AstraZeneca Ab v. Macleods Pharma Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: AstraZeneca AB (Sweden) and AstraZeneca Pharmaceuticals LP (Delaware)
  • Defendant: Macleods Pharmaceuticals Ltd. (India) and Macleods Pharma USA, Inc. (Delaware)
  • Plaintiff’s Counsel: McCARTER & ENGLISH, LLP; Finnegan, Henderson, Farabow, Garrett & Dunner, LLP.
• Case Identification: 1:20-cv-01180, D. Del., 09/03/2020
• Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Macleods Pharma USA, Inc. is a Delaware corporation and because Macleods Pharmaceuticals Ltd. is an alien corporation that may be sued in any judicial district.
• Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug BRILINTA® (ticagrelor) constitutes an act of infringement of a patent covering a method for long-term prevention of atherothrombotic events.
• Technical Context: The technology relates to long-term dual antiplatelet therapy, a treatment regimen used for the secondary prevention of cardiovascular events like heart attacks and strokes in patients with a history of myocardial infarction.
• Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendant's submission of an ANDA with a Paragraph IV certification to the FDA. The certification asserts that Plaintiff's patent is invalid, unenforceable, and/or will not be infringed by the proposed generic product.

Case Timeline

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

U.S. Patent No. 10,300,065 - Method of treating or prevention of atherothrombotic events in patients with history of myocardial infarction

• Patent Identification: U.S. Patent No. 10,300,065, "Method of treating or prevention of atherothrombotic events in patients with history of myocardial infarction," issued May 28, 2019 (the "’065 Patent").

The Invention Explained

• Problem Addressed: The patent addresses the challenge of providing long-term secondary prevention for patients who have previously suffered a myocardial infarction (MI) ('065 Patent, col. 2:61-63). While dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is a standard treatment for up to one year post-MI, the optimal intensity and duration of therapy beyond that initial period was not established, creating a need to balance the prevention of ischemic events against the increased risk of bleeding associated with long-term treatment ('065 Patent, col. 3:14-19, 3:44-55).
• The Patented Solution: The invention provides a specific method for long-term treatment by administering a 60 mg dose of ticagrelor twice daily, in combination with a low daily maintenance dose of aspirin ('065 Patent, Abstract). This regimen, tested in the PEGASUS-TIMI 54 clinical trial, was shown to reduce the rate of a composite endpoint of cardiovascular death, MI, or stroke in this specific patient population ('065 Patent, col. 5:22-26). Figure 2 of the patent graphically illustrates the reduced cumulative incidence of these events for the 60 mg ticagrelor group compared to placebo over time ('065 Patent, Fig. 2-Panel A).
• Technical Importance: The claimed method provides a clinically-validated, specific dosing regimen for chronic or long-term secondary prevention in post-MI patients, addressing a previous uncertainty in clinical practice regarding the risk-benefit profile of extending DAPT beyond one year ('065 Patent, col. 4:62-64).

Key Claims at a Glance

• The complaint asserts infringement of "at least one claim" of the ’065 Patent (Compl. ¶42). Independent claim 1 is representative:
• A method for reducing the rate of a composite endpoint of cardiovascular death, myocardial infarction, or stroke in a patient in recognized need thereof, comprising:
  • administering to the patient twice daily a pharmaceutical composition comprising 60 mg ticagrelor and a pharmaceutically acceptable carrier;
  • wherein the patient has a history of myocardial infarction;
  • wherein the patient is also administered a daily maintenance dose of aspirin of 75 mg to 150 mg; and
  • wherein the rate of the composite endpoint in the patient is reduced relative to a dosing regimen where the patient receives the daily maintenance dose of aspirin of 75 mg to 150 mg only.
• The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is the generic ticagrelor drug product described in Defendant's ANDA No. 212258 (Compl. ¶1).

Functionality and Market Context

• The complaint alleges that Defendant seeks FDA approval to manufacture and sell a generic version of AstraZeneca's BRILINTA® drug product (Compl. ¶1). As part of the ANDA process, the proposed generic product is intended to have the same active ingredient, dosage form, and strength as the branded drug and be bioequivalent. The complaint alleges that Defendant intends to market this generic product throughout the United States, including in Delaware, upon receiving FDA approval (Compl. ¶¶8-9). The infringement allegation is based on the submission of the ANDA itself as a statutory act of infringement and the future commercial activity that will follow regulatory approval (Compl. ¶¶41-42).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or detailed infringement allegations beyond the statutory claim that the filing of the ANDA constitutes infringement. The analysis below is based on the infringement theory inherent in a Hatch-Waxman action involving a method-of-use patent, where the proposed generic label is expected to instruct for the patented use.

’065 Patent Infringement Allegations

• Identified Points of Contention:
  • Scope Questions: A primary question in ANDA litigation is whether the defendant will induce infringement. This may turn on whether Defendant's proposed product label includes the specific indication that is covered by the asserted method claims or if it has "carved out" the patented use. The complaint proceeds on the assumption the label will not contain a sufficient carve-out.
  • Technical Questions: A potential dispute may arise over the final "wherein" clause, which recites a clinical outcome. The question for the court may be whether this clause is a limiting element that requires proof of efficacy for a finding of infringement, or if it is satisfied by performing the method steps that the patent teaches will produce the claimed reduction in cardiovascular events.

V. Key Claim Terms for Construction

• The Term: "a patient in recognized need thereof"

• Context and Importance: This term defines the patient population covered by the claim. Its construction is critical because if it is construed narrowly to match the specific patient profile of the PEGASUS clinical trial (e.g., MI occurring 1-3 years prior plus an additional risk factor), Defendant could argue for non-infringement if its label covers a broader population or if certain patient subgroups are excluded.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent repeatedly describes the patient population simply as those with "a history of myocardial infarction" ('065 Patent, col. 5:15-16), which may support a construction not limited by the specific enrollment criteria of the underlying clinical trial.
  • Evidence for a Narrower Interpretation: The patent's detailed description is grounded in the PEGASUS-TIMI 54 trial, which had specific inclusion criteria, such as a spontaneous MI "1-3 years prior" plus at least one additional risk factor like age ≥65 or diabetes ('065 Patent, col. 19:8-16). A party could argue the claims should be limited to this more specific population, which was the basis for the invention.

• The Term: "wherein the rate of the composite endpoint... is reduced"

• Context and Importance: This is an efficacy-defining "wherein" clause. Its status as a positive limitation is central to the infringement analysis. Practitioners may focus on this term because if it requires proof of a specific outcome in each instance of infringement, the evidentiary burden would be substantial.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: A party may argue that this clause simply states the intended purpose and result of performing the preceding active steps of administration, as established by the clinical trial data presented in the patent ('065 Patent, Fig. 2; col. 26:39-48). Under this view, infringement occurs by performing the administration steps, which the patent teaches will achieve the reduction.
  • Evidence for a Narrower Interpretation: A party could argue that this is a functional limitation that requires the method to actually achieve the recited reduction. The claims do not quantify the reduction, which could also raise questions of indefiniteness. The patent specification itself is predicated on the statistically significant reduction observed in a large-scale clinical trial ('065 Patent, col. 26:45-48), suggesting the "reduction" is a tangible and critical aspect of the invention.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will "further infringe... by making, using, offering to sell, and selling its generic ticagrelor tablets" (Compl. ¶42). Because the '065 Patent claims a method of treatment, this allegation encompasses induced infringement under 35 U.S.C. § 271(b). The basis for inducement would be Defendant's product labeling, which on information and belief would instruct physicians and patients to administer the drug in accordance with the patented method.
• Willful Infringement: The complaint does not contain an allegation of willful infringement. The action is based on the statutory act of infringement arising from the ANDA filing under 35 U.S.C. § 271(e)(2).

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

• A central issue will be one of claim construction: does the phrase "a patient in recognized need thereof" limit the claims to the specific patient population enrolled in the PEGASUS-TIMI 54 clinical trial, or does it cover a broader population of patients with any history of myocardial infarction? The interpretation of this term will directly impact the scope of the claims and the infringement analysis.
• A second core issue, common in ANDA litigation, will be validity. While not detailed in the complaint, Defendant's Paragraph IV certification asserts invalidity (Compl. ¶38). The case will likely turn on whether the claimed method—specifically, the long-term use of a 60 mg twice-daily dose of ticagrelor with aspirin—would have been obvious to a person of ordinary skill in the art based on prior knowledge of DAPT, ticagrelor's properties, and earlier clinical studies.