DCT

1:23-cv-01080

Azurity Pharma Inc v. Teva Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-01080, D. Del., 09/29/2023
  • Venue Allegations: Venue is alleged to be proper as to Teva Pharmaceuticals, Inc. because it is a Delaware corporation and has previously consented to venue in the district. Venue is alleged as to Teva Pharmaceutical Industries Ltd. on the basis that it is an alien corporation and may be sued in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiffs' hypertension drug EDARBYCLOR® constitutes infringement of three patents covering pharmaceutical compositions and methods of treatment.
  • Technical Context: The technology concerns combination drug formulations for treating hypertension, a prevalent cardiovascular condition, by balancing the stability and dissolution properties of multiple active pharmaceutical ingredients.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendants' ANDA No. 218737, which included a Paragraph IV certification asserting that Plaintiffs’ patents, listed in the FDA's Orange Book for the drug EDARBYCLOR®, are invalid, unenforceable, or would not be infringed by the proposed generic products. Plaintiffs filed this suit within the 45-day statutory window after receiving notice, triggering an automatic 30-month stay of FDA approval for the ANDA.

Case Timeline

Date Event
2007-03-28 Earliest Priority Date for U.S. Patent No. 9,066,936
2008-07-31 Earliest Priority Date for U.S. Patent No. 9,169,238
2008-12-23 Earliest Priority Date for U.S. Patent No. 9,387,249
2015-06-30 U.S. Patent No. 9,066,936 Issues
2015-10-27 U.S. Patent No. 9,169,238 Issues
2016-07-12 U.S. Patent No. 9,387,249 Issues
2023-08-17 Plaintiffs Receive Teva's ANDA Notice Letter
2023-09-29 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,” issued June 30, 2015 (’936 Patent)

The Invention Explained

  • Problem Addressed: The patent addresses a formulation challenge with a specific benzimidazole derivative, referred to as compound (I), used as an angiotensin II receptor antagonist. This compound is unstable at a neutral pH but exhibits low solubility at the acidic pH range where it is stable, making it difficult to formulate into a solid dosage form that is both stable and readily dissolvable in the body (’936 Patent, col. 2:6-15).
  • The Patented Solution: The invention is a solid pharmaceutical composition that combines compound (I) with a "pH control agent." This agent is designed to create an acidic micro-environment within the tablet or granule, thereby stabilizing the active drug while simultaneously promoting its dissolution upon administration (’936 Patent, col. 2:18-34).
  • Technical Importance: This formulation strategy enables the creation of a stable, solid oral dosage form for a potent antihypertensive drug that would otherwise be difficult to deliver effectively.

Key Claims at a Glance

  • The complaint asserts one or more claims of the ’936 Patent (Compl. Prayer for Relief ¶A). Independent claim 1 is representative.
  • Independent Claim 1 requires:
    • A solid pharmaceutical composition comprising a compound which is (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.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,169,238 - “Solid pharmaceutical composition,” issued October 27, 2015 (’238 Patent)

The Invention Explained

  • Problem Addressed: This patent expands on the challenge from the ’936 Patent, addressing the difficulty of formulating compound (I) in a combination product with a diuretic. Because the two active ingredients have different chemical properties, creating a single formulation that ensures the stability and proper dissolution of both is technically complex (’238 Patent, col. 2:11-28).
  • The Patented Solution: The invention claims a solid preparation that includes compound (I), a pH control agent, and a diuretic. A key aspect of the solution is physically separating the components into two parts during manufacturing, for example by granulating them separately before combining them into a single- or multi-layer tablet. This separation prevents undesirable interactions and allows for optimized stability and dissolution for both drugs (’238 Patent, col. 2:54-68; col. 3:45-4:4).
  • Technical Importance: The invention provides a method to formulate a stable and effective fixed-dose combination therapy, which can improve patient compliance and therapeutic outcomes in hypertension treatment.

Key Claims at a Glance

  • The complaint asserts one or more claims of the ’238 Patent (Compl. Prayer for Relief ¶B). Independent claim 1 is representative.
  • Independent Claim 1 requires:
    • A solid preparation comprising a first part comprising a compound which is (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 and a pH control agent.
    • A second part comprising chlorthalidone, which is obtained by granulating separately from the first part.
    • Wherein the pH control agent provides a pH of 2 to 5 under specified test conditions.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,387,249 - “Methods of treating hypertension with at least one angiotensin II receptor blocker and chlorthalidone,” issued July 12, 2016 (’249 Patent)

Technology Synopsis

This patent addresses a clinical problem associated with the diuretic chlorthalidone, a known side effect of which is hypokalemia (low potassium levels). The invention is a method of treating hypertension that involves administering an angiotensin II receptor blocker (ARB) in combination with chlorthalidone. This combination is alleged to not only effectively lower blood pressure but also to reduce the incidence of chlorthalidone-induced hypokalemia compared to treatment with chlorthalidone alone (’249 Patent, Abstract; cl. 1).

Asserted Claims

The complaint asserts one or more claims (Compl. Prayer for Relief ¶C). Independent claim 1 is representative.

Accused Features

The accused product is a fixed-dose combination of an ARB (azilsartan medoxomil) and chlorthalidone. The complaint alleges that the product's proposed labeling will instruct for its use in treating hypertension, thereby directing or encouraging infringement of the claimed method (Compl. ¶¶32-33, 54).

III. The Accused Instrumentality

Product Identification

Defendants’ proposed generic drug products, submitted to the FDA under ANDA No. 218737, for oral tablets containing either 40 mg azilsartan medoxomil / 12.5 mg chlorthalidone or 40 mg azilsartan medoxomil / 25 mg chlorthalidone (Compl. ¶32).

Functionality and Market Context

The products are proposed generic equivalents of Plaintiffs' branded drug, EDARBYCLOR®, and are intended for the treatment of hypertension (Compl. ¶¶30, 33). The complaint asserts that the filing of the ANDA itself, which seeks approval to market these products prior to the expiration of the patents-in-suit, constitutes an act of infringement under the Hatch-Waxman Act (Compl. ¶41). The complaint notes that Defendants have not provided a copy of the ANDA, so details of the proposed product's formulation are limited to the information in Teva's notice letter (Compl. ¶37).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide detailed infringement contentions or claim charts, as is common in initial ANDA filings. The infringement theory is statutory: the submission of ANDA No. 218737 for a product that is a generic copy of EDARBYCLOR®, covered by the patents-in-suit, is an act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶¶ 41, 47, 53). The following charts summarize the allegations based on the assertion that Teva's proposed products contain the same active ingredients and will have substantially the same labeling as EDARBYCLOR® (Compl. ¶33).

’936 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A solid pharmaceutical composition comprising a compound which is (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... The proposed ANDA product contains azilsartan medoxomil potassium salt as an active ingredient. ¶¶32-33 col. 21:14-20
...and 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. The complaint alleges that the proposed ANDA product will infringe the claim, which implies the proposed formulation will contain a solid pH control agent meeting the claim's functional requirements. ¶¶41-42 col. 21:20-22:2

’238 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
...a first part comprising a compound which is (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 and a pH control agent... The proposed ANDA product contains azilsartan medoxomil potassium salt, and the infringement allegation implies its formulation will contain a first part with a pH control agent as claimed. ¶¶32-33, 48 col. 19:56-62
...a second part comprising chlorthalidone, which is obtained by granulating separately from the first part... The proposed ANDA product contains chlorthalidone, and the infringement allegation implies its manufacturing process will involve separate granulation as claimed. ¶¶32-33, 48 col. 19:63-65
...wherein a pH of a solution or suspension obtained by dissolving or suspending the pH control agent in water at 25° C. at a concentration of 1 w/v % is 2 to 5. The infringement allegation implies the proposed formulation's pH control agent will meet the claim's functional requirements. ¶¶47-48 col. 20:1-5

Identified Points of Contention

  • Evidentiary Question: A primary point of contention will be the actual composition and manufacturing process described in Teva’s ANDA. Does the proposed formulation contain an excipient that functions as a "pH control agent" meeting the specific pH requirements of the claims, and is the chlorthalidone "obtained by granulating separately" as required by the ’238 Patent? The complaint lacks these specific factual allegations, as Plaintiffs have not yet seen the relevant portions of the ANDA (Compl. ¶37).
  • Scope Questions: For the ’249 Patent, a key question will be whether Teva's proposed product label will instruct or encourage physicians to perform the claimed method of treating hypertension, thus inducing infringement. The allegation that the labeling is "substantially the same" as that for EDARBYCLOR® suggests this will be a central part of Plaintiffs' case (Compl. ¶33).

V. Key Claim Terms for Construction

"pH control agent" (’936 Patent, cl. 1; ’238 Patent, cl. 1)

  • Context and Importance: This term is the central inventive concept of the two composition patents. The infringement and validity analyses will depend on whether an excipient in Teva's formulation qualifies as a "pH control agent." Practitioners may focus on this term because Teva could argue its formulation does not contain such an agent, or that its excipients primarily serve other functions (e.g., as fillers or binders) and only incidentally affect pH.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a long list of potential acidic substances that can be used, including tartaric acid, citric acid, and fumaric acid, suggesting the term is not limited to a specific chemical class (’936 Patent, col. 5:4-13).
    • Evidence for a Narrower Interpretation: The claims require the agent to provide a specific pH range (e.g., 3 to 5) under defined test conditions, a functional limitation that not every acidic excipient may meet (’936 Patent, col. 22:1-2). The specification also highlights "preferable examples" that have a "buffering ability," such as monosodium fumarate, which could be used to argue that the agent must do more than simply be acidic (’936 Patent, col. 5:36-41).

"obtained by granulating separately from the first part" (’238 Patent, cl. 1)

  • Context and Importance: This process limitation is a key distinguishing feature of the ’238 Patent. Infringement of this claim hinges on whether the manufacturing process detailed in Teva's ANDA includes this specific step.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A plaintiff might argue this term covers any manufacturing process where the granules containing compound (I) and the granules containing chlorthalidone are created in distinct, non-simultaneous steps before being combined.
    • Evidence for a Narrower Interpretation: The specification describes embodiments including multi-layer tablets and mixing of separately prepared granules to form a single-layer tablet (’238 Patent, col. 4:60-5:4). A defendant could argue the term requires one of these more structurally distinct forms of separation, rather than simply a temporal separation in the granulation process.

VI. Other Allegations

Indirect Infringement

The complaint alleges that upon approval, Defendants will induce and contribute to infringement of all three patents. This allegation is based on the proposed product labeling, which is expected to be substantially the same as that for EDARBYCLOR® and would instruct patients and physicians to use the product in an infringing manner (Compl. ¶¶ 42, 48, 54).

Willful Infringement

The complaint alleges that Defendants were "aware of the existence" of the patents-in-suit and knew the filing of the ANDA was an act of infringement (Compl. ¶¶ 45, 51, 57). This allegation is based on Defendants’ statutory obligation to provide a Paragraph IV certification against the Orange Book-listed patents, which establishes pre-suit knowledge.

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

  1. An Evidentiary Question of Formulation: The central factual dispute will concern the specific contents of Teva's ANDA. Does the proposed generic product contain an excipient that meets the functional definition of a "pH control agent" as claimed in the '936 and '238 patents, and does its manufacturing process involve the "separate granulation" step required by the '238 patent?
  2. A Definitional Question of Claim Scope: The case will likely turn on the construction of "pH control agent." Will the court adopt a broader, functional definition that could read on common pharmaceutical excipients, or a narrower one requiring the agent to be added for the primary purpose of pH modification and possess specific properties like buffering capacity, as suggested by preferred embodiments?
  3. A Methodological Question of Infringement: For the '249 method patent, a key issue will be whether Teva’s proposed product label instructs users to co-administer an ARB and chlorthalidone for treating hypertension in a manner that also results in a reduced incidence of hypokalemia, as claimed. The extent to which the label must mirror the patent's claimed benefits will be a point of contention.