DCT

1:24-cv-11529

Endo USA Inc v. Gland Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-11529, D.N.J., 12/31/2024
  • Venue Allegations: Venue is asserted on the basis that the defendant is a foreign company not residing in any U.S. judicial district and has designated an agent for service of process within New Jersey.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiffs' VASOSTRICT® product infringes eight patents related to stable vasopressin formulations and methods of use.
  • Technical Context: The technology concerns pharmaceutical formulations of vasopressin, a hormone used to treat life-threatening hypotension, with a focus on improving the drug's long-term chemical stability for clinical use.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by Defendant’s submission of ANDA No. 216963 with a Paragraph IV certification alleging that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic products.

Case Timeline

Date Event
2012-09-25 Original VASOSTRICT® New Drug Application (NDA) submitted
2014-04-17 FDA approves original VASOSTRICT® NDA
2015-01-30 Earliest Priority Date for all Patents-in-Suit
2018-03-20 U.S. Patent No. 9,919,026 issues
2018-03-27 U.S. Patent Nos. 9,925,233 and 9,925,234 issue
2018-05-08 U.S. Patent No. 9,962,422 issues
2018-05-15 U.S. Patent No. 9,968,649 issues
2018-05-22 U.S. Patent No. 9,974,827 issues
2018-05-29 U.S. Patent No. 9,981,006 issues
2018-07-03 U.S. Patent No. 10,010,575 issues
2020-04-15 FDA approves first VASOSTRICT® Premixed Product
2021-04-21 FDA approves second VASOSTRICT® Premixed Product
2024-11-18 Defendant sends Paragraph IV Certification Notice Letter to Plaintiffs
2024-12-31 Complaint filed

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

U.S. Patent No. 9,919,026 - "Vasopressin Formulations for Use in Treatment of Hypotension," issued March 20, 2018

The Invention Explained

  • Problem Addressed: The patent’s background section states that then-current formulations of vasopressin, a hormone used to treat low blood pressure, "suffer from poor long-term stability" (’026 Patent, col. 1:23-25).
  • The Patented Solution: The invention provides a stable, ready-to-use pharmaceutical composition of vasopressin for intravenous use. Stability is achieved by controlling the formulation's pH within a narrow range using a specific buffer (acetate) and by limiting the concentration of certain impurities that result from the degradation of vasopressin (’026 Patent, Abstract; col. 1:39-61).
  • Technical Importance: A stable, pre-mixed formulation of a critical care drug like vasopressin enhances patient safety by reducing the need for bedside dilution, minimizing preparation time in emergencies, and ensuring a predictable therapeutic dose (Compl. ¶24).

Key Claims at a Glance

The complaint does not identify specific asserted claims. The patent contains one independent claim, Claim 1, which requires:

  • A pharmaceutical composition for intravenous administration in a unit dosage form.
  • Comprising from about 0.1 µg/mL to about 2 µg/mL of vasopressin.
  • Wherein degradation product impurities have a concentration of about 0.1% to 1.7%.
  • Wherein the unit dosage form has from about 1 mM to about 10 mM acetate buffer.
  • Wherein the unit dosage form has a pH of 3.6 to 3.9.

U.S. Patent No. 9,925,233 - "Vasopressin Formulations for Use in Treatment of Hypotension," issued March 27, 2018

The Invention Explained

  • Problem Addressed: As with the ’026 Patent, the invention addresses the "poor long-term stability" of existing vasopressin formulations (’233 Patent, col. 1:23-25).
  • The Patented Solution: The patent claims a method of treating hypotension that involves administering a vasopressin composition with demonstrated stability. The key steps are storing the specific formulation (containing vasopressin, dextrose, and an acetic acid/sodium acetate buffer) for at least a month under defined temperature conditions (5°C or 25°C) during which it exhibits no more than a specified low level of degradation (1% or 2%, respectively), and then administering it to the patient (’233 Patent, Abstract; col. 171:10-172:30).
  • Technical Importance: This method provides clinicians with confidence in the potency and purity of the vasopressin being administered, even after extended storage, which is essential for effective treatment of life-threatening conditions.

Key Claims at a Glance

The complaint does not identify specific asserted claims. The patent contains two independent claims, Claim 1 and Claim 11.

  • Claim 1 requires:
    • A method of increasing blood pressure in a human.
    • Comprising a step of "storing at 5° C. for at least about one month" a specific pharmaceutical composition (vasopressin, dextrose, acetic acid/sodium acetate).
    • Wherein the composition exhibits "no more than about 1% degradation" after storage.
    • Comprising a step of "administering the pharmaceutical composition" to the human.
  • Claim 11 requires:
    • A method of increasing blood pressure in a human.
    • Comprising a step of "storing at 25° C. for at least about one month" a similar pharmaceutical composition.
    • Wherein the composition exhibits "no more than about 2% degradation" after storage.
    • Comprising a step of "administering the pharmaceutical composition" to the human.

Multi-Patent Capsule: U.S. Patent No. 9,925,234

  • Patent Identification: 9,925,234, "Vasopressin Formulations for Use in Treatment of Hypotension," issued March 27, 2018 (Compl. ¶18).
  • Technology Synopsis: This patent claims a method for increasing blood pressure by administering a vasopressin formulation containing an acetate buffer and dextrose. The invention is defined by the formulation's high stability, characterized by having no more than 0-2% degradation products after being stored for a specified time and temperature, and by maintaining a pH of 3.6 to 3.9 (’234 Patent, Claim 1).
  • Asserted Claims: Independent Claim 1.
  • Accused Features: The complaint alleges that the manufacture, use, or sale of Gland's ANDA Products will infringe the patented method (Compl. ¶¶ 63-65).

Multi-Patent Capsule: U.S. Patent No. 9,962,422

  • Patent Identification: 9,962,422, "Vasopressin Formulations for Use in Treatment of Hypotension," issued May 8, 2018 (Compl. ¶19).
  • Technology Synopsis: This patent claims a method of increasing blood pressure by administering a vasopressin composition. The composition is defined by its components (vasopressin, acetate buffer) and a specific pH range (3.6 to 3.9). The method requires storing the unit dose for at least 24 hours at 2-8° C. before administration (’422 Patent, Claim 1).
  • Asserted Claims: Independent Claim 1.
  • Accused Features: The complaint alleges that Gland's ANDA Products are intended for use in a manner that infringes the patented method (Compl. ¶¶ 73-75).

Multi-Patent Capsule: U.S. Patent No. 9,968,649

  • Patent Identification: 9,968,649, "Vasopressin Formulations for Use in Treatment of Hypotension," issued May 15, 2018 (Compl. ¶20).
  • Technology Synopsis: This patent claims a method of increasing blood pressure by using a vasopressin formulation that is defined by its specific, low-level impurity profile. The claims quantify the permissible amounts of several vasopressin-related degradation products and require a pH of 3.6 to 3.9. The patent also claims a specific chromatography method for identifying and quantifying these impurities (’649 Patent, Claim 1, 11).
  • Asserted Claims: Independent Claims 1 and 11.
  • Accused Features: The complaint alleges Gland's ANDA Products will be used in the patented method of treatment (Compl. ¶¶ 83-85).

Multi-Patent Capsule: U.S. Patent No. 9,974,827

  • Patent Identification: 9,974,827, "Vasopressin Formulations for Use in Treatment of Hypotension," issued May 22, 2018 (Compl. ¶21).
  • Technology Synopsis: This patent claims a method for increasing blood pressure that involves storing a specific vasopressin formulation for at least 24 hours at 2-8° C. before administration. The formulation is defined as containing vasopressin, dextrose, and an acetate buffer, and having a pH of 3.6 to 3.9 (’827 Patent, Claim 1).
  • Asserted Claims: Independent Claim 1.
  • Accused Features: The complaint alleges that Gland's ANDA Products will be used in a manner that infringes the patented method (Compl. ¶¶ 93-95).

Multi-Patent Capsule: U.S. Patent No. 9,981,006

  • Patent Identification: 9,981,006, "Vasopressin Formulations for Use in Treatment of Hypotension," issued May 29, 2018 (Compl. ¶22).
  • Technology Synopsis: This patent claims a method of increasing blood pressure using a vasopressin formulation characterized by specific ratios of vasopressin to certain degradation products (SEQ ID NO: 2 and SEQ ID NO: 7). The formulation also requires an acetate buffer and a pH of 3.6 to 3.9 (’006 Patent, Claim 1).
  • Asserted Claims: Independent Claim 1.
  • Accused Features: The complaint alleges that Gland's ANDA Products will be used in accordance with the patented method (Compl. ¶¶ 103-105).

Multi-Patent Capsule: U.S. Patent No. 10,010,575

  • Patent Identification: 10,010,575, "Vasopressin Formulations for Use in Treatment of Hypotension," issued July 3, 2018 (Compl. ¶23).
  • Technology Synopsis: This patent claims a method of increasing blood pressure using a vasopressin formulation characterized by a specific ratio of vasopressin to a different degradation product (SEQ ID NO: 3). The formulation also requires an acetate buffer, dextrose, and a pH of 3.6 to 3.9 (’575 Patent, Claim 1).
  • Asserted Claims: Independent Claim 1.
  • Accused Features: The complaint alleges that Gland's ANDA Products will be used in a manner that infringes the patented method (Compl. ¶¶ 113-115).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendant Gland Pharma Limited’s proposed generic vasopressin drug products, for which it has submitted ANDA No. 216963 to the FDA for approval (Compl. ¶1, 35). The products are described as "vasopressin in dextrose injection, 20 units/100ml and 40 units/100ml solution for intravenous use" (Compl. ¶35).
  • Functionality and Market Context: The Gland ANDA Products are intended to be generic equivalents of Plaintiffs’ VASOSTRICT® brand vasopressin (Compl. ¶1). They are indicated to "increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines," mirroring the approved use of the branded drug (Compl. ¶29). The filing of the ANDA with a Paragraph IV certification constitutes a statutory act of infringement designed to allow for the resolution of patent disputes before the generic product enters the market (Compl. ¶35).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element infringement analysis or include claim charts. Instead, it asserts a general theory of infringement under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a generic version of a patented drug as an act of infringement (Compl. ¶45, 55, 65, 75, 85, 95, 105, 115). The complaint alleges that the Gland ANDA Products, if approved and marketed, will possess the formulation characteristics (e.g., pH, impurity levels, stability) and be administered according to the methods claimed in the patents-in-suit.

  • Identified Points of Contention:
    • Factual Questions: A primary point of contention will likely be whether Gland's proposed products, as described in its confidential ANDA submission, actually meet the specific numerical limitations of the claims. This includes the required pH ranges (e.g., "pH of 3.6 to 3.9"), the concentration of vasopressin, and the precise percentages and ratios of specified degradation products.
    • Scope Questions (Method Claims): For the asserted method claims, a key question will be whether Gland's proposed product label will direct or instruct medical professionals to perform the claimed "storing" steps for the required durations and at the specified temperatures before administration, thereby inducing infringement.
    • Technical Questions (Impurity Profile): The dispute may involve the methods used to measure impurities. The court may need to determine if Gland's product contains the specific degradation products claimed (e.g., SEQ ID NO: 2, 3, 7) in the amounts claimed, and whether the analytical methods used to establish those levels are consistent with those described in patents like the ’649 Patent.

V. Key Claim Terms for Construction

  • The Term: "a pH of 3.6 to 3.9" (e.g., ’026 Patent, Claim 1)

    • Context and Importance: This precise pH range appears in the independent claims of numerous asserted patents. Its interpretation is critical because infringement will be a binary question of whether Gland's ANDA specifies a final product pH that falls within this range. Unlike ranges modified by "about," this term appears definite, suggesting a narrow scope.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party might argue that standard industry practice allows for minor variations in pH during manufacturing, suggesting the range should not be interpreted with absolute rigidity, although the lack of the word "about" weakens this position.
      • Evidence for a Narrower Interpretation: The specification repeatedly highlights the criticality of pH for stability. For example, Figure 9 in the patents (’026 Patent, Fig. 9) graphically depicts how vasopressin stability peaks and impurity levels are minimized within a narrow pH window centered around 3.5-3.8, suggesting the inventors intentionally selected this precise range to achieve the invention.

  • The Term: "impurities that are degradation products of the vasopressin" (e.g., ’026 Patent, Claim 1)

    • Context and Importance: Several patents are defined by the absence or limitation of specific impurities. How this term is construed will determine which substances must be measured in the accused product to assess infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification provides a general description of vasopressin degradation pathways, such as deamidation and dimerization, which could support an interpretation covering any substance resulting from such processes (’026 Patent, col. 5:21-6:13).
      • Evidence for a Narrower Interpretation: The patents provide an explicit list of known degradation products, identified as SEQ ID NOs and shown in tables (’026 Patent, Table 1). A defendant could argue the term is limited to these specifically identified and characterized compounds.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Gland will induce infringement by instructing users (via its product labeling) to use the generic drug in an infringing manner and will contributorily infringe because the product is especially adapted for this infringing use with no substantial non-infringing use (Compl. ¶¶ 46-47, 56-57).
  • Willful Infringement: The complaint alleges that Gland's infringement is and will be willful, wanton, and deliberate (Compl. ¶50). This allegation is based on Gland's pre-suit knowledge of the patents-in-suit, evidenced by its sending of a Paragraph IV Notice Letter to Endo (Compl. ¶36).

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

This case appears to be a technically-focused ANDA dispute centered on the precise chemical characteristics of a pharmaceutical formulation. The outcome will likely depend on the answers to three central questions:

  1. A core issue will be one of analytical chemistry: Does Gland's proposed generic vasopressin formulation, as defined in its confidential ANDA, meet the specific, narrow ranges for pH, impurity profiles, and degradation product ratios claimed across the eight asserted patents?
  2. A second key issue will be one of label-based inducement: For the method-of-use patents, do the instructions for use in Gland's proposed product label direct medical professionals to store and administer the drug in a way that practices all steps of the claimed methods?
  3. A final question will be one of definitional precision: Can the stability and purity limitations of the claims, defined by numerical ranges and specific molecular structures (SEQ ID NOs), be interpreted to read on the characteristics of Gland's product, or will claim construction narrow the scope of the patents to exclude Gland's specific formulation?