed by Plaintiff against the previous manufacturer (CoreRx, Inc.) and distributor (Bionpharma Inc.) of the same ANDA product.

Case Timeline

Date	Event
2016-03-18	Priority Date for ’023 and ’405 Patents
2021-06-22	’023 Patent Issued
2021-06-22	Plaintiff files suit against Bionpharma for infringement of the ’023 Patent
2021-08-10	ANDA No. 212408 approved by FDA
2021-10-12	’405 Patent Issued
2021-10-15	Plaintiff files suit against Bionpharma for infringement of the ’405 Patent
c. 2021-12-01	Previous supplier CoreRx allegedly stops supplying the ANDA formulation
2022-04-01	Plaintiff files suit against CoreRx for infringement of the ’023 and ’405 Patents
2022-06-01	Defendant Novitium allegedly lists itself as manufacturer of the ANDA formulation
2023-08-03	Complaint Filing Date
2036-03-25	Expiration Date for ’023 and ’405 Patents

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

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

The Invention Explained

• Problem Addressed: The patent describes that while enalapril is commonly administered in tablet form, certain patient populations, such as children and the elderly, have difficulty swallowing solid dosage forms. Compounding pharmacists often crush tablets to create liquid suspensions, but these methods can lead to inaccurate dosing, rapid instability of the active ingredient, and potential contamination. (’023 Patent, col. 5:32-6:4).
• The Patented Solution: The invention is a stable, ready-to-use oral liquid formulation of enalapril. The solution achieves stability through a specific combination of components, including a sweetener, a preservative (such as sodium benzoate or parabens), and water, maintained at a controlled pH of less than 3.5 to minimize degradation of the active ingredient for at least 12 months under refrigerated conditions. (’023 Patent, Abstract; col. 2:31-38).
• Technical Importance: This technology provides a commercially prepared, stable liquid dosage form of enalapril, which may offer improved dosing accuracy and a longer shelf-life compared to extemporaneously compounded suspensions. (Compl. ¶9).

Key Claims at a Glance

• The complaint asserts at least independent claim 1. (Compl. ¶38).
• Claim 1 requires a stable oral liquid formulation "consisting essentially of":
  • about 0.6 to about 1.2 mg/ml enalapril (or a salt/solvate thereof);
  • a sweetener;
  • a preservative comprising sodium benzoate, a paraben, or a mixture of parabens;
  • water; and
  • optionally a flavoring agent.
• The claim further requires that the formulation is stable at 5±3° C. for at least 12 months, defined as retaining at least 95% of the initial enalapril amount with 5% or less total impurities. (’023 Patent, col. 39:41-40:59).

U.S. Patent No. 11,141,405 - "Enalapril Formulations"

The Invention Explained

• Problem Addressed: The ’405 Patent addresses the same technical problem as the ’023 Patent: the need for a stable, ready-to-use liquid formulation of enalapril to serve patients unable to take solid tablets. (’405 Patent, col. 5:32-6:4).
• The Patented Solution: The invention is a stable oral liquid formulation of enalapril that also uses a controlled chemical environment to achieve long-term stability. This patent claims the formulation with a broader list of potential preservatives while making other components, such as a sweetener and a pH-adjusting buffer, optional. (’405 Patent, Abstract; col. 39:40-40:5).
• Technical Importance: As with the ’023 Patent, this technology aims to provide a reliable, pre-formulated liquid alternative to compounded enalapril suspensions. (Compl. ¶9).

Key Claims at a Glance

• The complaint asserts at least independent claim 1. (Compl. ¶38).
• Claim 1 requires a stable oral liquid formulation "consisting essentially of":
  • about 0.6 to about 1.2 mg/ml enalapril (or a salt/solvate thereof);
  • a preservative selected from a specific list including sodium benzoate, various acids, and parabens; and
  • water.
• The claim further specifies the formulation "optionally comprises a buffer to maintain the pH about 4.5 or below, a sweetener, a flavoring agent, or any combination thereof." Like the ’023 Patent, it requires stability for at least 12 months, defined by the same 95% potency and 5% impurity limits. (’405 Patent, col. 39:40-40:5).

III. The Accused Instrumentality

Product Identification

The accused product is the "Novitium Formulation," which is the subject of Bionpharma Inc.'s ANDA No. 212408 for a generic version of Azurity's Epaned® product. (Compl. ¶1).

Functionality and Market Context

The Novitium Formulation is a ready-to-use oral solution of enalapril maleate intended for the treatment of hypertension. (Compl. ¶8). The complaint alleges that Novitium became the manufacturer of this ANDA product for Bionpharma in or around June 2022, taking over from a previous manufacturer, CoreRx. (Compl. ¶21, ¶34, ¶36). The complaint alleges the Novitium Formulation is the "same formulation" as that previously sold by Bionpharma. (Compl. ¶22).
No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or a detailed narrative infringement theory mapping specific components of the Novitium Formulation to the elements of the asserted claims. The infringement allegations are pleaded generally, stating that the Novitium Formulation is covered by one or more claims of the patents-in-suit, including at least claim 1 of each patent. (Compl. ¶23, ¶38).

• Identified Points of Contention: Based on the patent language and the nature of the dispute, the infringement analysis will likely focus on several key questions to be resolved in discovery and at trial.
  • Scope Questions: The use of the transitional phrase "consisting essentially of" in the asserted claims will be a central issue. A primary question for the court will be whether the Novitium Formulation contains any unrecited ingredients and, if so, whether those ingredients materially affect the "basic and novel characteristics" of the invention—namely, the specific stability profile defined in the claims.
  • Technical Questions: The dispute will involve a direct factual comparison of the accused product's composition and performance against the claim limitations. Key questions include:
    • Does the Novitium Formulation contain a preservative and/or sweetener falling within the scope of the asserted claims?
    • What is the tested stability of the Novitium Formulation under the conditions specified in the claims (i.e., does it retain ≥95% enalapril with ≤5% impurities after 12 months at 5±3° C.)?

V. Key Claim Terms for Construction

• The Term: "consisting essentially of"

• Context and Importance: This transitional phrase defines the scope of the claims as including the specifically recited ingredients and any unrecited ingredients that do not materially affect the basic and novel properties of the formulation. Practitioners may focus on this term because infringement will depend on the chemical composition of the Novitium Formulation and whether any additional excipients are deemed to materially alter the claimed stability.

• Intrinsic Evidence for Interpretation: The patents do not explicitly define the term.

  • Evidence for a Broader Interpretation: A party seeking a broader scope might argue that only unrecited ingredients that degrade the claimed stability profile should be considered "material," allowing for the presence of other common, inert pharmaceutical excipients.
  • Evidence for a Narrower Interpretation: A party seeking a narrower scope could argue that the "basic and novel" characteristic is the precise stability achieved by a minimalist formulation, and thus the addition of any unrecited component that alters the chemical environment, even neutrally, is a material change.

• The Term: "stable"

• Context and Importance: The definition of "stable" is the technical anchor of the asserted claims and the primary metric for infringement. The dispute will be factual, centered on whether the accused product meets the specific performance criteria set forth in the patent.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The term is explicitly defined within the claims themselves, which could limit the need for extensive construction. A party could argue the definition is plain and requires no further interpretation beyond its express terms. (’023 Patent, col. 40:1-5).
  • Evidence for a Narrower Interpretation: The specification provides examples of stability testing and discusses various degradants. (’023 Patent, col. 18:50-19:10; Tables A-2, B-2). A party could argue these examples inform the meaning of "stable" and the types of "impurities" that must be measured to satisfy the claim limitation.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Novitium induces and contributes to infringement by intentionally encouraging acts of direct infringement with knowledge of the patents-in-suit. (Compl. ¶43-44, ¶55-56).
• Willful Infringement: Willfulness is alleged based on Defendant’s purported knowledge of the patents-in-suit and its awareness of prior infringement litigation Plaintiff initiated against the previous manufacturer (CoreRx) and distributor (Bionpharma) for the same ANDA product. (Compl. ¶47, ¶59).

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

• A central issue will be one of compositional fact: does discovery show that the accused Novitium Formulation contains the specific active ingredient concentration, preservative type, and optional components (e.g., sweetener, buffer) recited in the asserted claims, and does it operate within the claimed pH range?
• The case will likely turn on the scope of closure: can the phrase "consisting essentially of" be interpreted to read on a commercial generic formulation that may contain unrecited manufacturing excipients, and if so, do those excipients materially alter the claimed long-term stability profile?
• A key evidentiary question will be one of technical performance: what data from stability studies of the Novitium Formulation will be presented to prove or disprove that it meets the specific, quantitative definition of "stable" required by the claims (≥95% potency and ≤5% impurities over 12 months)?