DCT

1:17-cv-01877

Mallinckrodt IP Unltd Co v. Aurobindo Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-01877, D. Del., 12/29/2017
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because the Defendant is a Delaware corporation and therefore resides in the judicial district.
  • Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs’ OFIRMEV® product constitutes an act of infringement of three U.S. patents related to the formulation and method of use of intravenous acetaminophen.
  • Technical Context: The technology concerns stable aqueous formulations of intravenous acetaminophen and specific dosing regimens for managing pain and fever, primarily in a post-operative clinical setting.
  • Key Procedural History: The complaint notes that U.S. Patent No. 6,992,218 and U.S. Patent No. 9,399,012 have been the subject of prior litigation in the District of Delaware against other generic drug manufacturers. The complaint also references a prior claim construction ruling from related litigation concerning an "optional" limitation in claim 1 of the '218 patent, a ruling that may be significant in the current dispute.

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 Issue Date
2007-11-13 U.S. Patent Nos. 9,399,012 & 9,610,265 Priority Date
2010-11-02 OFIRMEV® approved by the FDA
2016-07-26 U.S. Patent No. 9,399,012 Issue Date
2017-04-04 U.S. Patent No. 9,610,265 Issue Date
2017-11-21 Plaintiffs receive Defendant's letter regarding ANDA filing
2017-12-29 Complaint Filing Date

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 that active pharmaceutical ingredients of a phenolic nature, such as paracetamol (acetaminophen), are highly susceptible to degradation from oxidation when in an aqueous solution (Compl. ¶22; ’218 Patent, col. 1:12-34). This instability can lead to a loss of efficacy and the formation of colored or allergenic byproducts, posing a significant challenge for creating a commercially viable, long-shelf-life injectable product, particularly one that must undergo heat-sterilization (Compl. ¶40; ’218 Patent, col. 2:36-54).
  • The Patented Solution: The invention is a method to create a stable formulation by first subjecting the aqueous solution to "extreme deoxygenation" to reduce the dissolved oxygen content to below 2 parts per million (ppm) (Compl. ¶22; ’218 Patent, col. 3:5-14). The deoxygenated solution is then packaged in a container that has been purged with an inert gas, and the container is stoppered under a low-pressure vacuum (maximum 65,000 Pa) to prevent subsequent oxygen contamination and ensure long-term stability (’218 Patent, col. 4:56-65).
  • Technical Importance: This method provided a way to produce the first stable, ready-to-use intravenous formulation of acetaminophen, overcoming the long-standing problem of its oxidative degradation in solution (Compl. ¶30).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 19 (Compl. ¶¶ 75-76).
  • Independent Claim 1 recites the key elements of the preparation method:
    • A method for preparing an aqueous solution of paracetamol.
    • Deoxygenating the solution (by bubbling with 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.
  • The complaint does not explicitly reserve the right to assert other claims but infringement is alleged for "at least claims 1 and 19" (Compl. ¶76).

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

The Invention Explained

  • Problem Addressed: The standard intravenous dose of acetaminophen (1000 mg) is limited to administration every six hours to avoid liver toxicity (’012 Patent, col. 3:10-18). However, the analgesic effect may wear off in less than six hours, creating a "gap in coverage" where a patient's pain is not adequately controlled (’012 Patent, col. 3:25-34).
  • The Patented Solution: The patent proposes a method of treatment using a "reduced dose" of IV acetaminophen, specifically between 550 mg and 800 mg, which can be administered at more frequent intervals of 3 to 5 hours (’012 Patent, col. 4:32-43). This approach is intended to provide more consistent, around-the-clock pain relief without exceeding the maximum recommended daily dosage limit (Compl. ¶45; ’012 Patent, col. 4:35-43).
  • Technical Importance: This dosing strategy offers physicians greater flexibility to customize pain management to a patient's needs, potentially providing superior pain control compared to the standard, less frequent high-dose regimen (Compl. ¶45; ’012 Patent, col. 4:38-43).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 39 (Compl. ¶¶ 86-87).
  • Independent Claim 1 recites the key elements of the treatment method:
    • A method for treating pain or fever in a human subject weighing at least 50 kg.
    • Administering intravenously a composition comprising about 550 mg to 800 mg of acetaminophen.
    • Repeating the administration at least once at an interval of about 3 to 5 hours.
  • The complaint alleges infringement of "at least claims 1 and 39" (Compl. ¶86).

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 (Compl. ¶27).
  • Technology Synopsis: This patent covers a method of treating pain by co-administering a reduced intravenous dose of acetaminophen (about 500 mg to 750 mg) with a second pharmaceutical composition comprising an opioid analgesic (Compl. ¶28). The invention applies the reduced-dose concept of the ’012 patent to the context of multi-modal pain therapy, where combining different types of analgesics can improve pain relief (’265 Patent, col. 4:44-51).
  • Asserted Claims: Independent claim 1 and dependent claim 7 (Compl. ¶¶ 99-100).
  • Accused Features: The complaint alleges that Aurobindo's proposed product labeling will encourage co-administration of its acetaminophen product with an opioid analgesic, thereby inducing infringement of the claimed method (Compl. ¶¶ 59-60, 65).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant Aurobindo's proposed generic "acetaminophen 1g/100 mL solution for IV infusion," identified as ANDA No. 210969 ("Aurobindo's ANDA Product") (Compl. ¶13).

Functionality and Market Context

  • The product is a sterile, injectable solution of acetaminophen intended for the treatment of pain and fever in a clinical setting (Compl. ¶13). As a generic version of Plaintiffs' OFIRMEV® brand product, it is required to be bioequivalent and have a comparable label (Compl. ¶47). The complaint alleges that the instructions on the proposed product label for dosing and administration will encourage medical professionals to use the product in a manner that infringes the ’012 and ’265 patents (Compl. ¶¶ 44, 59). For example, the complaint references Table 1 of the OFIRMEV® labeling, which recommends a 650 mg dose every 4 hours for certain patients, as evidence of what Aurobindo's label will instruct (Compl. ¶¶ 50, 67).

IV. Analysis of Infringement Allegations

6,992,218 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 principle of phenolic nature susceptible to oxidation, which is paracetamol... Defendant’s ANDA Product is an aqueous solution of paracetamol, which is a phenolic compound susceptible to oxidation. ¶13 col. 12:53-56
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, Upon information and belief, Plaintiffs allege that deoxygenating the solution to below 2 ppm oxygen is the "only viable way" of manufacturing an acetaminophen solution with prolonged stability. ¶40 col. 4:50-55
and optionally the aforementioned aqueous solution with an active principle is topped with an inert gas atmosphere heavier than air and placed in a closed container in which the prevailing pressure is 65,000 Pa maximum... Plaintiffs allege this step is optional and not required for infringement, citing a prior court construction. The complaint notes that Defendant’s infringement notice denies that its process includes this step. ¶¶37-38 col. 3:10-14
  • Identified Points of Contention:
    • Technical Question: A key evidentiary issue will be whether Plaintiffs can prove that Defendant's confidential manufacturing process necessarily results in a paracetamol solution with a dissolved oxygen content below the claimed 2 ppm threshold. The complaint asserts this on "information and belief" (Compl. ¶40).
    • Scope Question: The primary dispute appears to center on the "optional" vacuum-sealing limitation. The complaint preemptively raises this issue, citing a prior court ruling that the step is not necessary for a finding of infringement (Compl. ¶38). The case may turn on whether that construction is adopted or revisited, and its application to Defendant's process, which allegedly omits this step (Compl. ¶37).

9,399,012 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, in need thereof, The proposed labeling for Defendant's product is expected to be indicated for this patient population, mirroring the OFIRMEV® label. ¶¶45, 49 col. 2:10-15
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; Defendant's proposed labeling will allegedly recommend and instruct a dose of 650 mg, which is within the claimed range. The complaint points to the OFIRMEV® label, which explicitly recommends a 650 mg dose. ¶¶44, 49-50 col. 5:27-33
and repeating said administration at least once at an interval of about 3 to about 5 hours. Defendant's proposed labeling will allegedly recommend repeating the 650 mg dose "every 4 hours," which falls within the claimed interval. ¶¶46, 49 col. 2:20-22
  • Identified Points of Contention:
    • Technical Question: The infringement theory for the ’012 patent relies entirely on induced infringement. The central question will be factual: what will the final, FDA-approved labeling for Aurobindo's ANDA Product actually instruct? The complaint's allegations are based on the label of the reference drug, OFIRMEV®, and the regulatory requirement for generic labels to be substantially similar (Compl. ¶¶ 47-54).
    • Scope Question: The claim language appears to map directly onto the alleged instructions in the product labeling. Barring an invalidity challenge, the dispute is less likely to be about claim scope and more about the evidence of what Defendant's label will direct users to do.

V. Key Claim Terms for Construction

For the ’218 Patent

  • The Term: "and optionally the aforementioned aqueous solution... is topped with an inert gas atmosphere heavier than air and placed in a closed container in which the prevailing pressure is 65,000 Pa maximum..." (Claim 1)
  • Context and Importance: This limitation is the explicit basis for Defendant's stated non-infringement position (Compl. ¶37). The construction of "optionally" and the effect of this clause on the overall claim scope is therefore dispositive for the infringement analysis of the ’218 patent. Practitioners may focus on this term because the complaint itself highlights a prior judicial construction of this very language (Compl. ¶38).
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation (i.e., step is not required): The plain meaning of the word "optionally" suggests the patentee intended for the claim to cover methods that both include and exclude this final vacuum-sealing step. The complaint cites a prior court decision construing the phrase to mean "may, but not necessarily, include the steps..." (Compl. ¶38).
    • Evidence for a Narrower Interpretation (i.e., step is essential): The patent's abstract and detailed description repeatedly emphasize the importance of stoppering under low pressure to achieve the invention's goal of long-term stability (’218 Patent, Abstract; col. 3:7-14). A party could argue that, in the context of the full specification, this "optional" step is an essential feature for achieving the patent's stated objective and should not be read out of the claim.

For the ’012 Patent

  • The Term: "therapeutically effective amount" (Claim 1)
  • Context and Importance: While the claim proceeds to define this amount with a specific numerical range ("about 550 mg to about 800 mg"), the construction of the phrase itself could be a point of contention. Practitioners may focus on this term because its definition links a dosage to a clinical outcome, raising the question of what must be proven for infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself provides an explicit definition by reciting a numerical range immediately after the term. This suggests the patentee acted as their own lexicographer, and infringement would only require administering a dose within that range.
    • Evidence for a Narrower Interpretation: The specification describes the purpose of the invention as providing better overall relief than the prior 1000 mg regimen (’012 Patent, col. 4:35-38). A party could argue that "therapeutically effective" requires not only meeting the dosage range but also achieving this superior clinical outcome, which would impose a higher evidentiary burden on the patentee.

VI. Other Allegations

  • Indirect Infringement: The complaint's allegations against the ’012 and ’265 patents are grounded in induced infringement. It is alleged that Aurobindo, by marketing its ANDA Product with a label that contains instructions and recommendations for use, will actively encourage and instruct medical professionals to directly infringe the claimed methods of treatment (Compl. ¶¶ 45-46, 60-61, 88, 101). The basis for this allegation is the existing label for OFIRMEV®, which allegedly contains these instructions (Compl. ¶¶ 48-54, 64-71).
  • Willful Infringement: The complaint alleges that Aurobindo had pre-suit knowledge of all three patents-in-suit. This knowledge is allegedly based on prior, well-publicized litigation involving the ’218 and ’012 patents, as well as the listing of all three patents in the FDA's Orange Book for OFIRMEV® (Compl. ¶¶ 18, 41, 56, 89, 102). The complaint further alleges that Defendant's actions were taken "without a reasonable basis for a good faith belief that it would not be liable for infringing" the patents (Compl. ¶¶ 77, 90, 103).

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

  • A core issue for the '218 patent will be one of procedural and legal weight: will the court adopt the prior claim construction ruling that the vacuum-sealing step is optional, thereby largely negating Defendant's stated non-infringement defense, or will it treat the matter anew?
  • A key evidentiary question for the '012 and '265 method patents will be one of predictive fact-finding: will the final, FDA-approved label for Defendant’s generic product contain the specific dosing and administration instructions (e.g., 650 mg every 4 hours, co-administration with opioids) that Plaintiffs allege are necessary to prove inducement of infringement by medical professionals?
  • An underlying technical question for the '218 patent is one of proof of process: given the confidential nature of Defendant's manufacturing, what discovery and evidence will be required for Plaintiffs to demonstrate that Defendant’s method necessarily achieves the claimed oxygen concentration of "below 2 ppm," an allegation currently made only on "information and belief"?