DCT

1:22-cv-07472

AstraZeneca Ab v. Unichem Laboratories Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-07472, D.N.J., 12/22/2022
  • Venue Allegations: Venue is alleged to be proper for Unichem USA because it is incorporated in New Jersey. Venue is alleged for Unichem India on the basis that it is an alien corporation that may be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market generic versions of the antiplatelet drug BRILINTA® (ticagrelor) constitutes an act of infringement of patents covering the ticagrelor compound and a method of its use for preventing cardiovascular events.
  • Technical Context: The technology relates to ticagrelor, an antiplatelet agent used as a long-term therapy to reduce the risk of cardiovascular death, myocardial infarction, and stroke in patients with a history of such events.
  • Key Procedural History: U.S. Reissue Patent No. RE46,276 is a reissue of U.S. Patent No. 6,525,060, which was surrendered. The complaint also identifies other pending litigation in the same district where Plaintiff has asserted the patents-in-suit against other pharmaceutical manufacturers, including HEC Pharm Co., Dr. Reddy’s Laboratories, and Taro Pharmaceuticals.

Case Timeline

Date Event
1998-12-04 ’276 Patent Priority Date
2003-02-25 Original U.S. Patent No. 6,525,060 Issue Date
2015-01-27 ’065 Patent Priority Date
2017-01-17 ’276 Patent Issue Date
2019-05-28 ’065 Patent Issue Date
2022-11-07 Defendant sends Paragraph IV Notice Letter to Plaintiff
2022-12-22 Complaint Filing Date

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," issued May 28, 2019

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of providing safe and effective long-term secondary prevention for patients with a history of myocardial infarction (MI) (Compl. ¶35; ’065 Patent, col. 3:1-4). Standard antiplatelet therapy guidelines often recommend treatment for only up to one year post-event, leaving an unmet need for managing the heightened long-term risk of recurrent ischemic events while balancing the corresponding risk of bleeding associated with such therapies (’065 Patent, col. 3:14-55).
  • The Patented Solution: The patent claims a specific method of treatment based on the results of the PEGASUS-TIMI 54 clinical trial (’065 Patent, col. 4:14-16). The solution is the administration of a 60 mg dose of ticagrelor twice daily, in combination with low-dose aspirin, to patients with a prior MI. This lower-dose, long-term regimen was shown to reduce the rate of cardiovascular death, MI, or stroke compared to treatment with aspirin alone, as illustrated by Kaplan-Meier curves from the trial presented in the patent’s figures (’065 Patent, Fig. 2-Panel A; col. 4:26-34).
  • Technical Importance: The invention provided clinical evidence for a specific, lower-dose ticagrelor regimen for long-term use, offering a new therapeutic strategy to improve the balance between efficacy in preventing thrombotic events and the risk of bleeding in a chronic-care setting (’065 Patent, col. 4:56-60).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶45).
  • The essential elements of independent claim 1 include:
    • A method for reducing the rate of a composite endpoint of cardiovascular death, myocardial infarction, or stroke in a patient in recognized need thereof.
    • 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.
    • Wherein the rate of the composite endpoint in the patient is reduced relative to a dosing regimen with aspirin alone.

U.S. Reissue Patent No. RE46,276 - "Triazolo(4,5-D)Pyrimidine Compounds," issued January 17, 2017

The Invention Explained

  • Problem Addressed: The patent background describes arterial thrombosis, initiated by platelet adhesion and aggregation, as a primary cause of high-morbidity events like myocardial infarction and unstable angina (’276 Patent, col. 1:29-39). The patent identifies the P2Y₁₂ receptor on platelets as a key mediator of this process and notes the need for effective antagonist compounds to serve as anti-thrombotic agents (’276 Patent, col. 2:9-21).
  • The Patented Solution: The patent discloses a class of chemical compounds—triazolo[4,5-d]pyrimidines—that act as P2Y₁₂ receptor antagonists. The invention specifically claims the molecular structure of ticagrelor (as encompassed by Formula (I)) and related compounds, which inhibit platelet aggregation and are therefore useful as anti-thrombotic therapies (’276 Patent, col. 2:22-31; col. 25:46-67).
  • Technical Importance: This invention provided a new chemical entity, ticagrelor, which is a direct-acting and reversibly-binding P2Y₁₂ antagonist, offering a novel mechanism and therapeutic option for the prevention of thrombosis (’276 Patent, Abstract).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶50).
  • The essential elements of independent claim 1 include:
    • A compound of formula (I), which defines a chemical structure with various substituent groups. The claim defines a class of compounds that includes the active ingredient ticagrelor.

III. The Accused Instrumentality

Product Identification

  • Defendant’s proposed generic ticagrelor tablets in 60 mg and 90 mg dosage strengths, which are the subject of Abbreviated New Drug Application (ANDA) No. 217984 (Compl. ¶1, 40).

Functionality and Market Context

  • The complaint alleges Defendant filed its ANDA to obtain FDA approval to market a generic version of AstraZeneca’s BRILINTA® drug product (Compl. ¶1). As a generic equivalent, the accused product contains ticagrelor as its active pharmaceutical ingredient and is intended to be used for the same approved indications, which include reducing the rate of cardiovascular events in patients with acute coronary syndrome or a history of myocardial infarction (Compl. ¶37, 40).
  • The filing of the ANDA is alleged to be an act of infringement under the Hatch-Waxman Act, signaling Defendant’s intent to engage in the commercial manufacture, use, and sale of the generic tablets in the United States upon approval (Compl. ¶40, 44, 49).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

RE46,276 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound of formula (I) ... The active pharmaceutical ingredient in Defendant’s ANDA product is ticagrelor, a compound alleged to be described by formula (I) of the asserted claim. ¶40, 50 col. 25:46-67

U.S. Patent No. 10,300,065 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... Defendant is seeking FDA approval for its generic ticagrelor product with proposed labeling that will instruct physicians and patients to use the drug for this patented therapeutic purpose. ¶37, 45 col. 88:55-58
...comprising administering to the patient twice daily a pharmaceutical composition comprising 60 mg ticagrelor... Defendant’s ANDA includes a 60 mg ticagrelor tablet, and its proposed labeling will instruct twice-daily administration, thereby directing users to perform the claimed administration step. ¶40, 45 col. 88:59-62
...wherein the patient has a history of myocardial infarction... The proposed labeling for Defendant's product will identify patients with a history of myocardial infarction as the target population for the treatment method. ¶37, 45 col. 88:63-64
...wherein the patient is also administered a daily maintenance dose of aspirin of 75 mg to 150 mg... The proposed labeling will instruct that the generic ticagrelor product be co-administered with a daily maintenance dose of aspirin, consistent with the claimed method. ¶37, 45 col. 88:64-66

Identified Points of Contention

  • Scope Questions: For the ’065 Patent, a central question may be whether the instructions in Defendant’s proposed product label will direct or encourage medical professionals and patients to perform every limitation of the claimed method. The analysis will depend on the specific language of the proposed label relative to the claim language.
  • Technical Questions: For the ’276 Patent, infringement analysis in an ANDA case typically centers on whether the active pharmaceutical ingredient (API) in the generic product is structurally identical to the claimed compound. A question for the court is whether there are any structural, isomeric, or polymorphic differences between Unichem’s ticagrelor API and the compound protected by claim 1 that would support a non-infringement argument.

V. Key Claim Terms for Construction

  • The Term: "patient in recognized need thereof" (from claim 1 of the ’065 Patent)
  • Context and Importance: This term defines the patient population eligible for the claimed method. Its construction is critical because it determines the breadth of the patented method. Practitioners may focus on this term because Defendant could argue for a narrow construction limited to the specific patient population studied in the PEGASUS-TIMI 54 trial, while Plaintiff may argue for a broader construction covering any patient a clinician would identify as benefiting from the therapy.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The plain meaning of the phrase suggests it encompasses any patient for whom a medical professional, using their clinical judgment, determines that reducing the specified cardiovascular risks is needed.
    • Evidence for a Narrower Interpretation: The specification is heavily based on the PEGASUS-TIMI 54 clinical trial, which had detailed inclusion and exclusion criteria (’065 Patent, col. 4:14-16; col. 19:5-35). A party could argue that the term should be limited to patients who would have been eligible for that trial, as this is the only population for which the patent provides evidence of efficacy.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will infringe under 35 U.S.C. §§ 271(b) and/or 271(c) (Compl. ¶45, 50). The basis for this allegation is that Defendant’s sale of its generic ticagrelor products will be accompanied by a product label and instructions that will actively induce and encourage physicians to prescribe and patients to use the drug in a manner that directly infringes the asserted claims of the ’065 method 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. However, it does allege that Defendant provided a "paragraph IV certification" in its Notice Letter, which asserts that the patents are invalid, unenforceable, or will not be infringed (Compl. ¶41). This certification establishes that Defendant had pre-suit knowledge of the patents-in-suit.

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

  • A core issue will be one of induced infringement: for the ’065 method-of-use patent, can AstraZeneca establish that the language of Unichem’s proposed product label will inevitably lead medical professionals to prescribe, and patients to administer, the 60 mg generic ticagrelor tablet in a manner that satisfies every limitation of the asserted claims?
  • A key question for the ’276 compound patent will likely center on validity, which is typically the primary defense in ANDA litigation involving a known compound. While infringement appears straightforward if the generic API is the same molecule, the ultimate dispute will likely turn on whether Unichem can successfully challenge the patent’s novelty, non-obviousness, or other requirements for patentability.
  • A central strategic question is one of claim scope versus clinical reality: for the ’065 patent, will the term "patient in recognized need thereof" be construed broadly based on its plain meaning, or will it be narrowed by the court to the specific patient population defined in the PEGASUS-TIMI 54 trial, potentially limiting the scope of infringement?