DCT

3:23-cv-04152

Azurity Pharma Inc v. Zydus Worldwide DMCC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:23-cv-04152, D.N.J., 08/03/2023
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Zydus USA is incorporated and resides in the district, while the other two Zydus defendants are foreign entities that may be sued in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of Abbreviated New Drug Applications (ANDAs) for generic versions of the hypertension drugs EDARBI® and EDARBYCLOR® constitutes infringement of three patents covering pharmaceutical compositions and methods of treatment.
  • Technical Context: The technology concerns solid oral dosage forms for azilsartan medoxomil, an angiotensin II receptor blocker used to treat high blood pressure, focusing on formulations that improve the drug's stability and dissolution properties.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Plaintiffs’ receipt of notice letters regarding Defendants' ANDA submissions. The notice letters included Paragraph IV certifications asserting that the patents-in-suit are invalid, unenforceable, or would not be infringed by the proposed generic products.

Case Timeline

Date Event
2007-03-28 Earliest Priority Date for ’936 Patent
2008-07-31 Earliest Priority Date for ’238 Patent
2008-12-23 Earliest Priority Date for ’249 Patent
2015-06-30 ’936 Patent Issued
2015-10-27 ’238 Patent Issued
2016-07-12 ’249 Patent Issued
2023-06-19 Plaintiffs received notice letter for ANDA No. 218451
2023-07-19 Plaintiffs received notice letter for ANDA No. 218658
2023-08-03 Complaint Filed

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

U.S. Patent No. 9,066,936 - "Solid pharmaceutical composition comprising a benzimidazole-7-carboxylate derivative and a pH control agent"

The Invention Explained

  • Problem Addressed: The patent’s background section describes a significant formulation challenge: the active pharmaceutical ingredient, azilsartan medoxomil (referred to as compound (I)), is unstable in the neutral pH range typically used for producing pharmaceutical preparations. Conversely, in the acidic pH range where the compound is stable, its solubility is low, which could negatively impact its absorption in the body (’936 Patent, col. 2:5-15).
  • The Patented Solution: The invention claims a solid pharmaceutical composition that combines the active ingredient with a "pH control agent." This agent is selected to create a pH environment between 3 and 5 within the composition. The inventors found that by adjusting the formulation to a pH range where the drug's solubility is low, they could unexpectedly achieve both superior stability of the drug and good dissolution properties from the final tablet (’936 Patent, Abstract; col. 2:21-34).
  • Technical Importance: The invention provided a method to overcome the inherent trade-off between stability and solubility for a promising new hypertension drug, facilitating its development into a commercially viable product (’936 Patent, col. 2:11-15).

Key Claims at a Glance

  • The complaint asserts infringement of the ’936 Patent generally, which contains one independent claim.
  • Independent Claim 1 requires:
    • A solid pharmaceutical composition comprising the compound (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate potassium salt.
    • A solid pH control agent which provides a pH of 3 to 5 when dissolved or suspended in water at a concentration of 1% w/v at 25° C.

U.S. Patent No. 9,169,238 - "Solid Pharmaceutical Composition"

The Invention Explained

  • Problem Addressed: This patent addresses the challenges of formulating azilsartan medoxomil in a combination drug product with a diuretic. In addition to the stability and solubility issues of azilsartan medoxomil itself, combining it with another active ingredient like a diuretic introduces the risk of chemical interactions that could degrade one or both drugs (’238 Patent, col. 2:5-18).
  • The Patented Solution: The invention is a solid preparation formulated using a "separating granulation" method. It comprises two distinct parts: a first part containing the azilsartan medoxomil and a pH control agent, and a second part containing the diuretic (chlorthalidone). By granulating these two parts separately before combining them into a final dosage form (such as a bilayer tablet), the invention aims to prevent detrimental interactions, thereby stabilizing both active ingredients while maintaining good dissolution properties for each (’238 Patent, Abstract; col. 4:59-65).
  • Technical Importance: The claimed method provides a formulation strategy to create a stable and effective combination therapy product, which is often more complex than formulating single-agent drugs (’238 Patent, col. 2:12-18).

Key Claims at a Glance

  • The complaint asserts infringement of the ’238 Patent generally, which contains one independent claim.
  • Independent Claim 1 requires:
    • A solid preparation comprising a first part, which contains azilsartan medoxomil potassium salt and a pH control agent.
    • A second part, which contains the diuretic chlorthalidone.
    • The second part is "obtained by granulating separately from the first part."
    • The pH control agent provides a pH of 2 to 5 under specified test conditions.

U.S. Patent No. 9,387,249 - "Methods of treating hypertension with at least one angiotensin II receptor blocker and chlorthalidone"

Technology Synopsis

This patent claims methods of treating hypertension by administering a combination of an angiotensin II receptor blocker (ARB), specifically a class of benzimidazole derivatives that includes azilsartan medoxomil, and the diuretic chlorthalidone (’249 Patent, Abstract). A key aspect of the claimed method is the reduction in the incidence of hypokalemia (abnormally low potassium levels), a known side effect of diuretic therapy, when the ARB is co-administered (’249 Patent, col. 48:19-34).

Asserted Claims

The complaint asserts infringement of the ’249 patent generally; Claim 1 is the sole independent claim.

Accused Features

The accused feature is the use of Defendants’ Azilsartan Medoxomil and Chlorthalidone ANDA Product to treat hypertension, as will be directed by its proposed labeling (Compl. ¶¶ 47, 74).

III. The Accused Instrumentality

Product Identification

The complaint identifies two accused products by their ANDA numbers:

  1. ANDA No. 218658: A proposed generic version of EDARBI®, described as an oral tablet containing 40 mg or 80 mg of azilsartan medoxomil (referred to as “Zydus’s Azilsartan Medoxomil ANDA Product”) (Compl. ¶36).
  2. ANDA No. 218451: A proposed generic version of EDARBYCLOR®, described as an oral tablet containing 40 mg of azilsartan medoxomil combined with either 12.5 mg or 25 mg of chlorthalidone (referred to as “Zydus’s Azilsartan Medoxomil and Chlorthalidone ANDA Product”) (Compl. ¶46).

Functionality and Market Context

The products are intended to be generic equivalents for the treatment of hypertension (Compl. ¶¶ 36, 46). The complaint alleges that the proposed generic products contain the same active ingredients as their brand-name counterparts and will have the same or substantially the same proposed labeling (Compl. ¶¶ 37, 47). The filing of the ANDAs seeking FDA approval to market these generic products prior to the expiration of the patents-in-suit is the statutorily defined act of infringement giving rise to the litigation (Compl. ¶¶ 55, 61, 67, 73).

Visual Evidence

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-by-claim chart analysis, as Plaintiffs state they have not been provided with a copy of Defendants' ANDAs or detailed information about the proposed products' composition or manufacturing processes (Compl. ¶¶ 41, 51). The infringement allegations are based on the statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), which arises from the submission of an ANDA for a drug claimed in a patent.

Narrative Infringement Theory

  • ’936 Patent: The complaint alleges that both of Zydus’s proposed ANDA products, upon approval and commercialization, will infringe the ’936 patent. The theory is that the products are solid pharmaceutical compositions that will necessarily contain the claimed azilsartan medoxomil potassium salt and a pH control agent meeting the functional requirements of claim 1 in order to be bioequivalent to the EDARBI® and EDARBYCLOR® products (Compl. ¶¶ 56, 62).
  • ’238 Patent: The complaint alleges that Zydus’s combination ANDA product (No. 218451) will infringe the ’238 patent. The infringement theory rests on the belief that to achieve the necessary stability and bioequivalence for a combination of azilsartan medoxomil and chlorthalidone, Zydus’s product will be manufactured using a process that includes the claimed step of separately granulating the azilsartan/pH agent components from the chlorthalidone component (Compl. ¶68).

Identified Points of Contention

  • Compositional Questions (’936 Patent): A central point of contention will be compositional. Does the formulation described in Zydus's ANDAs contain an excipient that qualifies as a "solid pH control agent" providing the specific pH of 3 to 5 as functionally defined in the claim? The case may turn on whether Zydus has designed a formulation that achieves stability and bioequivalence through an alternative, non-infringing mechanism or using excipients that do not meet the claim's functional requirements.
  • Process Questions (’238 Patent): The dispute over the ’238 patent will likely focus on the manufacturing process. Does the process detailed in ANDA No. 218451 meet the claim limitation of being "obtained by granulating separately"? Discovery will likely focus on the precise steps of Zydus’s manufacturing method to determine if it employs separate granulation, co-granulation, simple blending, or another technique that may fall outside the claim scope.

V. Key Claim Terms for Construction

Term: "a solid pH control agent which provides a pH of 3 to 5 when dissolved or suspended in water at a concentration of 1% w/v at 25° C." (’936 Patent, Claim 1)

Context and Importance

This term is the central inventive concept of the ’936 patent. The infringement analysis will depend entirely on whether any excipient in Zydus’s products meets this functional definition. Practitioners may focus on this term because it defines the invention not by a specific chemical structure but by a functional outcome, which can lead to disputes over the scope and method of testing for infringement.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification provides a long list of exemplary acidic substances that can be used, including tartaric acid, citric acid, fumaric acid, and malic acid, as well as combinations of acids and bases, suggesting the term is not limited to a single class of compounds (’936 Patent, col. 5:4-34).
  • Evidence for a Narrower Interpretation: The specification notes that preferable examples are those whose solutions "have a buffering ability at said pH," and identifies "monosodium fumarate" as "particularly preferable" (’936 Patent, col. 5:36-41). A defendant could argue that the term should be construed to require a buffering capacity, not merely the ability to produce a certain pH, potentially narrowing its scope.

Term: "obtained by granulating separately from the first part" (’238 Patent, Claim 1)

Context and Importance

This process limitation is the key feature distinguishing the ’238 patent's claims for a combination product. Infringement hinges on whether Zydus’s manufacturing method for its combination product includes this specific step. The construction of "granulating separately" will determine whether Zydus's process infringes.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The claim language itself is direct. The specification describes combining the separately granulated parts into various final forms, such as single-layer or multi-layer tablets, suggesting the specific final form is not limiting as long as the initial granulation is separate (’238 Patent, col. 8:46-54).
  • Evidence for a Narrower Interpretation: A defendant may argue that the term requires absolute physical separation during the granulation steps, and that processes involving intermediate mixing or potential for cross-contamination would not qualify. The patent's examples detail distinct and separate granulation procedures for the part containing azilsartan and the part containing the diuretic, which could be used to support a narrower interpretation tied to these specific embodiments (’238 Patent, Example 1, col. 13:5-32).

VI. Other Allegations

Indirect Infringement

The complaint alleges inducement and contributory infringement for all three patents. The basis for these allegations is that Defendants' proposed product labeling will instruct physicians and patients to administer the drugs for treating hypertension, thereby causing direct infringement of the composition and method claims (Compl. ¶¶ 56, 62, 68, 74).

Willful Infringement

The complaint alleges that Zydus "was aware of the existence" of each asserted patent and that its filing of the ANDAs with Paragraph IV certifications constituted an act of infringement (Compl. ¶¶ 59, 65, 71, 77). This assertion of pre-suit knowledge forms the basis for a potential claim of willfulness.

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

The resolution of this case will likely depend on the facts revealed during discovery regarding the specific composition and manufacturing processes of Defendants’ proposed generic products. The central questions for the court appear to be:

  • A core issue will be one of compositional identity: do the excipients listed in Zydus’s ANDAs for its generic products include a "pH control agent" that functions in the specific manner required by the ’936 patent claims (i.e., providing a pH of 3-5 under specified conditions), or will discovery reveal a formulation that achieves stability through a non-infringing chemical environment?
  • A key evidentiary question will be one of process definition: for the combination product, does the manufacturing method detailed in ANDA No. 218451 involve the "separately granulating" process required by claim 1 of the ’238 patent, or does it employ an alternative technique such as co-granulation or simple blending that would place it outside the claim's scope?