Bayer IP GmbH v. Epic Pharma LLC

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bayer Intellectual Property GmbH (Germany), Bayer Pharma AG (Germany), Bayer AG (Germany), and Janssen Pharmaceuticals, Inc. (Pennsylvania)
  • Defendant: Epic Pharma, LLC (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:22-cv-01481, D. Del., 11/10/2022
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a Delaware limited liability company and is subject to personal jurisdiction in the district.
• Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for generic versions of Plaintiffs' XARELTO® (rivaroxaban) products constitutes an act of infringement of two patents covering methods of use.
• Technical Context: The technology relates to pharmaceutical methods for using rivaroxaban, a direct factor Xa inhibitor, to treat and prevent thromboembolic disorders and to reduce the risk of major cardiovascular events.
• Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 216255 with a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed. Plaintiffs received a notice letter from Defendant regarding the ANDA submission on September 28, 2022. The patents-in-suit are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book") for XARELTO®.

Case Timeline

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

U.S. Patent No. 9,539,218 - "Prevention and Treatment of Thromboembolic Disorders," issued January 10, 2017

The Invention Explained

• Problem Addressed: The patent describes a need for improved anticoagulants, noting that prior therapies such as heparin required injection and non-selective action, while oral vitamin K antagonists like warfarin have a slow onset of action and a narrow therapeutic index requiring frequent patient monitoring ('218 Patent, col. 2:1-21).
• The Patented Solution: The invention is a method of treating certain thromboembolic disorders (pulmonary embolism, deep vein thrombosis, stroke) by administering the direct factor Xa inhibitor rivaroxaban in a specific regimen: "no more than once daily for at least five consecutive days in a rapid-release tablet" ('218 Patent, col. 11:11-13). The patent presents clinical data suggesting that this once-daily regimen is surprisingly effective, despite the drug's relatively short plasma half-life which might otherwise suggest a need for more frequent administration ('218 Patent, col. 2:35-43; col. 9:1-4).
• Technical Importance: The claimed once-daily oral regimen offered a potential improvement in patient convenience and compliance over injectable therapies or those requiring intensive monitoring for the treatment of serious thromboembolic events ('218 Patent, col. 2:35-43).

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 1 (Compl. ¶39).
• The essential elements of claim 1 are:
  • A method of treating a thromboembolic disorder
  • comprising administering the specific chemical compound rivaroxaban
  • no more than once daily for at least five consecutive days
  • in a rapid-release tablet
  • to a patient in need thereof
  • wherein the disorder is selected from pulmonary embolisms, deep vein thromboses, and stroke.
• The complaint alleges infringement of "at least claim 1" of the '218 patent, which may suggest an intent to assert dependent claims later (Compl. ¶39).

U.S. Patent No. 10,828,310 - "Reducing the Risk of Cardiovascular Events," issued November 10, 2020

The Invention Explained

• Problem Addressed: The patent addresses the challenge of reducing major adverse cardiovascular events in patients with stable coronary artery disease (CAD) and/or peripheral artery disease (PAD), noting that prior antithrombotic strategies either lacked sufficient efficacy or posed an unacceptably high risk of major bleeding ('310 Patent, col. 2:1-29).
• The Patented Solution: The invention is a specific combination therapy using a low dose of rivaroxaban (2.5 mg twice daily) administered with a daily dose of aspirin (75-100 mg) ('310 Patent, Abstract). The specification is centered on the results of the COMPASS clinical trial, which allegedly demonstrated that this particular combination therapy was effective at reducing the risk of myocardial infarction, stroke, or cardiovascular death compared to aspirin alone, while maintaining a manageable bleeding risk profile ('310 Patent, col. 3:26-40).
• Technical Importance: The claimed therapy provided a novel, evidence-based approach for long-term secondary prevention in patients with stable atherosclerotic vascular disease, a population for whom previous attempts to combine anticoagulants with antiplatelet therapy had not established a favorable risk-benefit balance ('310 Patent, col. 18:41-52).

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 1 (Compl. ¶46).
• The essential elements of claim 1 are:
  • A method of reducing the risk of myocardial infarction, stroke or cardiovascular death in a patient with CAD and/or PAD
  • comprising administering rivaroxaban and aspirin in "amounts that are clinically proven effective"
  • wherein rivaroxaban is administered as 2.5 mg twice daily
  • and aspirin is administered as 75-100 mg daily.
• The complaint alleges infringement of "at least claim 1" of the '310 patent (Compl. ¶46).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are "Epic’s ANDA Products," which are generic rivaroxaban tablets in 2.5 mg, 10 mg, 15 mg, and 20 mg dosage strengths, for which Defendant submitted ANDA No. 216255 to the FDA for approval (Compl. ¶8).

Functionality and Market Context

The products are oral tablets containing the active ingredient rivaroxaban (Compl. ¶¶32, 37). The act of infringement is the statutory infringement defined by 35 U.S.C. § 271(e)(2)—the submission of an ANDA to obtain approval to market a generic drug for patented uses prior to patent expiration (Compl. ¶1). The complaint alleges that the proposed labeling for Epic's ANDA Products will direct physicians and patients to use the drugs in a manner that directly infringes the claims of the patents-in-suit (Compl. ¶¶38, 45). XARELTO®, the reference listed drug, is a major commercial anticoagulant product with numerous approved indications (Compl. ¶17).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'218 Patent Infringement Allegations

'310 Patent Infringement Allegations

Identified Points of Contention

• The complaint alleges that Epic, in its Paragraph IV notice letter, "did not contest infringement of any claim of the '218 patent" and "did not contest infringement of claim 1 of the '310 patent" (Compl. ¶¶40, 47). In ANDA litigation, such a posture typically signals that the defendant’s primary defense will be patent invalidity rather than non-infringement.
• Technical Questions: A potential factual question for the '218 patent is whether Epic's formulation meets the definition of a "rapid-release tablet." The complaint's allegation is made on "information and belief," suggesting this will be a subject of discovery (Compl. ¶37). For the '310 patent, a question may arise concerning the precise instructions on the proposed label regarding the co-administration of aspirin. The complaint alleges the label "directs" this combination, which will need to be confirmed through the ANDA file (Compl. ¶45).

V. Key Claim Terms for Construction

• The Term: "rapid-release tablet" ('218 Patent, Claim 1)

  • Context and Importance: This term defines the claimed dosage form. Infringement of the '218 patent hinges on whether Epic’s generic product meets this definition. Practitioners may focus on this term because the patent appears to provide its own lexicography, potentially narrowing the scope from its plain meaning.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue for the plain and ordinary meaning of the term as understood in the pharmaceutical arts, which is generally a solid oral dosage form that releases the active ingredient quickly upon administration.
    • Evidence for a Narrower Interpretation: The specification states that "rapid-release tablets are in particular those which, according to the USP release method using apparatus 2 (paddle), have a Q value (30 minutes) of 75%" ('218 Patent, col. 8:21-24). This provides a specific, quantitative definition that a court may find controlling.

• The Term: "clinically proven effective" ('310 Patent, Claim 1)

  • Context and Importance: This term qualifies the claimed method, requiring that the administered amounts of rivaroxaban and aspirin achieve a certain standard of efficacy. The definition is critical, as it sets the benchmark for what the administration must accomplish.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party could argue the term refers to any valid clinical proof demonstrating efficacy, not limited to the studies cited in the patent.
    • Evidence for a Narrower Interpretation: The '310 patent specification is predicated entirely on the results of the COMPASS clinical trial ('310 Patent, col. 3:26-40). The patentee would likely argue that the patent acts as its own dictionary, defining "clinically proven effective" by the specific data and outcomes from the COMPASS trial disclosed throughout the specification (e.g., '310 Patent, col. 17:41-52; col. 12:1-15).

VI. Other Allegations

• Indirect Infringement: The complaint alleges both inducement and contributory infringement for both patents. The allegations are based on Epic's proposed product labeling, which allegedly instructs physicians and patients to use the generic products in accordance with the patented methods (Compl. ¶¶42, 49). The complaint further alleges the products are especially made or adapted for infringing use and are not suitable for substantial non-infringing use (Compl. ¶¶43, 50).
• Willful Infringement: The complaint alleges that Epic had pre-suit knowledge of both patents via their Orange Book listings and its own Paragraph IV certifications (Compl. ¶¶34, 41, 48). It further alleges that Epic "specifically intends to infringe" (Compl. ¶¶41, 48). While the term "willful" is not used, these allegations of knowing and intentional conduct, combined with a prayer for a finding of an "exceptional case" for attorneys' fees, lay the foundation for a potential future claim of willful infringement, particularly for any post-filing conduct (Compl. p. 16, ¶(h)).

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

Given the complaint’s allegation that the defendant did not contest infringement in its pre-suit correspondence, the central focus of this case will likely be the validity of the asserted patents.

• A core issue for the '218 patent will be one of obviousness: Was it obvious for a person of ordinary skill in the art to administer rivaroxaban—a drug with a known short half-life—in a once-daily regimen for the claimed indications with a reasonable expectation of success, or do the patent’s clinical results demonstrate surprising and unexpected efficacy sufficient to overcome a prima facie case of obviousness?
• A key question for the '310 patent will also be one of obviousness: Was the specific combination of low-dose (2.5 mg twice daily) rivaroxaban and daily aspirin (75-100 mg) an obvious-to-try therapeutic strategy for reducing cardiovascular risk in patients with stable CAD or PAD, or does the positive risk-benefit profile shown in the patent’s disclosed clinical trial data represent a non-obvious solution to a long-felt but unmet need?
• A secondary evidentiary question will be one of infringement confirmation: Although infringement was not contested pre-suit, discovery will need to confirm that Epic's proposed product and labeling meet every limitation of the asserted claims, including whether the formulation is a "rapid-release tablet" as defined in the '218 patent and whether the label for the 2.5 mg product definitively instructs co-administration with aspirin as required by the '310 patent.