DCT

3:24-cv-11529

Endo USA Inc v. Gland Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-11529, D.N.J., 12/31/2024
  • Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign company not residing in any U.S. judicial district and has designated an agent for service of process in 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 constitutes an act of patent infringement.
  • Technical Context: The technology concerns stable, injectable pharmaceutical formulations of vasopressin, a hormone used to treat hypotension (critically low blood pressure) in hospital settings.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendant’s submission of ANDA No. 216963 and its accompanying Paragraph IV certification notice letter, which asserted that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product. The patents are listed in the FDA's "Orange Book" for VASOSTRICT®.

Case Timeline

Date Event
2012-09-25 Original New Drug Application (NDA) for VASOSTRICT® submitted
2014-04-17 Original NDA for VASOSTRICT® approved by FDA
2015-01-30 Earliest Patent Priority Date for all Patents-in-Suit
2018-03-20 U.S. Patent No. 9,919,026 Issued
2018-03-27 U.S. Patent No. 9,925,233 Issued
2018-03-27 U.S. Patent No. 9,925,234 Issued
2018-05-08 U.S. Patent No. 9,962,422 Issued
2018-05-15 U.S. Patent No. 9,968,649 Issued
2018-05-22 U.S. Patent No. 9,974,827 Issued
2018-05-29 U.S. Patent No. 9,981,006 Issued
2018-07-03 U.S. Patent No. 10,010,575 Issued
2020-04-15 First supplemental NDA for VASOSTRICT® Premixed Products approved
2021-04-21 Second supplemental NDA for VASOSTRICT® Premixed Products approved
2024-11-18 Defendant sent Paragraph IV 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"

The Invention Explained

  • Problem Addressed: The patent’s background section states that then-current formulations of vasopressin, a hormone used to treat conditions like low blood pressure, "suffer from poor long-term stability" (’026 Patent, col. 1:22-24).
  • The Patented Solution: The invention claims to solve this stability problem through a specific pharmaceutical composition. The solution comprises vasopressin in a unit dosage form combined with an acetate buffer and adjusted to a specific acidic pH range (3.6 to 3.9), which is asserted to increase the shelf life and stability of the drug, particularly by controlling the level of specific degradation products (’026 Patent, Abstract; col. 4:50-58).
  • Technical Importance: A stable, ready-to-use injectable formulation of a critical care drug like vasopressin may reduce preparation time and the risk of contamination or dosing errors in emergency medical situations (Compl. ¶24).

Key Claims at a Glance

The complaint asserts infringement of "one or more claims" of the ’026 Patent (Compl. ¶45). Independent claim 1 is representative:

  • A pharmaceutical composition for intravenous administration comprising, in a unit dosage form:
    • from about 0.1 µg/mL to about 2 µg/mL of vasopressin or a pharmaceutically-acceptable salt thereof;
    • impurities that are present in an amount of from about 0.1% to 1.7%, wherein the impurities have about 85% to about 100% sequence homology to SEQ ID NO: 1;
    • and from about 1 mM to about 10 mM acetate buffer;
    • and where 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"

The Invention Explained

  • Problem Addressed: Similar to the ’026 Patent, this patent addresses the "poor long-term stability" of existing vasopressin formulations (’233 Patent, col. 1:20-22).
  • The Patented Solution: This patent claims a method of increasing a patient's blood pressure that involves storing a specific vasopressin formulation and then administering it. The claimed method requires storing a composition containing vasopressin, dextrose, and an acetate buffer at 5° C. for at least a month, during which it exhibits no more than a specified level of degradation, before it is administered to a hypotensive human (’233 Patent, col. 171:7-29).
  • Technical Importance: The claimed method provides a framework for ensuring that a stable and effective dose of vasopressin is administered, linking the formulation's storage conditions and stability profile directly to its therapeutic use.

Key Claims at a Glance

The complaint asserts infringement of "one or more claims" of the ’233 Patent (Compl. ¶55). Independent claim 1 is representative:

  • A method of increasing blood pressure in a human, comprising:
    • a) storing a pharmaceutical composition at 5° C. for at least about one month, where the composition comprises vasopressin, dextrose, and an acetate buffer at a pH of 3.6 to 3.9;
    • wherein the composition exhibits no more than about 1% degradation after storage; and
    • b) administering the composition to a hypotensive human at a rate of about 0.01 to 0.1 units per minute.

U.S. Patent No. 9,925,234 - "Vasopressin Formulations for Use in Treatment of Hypotension"

  • Technology Synopsis: The ’234 Patent claims a method of increasing blood pressure in a human by administering a specific vasopressin formulation. The claims focus on a composition with a defined amount of vasopressin, a specific buffer and pH, and a quantified level of degradation products (’234 Patent, col. 175:18-40). The invention aims to provide a stable formulation for therapeutic use (Compl. ¶18).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶65). The ’234 patent contains one independent claim (Claim 1).
  • Accused Features: The accused instrumentality is Gland's proposed generic vasopressin product, which Plaintiffs allege will be manufactured, used, and sold according to the patented methods (Compl. ¶35, ¶66).

U.S. Patent No. 9,962,422 - "Vasopressin Formulations for Use in Treatment of Hypotension"

  • Technology Synopsis: The ’422 Patent claims a method of increasing blood pressure by administering a vasopressin formulation with specific components. The claims recite a method comprising providing a unit dosage form containing vasopressin, an acetate buffer, and a plurality of peptides, all within defined concentration and pH ranges, and then administering it to a patient (’422 Patent, col. 175:53-176:8). This is intended to ensure a stable and effective treatment (Compl. ¶19).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶75). The ’422 patent contains one independent claim (Claim 1).
  • Accused Features: The accused instrumentality is Gland's proposed generic vasopressin product, which Plaintiffs allege will be used in a manner that practices the patented method (Compl. ¶35, ¶76).

U.S. Patent No. 9,968,649 - "Vasopressin Formulations for Use in Treatment of Hypotension"

  • Technology Synopsis: The ’649 Patent claims a method of increasing blood pressure by administering a vasopressin formulation and then determining its impurity profile. The claimed method requires providing a unit dose with specific pH and buffer characteristics, administering it, and then using chromatography to determine the amount of specific impurities, such as those identified as SEQ ID NO: 2 and SEQ ID NO: 4 (’649 Patent, col. 171:60-174:11).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶85). The ’649 patent contains one independent claim (Claim 1).
  • Accused Features: Plaintiffs allege Gland's proposed generic vasopressin product will infringe the patented method (Compl. ¶35, ¶86).

U.S. Patent No. 9,974,827 - "Vasopressin Formulations for Use in Treatment of Hypotension"

  • Technology Synopsis: The ’827 Patent claims a method of increasing blood pressure involving storing and administering a vasopressin formulation. The method requires providing a unit dose containing vasopressin, dextrose, and a buffer at a specific pH, storing it for at least 24 hours, and then intravenously administering it to a hypotensive human (’827 Patent, col. 173:25-46).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶95). The ’827 patent contains one independent claim (Claim 1).
  • Accused Features: Plaintiffs allege Gland's proposed generic vasopressin product will infringe the patented method (Compl. ¶35, ¶96).

U.S. Patent No. 9,981,006 - "Vasopressin Formulations for Use in Treatment of Hypotension"

  • Technology Synopsis: The ’006 Patent claims a method of increasing blood pressure by administering a vasopressin formulation with a defined ratio of vasopressin to a specific impurity (SEQ ID NO: 2). The claims require providing a unit dose with vasopressin, a buffer, and a pH of 3.6 to 3.9, where the ratio of vasopressin to the SEQ ID NO: 2 impurity is from about 950:1 to about 30:1, and then administering it (’006 Patent, col. 171:22-47).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶105). The ’006 patent contains one independent claim (Claim 1).
  • Accused Features: Plaintiffs allege Gland's proposed generic vasopressin product will infringe the patented method (Compl. ¶35, ¶106).

U.S. Patent No. 10,010,575 - "Vasopressin Formulations for Use in Treatment of Hypotension"

  • Technology Synopsis: The ’575 Patent claims a method of increasing blood pressure by administering a vasopressin formulation containing dextrose. The method requires providing a unit dosage form comprising vasopressin, a buffer, and dextrose at a pH of 3.6 to 3.9, and then administering the dose intravenously to a hypotensive human (’575 Patent, col. 169:40-170:12).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶115). The ’575 patent contains one independent claim (Claim 1).
  • Accused Features: Plaintiffs allege Gland's proposed generic vasopressin product will infringe the patented method (Compl. ¶35, ¶116).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendant Gland’s generic vasopressin drug products for which it seeks FDA approval under ANDA No. 216963 (Compl. ¶1, ¶35). Specifically, the ANDA covers "vasopressin in dextrose injection, 20 units/100ml and 40 units/100ml solution for intravenous use" (Compl. ¶35).
  • Functionality and Market Context: Gland's ANDA Products are intended to be generic versions of Endo's VASOSTRICT®, a drug indicated "to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines" (Compl. ¶29, ¶35). As a generic, Gland's product is expected to have the same active ingredient, dosage form, strength, and route of administration as VASOSTRICT® (Compl. ¶1, ¶35). The complaint characterizes VASOSTRICT® as a "lifesaving drug" used when a critical care patient's blood pressure drops precipitously (Compl. ¶24). The lawsuit arises from Gland's attempt to market its generic versions before the expiration of the patents listed in the Orange Book for VASOSTRICT® (Compl. ¶33, ¶35).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed claim chart or specific factual allegations mapping individual claim elements to the features of Gland's ANDA Products. The infringement theory is based on 35 U.S.C. § 271(e)(2), where the submission of an ANDA for a drug claimed in a patent is an act of infringement (Compl. ¶45, ¶55). The complaint alleges that Gland's ANDA Products, being generic versions of VASOSTRICT®, will necessarily meet the limitations of the asserted claims covering specific formulations and methods of use. The specific details of Gland's formulation and stability data are contained within the confidential ANDA and are not public.

  • Identified Points of Contention:
    • Technical Questions: A primary question will be factual: does the product described in Gland's confidential ANDA actually possess the specific combination of features required by each asserted claim? This includes the precise pH range, buffer type and concentration, impurity profiles (including specific degradation products and their ratios to vasopressin), and stability characteristics (e.g., degradation rate under specific storage conditions).
    • Scope Questions: For the method claims (e.g., in the ’233 Patent), a key question may be whether Gland's ANDA filing and proposed product label constitute infringement of steps like "storing" the drug or "administering" it to a human. The analysis will likely focus on whether the proposed label instructs or encourages end-users (physicians, hospitals) to perform the patented method.

V. Key Claim Terms for Construction

  • The Term: "impurities that are present in an amount of from about 0.1% to 1.7%, wherein the impurities have about 85% to about 100% sequence homology to SEQ ID NO: 1" (from ’026 Patent, Claim 1).

  • Context and Importance: This term defines the patented composition by its specific purity profile, including both the quantity and type of degradation-related impurities. Practitioners may focus on this term because infringement will depend on whether Gland's product falls within this defined profile. Gland could argue its product is manufactured differently, resulting in an impurity profile outside the claimed ranges, thereby avoiding infringement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The repeated use of "about" in the claim suggests the numerical ranges are not intended to be exact and may encompass values reasonably close to the stated endpoints (’026 Patent, col. 174:28-30).
    • Evidence for a Narrower Interpretation: The specification provides detailed descriptions of the specific impurities and the HPLC methods used to detect them, including Table 3, which lists known vasopressin degradation products (’026 Patent, col. 61:1-29; col. 64). A party could argue that the term "impurities" should be construed as being limited to the specific species and measurement techniques disclosed in these detailed examples.

  • The Term: "storing the unit dosage form at 5° C. for at least about one month" (from ’233 Patent, Claim 1).

  • Context and Importance: This is a method step that occurs before the administration of the drug. Its construction is critical because Gland is an ANDA filer, not an end-user. Infringement will turn on whether Gland's actions (e.g., via its proposed product label) can be seen as practicing or inducing this step.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification extensively discusses long-term stability and shelf life, providing data for storage up to 24 months (’233 Patent, Tables 7-12, col. 70-72). A plaintiff might argue that "storing" for "at least about one month" is inherent to the product's intended commercial lifecycle and distribution, as described by the patent's focus on long-term stability.
    • Evidence for a Narrower Interpretation: A defendant could argue this is an active step that it does not perform. Furthermore, the claim links this storage step to a specific outcome ("exhibits no more than about 1% degradation"). Gland may argue that this combination of a specific action and a specific result is not something it induces, especially if its label provides different storage instructions or its stability data does not align perfectly with the claimed degradation limit.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval of its ANDA, Gland will induce infringement by "intentionally encourag[ing] acts of direct infringement" and will contributorily infringe by selling a product "especially adapted for a use that infringes" for which there is "no substantial non-infringing use" (Compl. ¶46-47, ¶56-57). This is a standard allegation in ANDA litigation, where the basis for inducement is typically the proposed product label instructing medical professionals to use the generic drug in a manner that practices the patented methods.
  • Willful Infringement: The complaint alleges that Gland's infringement is "willful, wanton, and deliberate" (Compl. ¶50, ¶60). The basis for this allegation is Gland's knowledge of the patents, which is established by its submission of a Paragraph IV certification notice letter identifying the patents-in-suit (Compl. ¶36).

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

  • A core issue will be one of technical identity: Does the formulation detailed in Gland's confidential ANDA filing—including its precise pH, buffer, active ingredient concentration, and impurity profile—fall within the literal scope of the asserted composition claims, or can Gland demonstrate a meaningful chemical difference?
  • A key legal and factual question will be one of infringement by instruction: For the numerous method claims, can Endo prove that Gland's proposed product label will inevitably lead medical professionals to perform the claimed steps, including not only the administration of the drug but also preliminary steps such as "storing" the product under specific conditions to achieve a claimed stability profile?
  • The case will likely involve a significant claim construction dispute centered on terms of degree such as "about," and on terms defining specific chemical properties like impurity levels and degradation rates, the interpretation of which will be dispositive for the infringement analysis.