DCT
1:22-cv-01596
Bayer Pharma AG v. Apotex Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bayer Pharma AG, Bayer AG (Germany), and Janssen Pharmaceuticals, Inc. (Pennsylvania)
- Defendant: Apotex Inc. (Canada) and Apotex Corp. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:22-cv-01596, D. Del., 12/14/2022
- Venue Allegations: Venue is alleged to be proper as Defendant Apotex Corp. is a Delaware corporation and both Defendants are subject to personal jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the 2.5 mg XARELTO® product constitutes an act of infringement of a patent covering a combination therapy method.
- Technical Context: The technology relates to a pharmaceutical method using a combination of the anticoagulant rivaroxaban and aspirin to reduce the risk of major cardiovascular events in patients with coronary or peripheral artery disease.
- Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a notice letter from Apotex, dated October 31, 2022, which included a Paragraph IV certification against the patent-in-suit. The patent is listed in the FDA's "Orange Book" for the 2.5 mg strength of XARELTO®.
Case Timeline
| Date | Event |
|---|---|
| 2018-02-02 | U.S. Patent No. 10,828,310 Priority Date |
| 2020-11-10 | U.S. Patent No. 10,828,310 Issues |
| 2022-10-31 | Date of Apotex's Notice Letter to Plaintiffs |
| 2022-12-14 | 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, "REDUCING THE RISK OF CARDIOVASCULAR EVENTS", issued November 10, 2020 (’310 Patent).
The Invention Explained
- Problem Addressed: The patent describes that patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) face a high risk of major adverse cardiovascular events (’310 Patent, col. 2:1-4). Prior therapeutic approaches, such as combining traditional anticoagulants like warfarin with aspirin, did not sufficiently reduce these events and significantly increased the risk of life-threatening bleeding (’310 Patent, col. 2:7-13).
- The Patented Solution: The invention is a combination therapy using a specific low dose of rivaroxaban (2.5 mg twice daily), a factor Xa inhibitor, together with a low dose of aspirin (75-100 mg daily) (’310 Patent, col. 3:55-67). This specific regimen is asserted to achieve a significant reduction in the risk of myocardial infarction, stroke, or cardiovascular death without an unacceptably high risk of major bleeding, a balance that prior art therapies allegedly failed to achieve (’310 Patent, col. 3:49-55).
- Technical Importance: The claimed method provided a novel treatment regimen that demonstrated a positive net clinical benefit, addressing a long-standing challenge in finding a therapy superior to aspirin alone for long-term prevention in this patient population (’310 Patent, col. 2:15-30).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶38).
- Essential elements of independent claim 1:
- 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 said risk,
- 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 but alleges infringement of "at least claim 1" (Compl. ¶38).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Apotex's ANDA No. 217810 product, a generic version of the 2.5 mg rivaroxaban tablet, and its proposed use as directed by its product labeling (Compl. ¶¶ 9, 32, 35).
Functionality and Market Context
- The complaint alleges that Apotex's proposed product labeling directs the administration of its generic rivaroxaban product in combination with aspirin for reducing the risk of major cardiovascular events in patients with coronary or peripheral artery disease (Compl. ¶35). The alleged infringing use involves administering the 2.5 mg rivaroxaban tablet twice daily along with 75-100 mg of aspirin daily, thereby mirroring the method claimed in the ’310 Patent (Compl. ¶35). The infringement is predicated on the future marketing and sale of this generic product for the patented indication upon FDA approval (Compl. ¶37).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’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 complaint alleges that Apotex's proposed product labeling directs a method for 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. 3:56-60 |
| ...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 complaint alleges that Apotex's ANDA Product contains rivaroxaban and that its proposed labeling directs co-administration with aspirin in amounts that are clinically proven effective for the indicated patient population (Compl. ¶¶ 34, 35). | ¶¶34, 35 | col. 4:5-11 |
| ...wherein rivaroxaban is administered in an amount of 2.5 mg twice daily... | The complaint alleges Apotex's ANDA is for a 2.5 mg rivaroxaban product and that its proposed labeling will direct administration twice daily (Compl. ¶¶ 32, 35). | ¶¶32, 35 | col. 4:9-10 |
| ...and aspirin is administered in an amount of 75-100 mg daily. | The complaint alleges that the proposed labeling for Apotex's ANDA Product directs that aspirin be administered in an amount of 75-100 mg daily (Compl. ¶35). | ¶35 | col. 4:10-11 |
- Identified Points of Contention:
- Technical Questions: In a Hatch-Waxman case, the primary technical question is whether the use described in the defendant's proposed product label meets every limitation of the asserted patent claim. The dispute will center on a comparison of Apotex's proposed label for ANDA No. 217810 against the elements of claim 1.
- Scope Questions: The analysis will likely focus on the scope of the limitation "clinically proven effective." Apotex may argue this term is indefinite under 35 U.S.C. § 112. The patent ties this phrase to the specific outcomes of the COMPASS clinical trial, which raises the question of whether the claim scope is limited to the exact hazard ratios and patient populations described in the specification.
V. Key Claim Terms for Construction
- The Term: "clinically proven effective"
- Context and Importance: This term appears in the body of independent claim 1 and defines the required outcome for the administered amounts of rivaroxaban and aspirin. Practitioners may focus on this term because its construction is central to both infringement and validity. A narrow construction could provide grounds for a non-infringement argument, while a finding that the term is fatally indefinite would invalidate the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification makes general statements about the invention concerning amounts that are "clinically proven effective," which might support an argument that the term should be understood by its plain meaning as of the filing date, not tied exclusively to one trial (e.g., ’310 Patent, col. 3:60-67).
- Evidence for a Narrower Interpretation: The specification heavily relies on the results of the COMPASS clinical trial to substantiate the "clinically proven effective" nature of the claimed dosage regimen (’310 Patent, col. 15:1-16:21). A party could argue that the term is defined by, and limited to, achieving the specific statistical outcomes and hazard ratios reported from that trial, such as the hazard ratio of 0.76 for the primary outcome (’310 Patent, col. 16:5-8).
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement of infringement, stating that Apotex's proposed product labeling will instruct physicians and patients to perform the patented method (Compl. ¶41). It further alleges contributory infringement, asserting that the proposed product is especially made for an infringing use and is not suitable for a substantial noninfringing use (Compl. ¶42).
- Willful Infringement: The complaint alleges that Apotex has had knowledge of the ’310 patent and its claims since at least the receipt of the notice letter, and that its continued intent to market the ANDA product constitutes willful infringement (Compl. ¶40).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue for the court will be one of claim construction: how should the phrase "clinically proven effective" be defined? Will the court determine that the term is limited by the specific quantitative results of the clinical trial data disclosed in the patent's specification, or does it carry a broader meaning? The answer will heavily influence both the infringement and potential indefiniteness analyses.
- A key infringement question, typical of ANDA litigation, will be whether the instructions for use in Apotex's proposed product label will inevitably lead healthcare providers and patients to practice each and every step of the patented method.
- The case will also present an evidentiary question regarding validity (as part of Apotex's likely defense). The court may need to consider whether the specific combination of 2.5 mg rivaroxaban and 75-100 mg aspirin would have been obvious to a person of ordinary skill in the art at the time of the invention, given the extensive prior art on anticoagulants and antiplatelet agents discussed in the patent's own background section.