DCT

1:24-cv-00459

AstraZeneca Ab v. Laurus Labs Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00459, D. Del., 04/11/2024
  • Venue Allegations: Venue is alleged to be proper for Laurus Generics Inc. because it is incorporated in Delaware, and for Laurus Labs Limited because it is an alien corporation that may be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic versions of the drug BRILINTA® (ticagrelor) constitutes an act of infringement of a patent covering a method of using the drug for long-term prevention of atherothrombotic events.
  • Technical Context: The technology relates to a specific pharmaceutical dosage regimen for ticagrelor, an antiplatelet agent used to reduce the risk of cardiovascular events like heart attack and stroke in high-risk patients.
  • Key Procedural History: The action arises under the Hatch-Waxman Act, initiated after Defendant sent Plaintiff a "Notice Letter" with a Paragraph IV certification asserting that Plaintiff's patent is invalid, unenforceable, and/or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2015-01-27 U.S. Patent No. 10,300,065 Priority Date
2019-05-28 U.S. Patent No. 10,300,065 Issued
2024-02-26 Defendant allegedly directs Notice Letter to Plaintiff
2024-04-11 Complaint Filed

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

U.S. Patent No. 10,300,065 - "Method of treating or prevention of atherothrombotic events in patients with history of myocardial infarction"

  • Patent Identification: U.S. Patent No. 10,300,065, issued May 28, 2019 (’065 Patent).

The Invention Explained

  • Problem Addressed: The patent describes a need for effective long-term (beyond one year) secondary prevention of cardiovascular events in patients who have previously suffered a myocardial infarction (MI) (’065 Patent, col. 3:4-18). While dual antiplatelet therapy was a cornerstone of treatment for up to one year post-MI, its long-term role and the optimal intensity of treatment to balance ischemic risk against bleeding risk were not well established (’065 Patent, col. 3:14-30, 3:51-62).
  • The Patented Solution: The invention provides a specific method of treatment identified in the PEGASUS-TIMI 54 clinical trial (’065 Patent, col. 3:31-35). The method involves administering a pharmaceutical composition comprising 60 mg of ticagrelor twice daily, in conjunction with low-dose aspirin, to patients with a history of MI to reduce the rate of a composite endpoint of cardiovascular death, MI, or stroke (’065 Patent, Abstract; col. 2:19-27). This lower 60 mg dose was evaluated to determine if it could improve the balance of efficacy and bleeding for chronic, long-term therapy compared to the 90 mg dose used for acute treatment (’065 Patent, col. 3:56-62).
  • Technical Importance: The invention provided clinical trial data supporting a specific, lower-dose ticagrelor regimen for long-term secondary prevention, addressing an area of clinical uncertainty for a large patient population at high risk of recurrent ischemic events (’065 Patent, col. 2:57-65).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶41).
  • The essential elements of Claim 1 are:
    • A method for reducing the rate of a composite endpoint of cardiovascular death, myocardial infarction, or stroke in a patient in recognized need thereof,
    • comprising administering to the patient twice daily a pharmaceutical composition comprising 60 mg ticagrelor,
    • wherein the patient has a history of myocardial infarction,
    • wherein the patient is also administered a daily maintenance dose of aspirin of 75 mg to 150 mg, and
    • wherein the rate of the composite endpoint in the patient is reduced relative to a dosing regimen where the patient receives only the daily maintenance dose of aspirin.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the proposed 60 mg and 90 mg generic ticagrelor tablets that are the subject of Defendant's Abbreviated New Drug Application (ANDA) No. 218869 (Compl. ¶1). The infringement allegations center on the future making, using, selling, and importing of the 60 mg version of this product (Compl. ¶41).

Functionality and Market Context

  • The complaint alleges that Defendant filed an ANDA seeking FDA approval to market a generic version of AstraZeneca's BRILINTA® product before the expiration of the ’065 patent (Compl. ¶¶1, 36). Under 35 U.S.C. § 271(e)(2)(A), the submission of such an ANDA for a drug claimed in a patent is a technical act of infringement to create federal court jurisdiction (Compl. ¶40).
  • The infringement theory is that upon FDA approval, Defendant will manufacture and sell its 60 mg generic ticagrelor tablets with a product label that will instruct physicians and patients to administer the drug in a manner that practices the patented method (Compl. ¶41). The complaint alleges that Defendant intends to engage in the commercial manufacture, use, and sale of its generic product after receiving FDA approval (Compl. ¶36).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a detailed claim chart or attach the proposed product label for the accused generic drug. The analysis below is based on the complaint's allegations regarding the nature of the ANDA filing and the asserted claim.

’065 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for reducing the rate of a composite endpoint of cardiovascular death, myocardial infarction, or stroke in a patient in recognized need thereof, The intended use of Defendant's generic ticagrelor product, as specified in its ANDA filing, is to reduce the rate of cardiovascular events in the same patient population treated by the brand-name drug, BRILINTA®. ¶¶1, 36, 41 col. 5:9-14
comprising administering to the patient twice daily a pharmaceutical composition comprising 60 mg ticagrelor and a pharmaceutically acceptable carrier; Defendant's ANDA seeks approval to market a 60 mg dosage strength of ticagrelor tablets. The product's eventual FDA-approved label is expected to instruct twice-daily administration consistent with the brand-name drug's label. ¶¶1, 36, 41 col. 2:22-27
wherein the patient has a history of myocardial infarction; The target patient population for ticagrelor, and thus for Defendant's generic product, includes patients with a history of myocardial infarction. ¶¶33, 41 col. 5:16-17
wherein the patient is also administered a daily maintenance dose of aspirin of 75 mg to 150 mg; and The standard of care and prescribing information for ticagrelor require co-administration with low-dose aspirin. The label for Defendant's generic product is expected to contain this instruction. ¶¶33, 41 col. 3:35-43
wherein the rate of the composite endpoint in the patient is reduced relative to a dosing regimen where the patient receives the daily maintenance dose of aspirin...only. As a generic product submitted via an ANDA, Defendant's product relies on the clinical trial data of the innovator, BRILINTA®, which demonstrated this efficacy. Defendant is therefore bound by the innovator's showing of this claimed clinical result. ¶¶1, 33, 41 col. 6:11-20

Identified Points of Contention

  • Scope Questions: An immediate question in ANDA litigation is whether the defendant will use a "skinny label" to carve out the patented indication. This raises the question: Does the proposed labeling submitted in Laurus's ANDA contain instructions that will necessarily lead physicians to prescribe the 60 mg product according to every limitation of Claim 1, or has Laurus attempted to omit the patented method of use from its proposed label?
  • Technical Questions: A potential dispute may arise over the final "wherein" clause, which defines the method's efficacy. The question for the court could be: Is the clause "wherein the rate of the composite endpoint... is reduced" a true, enforceable limitation of the method claim, or is it merely a statement of intended result that does not limit the claim's scope for infringement purposes?

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of specific claim term disputes. However, based on the patent and the nature of the litigation, the following terms may become central.

The Term: "a patient in recognized need thereof"

  • Context and Importance: This term defines the patient population covered by the claim. Its construction is critical to determining the scope of the patented method. Practitioners may focus on this term because a defendant could argue that the claim is limited to the specific high-risk patient population studied in the PEGASUS trial, potentially creating a non-infringement argument if their product label could be interpreted as targeting a different or broader group.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The plain meaning of the term suggests it covers any patient whom a medical professional, using their clinical judgment, identifies as requiring treatment to reduce the rate of the specified cardiovascular events.
    • Evidence for a Narrower Interpretation: The specification extensively describes the PEGASUS clinical trial, including detailed inclusion criteria for patients, such as having a spontaneous MI 1-3 years prior plus at least one additional risk factor (e.g., age ≥65, diabetes, a second prior MI) (’065 Patent, col. 19:8-16). A party could argue that "in recognized need thereof" is implicitly limited to patients meeting these specific criteria.

The Term: "history of myocardial infarction"

  • Context and Importance: This term specifies the core condition of the patient population. While seemingly straightforward, its temporal scope could become a point of contention. The PEGASUS trial, which forms the basis of the patent, enrolled patients whose MI occurred 1 to 3 years prior to enrollment (’065 Patent, col. 19:9-10). The question of whether the claim covers patients whose MI was more or less recent could be pivotal.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself does not include a time limitation (e.g., "within the last 3 years"). A party arguing for a broader scope would assert the plain meaning covers any patient with a prior MI, regardless of when it occurred.
    • Evidence for a Narrower Interpretation: The specification's detailed description of the PEGASUS trial as the basis for the invention could be used to argue that the claim is implicitly limited to the patient population studied, i.e., those whose MI occurred 1 to 3 years prior. The patent states, "Eligible patients had a history of a spontaneous myocardial infarction 1 to 3 years prior to enrollment" (’065 Patent, col. 19:8-10).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will induce infringement under 35 U.S.C. § 271(b) and contributorily infringe under § 271(c) (Compl. ¶41). The basis for inducement is the allegation that Defendant's actions, including the marketing and sale of its 60 mg generic ticagrelor tablets with corresponding labeling, will instruct and encourage medical professionals and patients to use the product in a manner that directly infringes the method claimed in the ’065 Patent.
  • Willful Infringement: The complaint does not contain an explicit allegation of willful infringement or a request for enhanced damages under 35 U.S.C. § 284.

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

  • A central issue will be one of induced infringement: As this is an ANDA case, will the specific language of the FDA-approved label for Laurus's 60 mg generic ticagrelor product instruct or encourage physicians to prescribe the drug for long-term administration to post-MI patients, thereby causing direct infringement of the patented method?
  • A second core issue, as signaled by the Defendant's Paragraph IV certification, will be one of validity, likely focused on obviousness: Was it obvious for a person of ordinary skill in the art, based on prior knowledge of the 90 mg ticagrelor dose from the PLATO trial and other clinical data, to select and administer the claimed 60 mg twice-daily dose for long-term secondary prevention with a reasonable expectation of achieving the claimed reduction in cardiovascular events?