DCT

1:24-cv-00336

Bayer IP GmbH v. Prinston Pharmaceutical Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00336, D. Del., 03/14/2024
  • Venue Allegations: Venue is alleged to be proper as Defendant is a corporation organized and existing under the laws of Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for generic versions of the anticoagulant XARELTO® constitutes an act of infringement of two patents covering methods of using rivaroxaban.
  • Technical Context: The technology concerns specific dosing regimens for the factor Xa inhibitor rivaroxaban to treat and prevent thromboembolic disorders and reduce the risk of major cardiovascular events.
  • Key Procedural History: This Hatch-Waxman action was triggered by Defendant’s submission of ANDA No. 208459 to the FDA, seeking approval to market generic rivaroxaban tablets prior to the expiration of the patents-in-suit. The complaint states Defendant filed Paragraph IV certifications asserting the patents are invalid, unenforceable, or will not be infringed, and sent a corresponding notice letter to Plaintiffs on February 1, 2024.

Case Timeline

Date Event
2005-01-31 ’218 Patent Priority Date
2017-01-10 ’218 Patent Issue Date
2018-02-02 ’310 Patent Priority Date
2020-11-10 ’310 Patent Issue Date
2024-02-01 Defendant’s ANDA Notice Letter Date
2024-03-14 Complaint Filing Date

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

U.S. Patent No. 9,539,218 - "Prevention and Treatment of Thromboembolic Disorders"

  • Patent Identification: U.S. Patent No. 9,539,218, "Prevention and Treatment of Thromboembolic Disorders," issued January 10, 2017. (Compl. ¶18).

The Invention Explained

  • Problem Addressed: The patent describes the significant morbidity and mortality associated with thromboembolic disorders and notes the disadvantages of existing anticoagulants, such as the non-selective action and bleeding risk of heparin or the slow onset and narrow therapeutic index of vitamin K antagonists. (’218 Patent, col. 2:1-19, 41-54).
  • The Patented Solution: The invention is a method of treating specific thromboembolic disorders by administering the direct factor Xa inhibitor rivaroxaban "no more than once daily." (’218 Patent, col. 11:11-16). This is presented as a significant finding, as the compound was known to have a short plasma half-life (4-6 hours in humans), which would typically suggest a need for more frequent (e.g., twice-daily) administration to maintain therapeutic effect. (’218 Patent, col. 3:35-43, col. 8:56-65).
  • Technical Importance: A once-daily oral dosing regimen for a potent anticoagulant offers a substantial improvement in patient convenience and compliance over multi-dose or injectable therapies, which is a critical factor in the long-term management of these conditions. (’218 Patent, col. 2:35-40).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1. (Compl. ¶¶19, 38).
  • Essential elements of claim 1:
    • A method of treating a thromboembolic disorder selected from pulmonary embolisms, deep vein thromboses, and stroke.
    • The method comprises administering the specific factor Xa inhibitor rivaroxaban.
    • The administration is "no more than once daily."
    • The administration occurs for "at least five consecutive days."
    • The administration is "in a rapid-release tablet."
  • The complaint does not explicitly reserve the right to assert dependent claims.

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

  • Patent Identification: U.S. Patent No. 10,828,310, "Reducing the Risk of Cardiovascular Events," issued November 10, 2020. (Compl. ¶24).

The Invention Explained

  • Problem Addressed: The patent addresses the high risk of major adverse cardiovascular events in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD). It notes that prior attempts to combine various antithrombotic agents had either failed to show superiority over single-agent therapy or resulted in unacceptably high rates of major bleeding. (’310 Patent, col. 2:1-29).
  • The Patented Solution: The invention is a specific combination therapy comprising a low dose of rivaroxaban (2.5 mg twice daily) co-administered with a low dose of aspirin (75-100 mg daily). (’310 Patent, Abstract; col. 3:57-65). The specification extensively details the results of the COMPASS clinical trial, which demonstrated that this particular combination therapy was effective at reducing the risk of cardiovascular death, stroke, and myocardial infarction without causing an unacceptably high risk of fatal or critical-organ bleeding. (’310 Patent, col. 15:24-col. 17:5).
  • Technical Importance: The claimed method provided a new, evidence-based treatment paradigm with a favorable risk-benefit profile for a large population of patients with stable atherosclerotic vascular disease, a clinical setting where previous combination therapies had not been successful. (’310 Patent, col. 18:41-53).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1. (Compl. ¶¶25, 44).
  • Essential elements of claim 1:
    • A method of reducing the risk of myocardial infarction, stroke, or cardiovascular death in a human patient with CAD and/or PAD.
    • The method comprises administering rivaroxaban and aspirin in "amounts that are clinically proven effective."
    • Rivaroxaban is administered in an amount of "2.5 mg twice daily."
    • 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

  • Defendant's ANDA Products, which are rivaroxaban tablets in 2.5 mg, 10 mg, 15 mg, and 20 mg strengths, intended as generic versions of Plaintiffs' XARELTO® products. (Compl. ¶¶8, 30).

Functionality and Market Context

  • The infringement action is based on Defendant’s submission of ANDA No. 208459, which seeks FDA approval to market these generic products. (Compl. ¶1). The core of the infringement allegation is that the Defendant's proposed product labeling for these tablets will instruct physicians and patients to use the products in a manner that directly infringes the claimed methods. (Compl. ¶¶37, 43). Specifically, the 10 mg, 15 mg, and 20 mg products are accused of infringing the ’218 Patent, while the 2.5 mg product is accused of infringing the ’310 Patent. (Compl. ¶¶52, 62).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'218 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a thromboembolic disorder ... wherein the thromboembolic disorder is selected from the group consisting of pulmonary embolisms, deep vein thromboses, and stroke. The proposed labeling for the 10 mg, 15 mg, and 20 mg products allegedly directs their use for indications that include the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). ¶37 col. 7:31-48
comprising administering a direct factor Xa inhibitor that is 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide ... to a patient in need thereof, Defendant's ANDA products are alleged to contain rivaroxaban, the compound identified in the claim. ¶31 col. 3:13-22
no more than once daily for at least five consecutive days The proposed labeling allegedly directs the use of the products in a manner that satisfies the "no more than once daily for at least five consecutive days" requirement. ¶37 col. 8:56-65
in a rapid-release tablet The dosage form is a tablet, which the complaint alleges, upon information and belief, satisfies the "rapid-release tablet" requirement of the claim. ¶36 col. 7:17-21
  • Identified Points of Contention:
    • Technical Question: The complaint alleges "upon information and belief" that the accused products are "rapid-release" tablets. (Compl. ¶36). This suggests that the exact dissolution profile and formulation of Defendant's product may be a point of factual dispute, raising the question of whether its characteristics fall within the scope of the claim term "rapid-release tablet" as defined in the patent.
    • Scope Question: The infringement case for method claims in an ANDA context rests on the instructions in the proposed label. A central question for the court will be whether the language of Defendant's proposed label will inevitably instruct or encourage physicians to prescribe the drug in the specific manner required by all elements of claim 1.

'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 label for the 2.5 mg product allegedly directs a method of reducing the risk of these specific events in patients with CAD and/or PAD. ¶43 col. 3:57-65
comprising administering to the human patient rivaroxaban and aspirin in amounts that are clinically proven effective in reducing the risk ... The proposed labeling allegedly directs the administration of the 2.5 mg rivaroxaban product with aspirin in amounts that are clinically proven effective for the specified indication, mirroring the patented method. ¶43 col. 11:1-14
wherein rivaroxaban is administered in an amount of 2.5 mg twice daily The proposed labeling for the 2.5 mg product will allegedly direct administration twice daily. ¶43 col. 4:9-10
and aspirin is administered in an amount of 75-100 mg daily. The proposed labeling will allegedly direct co-administration with aspirin in a daily amount of 75-100 mg. ¶43 col. 4:10-11
  • Identified Points of Contention:
    • Scope Question: The claim requires administration in "amounts that are clinically proven effective." The interpretation of this phrase will be critical. The dispute may focus on whether this term is limited to the specific efficacy results of the COMPASS trial detailed in the patent, or if it has a broader meaning.
    • Evidentiary Question: As with the ’218 Patent, the case will depend on the specific text of the proposed generic label. The court will need to determine if the label's instructions for using the 2.5 mg tablet with aspirin for patients with CAD/PAD are sufficient to induce infringement of the patented method.

V. Key Claim Terms for Construction

  • '218 Patent Term: "rapid-release tablet"

    • Context and Importance: This term defines the physical dosage form. Since the complaint alleges this element is met "upon information and belief," its precise definition will likely be a focus of dispute to determine if Defendant's product infringes.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification points to a functional definition, stating that rapid-release tablets are those which, "according to the USP release method using apparatus 2 (paddle), have a Q value (30 minutes) of 75%." (’218 Patent, col. 7:17-21). Plaintiffs may argue this sets a clear, objective, and standard functional boundary for the term.
      • Evidence for a Narrower Interpretation: The patent also references a separate patent application (PCT/04/01289) for the preparation of such tablets. (’218 Patent, col. 7:27-30). A defendant could argue that this incorporation by reference limits the term to the specific formulations or manufacturing processes described in that document.

  • '310 Patent Term: "clinically proven effective"

    • Context and Importance: This term qualifies the claimed doses and connects the method to a standard of evidence. Its construction is central to defining the scope of the invention and assessing both infringement and validity. Practitioners may focus on this term because it is not a standard structural or process limitation and its meaning is tied to external evidence (clinical trials).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: Plaintiffs may argue the term simply means that the specified doses have been shown to work in a clinical trial setting for the stated purpose, with the patent’s own detailed description of the COMPASS trial serving as a primary example of such proof. (’310 Patent, col. 15:24-col. 17:5).
      • Evidence for a Narrower Interpretation: The patent specification provides highly specific efficacy data from the COMPASS trial, including precise hazard ratios and p-values (e.g., hazard ratio of 0.76, P<0.001 for the primary outcome). (’310 Patent, Table 2; col. 16:5-11). A defendant might argue that "clinically proven effective" should be narrowly construed to require this specific level of statistical significance and clinical benefit, potentially limiting the claim's scope to the exact findings of that one trial.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendant will actively induce infringement of both patents. The basis for this allegation is that Defendant's proposed product labeling for its generic rivaroxaban tablets will instruct physicians and patients to administer the drug in the exact manner recited in the patent claims. (Compl. ¶¶40, 46). The complaint also alleges contributory infringement, stating that the accused products are especially made or adapted for infringing use and are not suitable for substantial noninfringing use. (Compl. ¶¶41, 47).
  • Willful Infringement: While the term "willful" is not used, the complaint alleges that Defendant has knowledge of the patents and their claims and, notwithstanding this knowledge, "specifically intends to infringe" them by seeking to market its ANDA products with the proposed labeling. (Compl. ¶¶39, 45).

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

  • A central issue for the court will be one of induced infringement: does the specific language of Defendant’s proposed (and currently unavailable) generic drug label instruct, encourage, and therefore induce physicians and patients to perform all steps of the methods claimed in the ’218 and ’310 patents?
  • A key technical question for the ’218 patent will be one of formulation equivalence: does the Defendant's tablet meet the functional definition of a "rapid-release tablet" as that term is construed from the patent's specification and any incorporated references?
  • For the ’310 patent, the case may turn on a question of definitional scope: how will the court construe the term "clinically proven effective"? Will it be interpreted broadly as being effective in a clinical setting, or narrowly tied to the specific statistical outcomes of the COMPASS trial detailed in the patent's specification? The answer will be critical in determining the breadth of the claim and the likelihood of infringement.