DCT

1:23-cv-00229

Catalyst Pharma Inc v. Lupin Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00229, D. Del., 03/02/2023
  • Venue Allegations: Venue is asserted based on the Delaware incorporation of Lupin Inc. and Lupin Pharmaceuticals, Inc., and on allegations that all Defendants maintain extensive and systematic contacts with Delaware and have committed acts of infringement within the district by submitting an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA).
  • Core Dispute: Plaintiffs allege that Defendants' submission of an ANDA seeking approval to market a generic version of Plaintiffs' Firdapse® (amifampridine) tablets constitutes an act of infringement of six U.S. patents.
  • Technical Context: The technology involves the drug amifampridine, used to treat the rare neuromuscular disorder Lambert-Eaton Myasthenic Syndrome (LEMS), and patented methods for personalizing its dosage based on patient genetics and for detecting its degradation products.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' submission of ANDA No. 217996 to the FDA. As part of the ANDA, Defendants filed a Paragraph IV certification asserting that Plaintiffs' patents, which are listed in the FDA's "Orange Book" in connection with Firdapse®, are invalid, unenforceable, and/or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2011-06-30 Earliest Priority Date for ’893, ’128A, ’128B, ’331, and ’332 Patents
2016-06-10 Priority Date for ’088 Patent
2018-11-28 FDA Approval for Plaintiff's Firdapse Product
2020-04-21 ’088 Patent Issued
2020-10-06 ’893 Patent Issued
2021-07-13 ’128A Patent Issued
2022-03-08 ’128B Patent Issued
2022-03-15 ’331 Patent Issued
2022-03-15 ’332 Patent Issued
2023-01-26 Defendants Send Notice Letter of ANDA Filing
2023-03-02 Complaint Filed

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

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

  • Patent Identification: U.S. Patent No. 10,626,088, "Determining Degradation of 3,4-Diaminopyridine," issued April 21, 2020.

The Invention Explained

  • Problem Addressed: The patent addresses the need to detect and quantify impurities and degradation products in pharmaceutical compositions of 3,4-diaminopyridine to ensure proper quality control and patient safety (Compl. ¶33; ’088 Patent, col. 1:20-35).
  • The Patented Solution: The invention identifies a specific degradation product of 3,4-diaminopyridine—a dimer formed by the covalent linking of two 3,4-diaminopyridine molecules. The patent claims this dimer compound itself, as well as methods for using its presence as an indicator to determine the purity of a drug sample (’088 Patent, Abstract; col. 4:1-9).
  • Technical Importance: The identification and synthesis of this specific dimer provides a reference marker for use in quality control assays, such as high-performance liquid chromatography (HPLC), to assess the stability and shelf-life of drug products containing 3,4-diaminopyridine (’088 Patent, col. 5:62-67).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the patent without specifying any particular claims (Compl. ¶50). Independent claim 1 is a composition of matter claim directed to the degradation product itself.
  • Claim 1 Elements:
    • A 3,4-Diaminopyridine dimer that is [a specific chemical structure] or a tautomer thereof;
    • in the form of a salt, solvate, or complex, or a combination thereof.

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

  • Patent Identification: U.S. Patent No. 10,793,893, "Methods of Administering 3,4-Diaminopyridine," issued October 6, 2020.

The Invention Explained

  • Problem Addressed: The patent's background section describes that the pharmacokinetic profile of orally administered 3,4-diaminopyridine (3,4-DAP) is "highly variable between patients," which can lead to inconsistent efficacy and a risk of side effects, without a previously known rationale for this variability (’893 Patent, col. 2:11-26).
  • The Patented Solution: The inventors discovered that 3,4-DAP is metabolized by N-acetyl transferase 2 (NAT2) enzymes, and that the rate of this metabolism depends on a patient’s genetic polymorphisms, which classify them as "slow" or "fast" acetylators (Compl. ¶33; ’893 Patent, col. 5:23-41). The invention provides a method of personalized medicine: determining a patient's acetylator status based on their NAT2 genotype and administering a dose of 3,4-DAP that is adjusted for that status (’893 Patent, Abstract; col. 7:41-47).
  • Technical Importance: This genetic-based dosing method allows for tailoring the drug dosage to individual patient metabolism, with the goal of maximizing therapeutic effects while minimizing the risk of adverse events (’893 Patent, col. 8:1-9).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" without specifying particular claims (Compl. ¶58). Independent claim 1 is a representative method of treatment claim.
  • Claim 1 Elements:
    • A method of treating a human patient diagnosed with a 3,4-DAP sensitive disease;
    • wherein the patient is a slow acetylator having an N-acetyl transferase 2 (NAT2) gene comprising one of three specific combinations of genetic mutations (C282T and T341C);
    • comprising administering a dose of about 2.5 mg to about 30 mg of 3,4-DAP or a pharmaceutically acceptable salt thereof.

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

  • Patent Identification: U.S. Patent No. 11,060,128 ("the '128A Patent"), "Methods of Administering 3,4-Diaminopyridine," issued July 13, 2021 (Compl. ¶36).
  • Technology Synopsis: The patent relates to the same core discovery as the '893 Patent: the variability in 3,4-DAP metabolism is linked to a patient's NAT2 acetylator genotype. This patent claims methods of treating patients who are identified as fast acetylators by administering a specific dose of 3,4-DAP tailored to that metabolic profile (’128A Patent, Abstract).
  • Asserted Claims: "one or more claims" (Compl. ¶66). Independent claims 1 and 15 are asserted.
  • Accused Features: The proposed use of Defendants' ANDA Product in accordance with its label is alleged to infringe, which Plaintiffs allege will encourage administration to fast acetylators in a manner covered by the patent claims (Compl. ¶¶ 65-66).

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

  • Patent Identification: U.S. Patent No. 11,268,128 ("the '128B Patent"), "Methods of Administering 3,4-Diaminopyridine," issued March 8, 2022 (Compl. ¶37).
  • Technology Synopsis: This patent also relates to personalized dosing of 3,4-DAP based on a patient's NAT2 acetylator status. It claims methods of treating patients identified as slow acetylators by administering a total daily dose within a specific range (about 7.5 mg to about 30 mg) (’128B Patent, Abstract).
  • Asserted Claims: "one or more claims" (Compl. ¶74). Independent claims 1, 12, 15, and 18 are asserted.
  • Accused Features: The proposed use of Defendants' ANDA Product is alleged to infringe by encouraging administration to slow acetylators at dosages covered by the patent claims (Compl. ¶¶ 73-74).

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

  • Patent Identification: U.S. Patent No. 11,274,331 ("the '331 Patent"), "Methods of Administering 3,4-Diaminopyridine," issued March 15, 2022 (Compl. ¶38).
  • Technology Synopsis: This patent continues the theme of personalized 3,4-DAP dosing based on NAT2 genetics. It claims methods for treating a patient identified as a fast acetylator by administering a total daily dose of 3,4-DAP that is greater than or equal to about 30 mg (’331 Patent, Abstract).
  • Asserted Claims: "one or more claims" (Compl. ¶82). Independent claims 1 and 14 are asserted.
  • Accused Features: The proposed use of Defendants' ANDA Product is alleged to infringe by encouraging administration to fast acetylators at dosages covered by the patent claims (Compl. ¶¶ 81-82).

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

  • Patent Identification: U.S. Patent No. 11,274,332 ("the '332 Patent"), "Methods of Administering 3,4-Diaminopyridine," issued March 15, 2022 (Compl. ¶39).
  • Technology Synopsis: This patent also relates to personalized dosing based on NAT2 genetics. It claims methods for treating a patient identified as a slow acetylator by administering a total daily dose of about 7.5 mg to about 30 mg, provided as a series of divided doses (’332 Patent, Abstract).
  • Asserted Claims: "one or more claims" (Compl. ¶90). Independent claims 1, 18, 21, and 24 are asserted.
  • Accused Features: The proposed use of Defendants' ANDA Product is alleged to infringe by encouraging administration to slow acetylators at dosages covered by the patent claims (Compl. ¶¶ 89-90).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendants' ANDA Product, a generic version of Firdapse® (amifampridine) tablets, 10 mg, for which approval is sought under ANDA No. 217996 (Compl. ¶1).

Functionality and Market Context

The complaint alleges that by filing the ANDA, Defendants have represented to the FDA that their proposed generic product will have the same active ingredient (amifampridine), method of administration, dosage form, and strength as the branded Firdapse® product, and will be bioequivalent to it (Compl. ¶45). The product is a treatment for Lambert-Eaton Myasthenic Syndrome, a rare neuromuscular disorder (Compl. ¶¶ 1, 28). The legal basis for the suit is the filing of the ANDA itself, which constitutes a statutory act of infringement seeking to market the generic product before the expiration of the patents-in-suit (Compl. ¶1, 49).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or specific, element-by-element factual allegations of infringement for any of the asserted patents. The infringement allegations are framed generally for each count.

For the '088 Patent, which claims a degradation product of 3,4-diaminopyridine, the infringement theory is not explicitly detailed. The complaint alleges that the submission of the ANDA, and the subsequent commercial manufacture, use, or sale of the product, would constitute direct and indirect infringement (Compl. ¶¶ 49, 51). This suggests a potential allegation that the accused product either contains the claimed dimer as an impurity or will necessarily degrade to form it.

For the '893 Patent and the related family of method patents ('128A, '128B, '331, '332), the infringement theory is based on induced infringement. The complaint alleges that once the ANDA is approved, Defendants' product will be administered by patients and medical practitioners "according to the directions and instructions in the proposed package insert," which will constitute direct infringement (Compl. ¶58). The complaint alleges Defendants will "actively induce, encourage, aid, and abet that conduct" with knowledge and specific intent (Compl. ¶58). The central question for these method patents will be whether the final approved label for Defendants' generic product instructs or encourages physicians to identify patients by their NAT2 acetylator status and administer a dose that falls within the ranges recited in the asserted claims.

  • Identified Points of Contention:
    • Evidentiary Questions: For the ’088 Patent, a key question for the court will be one of evidence: does the complaint provide sufficient factual basis to plausibly allege that the Defendants' ANDA product contains, or will inevitably form, the specific dimer claimed in the patent?
    • Inducement Questions: For the ’893 Patent and its family members, the dispute will likely focus on the content of the proposed product label. The central question will be whether the label's instructions will lead physicians and patients to practice the steps of the claimed methods, specifically by linking NAT2 genetic status to specific dosage regimens.
    • Technical Questions: A potential point of dispute may arise regarding the definition of "slow" or "fast" acetylator. While the claims of the method patents are tied to specific genotypes, the infringement analysis may depend on whether the product label uses phenotypic descriptions (e.g., based on clinical response or side effects) or genotypic markers to guide dosing.

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

  • Patent: U.S. Patent No. 10,793,893
  • The Term: "a human patient who is a slow acetylator having an N-acetyl transferase 2 (NAT2) gene comprising: [a C282T mutation on both alleles of the NAT2 gene; a T341C mutation on both alleles of the NAT2 gene; or a C282T mutation on one allele of the NAT2 gene and a T341C mutation on the other allele of the NAT2 gene]" (from Claim 1).
  • Context and Importance: This limitation defines the specific patient population to which the claimed method applies. Practitioners may focus on this term because the infringement case for induced infringement will depend on whether the defendant's product label instructs physicians to identify patients with these exact genetic characteristics before administering the drug in the claimed dosage range.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discusses acetylator status more broadly, including phenotypic methods for its determination, such as a "caffeine test" (’893 Patent, col. 7:41-47). A party might argue this context suggests "slow acetylator" is the key limitation, with the genetic markers being exemplary.
    • Evidence for a Narrower Interpretation: The claim language itself is highly specific, defining the "slow acetylator" by requiring the presence ("having") of specific genetic mutations. The structure "a slow acetylator having..." suggests that the genetic markers are a required, limiting feature of the claimed patient group, not merely an example. This suggests the claim is narrowly tailored to patients identified by the recited genotypes.

VI. Other Allegations

  • Indirect Infringement: The core of the complaint for the five method patents (’893, ’128A, ’128B, ’331, ’332) rests on allegations of induced infringement. Plaintiffs allege that Defendants' proposed package insert for the generic product will instruct medical practitioners and patients to perform the claimed methods of administration, thereby inducing infringement (e.g., Compl. ¶¶ 57, 58). The complaint also makes conclusory allegations of contributory infringement, stating the ANDA product is not a staple article and is especially made or adapted for an infringing use (Compl. ¶59).
  • Willful Infringement: The complaint does not use the word "willful" but alleges for each patent that Defendants have had "knowledge of the... patent since at least the date Defendants submitted Defendants' ANDA" (e.g., Compl. ¶61). It further asserts that the case is "exceptional" and seeks an award of attorneys' fees under 35 U.S.C. § 285, which can be associated with findings of egregious infringement conduct (e.g., Compl. ¶62).

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

  • A central issue for the five method patents will be one of induced infringement: Will the final, FDA-approved label for Lupin's generic product contain explicit instructions or affirmative encouragements for physicians to determine a patient's specific NAT2 genotype and then prescribe the drug according to the dosage regimens claimed for "slow" or "fast" acetylators? The outcome of these claims will likely depend entirely on the language of the product's label.
  • A key evidentiary question for the '088 patent will be one of product composition: Does the complaint set forth a plausible claim that Lupin's ANDA product, as formulated, either contains the specific 3,4-diaminopyridine dimer as an impurity or that its degradation under normal conditions will necessarily result in the formation of the claimed dimer?
  • The case may also present a question of claim scope: Will the claims directed to methods of treating "slow acetylators" or "fast acetylators" be construed as limited to only those patients possessing the specific genetic mutations recited in the claims, or can the terms be interpreted more broadly based on phenotypic characteristics described in the specification?