Medicure Intl Inc v. Nexus Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Medicure International, Inc. (Barbados)
  • Defendant: Nexus Pharmaceuticals, Inc. (Illinois)
  • Plaintiff’s Counsel: Green, Griffith & Borg-Breen LLP
• Case Identification: Medicure International, Inc. v. Nexus Pharmaceuticals, Inc., 1:19-cv-07979, N.D. Ill., 12/05/2019
• Venue Allegations: Venue is based on Defendant being a corporation organized under Illinois law with its principal place of business in Lincolnshire, Illinois.
• Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA to market a generic version of Plaintiff's Aggrastat® product constitutes an act of infringement of a patent covering a specific method for administering the drug.
• Technical Context: The technology concerns a pharmaceutical method for inhibiting platelet aggregation, a key therapeutic goal in treating patients with acute coronary syndrome to prevent thrombotic cardiovascular events.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by Defendant's filing of an ANDA containing a Paragraph IV certification against the patent-in-suit. The patent is listed in the FDA's "Orange Book" as covering Plaintiff's drug, Aggrastat®. Defendant's Paragraph IV certification asserts that the patent is invalid or will not be infringed by its proposed generic product, which is a statutory act of infringement enabling this lawsuit prior to any commercial launch.

Case Timeline

Date	Event
2002-05-06	'660 Patent Priority Date
2004-08-03	'660 Patent Issue Date
2019-10-22	Nexus letter to Medicure regarding jurisdiction
2019-12-05	Complaint Filing Date
c. 2022-04-01	Alleged intended date for final ANDA approval

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

U.S. Patent No. 6,770,660 - "Method for Inhibiting Platelet Aggregation"

• Patent Identification: U.S. Patent No. 6,770,660, "Method for Inhibiting Platelet Aggregation," issued August 3, 2004. (Compl. ¶17).

The Invention Explained

• Problem Addressed: The patent's background section notes that prior intravenous treatments using the platelet aggregation inhibitor tirofiban, such as a 10 µg/kg initial bolus dose, achieved only a moderate level of platelet inhibition, stated to be between 61% and 66%. (’660 Patent, col. 2:1-6). The technical challenge was to achieve a more potent and effective inhibition.
• The Patented Solution: The invention is a method of administration claiming to achieve "substantially more effective inhibition" by using a higher initial "bolus" dose of tirofiban followed by a sustained infusion. (’660 Patent, col. 2:12-14). Specifically, the method claims an initial bolus of "about 25 µg/kg," which the patent asserts provides a platelet aggregation inhibition of greater than 90% without requiring an increase in the subsequent infusion concentration or incurring additional side effects. (’660 Patent, Abstract; col. 2:18-24). The specification presents data in Table 1 comparing the inhibitory effects of 10 µg/kg, 20 µg/kg, and 25 µg/kg bolus doses to support this claimed improvement. (’660 Patent, col. 4, Table 1).
• Technical Importance: By providing a method to achieve a more rapid and robust anti-platelet effect, the invention offered a potentially more effective treatment for patients with acute coronary syndrome, particularly during the critical period of a percutaneous coronary intervention. (’660 Patent, col. 4:62-67).

Key Claims at a Glance

• The complaint asserts infringement of "one or more" of the patent's claims. (Compl. ¶54). The patent contains two independent claims, Claim 1 and Claim 6.
• Independent Claim 1:
  • A method for inhibiting platelet aggregation in a patient in need thereof, comprising:
  • 1. administering to the patient a bolus injection of an active drug, in an amount of about 25 µg/kg, and
  • 2. administering to the patient, after the bolus injection, an intravenous infusion for a period of between about 12 hours and about 72 hours, of the active drug, in an amount of about 0.15 µg/kg/min,
  • wherein the active drug is tirofiban or a salt thereof.
• Independent Claim 6:
  • A method for reducing the risk of acute coronary syndrome in a patient at risk to acute coronary syndrome, comprising:
  • 1. administering to the patient a bolus injection of an active drug, in an amount of about 25 µg/kg, and
  • 2. administering to the patient, after the bolus injection, an intravenous infusion for a period of between about 12 hours and about 72 hours, of the active drug, in an amount of about 0.15 µg/kg/min,
  • wherein the active drug is tirofiban or a salt thereof.

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is the future commercial manufacture, use, and sale of Defendant's generic tirofiban hydrochloride injection product, as described in Abbreviated New Drug Application (ANDA) No. 213947 ("Nexus's ANDA Product"). (Compl. ¶9).

Functionality and Market Context

• The infringement allegation centers on the method of use that will be instructed in the proposed Prescribing Information (i.e., the drug label) for Nexus's ANDA Product. (Compl. ¶27, ¶53).
• The complaint alleges, upon information and belief, that this label will recommend that physicians administer the product using a dosage regimen that practices the patented method. (Compl. ¶53).
• Nexus's product is a proposed generic equivalent to Plaintiff's branded drug, Aggrastat®, and seeks approval for the same indication: reducing the rate of thrombotic cardiovascular events in patients with non-ST elevation acute coronary syndrome. (Compl. ¶15, ¶21, ¶50). The act of filing the ANDA to obtain approval for this use is the statutory basis of the infringement claim. (Compl. ¶36). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

Claim Chart Summary

• The complaint alleges that the instructions for use in the proposed label for Nexus's ANDA Product will direct physicians to perform a method that meets every limitation of the asserted claims.

’660 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method for inhibiting platelet aggregation in a patient in need thereof...	Physicians will administer Nexus's product to patients with non-ST elevation acute coronary syndrome to reduce thrombotic cardiovascular events, which involves inhibiting platelet aggregation.	¶50, ¶51	col. 2:27-34
...administering to the patient a bolus injection of an active drug, in an amount of about 25 µg/kg...	The proposed Prescribing Information will recommend administering a bolus injection of the active drug in an amount of "about 25 µg/kg."	¶53	col. 4:60-61
...administering to the patient, after the bolus injection, an intravenous infusion for a period of between about 12 hours and about 72 hours, of the active drug, in an amount of about 0.15 µg/kg/min...	The proposed Prescribing Information will recommend administering an intravenous infusion for a period between 12 and 72 hours, in an amount of "about 0.15 µg/kg/min."	¶53	col. 4:61-64
...wherein the active drug is tirofiban or a salt thereof.	Nexus's ANDA Product contains the active ingredient tirofiban hydrochloride, which is a pharmaceutically acceptable salt of tirofiban.	¶42, ¶43	col. 2:55-58

Identified Points of Contention

• Evidentiary Question: The infringement allegations are based "upon information and belief" regarding the contents of Nexus's proposed drug label. (Compl. ¶53). A primary evidentiary question for the court will be whether the Prescribing Information submitted to the FDA as part of ANDA No. 213947 actually contains the specific dosage instructions alleged in the complaint.
• Scope Questions: Should the label's instructions differ slightly from the claim language, the interpretation of the term "about" will become critical. For example, a key question would be whether a recommended dose of "24 µg/kg" falls within the scope of "about 25 µg/kg" as used in the patent. A further question may arise regarding non-infringing uses, as the complaint notes the label recommends a reduced infusion dosage (0.075 mcg/kg/min) for patients with renal impairment, which is different from the claimed "about 0.15 µg/kg/min." (Compl. ¶48).

V. Key Claim Terms for Construction

The Term

• "about 25 µg/kg" and "about 0.15 µg/kg/min"

Context and Importance

• These quantitative terms containing "about" are the central limitations defining the invention. The patent's entire premise rests on the superiority of the "about 25 µg/kg" bolus dose over prior art. The construction of "about" will define the boundaries of infringement. Practitioners may focus on this term because the outcome could determine whether Nexus's proposed label, if it specifies a dose numerically different from but close to 25, infringes the claim.

Intrinsic Evidence for Interpretation

Evidence for a Broader Interpretation

• The patent consistently uses the term "about" when reciting the dosage amounts in the claims and the summary of the invention, which may suggest the patentee did not intend to be limited to the precise numerical values. (’660 Patent, col. 2:30; col. 4:61). The specification also refers to identifying a "dosage range" that achieves the desired effect, further suggesting some flexibility was contemplated. (’660 Patent, col. 6:1-3).

Evidence for a Narrower Interpretation

• The specification presents experimental data for discrete dosage levels of 10, 20, and 25 µg/kg, with only the 25 µg/kg dose achieving the target >90% inhibition. (’660 Patent, col. 4, Table 1). A party could argue that "about 25 µg/kg" must be construed as a narrow range centered on 25 µg/kg that is patentably distinct from the 20 µg/kg level. Furthermore, dependent claim 3 recites the dose as exactly "25 µg/kg," which, under the doctrine of claim differentiation, implies that "about 25 µg/kg" in independent claim 1 must be broader, but also highlights 25 µg/kg as a specific, important value.

VI. Other Allegations

Indirect Infringement

• The complaint is premised on induced infringement. The primary allegation is that Nexus's filing of an ANDA with a Paragraph IV certification is a statutory act of infringement under 35 U.S.C. § 271(e)(2). (Compl. ¶36). For infringement post-approval, the complaint alleges Nexus would induce infringement by physicians who would prescribe the accused product according to its label. (Compl. ¶55). The complaint alleges Nexus possessed the requisite specific intent to encourage infringement, evidenced by its knowledge of the patent and its proposed label instructing the infringing use. (Compl. ¶57).

Willful Infringement

• The complaint alleges willful infringement based on Nexus's pre-suit knowledge of the ’660 Patent, evidenced by its filing of a Paragraph IV certification against it. (Compl. ¶56). It further alleges that Nexus acted without a reasonable basis for believing it would not be liable for infringement. (Compl. ¶61).

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

• A central legal issue will be one of quantitative scope: how broadly will the court construe the term "about" as applied to the dosage limitations? The case may turn on whether this term encompasses a wide range of numerical values or is narrowly defined by the specific experimental data in the patent that distinguishes the claimed invention from lower, less effective doses.
• A key evidentiary question will be one of label content: does the proposed Prescribing Information in Nexus's ANDA in fact instruct a method of use that falls within the scope of the asserted claims? The outcome of the infringement analysis is contingent on the precise language of a document not yet public.
• Given that this is a Hatch-Waxman action triggered by a Paragraph IV certification, a dispositive issue for the case will almost certainly be patent validity: can Nexus establish, by clear and convincing evidence, that the ’660 Patent’s claims to a specific dosage regimen are invalid, for example, as being obvious over prior art that taught the administration and dose-response relationship of tirofiban?