DCT

1:20-cv-00434

Mallinckrodt Hospital Products IP Ltd v. Baxter Healthcare Corp

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-00434, D. Del., 03/27/2020
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is incorporated in Delaware.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's OFIRMEV® product constitutes an act of infringement of five patents related to stable formulations and methods of using intravenous acetaminophen.
  • Technical Context: The technology concerns intravenous formulations of acetaminophen (paracetamol), a widely used non-opioid analgesic and antipyretic for managing pain and fever in clinical settings.
  • Key Procedural History: The complaint notes that all five patents-in-suit have been the subject of prior litigation in the District of Delaware against other generic drug manufacturers. The patents are listed in the FDA's Orange Book for the reference drug OFIRMEV®, and Defendant submitted a Paragraph IV certification alleging the '218 patent is "invalid, unenforceable, and/or will not be infringed." Plaintiff also alleges an extensive licensing history for the '218 patent.

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, ’238, and ’834 Patents
2010-11-02 Plaintiff’s OFIRMEV® Product Approved by FDA
2016-07-26 ’012 Patent Issued
2017-04-04 ’265 Patent Issued
2018-06-05 ’238 Patent Issued
2019-08-20 ’834 Patent Issued
2020-02-19 Date of Baxter Letter Notifying Plaintiff of ANDA Filing
2020-03-27 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"

The Invention Explained

  • Problem Addressed: The patent describes that active pharmaceutical ingredients susceptible to oxidation, such as paracetamol (acetaminophen), are unstable in aqueous solutions due to degradation from dissolved oxygen, leading to a loss of potency and the formation of colored, allergenic secondary products (’218 Patent, col. 1:22-40, col. 2:41-54).
  • The Patented Solution: The invention is a method for preparing a stable aqueous solution by subjecting it to "extreme deoxygenation," which involves bubbling it with an inert gas or placing it under a vacuum until the dissolved oxygen concentration falls below a 2 parts-per-million (ppm) threshold. The deoxygenated solution is then packaged in a sealed container under low pressure (less than 65,000 Pa) to prevent re-oxygenation and preserve stability for a prolonged period (’218 Patent, Abstract; col. 3:5-14).
  • Technical Importance: This method provided a way to create a ready-to-use, stable injectable formulation of acetaminophen, which was previously difficult to commercialize due to oxidative degradation.

Key Claims at a Glance

  • The complaint asserts at least Claim 1 (Compl. ¶12, ¶35).
  • Claim 1 of the ’218 Patent recites 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, until the oxygen content is below 2 ppm.
    • The solution is placed in a closed container in which the prevailing pressure is 65,000 Pa maximum.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 9,399,012 - "Reduced Dose Intravenous Acetaminophen"

The Invention Explained

  • Problem Addressed: The patent addresses a clinical challenge with the standard 1000 mg intravenous dose of acetaminophen, noting that its duration of analgesic effect can be shorter than the standard six-hour dosing interval. This mismatch can create a "gap in coverage" for pain relief, as dosing more frequently is limited by the maximum daily dose (’012 Patent, col. 3:36-44).
  • The Patented Solution: The invention discloses a method of treatment involving a reduced dose of intravenous acetaminophen (between approximately 550 mg and 800 mg) administered at a more frequent interval (between approximately 3 and 5 hours). This regimen is intended to provide more consistent therapeutic coverage without exceeding the daily safety limit for the drug (’012 Patent, col. 3:45-53; Claim 1).
  • Technical Importance: This method-of-use patent claims a specific dosing strategy to optimize the therapeutic benefit of intravenous acetaminophen, balancing efficacy with safety.

Key Claims at a Glance

  • The complaint asserts at least Claim 1 (Compl. ¶14, ¶38).
  • Claim 1 of the ’012 Patent recites 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 comprising 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.
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

Multi-Patent Capsule: U.S. Patent No. 9,610,265

  • Patent Identification: U.S. Patent No. 9,610,265, “Reduced Dose Intravenous Acetaminophen,” issued April 4, 2017.
  • Technology Synopsis: The patent claims a method of treating pain by co-administering a reduced dose of intravenous acetaminophen (about 500 mg to 750 mg) with a second composition comprising an opioid analgesic (’265 Patent, Abstract; Compl. ¶16). This addresses multimodal pain management strategies.
  • Asserted Claims: At least Claim 1 (Compl. ¶16, ¶50).
  • Accused Features: The complaint alleges infringement based on Baxter's proposed product labeling, which is expected to instruct use for "management of moderate to severe pain with adjunctive opioid analgesics" (Compl. ¶50, ¶52).

Multi-Patent Capsule: U.S. Patent No. 9,987,238

  • Patent Identification: U.S. Patent No. 9,987,238, “Reduced Dose Intravenous Acetaminophen,” issued June 5, 2018.
  • Technology Synopsis: The patent claims a method of treating pain by administering a reduced dose of intravenous acetaminophen (about 500 mg to 750 mg) and repeating the administration every four hours, where the therapeutic effect is comparable to the standard of care oral treatment of 1000 mg every six hours (’238 Patent, Abstract; Compl. ¶18).
  • Asserted Claims: At least Claim 1 (Compl. ¶18, ¶63).
  • Accused Features: The complaint alleges infringement based on Baxter's proposed labeling, which is expected to recommend a dosing regimen that falls within the claimed method, based on the labeling for the reference OFIRMEV® product (Compl. ¶63, ¶64).

Multi-Patent Capsule: U.S. Patent No. 10,383,834

  • Patent Identification: U.S. Patent No. 10,383,834, “Reduced Dose Intravenous Acetaminophen,” issued August 20, 2019.
  • Technology Synopsis: The patent claims a method of treating pain by administering an intravenous acetaminophen formulation of about 650 mg, repeating the administration every four hours, and ensuring the total maximum daily dose is less than 4000 mg (’834 Patent, Abstract; Compl. ¶20).
  • Asserted Claims: At least Claim 1 (Compl. ¶20, ¶75).
  • Accused Features: The complaint alleges infringement based on Baxter's proposed product labeling, which is expected to recommend a 650 mg dose every four hours, mirroring the instructions in the OFIRMEV® label (Compl. ¶75, ¶76).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant's proposed generic intravenous acetaminophen product, which is the subject of Abbreviated New Drug Application ("ANDA") No. 214331 submitted to the U.S. Food and Drug Administration (Compl. ¶7, ¶26).

Functionality and Market Context

  • The complaint alleges that Baxter's ANDA product is a generic pharmaceutical product that claims bioequivalence to Plaintiffs' OFIRMEV® brand injectable acetaminophen (Compl. ¶7). It is intended for intravenous administration for the management of pain and fever (Compl. ¶22, ¶38). The complaint alleges that Baxter did not perform its own clinical trials and will instead rely on the clinical trials and labeling information of OFIRMEV® for its proposed generic product (Compl. ¶40, ¶53).

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... The complaint alleges that Baxter's ANDA product is an aqueous solution of acetaminophen that will be prepared in a manner that infringes. ¶29, ¶30 col. 1:11-16
comprising deoxygenation of the solution by bubbling with at least one inert gas and/or placing under vacuum, until the oxygen content is below 2 ppm... The complaint alleges on information and belief that the "only viable way" to prepare a stable injectable acetaminophen solution is to deoxygenate it to below 2 ppm oxygen using such methods. ¶30, ¶35 col. 3:5-14
placed in a closed container in which the prevailing pressure is 65,000 Pa maximum... The complaint alleges that Baxter's preparation method will meet this limitation as part of the only viable method for creating a stable product. ¶12, ¶35 col. 4:5-14

’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... Baxter's proposed product labeling will allegedly encourage, promote, and/or recommend the use of its product to treat pain or fever in this patient population. ¶38, ¶45 col. 1:45-48
comprising administering to the subject, by an intravenous route of administration, a therapeutically effective amount of a pharmaceutical composition comprising about 550 mg to about 800 mg of acetaminophen... Baxter's proposed labeling will allegedly recommend a dose of 650 mg, which falls within the claimed range, based on the reference OFIRMEV® label. ¶38, ¶39, ¶41 col. 1:49-54
and repeating said administration at least once at an interval of about 3 to about 5 hours. Baxter's proposed labeling will allegedly recommend repeating administration every 4 hours, which falls within the claimed interval. ¶38, ¶39, ¶41 col. 2:26-28
  • Identified Points of Contention:
    • Factual Questions (’218 Patent): The infringement allegation for the ’218 Patent appears to rest on the assertion that deoxygenating the solution to below 2 ppm is the "only viable way" to manufacture a stable product (Compl. ¶30). A key question will be what evidence Plaintiff can produce to substantiate this claim about Defendant's confidential manufacturing process described in its ANDA.
    • Scope Questions (’012 Patent): The infringement theory for the ’012 Patent relies on the dosing instructions expected to be in Baxter's product label. A potential point of contention may arise from the use of the term "about" in the claim's dosage and interval limitations. The analysis will question whether the specific 650 mg dose and 4-hour interval expected on the label falls within the scope of "about 550 mg to about 800 mg" and "about 3 to about 5 hours."

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

  • The Term: "about 550 mg to about 800 mg" (from Claim 1 of the ’012 Patent)

  • Context and Importance: The construction of "about" is central to the induced infringement allegation. Defendant's product label is expected to specify a 650 mg dose, based on the reference product label (Compl. ¶39, ¶41). While 650 mg is literally within the claimed range, the scope of "about" will determine the breadth of the claim's coverage and may be relevant to validity challenges. Practitioners may focus on this term to understand the patent's reach beyond the explicitly stated numerical endpoints.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent consistently uses the term "about" when describing dosage ranges in the summary and claims, suggesting an intentional departure from precise numerical limits to encompass minor variations (’012 Patent, col. 1:52-53, Claim 1).
    • Evidence for a Narrower Interpretation: The specification provides a specific example of a 650 mg dose being used in clinical trials (’012 Patent, col. 12:5-7). A defendant may argue that the term "about" should be construed in light of this specific, preferred embodiment, potentially limiting its scope.

  • The Term: "deoxygenation of the solution... until the oxygen content is below 2 ppm" (from Claim 1 of the ’218 Patent)

  • Context and Importance: This term defines the critical technical step for achieving the claimed formulation stability. The infringement allegation hinges on whether Baxter's manufacturing process necessarily meets this quantitative limit (Compl. ¶30, ¶35). The construction of this phrase will be less about defining the words and more about the evidentiary standard required to prove that an accused, confidential process meets this specific functional requirement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim language allows for the deoxygenation to be achieved by "bubbling with at least one inert gas and/or placing under vacuum," providing flexibility in the method used to achieve the required oxygen level (’218 Patent, Claim 1).
    • Evidence for a Narrower Interpretation: The specification emphasizes "extreme deoxygenation" and notes that the 2 ppm limit is a "residual oxygen concentration limit" beyond which an oxidizing effect may occur (’218 Patent, col. 3:5-14). A defendant might argue this language implies a strict, not approximate, upper boundary.

VI. Other Allegations

  • Indirect Infringement: The complaint's primary theory for the method-of-use patents (’012, ’265, ’238, ’834) is induced infringement under 35 U.S.C. § 271(b). It alleges that Defendant's submission of its ANDA, and its intent to market a generic product with a label instructing infringing uses, will actively encourage and abet direct infringement by medical professionals (Compl. ¶38, ¶50, ¶98, ¶111). Knowledge is alleged based on the patents' listing in the Orange Book (Compl. ¶23, ¶100).
  • Willful Infringement: The complaint alleges that Defendant had knowledge of the patents-in-suit prior to filing its ANDA and that its infringing actions are willful (Compl. ¶47, ¶60, ¶72, ¶84, ¶101). This forms the basis for a request that the case be found exceptional under 35 U.S.C. § 285.

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

  • A central evidentiary question for the formulation patent (’218) will be one of technical necessity: can the Plaintiff prove that the only commercially viable method for manufacturing a stable generic intravenous acetaminophen product requires the specific deoxygenation steps and results in the sub-2 ppm oxygen concentration claimed in the patent?
  • A core issue for the method-of-use patents (’012, ’265, ’238, ’834) will be one of induced infringement: does the act of seeking FDA approval for a generic drug with a proposed label that mirrors the reference drug's approved (and patented) dosing regimen constitute inducement to infringe, and how will the court construe the scope of numerical limitations preceded by "about"?
  • A key strategic question concerns the patent thicket: how will the assertion of four distinct but related method-of-use patents, each covering slightly different aspects of similar reduced-dose acetaminophen regimens, affect the litigation strategy and the court's analysis of infringement and validity?