DCT

1:19-cv-00552

Mallinckrodt Hospital Products IP Ltd v. Altan Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00552, D. Del., 03/22/2019
  • Venue Allegations: Venue is asserted on the basis that Defendant is a foreign entity subject to personal jurisdiction in the district, having submitted a New Drug Application to the FDA with the intent to market its product throughout the United States, including in Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of a New Drug Application for a generic intravenous acetaminophen solution constitutes an act of infringement of four patents covering formulations and methods of use for Plaintiffs’ brand-name drug, OFIRMEV®.
  • Technical Context: The technology relates to creating stable aqueous formulations of oxidation-sensitive drugs like acetaminophen and specific intravenous dosing regimens for pain and fever management.
  • Key Procedural History: The complaint notes that all four Patents-in-Suit have been the subject of prior litigation in the District of Delaware against other parties, suggesting a history of enforcement and potential judicial interpretation of the patents. The patents are also listed in the FDA's Orange Book with respect to OFIRMEV®, which provides a basis for alleging Defendant's pre-suit knowledge.

Case Timeline

Date Event
2000-06-06 Earliest Priority Date for ’218 Patent
2006-01-31 ’218 Patent Issued
2007-11-13 Earliest Priority Date for ’012, ’265, and ’238 Patents
2010-11-02 OFIRMEV® Approved by FDA
2016-07-26 ’012 Patent Issued
2017-04-04 ’265 Patent Issued
2018-06-05 ’238 Patent Issued
2019-02-08 Date of Altan Letter Notifying Plaintiffs of NDA Submission
2019-03-22 Complaint Filed

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

U.S. Patent No. 6,992,218 - "Method for Obtaining Aqueous Formulations of Oxidation-Sensitive Active Principles" (Issued January 31, 2006)

The Invention Explained

  • Problem Addressed: The patent’s background section describes the problem of active pharmaceutical ingredients, particularly phenols like paracetamol (acetaminophen), degrading in aqueous solutions due to oxidation from dissolved oxygen, leading to loss of activity and the formation of colored, allergenic secondary products (’218 Patent, col. 1:12-54).
  • The Patented Solution: The invention claims to solve this problem through a method of "extreme deoxygenation," which involves bubbling an inert gas through the solution and/or placing it under a vacuum to reduce the dissolved oxygen content to below 2 parts per million (ppm) (’218 Patent, Abstract; col. 3:3-14). The deoxygenated solution is then packaged in containers that have been cleared of air and are stoppered under low pressure to prevent re-oxygenation (’218 Patent, col. 4:5-14).
  • Technical Importance: This method enabled the creation of the first stable, ready-to-use intravenous formulation of acetaminophen, a widely used analgesic and antipyretic, overcoming long-standing stability challenges that had previously limited its administration to oral or rectal routes (’218 Patent, col. 2:56-65).

Key Claims at a Glance

  • The complaint asserts at least Claim 1 (Compl. ¶47).
  • Independent Claim 1 recites a method with the following essential elements:
    • A method for preparing an aqueous solution with an active principle susceptible to oxidation, which is paracetamol.
    • Comprising deoxygenation of the solution by bubbling with at least one inert gas and/or placing under vacuum.
    • Continuing deoxygenation until the oxygen content is below 2 ppm.
    • Optionally topping the solution with an inert gas atmosphere heavier than air and placing it in a closed container.
    • The container has a prevailing pressure of 65,000 Pa maximum.
    • The oxygen content of the aqueous solution remains below 2 ppm.
    • Optionally completing deoxygenation by adding an antioxidant.

U.S. Patent No. 9,399,012 - "Reduced Dose Intravenous Acetaminophen" (Issued July 26, 2016)

The Invention Explained

  • Problem Addressed: The standard 1000 mg intravenous dose of acetaminophen is limited to administration every six hours to avoid hepatotoxicity, but its analgesic effect may wear off sooner, creating a potential gap in pain relief (’012 Patent, col. 3:10-24).
  • The Patented Solution: The invention provides a method of treatment using a reduced dose of intravenous acetaminophen, allowing for more frequent administration without exceeding the maximum daily dose. Specifically, the patent describes administering a dose between about 550 mg and 800 mg at an interval of about 3 to 5 hours, which is alleged to provide more consistent pain relief (’012 Patent, col. 4:33-42).
  • Technical Importance: This dosing regimen provides clinicians with greater flexibility to manage pain, particularly in a post-operative setting, by enabling more frequent administration to maintain therapeutic plasma concentrations of acetaminophen while managing the risk of toxicity (’012 Patent, col. 4:38-42).

Key Claims at a Glance

  • The complaint asserts at least Claim 1 (Compl. ¶50).
  • Independent Claim 1 recites a method with the following essential elements:
    • A method for the treatment of pain or fever in an adult or adolescent human subject weighing at least 50 kg.
    • Comprising administering to the subject, by an intravenous route, a therapeutically effective amount of a pharmaceutical composition.
    • The composition comprises about 550 mg to about 800 mg of acetaminophen.
    • Repeating said administration at least once at an interval of about 3 to about 5 hours.

U.S. Patent No. 9,610,265 - "Reduced Dose Intravenous Acetaminophen" (Issued April 4, 2017)

  • Technology Synopsis: This patent is directed to a method of treating pain by co-administering a reduced intravenous dose of acetaminophen (about 500 mg to 750 mg) with an opioid analgesic (Compl. ¶23-24). This combination therapy aims to provide effective pain relief, potentially with a reduced need for opioids.
  • Asserted Claims: At least Claim 1 (Compl. ¶62).
  • Accused Features: The complaint alleges that Altan's proposed product labeling will instruct and encourage the co-administration of its product with opioid analgesics for the management of moderate to severe pain, thereby inducing infringement of the ’265 Patent (Compl. ¶62, 64).

U.S. Patent No. 9,987,238 - "Reduced Dose Intravenous Acetaminophen" (Issued June 5, 2018)

  • Technology Synopsis: This patent covers a method of treating pain with a reduced intravenous dose of acetaminophen (about 500 mg to 750 mg) repeated every four hours, with the added limitation that the therapeutic effect is comparable to the standard oral treatment of 1000 mg every six hours (Compl. ¶25-26).
  • Asserted Claims: At least Claim 1 (Compl. ¶75).
  • Accused Features: The complaint alleges that because Altan's product is a generic of OFIRMEV®, its proposed labeling will rely on the same clinical data showing therapeutic comparability to the standard of care, thereby encouraging administration in a manner that infringes the ’238 Patent (Compl. ¶75).

III. The Accused Instrumentality

  • Product Identification: Defendant Altan’s "Acetaminophen Solution for Infusion 10 mg/mL," for which it submitted New Drug Application (NDA) No. 209841 (the "Altan NDA Product") (Compl. ¶8).
  • Functionality and Market Context: The Altan NDA Product is an injectable acetaminophen solution intended for the U.S. market (Compl. ¶4, 9). The complaint alleges it is a generic version of Plaintiffs’ OFIRMEV® product and claims bioequivalence (Compl. ¶8). As such, it is intended for the management of pain and reduction of fever in a clinical setting (Compl. ¶28, 50). The complaint asserts that Altan's product, if approved, will be used according to methods and made by a process covered by the Patents-in-Suit (Compl. ¶47, 50).
    No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

  • ’218 Patent Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
[a] method for preparing an aqueous solution with an active nature susceptible to oxidation, which is paracetamol... Altan manufactures an aqueous paracetamol (acetaminophen) solution. ¶8 col. 12:53-55
comprising deoxygenation of the solution by bubbling with at least one inert gas and/or placing under vacuum... The complaint alleges on information and belief that Altan's manufacturing process will deoxygenate its solution by bubbling with an inert gas and/or placing it under vacuum or an equivalent thereof. ¶47 col. 12:55-58
until the oxygen content is below 2 ppm... The complaint alleges on information and belief that the Altan NDA product will be deoxygenated to below 2 ppm oxygen, asserting this is the "only viable method" for preparing a stable solution. ¶47 col. 12:58-59

  • Identified Points of Contention:

    • Evidentiary Question: The complaint's allegations regarding infringement of the ’218 Patent are made "on information and belief" and are predicated on the assertion that deoxygenating below 2 ppm is the "only viable method" to prepare a stable product (Compl. ¶42, 47). A central question will be what manufacturing process Altan actually uses. The dispute may turn on whether Altan employs a different, non-infringing method for ensuring stability that does not involve the claimed deoxygenation steps.

  • ’012 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
[a] method for the treatment of pain or fever in an adult human or an adolescent human subject weighing at least 50 kg... Altan’s proposed labeling will allegedly recommend its product for treating pain or fever in this patient population. ¶50 col. 24:44-46
comprising administering... by an intravenous route... a pharmaceutical composition comprising about 550 mg to about 800 mg of acetaminophen... Altan’s proposed labeling will allegedly instruct administration of a dose within this range, based on its reliance on clinical trials for the reference drug OFIRMEV® which tested doses such as 650 mg. ¶50, 53 col. 24:46-51
and repeating said administration at least once at an interval of about 3 to about 5 hours. Altan’s proposed labeling will allegedly instruct repeated administration at an interval within this range, citing the OFIRMEV® label's instruction for administration "every 4 hours." ¶50, 51 col. 24:51-53
  • Identified Points of Contention:
    • Scope Questions: The infringement analysis for the ’012 Patent will depend on the specific instructions in Altan's final, FDA-approved product label. A key question will be whether the label's recommended dosage and frequency fall within the claimed ranges. The construction of the term "about" (e.g., "about 550 mg to about 800 mg" and "about 3 to about 5 hours") may be a point of contention, as the parties may dispute the permissible deviation from the stated numerical ranges.

V. Key Claim Terms for Construction

  • For the ’218 Patent:

    • The Term: "deoxygenation of the solution by bubbling with at least one inert gas and/or placing under vacuum"
    • Context and Importance: This term defines the core process step for achieving the required low-oxygen environment. Practitioners may focus on this term because Altan could argue that its manufacturing process, while potentially reducing oxygen, does not use the specific physical actions of "bubbling" or "placing under vacuum" and thus falls outside the claim's scope.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent frequently describes the goal of eliminating oxygen, which could suggest the specific means are exemplary. The claim language "and/or" provides some breadth, not requiring both actions.
      • Evidence for a Narrower Interpretation: The specification repeatedly and specifically describes these two physical processes as the means of elimination (e.g., ’218 Patent, col. 2:38-41, "elimination of the oxygen by... putting the aqueous solution under vacuum or by bubbling an inert gas"). This could support an interpretation limited to these explicit actions.

  • For the ’012 Patent:

    • The Term: "an interval of about 3 to about 5 hours"
    • Context and Importance: This defines the claimed dosing frequency, which is central to the infringement allegation. The complaint relies on the OFIRMEV® label instruction of "every 4 hours" to meet this limitation (Compl. ¶53). The scope of "about" will be critical to determining whether this or other dosing instructions on Altan's future label constitute infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification may describe the pharmacokinetic and pharmacodynamic rationale for this window, potentially supporting a flexible interpretation of "about" to capture intervals that achieve a similar therapeutic effect.
      • Evidence for a Narrower Interpretation: The prosecution history (not provided) or specific examples in the specification could limit the scope of "about." If the data presented in the patent show a sharp drop-off in efficacy or safety outside this specific range, it could support a narrower construction.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Altan will induce infringement of the ’012, ’265, and ’238 method patents. The alleged basis for inducement is Altan's proposed product labeling, which will allegedly instruct and encourage medical professionals to administer the Altan NDA Product in accordance with the patented methods (Compl. ¶50, 62, 75).
  • Willful Infringement: The complaint alleges that Altan was aware of the patents-in-suit prior to filing its NDA, citing their listing in the FDA's Orange Book (Compl. ¶29, 59, 72, 84). It further alleges that Altan's actions are willful and render the case "exceptional" under 35 U.S.C. § 285 (Compl. ¶59, 72, 84).

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

  • A central evidentiary issue will be one of process verification: for the ’218 patent, what are the specific steps of Altan's manufacturing process? As the complaint's allegations are based on the inference that no other viable stability method exists, the case will hinge on discovery revealing whether Altan’s process literally performs the claimed deoxygenation steps to achieve an oxygen content below 2 ppm.
  • A key issue of infringement scope will concern the method patents (’012, ’265, ’238): will the specific text of Altan’s final, FDA-approved label instruct or encourage administration within the precise dosage, frequency, and patient population parameters of the asserted claims? This will involve not only a factual comparison of the label to the claims but also a legal construction of terms such as "about."