DCT

1:17-cv-00365

Mallinckrodt IP v. B Braun Medical Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00365, D. Del., 04/03/2017
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Delaware because Defendant B. Braun regularly transacts business, derives substantial revenue from sales within the district, and has previously availed itself of the court by filing its own patent infringement lawsuits and counterclaims there.
  • Core Dispute: Plaintiffs allege that Defendant's submission of a New Drug Application for a generic intravenous acetaminophen product constitutes an act of infringement of patents covering stable aqueous formulations of oxidation-sensitive drugs and specific methods for their administration.
  • Technical Context: The technology relates to stable, ready-to-use injectable formulations of acetaminophen, a widely used analgesic and antipyretic, which are critical in post-operative and hospital settings where oral drug administration is often not feasible.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendant's New Drug Application (NDA) No. 204957, which seeks approval for a generic version of Plaintiffs' OFIRMEV® product. The complaint notes that the asserted patents have been the subject of prior litigation and licensing, including a prior judicial finding that a different generic product infringed the ’218 patent.

Case Timeline

Date Event
2000-06-06 U.S. Patent No. 6,992,218 Priority Date
2006-01-31 U.S. Patent No. 6,992,218 Issued
2007-11-13 U.S. Patent No. 9,399,012 Priority Date
2010-11-02 Plaintiffs' OFIRMEV® Product Approved by FDA
2013-11-14 Court finds infringement of '218 Patent in Cadence v. Exela
2016-07-26 U.S. Patent No. 9,399,012 Issued
2017-02-23 Plaintiffs receive "Braun Letter" regarding NDA filing
2017-04-03 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 describes the problem of chemical instability in aqueous solutions of active pharmaceutical ingredients that are sensitive to oxidation, such as paracetamol (acetaminophen) (ʼ218 Patent, col. 1:21-30). This degradation, which is accelerated by heat-sterilization, leads to a loss of therapeutic activity and the formation of undesirable, potentially allergenic, colored byproducts (ʼ218 Patent, col. 1:31-44).
  • The Patented Solution: The invention provides a method for creating a stable formulation by first subjecting the aqueous solution to "extreme deoxygenation," for example by bubbling it with an inert gas or placing it under vacuum, to reduce the dissolved oxygen concentration to below 2 parts per million (ppm) (ʼ218 Patent, col. 3:3-14). The deoxygenated solution is then packaged into a container that has been cleared of air and is sealed under low pressure to prevent oxygen from re-dissolving into the product over time (ʼ218 Patent, Abstract; col. 3:35-43).
  • Technical Importance: This method enabled the development of shelf-stable, ready-to-use injectable formulations of drugs like acetaminophen, which are crucial for pain management in hospital settings where oral administration is impractical (ʼ218 Patent, col. 1:45-53).

Key Claims at a Glance

  • The complaint alleges infringement of the patent generally, with a focus on its manufacturing method claims. Independent claim 1 is central.
  • Essential elements of independent claim 1 include:
    • A method for preparing an aqueous solution with an active principle of phenolic nature, which is paracetamol.
    • Comprising deoxygenation of the solution (by bubbling with an inert gas and/or placing under vacuum) until the oxygen content is below 2 ppm.
    • Optionally placing the solution in a closed container under an inert gas atmosphere where the pressure is 65,000 Pa maximum.

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

The Invention Explained

  • Problem Addressed: The patent notes that the standard 1000 mg intravenous dose of acetaminophen is limited to administration every six hours to stay within the 4-gram maximum daily limit, which can result in periods of inadequate pain relief as the drug's effect wanes before the next dose can be given (ʼ012 Patent, col. 3:10-24).
  • The Patented Solution: The invention discloses a method of treatment that uses a reduced dose of acetaminophen (between 550 mg and 800 mg) administered at a more frequent interval (every 3 to 5 hours) (ʼ012 Patent, col. 3:35-42). This dosing strategy is designed to provide more consistent therapeutic plasma concentrations for better pain and fever management, while still respecting the established daily toxicity limits (ʼ012 Patent, col. 4:30-42).
  • Technical Importance: This dosing regimen provides clinicians with greater flexibility to tailor pain management protocols for individual patients, potentially improving pain control in the critical post-operative period (ʼ012 Patent, col. 3:43-48).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 39.
  • Essential elements of independent claim 1 include:
    • A method for the treatment of pain or fever in an adult or adolescent human subject weighing at least 50 kg.
    • Comprising administering intravenously a pharmaceutical composition comprising about 550 mg to about 800 mg of acetaminophen.
    • Repeating the administration at least once at an interval of about 3 to about 5 hours.

III. The Accused Instrumentality

Product Identification

  • Defendant's proposed generic acetaminophen for injection, 10 mg/ml, which is the subject of New Drug Application (NDA) No. 204957 (Compl. ¶11).

Functionality and Market Context

  • The accused product is a generic version of Plaintiffs' OFIRMEV® brand injectable acetaminophen, intended for intravenous administration for the treatment of pain and fever (Compl. ¶¶11, 20). The complaint alleges that to achieve the necessary stability for a commercial product, the Defendant's manufacturing process must involve deoxygenating the solution to a level below 2 ppm oxygen (Compl. ¶25).
  • Furthermore, the complaint alleges that the FDA will require the labeling for Defendant's Generic Product to be substantially identical to the OFIRMEV® label, which includes instructions for administering a 650 mg dose every 4 hours for certain patients (Compl. ¶¶28-31, 39). The complaint highlights that OFIRMEV® was the first intravenous formulation of acetaminophen available in the U.S., positioning the accused product as a direct generic competitor (Compl. ¶17).

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...paracetamol...comprising deoxygenation of the solution...until the oxygen content is below 2 ppm... Upon information and belief, the only viable way of manufacturing an acetaminophen solution with prolonged stability is to deoxygenate the solution (or the equivalent thereof) to below 2 ppm oxygen. This assertion is supported by a prior court finding against a different generic manufacturer. ¶25 col. 12:55-59

’012 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
...administering...a therapeutically effective amount of a pharmaceutical composition comprising about 550 mg to about 800 mg of acetaminophen... The complaint alleges Defendant's product label will be required to be substantially identical to the OFIRMEV® label, which instructs administration of a 650 mg dose. A table in the OFIRMEV® labeling recommends a 650 mg dose for adults and adolescents weighing 50 kg and over (Compl. Exhibit C). ¶¶29, 31, 39 col. 25:1-4
...and repeating said administration at least once at an interval of about 3 to about 5 hours. The OFIRMEV® label allegedly recommends administering the 650 mg dose "every 4 hours," which falls within the claimed interval. ¶¶29, 30, 39 col. 25:4-6

Identified Points of Contention

  • ’218 Patent Scope & Evidence: The infringement theory for the ’218 patent is not based on direct evidence of Defendant's process but on the inference that any stable commercial product must use the patented method (Compl. ¶25). This raises an evidentiary question: What proof will Plaintiffs offer to show that Defendant's specific, confidential manufacturing process necessarily results in a dissolved oxygen content "below 2 ppm" as required by the claim?
  • ’012 Patent Scope & Inducement: The infringement theory for the ’012 patent hinges on induced infringement via the product's label. A key question will be whether Defendant's final, FDA-approved label will contain instructions that actively "encourage, recommend, or promote" administration in the claimed manner (e.g., 650 mg every 4 hours), thereby meeting the legal standard for inducing infringement by healthcare providers (Compl. ¶35).

V. Key Claim Terms for Construction

For the ’218 Patent

  • The Term: "oxygen content is below 2 ppm"
  • Context and Importance: This limitation defines the core technical achievement of the manufacturing method. The infringement analysis will depend entirely on whether Defendant's product meets this specific numerical threshold.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification repeatedly refers to the goal as "extreme deoxygenation" (ʼ218 Patent, col. 3:7), which may support an argument that the term encompasses any process that achieves a functionally equivalent level of stability, with "below 2 ppm" being the exemplary boundary.
    • Evidence for a Narrower Interpretation: The claim uses a clear numerical limit. The patent abstract and examples emphasize achieving levels "of the order of 1 ppm and even 0.5 ppm" (ʼ218 Patent, Abstract), and the reexamination certificate added new claims for specific, lower oxygen ranges (e.g., "0.5 to 1 ppm") (ʼ218 Patent, C1, col. 2:10-11). A party could argue these facts confine the term to a strict, literal interpretation.

For the ’012 Patent

  • The Term: "about 3 to about 5 hours"
  • Context and Importance: This term defines the more frequent dosing interval that distinguishes the invention from the prior art standard of every six hours. The allegation of infringement relies on the OFIRMEV® label's "every 4 hours" instruction falling within this range. The scope of "about" will determine how much deviation from the 3-to-5-hour window is permissible.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The word "about" is classic broadening language. The specification's background criticizes the inflexibility of the 6-hour interval, suggesting the invention's purpose is to allow for more frequent dosing generally, not just within a rigid window (ʼ012 Patent, col. 3:25-34).
    • Evidence for a Narrower Interpretation: The claims and the detailed description consistently recite the "3 to about 5 hours" range (ʼ012 Patent, e.g., col. 2:21-22). The clinical trial example in the specification, which forms a basis for the invention, involved a specific 4-hour interval ('012 Patent, col. 23-24). A party may argue that "about" provides only minimal flexibility beyond the explicitly stated and tested range.

VI. Other Allegations

  • Indirect Infringement: The complaint's primary theory against the ’012 patent is indirect infringement. It alleges inducement by asserting that Defendant's product label, which is expected to mirror the OFIRMEV® label, will necessarily instruct and encourage medical professionals to administer the drug in the patented "650 mg every 4 hours" manner (Compl. ¶¶35, 58). It further alleges contributory infringement, stating the product is especially adapted for this infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶41, 61).
  • Willful Infringement: The complaint alleges that Defendant had actual knowledge of both patents-in-suit prior to filing its NDA (Compl. ¶¶43, 48, 63). This is supported by the allegation that Defendant sent a letter on February 23, 2017, acknowledging both patents, which establishes a basis for pre-suit knowledge (Compl. ¶¶11, 26).

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

  • A central issue for the ’218 patent will be one of evidentiary proof: Can Plaintiffs produce evidence, either through discovery of Defendant's confidential process or through scientific inference, to prove that Defendant’s method of manufacturing necessarily reduces dissolved oxygen to the specific claimed level of "below 2 ppm"?
  • The core of the dispute over the ’012 patent will be a question of induced infringement: Will Defendant's final, FDA-approved product label contain instructions that are specific enough to meet the legal standard of actively encouraging or directing medical professionals to administer the generic product according to the patented regimen of a reduced dose (e.g., 650 mg) at an increased frequency (e.g., every 4 hours)?