DCT

1:24-cv-00588

Bayer IP GmbH v. Ascent Pharma Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00588, D. Del., 05/16/2024
  • Venue Allegations: Venue is alleged to be proper based on Defendants having previously consented to personal jurisdiction and venue in the District of Delaware in prior ANDA litigation, and because Defendant Hetero Labs is not a resident of the United States.
  • Core Dispute: Plaintiffs allege that Defendants' Abbreviated New Drug Application (ANDA) to market generic versions of the anticoagulant XARELTO® constitutes an act of infringement of two patents covering specific methods of using the drug rivaroxaban.
  • Technical Context: The technology involves methods of using rivaroxaban, a direct factor Xa inhibitor, to treat and prevent blood clots and related cardiovascular events, a key therapeutic area for managing patients with conditions like atrial fibrillation, deep vein thrombosis, and coronary artery disease.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following a notice letter from Ascent, dated April 1, 2024, informing Plaintiffs of its ANDA submission containing a Paragraph IV certification, which asserts that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product.

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
2024-04-01 Ascent sends Paragraph IV notice letter to Plaintiffs
2024-05-16 Complaint Filing Date

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 the limitations of prior anticoagulants like heparin and vitamin K antagonists, which can be non-selective, carry a high risk of bleeding, or have a slow onset of action, creating a need for a more effective and convenient oral therapy for thromboembolic disorders ('218 Patent, col. 2:1-21).
  • The Patented Solution: The invention is a method of treatment using the direct factor Xa inhibitor rivaroxaban. The core of the claimed invention is the discovery that administering rivaroxaban no more than once daily is effective for treating certain thromboembolic disorders, despite the drug possessing a short plasma half-life (4-6 hours in humans) that would conventionally suggest a twice- or thrice-daily dosing regimen ('218 Patent, Abstract; col. 2:64 - col. 3:2).
  • Technical Importance: This method provided a simplified, once-daily oral dosing schedule for a direct anticoagulant, which could enhance patient compliance compared to therapies requiring more frequent administration ('218 Patent, col. 2:35-42).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶43).
  • Independent Claim 1 Elements:
    • A method of treating a thromboembolic disorder 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 [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 thromboembolic disorder is selected from the group consisting of pulmonary embolisms, deep vein thromboses, and stroke.
  • 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," issued November 10, 2020

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of reducing major adverse cardiovascular events (e.g., heart attack, stroke) in patients with stable coronary or peripheral artery disease. It notes that while antiplatelet therapies are standard, adding traditional anticoagulants often leads to an unacceptable increase in major bleeding without a clear net benefit ('310 Patent, col. 2:1-29).
  • The Patented Solution: The invention is a specific combination therapy. It claims a method of administering a low dose of rivaroxaban (2.5 mg twice daily) together with a daily dose of aspirin (75-100 mg). This specific regimen was found in the COMPASS clinical trial to effectively reduce the risk of major cardiovascular events without causing an unacceptably high risk of fatal or critical organ bleeding ('310 Patent, Abstract; col. 3:26-34).
  • Technical Importance: This combination therapy offered a clinically validated treatment to improve cardiovascular outcomes for a large population of patients with stable atherosclerotic disease, a group for whom prior attempts to combine anticoagulants with antiplatelets had not demonstrated a favorable risk-benefit profile ('310 Patent, col. 2:30-44).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶49).
  • Independent Claim 1 Elements:
    • 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 instrumentalities are the generic rivaroxaban tablets for which Defendants Ascent Pharmaceuticals and Hetero Labs submitted ANDA No. 219332, seeking FDA approval to market them in 2.5 mg, 10 mg, 15 mg, and 20 mg dosage strengths ("Ascent's ANDA Products") (Compl. ¶10).
  • Functionality and Market Context: The products contain rivaroxaban, the same active ingredient as the brand-name drug XARELTO® (Compl. ¶36). The infringement allegations are based on the proposed labeling for these generic products. The complaint alleges the labeling for the 10, 15, and 20 mg products will instruct their use in a manner that infringes the ’218 Patent (Compl. ¶42), while the labeling for the 2.5 mg product will instruct use in a manner that infringes the ’310 Patent (Compl. ¶48). The filing of the ANDA is a statutory act of infringement intended to bring a lower-cost generic equivalent to market upon approval.

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 Ascent's 10, 15, and 20 mg ANDA Products allegedly directs their use for treating deep vein thrombosis (DVT) and pulmonary embolism (PE), and for reducing the risk of stroke. ¶42 col. 12:3-5
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 Ascent’s ANDA Products contain rivaroxaban, the chemical compound recited in the claim. ¶36 col. 11:61-65
no more than once daily for at least five consecutive days The proposed labeling allegedly directs the administration of Ascent's 10, 15, and 20 mg products in a manner that satisfies the "no more than once daily for at least five consecutive days" requirement. ¶42 col. 11:59-60
in a rapid-release tablet Ascent allegedly stated in its notice letter that the dosage form is a tablet, which Plaintiffs allege, on information and belief, is a "rapid-release tablet" as required by the claim. ¶41 col. 12:1

'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 Ascent's 2.5 mg ANDA Product allegedly directs a method for this indication. ¶48 col. 18:57-60
comprising administering to the human patient rivaroxaban and aspirin The proposed labeling allegedly directs administration of the 2.5 mg rivaroxaban product in combination with aspirin. ¶48 col. 18:61-62
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 proposed labeling allegedly directs administration of Ascent's 2.5 mg product twice daily and aspirin in an amount of 75-100 mg daily, matching the claimed dosages. ¶48 col. 18:65 - col. 19:2
  • Identified Points of Contention:
    • Scope Questions: For the '218 Patent, a potential dispute centers on the term "rapid-release tablet". The infringement allegation relies on "information and belief" (Compl. ¶41), raising the question of what evidence Plaintiffs have that the ANDA product meets the specific release profile required by the patent, which the specification links to a USP standard ('218 Patent, col. 8:14-17).
    • Technical Questions: For the '310 Patent, the infringement theory appears to rely on the ANDA label mirroring the branded drug's label for the 2.5 mg strength. A central question for the court will be whether Ascent's proposed label will indeed contain instructions that directly correspond to every element of the claimed method, or if a "carve-out" of the patented indication is possible and has been attempted.

V. Key Claim Terms for Construction

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

    • Context and Importance: This term defines the formulation of the drug product. Infringement by Ascent's product will depend on whether its formulation falls within the scope of this term. Practitioners may focus on this term because the defendant could seek to distinguish its product by arguing for a different release profile.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification suggests a standard definition, stating 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. 8:14-17). Plaintiffs may argue this provides a clear, objective, and commonly understood standard.
      • Evidence for a Narrower Interpretation: A defendant could argue that the term should be interpreted more narrowly in the context of the invention, which touts the surprising efficacy of a once-daily dose for a short half-life drug. This might open an argument that the term implies a specific pharmacokinetic profile beyond the simple USP test, although the patent's explicit reference to the USP standard makes this a more difficult position.

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

    • Context and Importance: This term is a functional limitation requiring that the administered amounts achieve a certain outcome. Its construction is critical because defendants in ANDA litigation often challenge such terms as being indefinite under 35 U.S.C. § 112.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification is based on the results of the COMPASS clinical trial, which it describes in detail ('310 Patent, col. 3:26-34; Figs. 1-9). Plaintiffs will likely argue that the patent itself provides the "proof" and thus gives the term an objective and definite meaning tied directly to the data disclosed.
      • Evidence for a Narrower Interpretation: Defendants may argue that the term is subjective, depending on the opinion of one of ordinary skill in the art, or that it requires a level of proof that is not met by the ANDA filer. The argument would be that the term lacks objective boundaries, a common defense strategy against functional claiming.

VI. Other Allegations

  • Indirect Infringement: The complaint's primary infringement theory is indirect. It alleges that Ascent will actively induce infringement by marketing its ANDA Products with proposed labeling that will instruct physicians and patients to administer the drugs according to the patented methods (Compl. ¶¶ 45, 51). It also pleads contributory infringement, alleging the products are a material part of the invention, are especially made for an infringing use, and are not suitable for substantial noninfringing use (Compl. ¶¶ 46, 52).
  • Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it alleges that Ascent had knowledge of the patents (Compl. ¶¶ 44, 50) and seeks a declaration that the case is "exceptional" for the purpose of awarding attorneys' fees under 35 U.S.C. § 285 (Compl. p. 17, ¶(i)).

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

  • A central issue will be one of validity: will the Defendants be able to prove, by clear and convincing evidence, that the claimed methods were obvious? For the '218 Patent, the question will be whether it was obvious to try a once-daily dosing regimen for rivaroxaban given its known short half-life. For the '310 Patent, the question will be whether the specific low-dose rivaroxaban and aspirin combination was obvious to try to achieve a net clinical benefit in patients with stable cardiovascular disease.
  • A key question of infringement will be one of label-based inducement: will the final, FDA-approved label for Ascent’s generic products contain instructions that satisfy all limitations of the asserted claims, or will Defendants be able to "carve out" the patented indications to design a non-infringing label?
  • A potential dispute will be one of claim construction: specifically, whether the formulation term "rapid-release tablet" in the '218 Patent is met by Ascent's product, and whether the functional term "clinically proven effective" in the '310 Patent is sufficiently definite to be enforceable.