DCT

1:23-cv-00665

Bayer Pharma AG v. Macleods Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00665, D. Del., 06/16/2023
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Macleods USA, Inc. is incorporated in Delaware and Defendant Macleods Pharmaceuticals Ltd. is subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the 2.5 mg XARELTO® product constitutes an act of infringement of a patent covering a method of using rivaroxaban in combination with aspirin.
  • Technical Context: The technology relates to a combination drug therapy designed to reduce the risk of major cardiovascular events, such as heart attack and stroke, in patients with coronary or peripheral artery disease.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 213114 to the FDA. The complaint states that on May 2, 2023, Defendants sent a "Notice Letter" to Plaintiffs, which included a Paragraph IV Certification asserting that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product. This notice letter serves as the basis for Plaintiffs' knowledge of Defendants' intent.

Case Timeline

Date Event
2018-02-02 U.S. Patent No. 10,828,310 Priority Date
2020-11-10 U.S. Patent No. 10828310 Issued
2023-05-02 Macleods sends Notice Letter with Paragraph IV Certification to Plaintiffs
2023-06-16 Complaint Filed

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

U.S. Patent No. 10,828,310 - "Reducing the Risk of Cardiovascular Events"

  • Patent Identification: U.S. Patent No. 10,828,310 ("the '310 patent"), "Reducing the Risk of Cardiovascular Events", issued November 10, 2020.

The Invention Explained

  • Problem Addressed: The patent addresses the high risk of major adverse cardiovascular events (e.g., myocardial infarction, stroke, cardiovascular death) in patients with coronary artery disease (CAD) or peripheral artery disease (PAD) ('310 Patent, col. 2:1-4). The background notes that prior anticoagulant therapies were not demonstrably superior to standard antiplatelet therapy and often came with unacceptably high risks of major bleeding ('310 Patent, col. 2:5-15).
  • The Patented Solution: The invention is a specific combination therapy using a low dose of the Factor Xa inhibitor rivaroxaban (2.5 mg twice daily) co-administered with a low dose of aspirin (75-100 mg daily) ('310 Patent, Abstract; col. 3:56-62). This regimen is described as showing efficacy in reducing cardiovascular events in patients with stable atherosclerotic vascular disease without causing an unacceptably high risk of fatal bleeding, a discovery attributed to the results of the COMPASS clinical trial ('310 Patent, col. 3:26-40, 50-55).
  • Technical Importance: This specific low-dose combination therapy provided a novel treatment approach that demonstrated a positive benefit-risk profile for long-term prevention in a patient population where previous attempts to use anticoagulants had failed to achieve a similar balance of efficacy and safety ('310 Patent, col. 2:31-44).

Key Claims at a Glance

  • The complaint asserts infringement of at least claim 1 (Compl. ¶38).
  • The essential elements of independent claim 1 are:
    • A method of reducing the risk of myocardial infarction, stroke or cardiovascular death
    • in a human patient with coronary artery disease and/or peripheral artery disease,
    • comprising administering to the human patient rivaroxaban and aspirin in amounts that are clinically proven effective in reducing the risk of myocardial infarction, stroke or cardiovascular death in a human patient with coronary artery disease and/or peripheral arterial disease,
    • wherein rivaroxaban is administered in an amount of 2.5 mg twice daily
    • and aspirin is administered in an amount of 75-100 mg daily.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Macleods' ANDA Product," identified as a generic version of Plaintiffs' 2.5 mg rivaroxaban tablets, submitted for FDA approval under ANDA No. 213114 (Compl. ¶¶ 9, 32).

Functionality and Market Context

  • The complaint alleges that Macleods' ANDA Product contains rivaroxaban and is a generic version of the 2.5 mg strength of XARELTO® (Compl. ¶¶ 32, 34). The infringement allegation is predicated on the proposed labeling for Macleods' ANDA Product, which allegedly directs its use in a manner that practices the patented method (Compl. ¶35). Specifically, the proposed labeling is alleged to direct administration of the 2.5 mg rivaroxaban product twice daily in combination with aspirin (75-100 mg daily) to reduce the risk of major cardiovascular events in patients with CAD and/or PAD (Compl. ¶35). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'310 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of reducing the risk of myocardial infarction, stroke or cardiovascular death in a human patient with coronary artery disease and/or peripheral artery disease... The proposed labeling for Macleods' ANDA Product is alleged to direct a method of reducing the risk of major cardiovascular events (including myocardial infarction and stroke) in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD) (Compl. ¶35). ¶35 col. 3:56-62
comprising administering to the human patient rivaroxaban and aspirin in amounts that are clinically proven effective in reducing the risk of myocardial infarction, stroke or cardiovascular death in a human patient with coronary artery disease and/or peripheral arterial disease... The proposed labeling allegedly directs the administration of Macleods' rivaroxaban product and aspirin in amounts that are clinically proven effective for the claimed indication (Compl. ¶35). The ANDA filing itself is an act of infringement under 35 U.S.C. § 271(e)(2) for the purpose of obtaining approval for this use (Compl. ¶42). ¶35 col. 4:5-9
wherein rivaroxaban is administered in an amount of 2.5 mg twice daily... Macleods' ANDA seeks approval for a 2.5 mg rivaroxaban tablet, and the proposed labeling allegedly directs that the product be administered twice daily (Compl. ¶¶32, 35). ¶¶32, 35 col. 4:9-11
and aspirin is administered in an amount of 75-100 mg daily. The proposed labeling for Macleods' ANDA Product allegedly directs co-administration with aspirin in an amount of 75-100 mg daily (Compl. ¶35). ¶35 col. 4:11-12
  • Identified Points of Contention:
    • Scope Questions: The dispute may turn on the construction of the phrase "clinically proven effective." Does this phrase limit the claim to the specific results of the COMPASS trial detailed in the patent, or is it satisfied by an FDA finding that the proposed generic product is bioequivalent and has an approved label for the same indication?
    • Technical Questions: A key evidentiary question for induced infringement will be whether the final, FDA-approved label for Macleods' product will instruct users to perform all steps of the claimed method, including co-administration with aspirin within the specified 75-100 mg daily dosage range for the specified patient population.

V. Key Claim Terms for Construction

  • The Term: "clinically proven effective"
  • Context and Importance: This term appears in the central "comprising administering" element of claim 1. Its construction is critical because it could define the scope of evidence required to prove infringement. Practitioners may focus on this term because it is not a standard structural or process limitation and could be susceptible to arguments of indefiniteness or as a limitation tying the claim's scope to the specific clinical trial data disclosed in the patent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification makes general statements about the invention concerning amounts that are "clinically proven effective" ('310 Patent, col. 4:5-9), which could support an interpretation that any regimen meeting FDA approval for the claimed indication satisfies the limitation, rather than being restricted to a specific trial's data.
    • Evidence for a Narrower Interpretation: The patent repeatedly grounds its discovery in the results of the "phase III COMPASS trial" ('310 Patent, col. 3:26-31). A defendant may argue that "proven" refers specifically to the hazard ratios and statistical significance levels reported from that trial ('310 Patent, col. 16:1-10; Fig. 2A), suggesting that any infringing method must demonstrate a comparable level of proof.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement, stating that Macleods' proposed product labeling will instruct physicians and patients to co-administer the generic rivaroxaban with aspirin in a manner that directly infringes the '310 patent (Compl. ¶¶ 35, 40). It also alleges contributory infringement, claiming Macleods' product is especially adapted for this infringing use and is not suitable for a substantial noninfringing use (Compl. ¶41).
  • Willful Infringement: Willfulness is not explicitly pleaded as a separate count, but the facts alleged could support such a claim. The complaint states that Macleods has had knowledge of the '310 patent since at least receiving the May 2, 2023 Notice Letter and has "continued to assert its intent to engage" in infringing activities, which it "specifically intends" to do (Compl. ¶¶ 32, 39).

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

  • A central issue will be one of claim scope: How will the court construe the phrase "clinically proven effective"? The case may turn on whether this phrase is satisfied by the act of gaining FDA approval for a label that mirrors the branded indication, or if it requires a specific evidentiary showing tied to the clinical trial data disclosed in the patent specification.
  • A second key question will be one of induced infringement: Assuming the patent is valid, will the instructions in Macleods' final, FDA-approved product label be found to affirmatively encourage, recommend, or promote the combined use of its rivaroxaban product with aspirin in the patented dosage and for the patented patient population, thereby establishing the requisite intent for inducement?