DCT

1:23-cv-18420

Azurity Pharma Inc v. Annora Pharma Private Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-18420, D.N.J., 09/07/2023
  • Venue Allegations: Plaintiff alleges venue is proper because Defendant is a foreign corporation, making it subject to suit in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's QBRELIS® product constitutes infringement of eight U.S. patents related to stable oral liquid formulations of lisinopril.
  • Technical Context: The patents relate to formulations of lisinopril, a widely used angiotensin-converting enzyme (ACE) inhibitor for treating hypertension, as a stable oral liquid, which is significant for pediatric, geriatric, and other patient populations unable to swallow solid tablets.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following a July 24, 2023 notification letter from Defendant to Plaintiff regarding the submission of ANDA No. 218419 to the U.S. Food and Drug Administration. The patents-in-suit are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book") in connection with Plaintiff’s QBRELIS® product. The asserted patents are all part of the same family and several note on their face that they are subject to a terminal disclaimer.

Case Timeline

Date Event
2015-10-30 Earliest Priority Date for all Patents-in-Suit
2016-10-11 U.S. Patent No. 9,463,183 Issues
2017-04-11 U.S. Patent No. 9,616,096 Issues
2017-11-14 U.S. Patent No. 9,814,751 Issues
2018-08-07 U.S. Patent No. 10,039,800 Issues
2019-04-23 U.S. Patent No. 10,265,370 Issues
2019-09-10 U.S. Patent No. 10,406,199 Issues
2021-03-09 U.S. Patent No. 10,940,177 Issues
2021-11-23 U.S. Patent No. 11,179,434 Issues
2023-07-24 Defendant Notifies Plaintiff of ANDA Filing
2023-09-07 Complaint Filed

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

U.S. Patent No. 9,463,183 - "Lisinopril Formulations"

Issued October 11, 2016 (’183 Patent)

The Invention Explained

  • Problem Addressed: The patent’s background section notes that lisinopril is typically administered as oral tablets, but certain patient populations, such as children and the elderly, have difficulty swallowing solid dosage forms (’183 Patent, col. 4:45-49). Compounding tablets into a liquid format by pharmacists is described as a suboptimal solution due to "large variability in the actual dosage, incomplete solubilizing of the lisinopril tablet in the liquid, rapid instability, [and] inconsistent formulation methods" (’183 Patent, col. 3:55-4:6).
  • The Patented Solution: The patent discloses stable oral liquid formulations of lisinopril designed to overcome the problems of extemporaneous compounding. The solution involves a specific combination of lisinopril, a sweetener (xylitol), a buffer system (citric acid and sodium citrate), and a preservative (sodium benzoate) in water, maintained within a specific pH range of about 4 to 5 to ensure long-term stability (’183 Patent, Abstract; col. 2:9-15).
  • Technical Importance: This technology provides a standardized, stable, and effective oral liquid dosage form of lisinopril, enabling accurate dosing and administration for patients who cannot take solid tablets.

Key Claims at a Glance

The complaint does not assert specific claims but alleges infringement of at least one claim (Compl. ¶16). Claim 1 is the first independent claim.

  • Independent Claim 1:
    • A stable oral liquid formulation, comprising:
      • (i) about 1 mg/ml lisinopril or a pharmaceutically acceptable salt or solvate thereof;
      • (ii) about 150 mg/ml of a sweetener that is xylitol;
      • (iii) a buffer comprising about 0.86 mg/ml citric acid and about 1.44 mg/ml sodium citrate;
      • (iv) about 0.8 mg/ml of a preservative that is sodium benzoate; and
      • (v) water;
    • wherein the pH of the formulation is between about 4 and about 5; and
    • wherein the formulation is stable at about 25±5° C. for at least 12 months.

U.S. Patent No. 9,616,096 - "Lisinopril Formulations"

Issued April 11, 2017 (’096 Patent)

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’183 Patent, the ’096 Patent addresses the same technical problem: the lack of a stable, ready-to-use oral liquid formulation of lisinopril suitable for patients who cannot swallow tablets (’096 Patent, col. 3:55-4:6).
  • The Patented Solution: The patent describes a stable oral liquid formulation with the same core components as the ’183 Patent but claims a more specific pH value and a longer period of stability. The formulation combines lisinopril, xylitol, a citric acid/sodium citrate buffer, and sodium benzoate in water to achieve stability for at least 18 months at a pH of about 4.9 (’096 Patent, col. 2:9-20).
  • Technical Importance: This patent claims a lisinopril formulation with a refined pH and an extended shelf-life, representing a further development in ensuring a reliable liquid dosage form for long-term use.

Key Claims at a Glance

The complaint does not assert specific claims but alleges infringement of at least one claim (Compl. ¶18). Claim 1 is the first independent claim.

  • Independent Claim 1:
    • A stable oral liquid formulation, comprising:
      • (i) about 1 mg/ml lisinopril or a pharmaceutically acceptable salt or solvate thereof;
      • (ii) about 150 mg/ml of a sweetener that is xylitol;
      • (iii) a buffer comprising about 0.86 mg/ml citric acid and about 1.44 mg/ml sodium citrate;
      • (iv) about 0.8 mg/ml of a preservative that is sodium benzoate; and
      • (v) water;
    • wherein the pH of the formulation is about 4.9; and
    • wherein the formulation is stable at about 25±5° C. for at least 18 months.

U.S. Patent No. 9,814,751 - "Lisinopril Formulations"

Issued November 14, 2017

  • Technology Synopsis: This patent claims methods of treating hypertension by administering a stable oral liquid lisinopril formulation. The formulation comprises lisinopril, a sweetener, a citric acid/sodium citrate buffer, and a preservative, and is stable for at least 6 months (’751 Patent, col. 39:4-22).
  • Asserted Claims: The complaint does not specify claims (Compl. ¶20). Independent claims 1 and 10 cover methods of treating hypertension.
  • Accused Features: The Defendant’s ANDA Product, an oral liquid formulation of lisinopril, is accused of infringement, along with its proposed labeling directing its use for treating hypertension (Compl. ¶¶45-46).

U.S. Patent No. 10,039,800 - "Lisinopril Formulations"

Issued August 7, 2018

  • Technology Synopsis: This patent claims methods for treating hypertension, heart failure, or acute myocardial infarction by administering a stable oral liquid lisinopril formulation. The formulation includes lisinopril, a sweetener (xylitol, mannitol, sucralose, or saccharin), a citric acid/sodium citrate buffer, and a preservative (’800 Patent, col. 39:4-40:10).
  • Asserted Claims: The complaint does not specify claims (Compl. ¶22). Independent claims 1, 11, and 16 cover methods of treatment.
  • Accused Features: The Defendant’s ANDA Product and its proposed labeling directing use for treating hypertension and related conditions are accused of infringement (Compl. ¶¶50-51).

U.S. Patent No. 10,265,370 - "Lisinopril Formulations"

Issued April 23, 2019

  • Technology Synopsis: This patent claims a stable oral liquid formulation of lisinopril comprising the active ingredient, a sweetener, a citric acid/sodium citrate buffer, a preservative, and water, with stability for at least 6 months (’370 Patent, col. 37:50-38:13).
  • Asserted Claims: The complaint does not specify claims (Compl. ¶24). Independent claims 1 and 19 are directed to the formulation itself.
  • Accused Features: The composition of Defendant’s ANDA Product is accused of infringing the patent’s formulation claims (Compl. ¶55).

U.S. Patent No. 10,406,199 - "Lisinopril Formulations"

Issued September 10, 2019

  • Technology Synopsis: This patent claims methods for treating hypertension, heart failure, or acute myocardial infarction by administering a stable oral liquid lisinopril formulation containing specific components, including a sweetener and a citric acid/sodium citrate buffer (’199 Patent, col. 41:10-42:19).
  • Asserted Claims: The complaint does not specify claims (Compl. ¶26). Independent claims 1, 11, and 16 cover methods of treatment.
  • Accused Features: The Defendant’s ANDA Product and its proposed labeling directing use for treating hypertension and related conditions are accused of infringement (Compl. ¶¶60-61).

U.S. Patent No. 10,940,177 - "Lisinopril Formulations"

Issued March 9, 2021

  • Technology Synopsis: This patent claims a stable oral liquid formulation of lisinopril that is defined by its components, including a sweetener, a preservative, and a liquid vehicle comprising water. The claims are notable for not explicitly requiring a separate buffer (’177 Patent, col. 39:46-64).
  • Asserted Claims: The complaint does not specify claims (Compl. ¶28). Independent claims 1 and 19 are directed to the formulation.
  • Accused Features: The composition of Defendant’s ANDA Product is accused of infringing the patent’s formulation claims (Compl. ¶65).

U.S. Patent No. 11,179,434 - "Lisinopril Formulations"

Issued November 23, 2021

  • Technology Synopsis: This patent claims a stable oral liquid formulation of lisinopril comprising the active ingredient, a preservative, and a liquid vehicle, and optionally a sweetener. The claims are structured to be broader by not requiring certain components like a buffer as essential elements (’434 Patent, col. 39:51-40:20).
  • Asserted Claims: The complaint does not specify claims (Compl. ¶30). Independent claims 1 and 14 are directed to the formulation.
  • Accused Features: The composition of Defendant’s ANDA Product is accused of infringing the patent’s formulation claims (Compl. ¶70).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant Annora’s proposed generic oral liquid formulation of lisinopril, which is the subject of Abbreviated New Drug Application (ANDA) No. 218419 (the “Annora ANDA Product”) (Compl. ¶¶2, 31).

Functionality and Market Context

  • The complaint alleges that by filing its ANDA, Annora has represented to the FDA that its product has the same active ingredients, route of administration, dosage form, use, and strength as Azurity’s QBRELIS® product, and is bioequivalent to it (Compl. ¶33). QBRELIS® is an FDA-approved ACE inhibitor used for treating hypertension in adults and children, as well as for adjunct therapy for heart failure and treatment of acute myocardial infarction (Compl. ¶13). Annora’s product is intended to be a generic substitute for QBRELIS® to be sold in the United States market (Compl. ¶6). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide specific technical details about the Annora ANDA Product’s formulation. Infringement is alleged on the basis that, as a generic equivalent submitted under an ANDA, the accused product is represented to have the same characteristics as Plaintiff's QBRELIS® product, which is covered by the patents-in-suit (Compl. ¶¶16, 33). The following charts summarize the allegations for the representative independent claims of the lead patents based on this theory.

’183 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A stable oral liquid formulation, comprising: (i) about 1 mg/ml lisinopril... The Annora ANDA Product is an oral liquid formulation of lisinopril with the same strength as QBRELIS®. ¶33 col. 2:9-10
(ii) about 150 mg/ml of a sweetener that is xylitol; The Annora ANDA Product is alleged to be bioequivalent to and have the same formulation characteristics as QBRELIS®. ¶33 col. 2:10-11
(iii) a buffer comprising about 0.86 mg/ml citric acid and about 1.44 mg/ml sodium citrate; The Annora ANDA Product is alleged to be bioequivalent to and have the same formulation characteristics as QBRELIS®. ¶33 col. 2:11-13
(iv) about 0.8 mg/ml of a preservative that is sodium benzoate; and (v) water; The Annora ANDA Product is alleged to be bioequivalent to and have the same formulation characteristics as QBRELIS®. ¶33 col. 2:13-14
wherein the pH of the formulation is between about 4 and about 5; The Annora ANDA Product is alleged to be bioequivalent to and have the same formulation characteristics as QBRELIS®. ¶33 col. 2:14-15
and wherein the formulation is stable at about 25±5° C. for at least 12 months. The Annora ANDA Product is alleged to be bioequivalent to and have the same formulation characteristics as QBRELIS®. ¶33 col. 2:14-15

’096 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
...wherein the pH of the formulation is about 4.9; The Annora ANDA Product is alleged to be bioequivalent to and have the same formulation characteristics as QBRELIS®. ¶33 col. 2:16-17
and wherein the formulation is stable at about 25±5° C. for at least 18 months. The Annora ANDA Product is alleged to be bioequivalent to and have the same formulation characteristics as QBRELIS®. ¶33 col. 2:17-20
  • Identified Points of Contention:
    • Scope Questions: The infringement analysis may turn on the construction of several quantitative terms. A key question will be the scope of the term "about" as it applies to the concentration of each ingredient (e.g., "about 150 mg/ml" xylitol) and the pH range (e.g., "about 4.9"). Whether Defendant's formulation, even if bioequivalent, uses concentrations or a pH that falls outside the legally permissible range of "about" will be a central dispute.
    • Technical Questions: A primary factual question will be whether the Annora ANDA Product actually meets the claimed stability requirements (e.g., "stable... for at least 12 months"). The complaint does not provide evidence of the accused product's stability data. The definition of "stable" itself, which is defined in the specification as retaining 95% or more of the active ingredient and having 5% or less total impurities, presents a specific technical threshold that must be proven (’183 Patent, col. 15:25-30).

V. Key Claim Terms for Construction

  • The Term: "stable at about 25±5° C. for at least 12 months" (’183 Patent, Claim 1)

  • Context and Importance: This limitation defines a required performance characteristic of the formulation. The definition of "stable" and the method for measuring it will be critical to the infringement analysis. Defendant may argue its formulation, while therapeutically equivalent, does not meet this specific, long-term stability profile under the patent's definition.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party might argue that "stable" should be interpreted in the context of what one of ordinary skill in the art would consider stable for a commercial pharmaceutical product, potentially allowing for minor deviations from the specification's precise numerical thresholds.
    • Evidence for a Narrower Interpretation: The specification provides an explicit definition: "Stable as used herein refer to lisinopril oral liquid formulations having about 95% or greater of the initial lisinopril amount and about 5% w/w or less total impurities or related substances at the end of a given storage period" (’183 Patent, col. 15:25-30). This provides strong evidence for a narrow, numerically-bound definition.

  • The Term: "about 4.9" (’096 Patent, Claim 1)

  • Context and Importance: This term distinguishes Claim 1 of the ’096 Patent from the broader pH range of "between about 4 and about 5" in the ’183 Patent. The scope of "about" in this context is crucial; a narrow construction could provide a path for non-infringement if the accused product's pH is, for example, 4.7 or 5.1, while a broader construction might still cover it. Practitioners may focus on this term because it represents a specific point of novelty over prior art or related patents.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes the pH range of "between about 4 and about 5" as desirable for minimizing degradation products, suggesting that values near 4.9 but not exactly 4.9 still achieve the invention's purpose (’096 Patent, col. 12:14-29).
    • Evidence for a Narrower Interpretation: The claim's use of a specific value ("about 4.9") rather than the broader range ("about 4 and about 5") used in the parent '183 patent could be argued as a deliberate narrowing of scope during prosecution, suggesting "about" should be construed narrowly to mean very close to 4.9.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement, stating that if Annora's ANDA is approved, its commercial activities and proposed labeling will direct and encourage medical professionals and patients to use the ANDA product in a manner that infringes the asserted method-of-use claims (Compl. ¶¶36, 41, 46, 51, 56, 61, 66, 71).
  • Willful Infringement: The complaint alleges that Annora had "actual and constructive knowledge" of the patents-in-suit prior to filing its ANDA and had "specific intent to infringe" (Compl. ¶¶37, 42, 47, 52, 57, 62, 67, 72). This forms the basis for a claim of willful infringement based on alleged pre-suit knowledge.

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

  • A core issue will be one of definitional scope: can the term "about" as applied to specific concentrations and the pH value of "4.9" be construed broadly enough to cover a bioequivalent formulation that may have been designed to operate at the edges of, or just outside, these claimed parameters? The interpretation of these terms will define the boundary between infringement and non-infringement.
  • A key evidentiary question will be one of compositional and functional proof: what are the actual ingredients, concentrations, pH, and long-term stability data of the Annora ANDA Product? As the complaint relies on the legal framework of the Hatch-Waxman Act rather than on direct technical analysis of the accused product, the case will hinge on discovery and expert testimony to establish whether Annora's formulation literally meets every limitation of the asserted claims.