DCT

1:23-cv-01331

Catalyst Pharma Inc v. Inventia Healthcare Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-01331, D. Del., 11/20/2023
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Delaware because Defendant derives substantial revenue from selling generic pharmaceutical products in the district and has previously been subject to personal jurisdiction in this Court in other patent cases.
  • Core Dispute: Plaintiffs allege that Defendant's submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs' Firdapse® tablets constitutes an act of infringement of six U.S. patents related to the drug's purity testing and methods of administration.
  • Technical Context: The dispute centers on amifampridine, a treatment for Lambert-Eaton Myasthenic Syndrome (LEMS), a rare autoimmune disorder affecting neuromuscular transmission.
  • Key Procedural History: The action was precipitated by a Notice Letter, dated October 6, 2023, in which Defendant informed Plaintiffs of its ANDA submission seeking FDA approval to market a generic amifampridine product. This letter included a Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed.

Case Timeline

Date Event
2011-06-30 Priority Date for ’893, ’128A, ’128B, ’331, and ’332 Patents
2016-06-10 Priority Date for ’088 Patent
2018-11-28 FDA Approval for Catalyst's Firdapse® Product
2020-04-21 Issue Date for U.S. Patent No. 10,626,088
2020-10-06 Issue Date for U.S. Patent No. 10,793,893
2021-07-13 Issue Date for U.S. Patent No. 11,060,128
2022-03-08 Issue Date for U.S. Patent No. 11,268,128
2022-03-15 Issue Date for U.S. Patent No. 11,274,331
2022-03-15 Issue Date for U.S. Patent No. 11,274,332
2023-10-06 Defendant Inventia sends ANDA Notice Letter to Plaintiffs
2023-11-20 Complaint Filing Date

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

U.S. Patent No. 10,626,088 - Determining Degradation of 3,4-Diaminopyridine

The Invention Explained

  • Problem Addressed: The patent addresses the need to ensure the quality and purity of the drug 3,4-diaminopyridine, noting that impurities, whether from synthesis or degradation, can be associated with adverse effects such as increased toxicity or decreased efficacy (Compl. ¶1; ’088 Patent, col. 1:21-35).
  • The Patented Solution: The invention provides methods for determining the purity of a 3,4-diaminopyridine sample by detecting and quantifying a specific degradation product: a dimer of 3,4-diaminopyridine. The patent describes using high-performance liquid chromatography (HPLC) to identify and measure the amount of this dimer, thereby providing a metric to assess sample purity and degradation (’088 Patent, col. 5:58 - col. 6:9).
  • Technical Importance: This technology provides a specific, quantifiable method for quality control in the manufacturing and storage of a pharmaceutical product used to treat a rare disease, which is critical for patient safety and regulatory compliance (Compl. ¶21).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’088 Patent without specifying which claims are asserted (Compl. ¶38). Independent claim 1 is representative of the invention.
  • Claim 1 includes the following essential elements:
    • A method of determining the purity of a sample of 3,4-diaminopyridine.
    • The method comprises determining the presence, absence, or amount of a dimer of 3,4-diaminopyridine in the sample.
    • The amount of the dimer in the sample is indicative of the purity of the 3,4-diaminopyridine sample.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 10,793,893 - Methods of Administering 3,4-Diaminopyridine

The Invention Explained

  • Problem Addressed: The patent describes that the pharmacokinetic profile of orally administered 3,4-diaminopyridine (3,4-DAP) is "highly variable between patients," with significant differences in key metrics like maximum plasma concentration (Cmax) and area under the curve (AUC) (’893 Patent, col. 2:11-18). This variability makes consistent and safe dosing a challenge.
  • The Patented Solution: The invention provides a personalized medicine approach to solve this problem. It discloses methods for determining a subject's N-acetyl transferase (NAT) acetylation status—classifying them as a "slow acetylator" or "fast acetylator"—and then administering a dose of 3,4-DAP that is adjusted to that status. This tailoring of the dose is intended to improve efficacy and reduce the frequency or severity of adverse events (’893 Patent, Abstract; col. 2:31-45).
  • Technical Importance: This invention shifts the treatment paradigm from a one-size-fits-all approach to a personalized one, potentially improving the safety and efficacy of 3,4-DAP for patients with rare diseases like LEMS (Compl. ¶21).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’893 Patent without specifying which claims are asserted (Compl. ¶46). Independent claim 1 is representative of the invention.
  • Claim 1 includes the following essential elements:
    • A method of treating a 3,4-DAP-sensitive disease in a human patient.
    • Determining whether the patient is a slow acetylator or a fast acetylator of 3,4-DAP.
    • Administering to the patient a dose of 3,4-DAP or a pharmaceutically acceptable salt thereof.
    • The administered amount is adjusted to the patient's acetylator status.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 11,060,128 - Methods of Administering 3,4-Diaminopyridine

  • Technology Synopsis: This patent relates to methods of treating a patient with a 3,4-DAP sensitive disease, such as LEMS, by tailoring the drug dosage to the patient's genetic makeup (’128A Patent, Abstract). The problem addressed is inter-patient variability in drug metabolism, and the solution is to administer a specific dose based on whether the patient is a "slow acetylator," identified by specific mutations in the NAT2 gene (’128A Patent, col. 2:31-45; Claim 1).
  • Asserted Claims: The complaint asserts infringement of one or more claims of the ’128A patent (Compl. ¶54). Independent claim 1 is asserted.
  • Accused Features: Plaintiffs allege that Defendant will induce infringement because its proposed product label will instruct administration methods covered by the patent's claims (Compl. ¶¶ 53-54).

U.S. Patent No. 11,268,128 - Methods of Administering 3,4-Diaminopyridine

  • Technology Synopsis: This patent is directed to methods of treating LEMS by administering a specific total daily dose of 3,4-DAP (or a salt thereof) to a patient who is a "slow acetylator" (’128B Patent, Abstract; Claim 1). This approach aims to provide a safe and effective treatment regimen for a specific sub-population of patients with characterized metabolic profiles, thereby addressing the issue of high pharmacokinetic variability observed in the general patient population (Compl. ¶21).
  • Asserted Claims: The complaint asserts infringement of one or more claims of the ’128B patent (Compl. ¶62). Independent claim 1 is asserted.
  • Accused Features: Plaintiffs allege that Defendant will induce infringement through the instructions for use that will be provided with its generic product (Compl. ¶¶ 61-62).

U.S. Patent No. 11,274,331 - Methods of Administering 3,4-Diaminopyridine

  • Technology Synopsis: This patent claims methods of treating LEMS by administering a specific total daily dose of 3,4-DAP to a human patient who has two "fast" NAT2 alleles (’331 Patent, Abstract; Claim 1). The invention provides a dosing regimen tailored to the "fast acetylator" patient population to account for metabolic differences and optimize treatment outcomes (Compl. ¶21).
  • Asserted Claims: The complaint asserts infringement of one or more claims of the ’331 patent (Compl. ¶70). Independent claim 1 is asserted.
  • Accused Features: The infringement allegation is based on induced infringement, where Defendant's proposed product labeling will allegedly direct medical professionals and patients to practice the claimed method (Compl. ¶¶ 69-70).

U.S. Patent No. 11,274,332 - Methods of Administering 3,4-Diaminopyridine

  • Technology Synopsis: This patent covers methods of treating a patient with LEMS by administering a total daily dose of 3,4-DAP (or a salt thereof) as a series of divided doses to a patient identified as a "slow acetylator" (’332 Patent, Abstract; Claim 1). This method addresses the problem of inter-patient variability by defining a specific dosing protocol for a genetically-defined patient subgroup (Compl. ¶21).
  • Asserted Claims: The complaint asserts infringement of one or more claims of the ’332 patent (Compl. ¶78). Independent claim 1 is asserted.
  • Accused Features: Plaintiffs allege that the instructions accompanying Defendant's ANDA product will induce infringement by directing users to follow the patented method of administration (Compl. ¶¶ 77-78).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant Inventia's proposed generic version of Firdapse® (amifampridine) 10 mg tablets, identified as ANDA No. 218760 ("Inventia's ANDA Product") (Compl. ¶1).

Functionality and Market Context

  • The complaint alleges that by filing its ANDA, Inventia has represented to the FDA that its product will have the same active ingredient, method of administration, dosage form, and strength as Catalyst's Firdapse®, and will be bioequivalent (Compl. ¶33). Amifampridine functions as a nonspecific voltage-dependent potassium channel blocker, which improves neuromuscular transmission and is used for the treatment of LEMS (Compl. ¶18).
  • The complaint asserts that Firdapse® was the first product approved by the FDA for the treatment of LEMS, having received breakthrough therapy and orphan drug designations (Compl. ¶19). Inventia's product is positioned to be a generic competitor upon receiving FDA approval (Compl. ¶1).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-chart analysis. The infringement allegations are based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2) and on anticipated future acts of induced and contributory infringement once the ANDA product is approved and marketed. The central infringement theories are summarized below.

  • ’088 Patent (Method of Determining Purity):

    • The complaint alleges that Inventia's submission of its ANDA, and the future manufacturing and sale of the ANDA Product, will infringe the claimed method of determining purity (Compl. ¶¶ 37, 39). The complaint does not contain factual allegations explaining how Inventia’s quality control or manufacturing processes would practice the specific steps of the asserted claims, such as "determining the presence, absence, or amount of a dimer."

  • ’893 Patent Family (’893, ’128A, ’128B, ’331, ’332 Patents - Methods of Administration):

    • The complaint alleges that once Inventia's ANDA product is approved, it will be administered by patients and medical practitioners "according to the directions and instructions in the proposed package insert" (e.g., Compl. ¶46, ¶54, ¶62, ¶70, ¶78). This administration, according to Plaintiffs, will constitute direct infringement of the method claims. The complaint further alleges that by providing these instructions, Inventia will actively induce infringement of these method patents (e.g., Compl. ¶45, ¶53, ¶61, ¶69, ¶77).

  • Identified Points of Contention:

    • Scope Questions: A primary question for the ’088 patent will be whether the act of submitting an ANDA for a drug product can, as a matter of law, constitute infringement of a claim directed to a method of testing the purity of that drug. The court may need to consider what evidence is required to show that the commercial manufacture contemplated by the ANDA would necessarily involve the claimed testing method.
    • Technical Questions: For the ’893 patent family, the central question will be factual: what will Inventia's FDA-approved label actually instruct? The infringement analysis will depend entirely on whether the label's language encourages or requires physicians to determine a patient's acetylator status (the "determining" step of the claims) and adjust dosing based on that status (the "administering" step).

V. Key Claim Terms for Construction

  • For the ’088 Patent:
    • The Term: "determining the presence, absence, or amount of a dimer" (Claim 1)
    • Context and Importance: This term defines the core step of the patented method. Practitioners may focus on this term because the infringement allegation against Inventia depends on whether its manufacturing and quality control processes, as described in its confidential ANDA, perform this specific determination.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language itself is broad and not limited to any particular analytical technique, which could support a construction covering any method used to detect the specified dimer.
      • Evidence for a Narrower Interpretation: The specification repeatedly describes using HPLC to identify and quantify the dimer (’088 Patent, col. 5:58 - col. 6:9). A defendant may argue this context limits the claim to the specific methods disclosed.
  • For the ’893 Patent:
    • The Term: "determining... whether a subject is a slow acetylator or fast acetylator" (Claim 1)
    • Context and Importance: This term defines the diagnostic step that precedes the therapeutic step. Practitioners may focus on this term because the inducement case will require proof that Inventia's label instructs or encourages physicians to perform this specific "determining" step before prescribing the drug.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language does not specify the means of determination. This may support a construction covering any method a physician might use to assess a patient's metabolic rate, including observing their response to initial doses.
      • Evidence for a Narrower Interpretation: The patent's detailed description provides specific examples of "determining" this status, such as through genotyping for NAT2 gene polymorphisms or phenotyping with a caffeine test (’893 Patent, col. 5:6-10; col. 11:51-67). A defendant may argue that the claim should be limited to these objective, specified tests rather than general clinical observation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendant will induce infringement of all six patents by providing a product with a label that will instruct users and medical practitioners to perform the claimed methods (e.g., Compl. ¶¶ 38, 46). The complaint also alleges contributory infringement for the ’088 patent, asserting that the ANDA Product is especially adapted for use in infringing the patent and is not suitable for a substantial non-infringing use (Compl. ¶39).
  • Willful Infringement: The complaint does not use the term "willful infringement," but it does allege that Inventia has had knowledge of the patents-in-suit since at least the date it submitted its ANDA (e.g., Compl. ¶41, ¶49). It further alleges that the case is "exceptional" and seeks an award of attorneys' fees under 35 U.S.C. § 285 (e.g., Compl. ¶42, ¶50).

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

  • A core issue will be one of infringement linkage: For the ’088 patent, what factual and legal basis connects the regulatory act of an ANDA submission to infringement of a claim for a method of quality control? The case may test the boundaries of the artificial act of infringement under the Hatch-Waxman Act.
  • A key evidentiary question will be one of inducement via labeling: For the five method-of-administration patents, does the specific language of Inventia’s proposed product label—which is not yet public—actively instruct or encourage physicians to perform the claimed diagnostic step of determining a patient's "acetylator status" before administering the drug?
  • A central claim construction dispute may focus on definitional precision: Will the "determining" steps in the asserted claims be construed broadly to cover routine clinical observations, or narrowly to require the specific analytical (e.g., HPLC) or genetic (e.g., NAT2 genotyping) tests disclosed in the patent specifications?