DCT

1:24-cv-01270

SK Biopharma Co Ltd v. MSN Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01270, D. Del., 11/19/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant MSN Inc. is a Delaware corporation and both defendants are alleged to have systematic contacts with the state, intend to sell the accused products in Delaware, and have consented to jurisdiction in prior ANDA litigation.
  • Core Dispute: Plaintiff alleges that Defendant's Abbreviated New Drug Application (ANDA) to market generic versions of the epilepsy drug XCOPRI® (cenobamate) constitutes an act of infringement of a patent covering methods of using cenobamate in combination with other specific antiepileptic drugs.
  • Technical Context: The technology concerns pharmaceutical combination therapy for treating epilepsy, specifically addressing the pharmacokinetic interactions that occur when multiple antiepileptic drugs are co-administered.
  • Key Procedural History: The action arises from Defendant’s submission of ANDA No. 219436 with a Paragraph IV certification, noticed to the Plaintiff on October 7, 2024. This certification asserts that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product. The filing of the complaint within the 45-day statutory window triggers a 30-month stay of FDA approval for the ANDA.

Case Timeline

Date Event
2018-03-21 U.S. Patent No. 11,654,133 Priority Date
2020-03-10 FDA approves New Drug Application for XCOPRI® (cenobamate)
2023-05-23 U.S. Patent No. 11,654,133 Issues
2024-10-07 Defendant sends Paragraph IV certification notice concerning its ANDA
2024-11-19 Complaint for Patent Infringement Filed

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

U.S. Patent No. 11,654,133 - Use of [(1R)-1-(2-chlorophenyl)-2-(tetrazol-2-yl)ethyl] Carbamate in Combination Therapy (Issued May 23, 2023)

The Invention Explained

  • Problem Addressed: The patent background describes the challenge of treating refractory epilepsy, where patients often require long-term adjunctive therapy with multiple antiepileptic drugs (AEDs) (’133 Patent, col. 1:45-49). It notes that many AEDs have narrow therapeutic indices and are "highly susceptible to drug interactions," which can lead to treatment failure or safety concerns when their pharmacokinetics (PK) are altered (’133 Patent, col. 1:49-52).
  • The Patented Solution: The invention provides a method for treating epilepsy by co-administering cenobamate with other specific AEDs (phenytoin or phenobarbital). The core of the method is a specific instruction: "modifying the therapeutically effective amount of the antiepileptic drug" to adjust its Area Under the Curve (AUC), a key measure of drug exposure (’133 Patent, col. 2:32-39). This dose adjustment is intended to manage the drug-drug interaction, thereby allowing for the safe and effective use of the combination therapy (’133 Patent, col. 2:21-25).
  • Technical Importance: The claimed method provides a specific, data-driven approach to managing known pharmacokinetic interactions, a critical consideration for clinicians prescribing combination therapies for complex conditions like epilepsy (’133 Patent, col. 2:15-25).

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 1 (Compl. ¶49).
  • Independent Claim 1 recites a method with the following essential elements:
    • A method for treating a patient with epilepsy by co-administering therapeutically effective amounts of cenobamate and one or two other antiepileptic drugs.
    • The method comprises a step of "modifying" the amount of the other antiepileptic drug to "adjust" its AUC by at least 5% compared to its administration without cenobamate.
    • The therapeutically effective amount of cenobamate is between about 100 mg/day and 400 mg/day.
    • The other antiepileptic drug is either phenobarbital or phenytoin.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are Defendant’s proposed generic cenobamate tablets in 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg strengths ("MSN's ANDA Products") (Compl. ¶1, ¶40).

Functionality and Market Context

  • The act of infringement alleged is the filing of ANDA No. 219436, which seeks FDA approval to market a generic version of Plaintiff's XCOPRI® product before the expiration of the ’133 Patent (Compl. ¶1, ¶39).
  • The infringement theory is based on the future use of the generic product. The complaint alleges that MSN's ANDA Products will be sold with prescribing information "substantially the same as the FDA-approved XCOPRI® Prescribing Information" (Compl. ¶41). This label, if followed by physicians, would allegedly lead to direct infringement of the patented method by instructing the co-administration of cenobamate with phenytoin or phenobarbital and including instructions to modify the dosage of those drugs (Compl. ¶52, ¶60).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’133 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating a patient who is suffering from epilepsy with co-administering a therapeutically effective amount of (i) ... cenobamate ... and (ii) one or two antiepileptic drugs... The proposed prescribing information for MSN's ANDA Products will instruct their use for treating epilepsy in combination with other AEDs, thereby inducing physicians and patients to perform the co-administration step (Compl. ¶31, ¶41). ¶52, ¶60 col. 2:25-32
modifying the therapeutically effective amount of the antiepileptic drug to adjust AUC of the antiepileptic drug obtained after the co-administration having at least 5% difference to the level of AUC obtained after the administration of antiepileptic drug to the patient without cenobamate... The proposed prescribing information will allegedly instruct physicians to modify the dose of phenytoin or phenobarbital when co-administered with cenobamate, which will adjust the AUC of those drugs as claimed (Compl. ¶35, ¶37, ¶38). ¶52, ¶60 col. 2:32-39
wherein the therapeutically effective amount of cenobamate or a pharmaceutically acceptable salt thereof is from about 100 mg/day to about 400 mg/day The proposed prescribing information will instruct the administration of cenobamate at dosages within this range, including a recommended maintenance dosage of 200 mg/day (Compl. ¶30). ¶52 col. 2:50-53
wherein the antiepileptic drug is selected from the group consisting of phenobarbital and phenytoin. The proposed prescribing information will provide specific instructions regarding the co-administration of cenobamate with phenobarbital and phenytoin, thereby instructing the use of the claimed drug combination (Compl. ¶35). ¶52 col. 10:50-51

Identified Points of Contention

  • Scope Questions: The primary dispute will likely center on whether the instructions in the proposed generic label rise to the level of inducing infringement. A question for the court will be whether the label's instructions to, for example, "gradually decrease phenytoin dosage by up to 50%" (Compl. ¶35) are sufficient to meet the claim limitation of "modifying... to adjust AUC."
  • Technical Questions: A factual question may be whether the dose modifications described in the proposed label necessarily result in an AUC adjustment of "at least 5%." While the complaint alleges this (Compl. ¶37, ¶38), the defendant may challenge the evidentiary basis for this assertion as it applies to the specific instructions in its proposed label.

V. Key Claim Terms for Construction

  • The Term: "modifying the therapeutically effective amount of the antiepileptic drug to adjust AUC"
  • Context and Importance: The construction of this phrase is central to the infringement analysis. It defines the specific action that a physician must be induced to perform. The dispute will likely focus on whether the instruction must explicitly state the purpose of the modification is to adjust the AUC, or if an instruction to modify the dose for other reasons (e.g., safety) that has the result of adjusting the AUC is sufficient. Practitioners may focus on this term because it links a physical act ("modifying") with a specific pharmacokinetic outcome ("to adjust AUC").
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A patentee might argue the claim language does not require the physician to be thinking about AUC, only that the instructed modification achieves the claimed AUC adjustment. The patent describes the AUC change as a result of co-administration and dose modification, without requiring the physician's specific intent to target AUC (’133 Patent, col. 18, Table 2).
    • Evidence for a Narrower Interpretation: An accused infringer could argue that the phrase "to adjust" imparts a purpose, meaning the label must instruct the modification for the purpose of adjusting the AUC. The patent's "Solution to Problem" section explicitly frames the invention around obtaining safety by "adjusting the dose ... to adjust AUC," suggesting this purpose is integral to the invention (’133 Patent, col. 2:25-39).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). The factual basis is the allegation that MSN's proposed product label will knowingly and intentionally instruct and encourage physicians and other healthcare professionals to perform the steps of the patented method, leading to direct infringement (Compl. ¶52).
  • Willful Infringement: The complaint alleges that MSN had "actual and constructive notice" of the ’133 Patent prior to filing its ANDA and had "no reasonable basis" for its Paragraph IV certification that the patent was invalid or not infringed (Compl. ¶53, ¶54). This alleged conduct is presented as the basis for the case being "exceptional" under 35 U.S.C. § 285 (Compl. ¶54).

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

The resolution of this case will likely depend on two central questions:

  1. A core issue will be one of induced infringement: will the instructions in Defendant's proposed generic label be interpreted as actively encouraging or instructing physicians to perform every step of the claimed method? Or, could the label's dosage recommendations be construed as mere information that falls short of the specific intent required to find inducement?
  2. A key question of claim construction will be determinative: does the claim limitation "modifying ... to adjust AUC" require the product label to explicitly state that the purpose of the dose modification is to alter the drug's AUC? Or is it sufficient that the label instructs a dose modification that, in practice, results in the claimed AUC adjustment, regardless of the stated reason in the label?