DCT

2:23-cv-01194

Catalyst Pharma Inc v. Annora Pharma Pvt Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-01194, D.N.J., 03/01/2023
  • Venue Allegations: Venue is asserted based on Defendants having a regular and established physical place of business in New Jersey, deriving substantial revenue from the state, and engaging in systematic and continuous contacts, including the preparation and submission of drug applications to the FDA within the district.
  • Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) seeking to market a generic version of Plaintiff's Firdapse® tablets constitutes infringement of six patents related to methods of determining drug purity and methods of administering the drug based on patient genotype.
  • Technical Context: The technology concerns amifampridine, a treatment for the rare neuromuscular disorder Lambert-Eaton Myasthenic Syndrome (LEMS), and methods for personalizing its administration.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Defendants' January 20, 2023 notification letter, which included a Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, 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, ’332 Patents
2016-06-10 Earliest Priority Date for ’088 Patent
2018-11-28 Plaintiff's Firdapse® product receives FDA approval
2020-04-21 U.S. Patent No. 10,626,088 Issues
2020-10-06 U.S. Patent No. 10,793,893 Issues
2021-07-13 U.S. Patent No. 11,060,128 Issues
2022-03-08 U.S. Patent No. 11,268,128 Issues
2022-03-15 U.S. Patent No. 11,274,331 Issues
2022-03-15 U.S. Patent No. 11,274,332 Issues
2023-01-20 Defendants send Notice Letter regarding ANDA submission
2023-03-01 Complaint Filed

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 for highly sensitive methods to detect impurities and degradation in pharmaceutical samples of 3,4-diaminopyridine, the active ingredient in Firdapse® (’088 Patent, col. 1:26-34).
    • The Patented Solution: The invention identifies a specific degradation product—a dimer of 3,4-diaminopyridine—and provides methods for determining the purity of a drug sample by detecting the presence, absence, or amount of this dimer (’088 Patent, Abstract; col. 1:41-47). This allows for quantitative assessment of drug degradation over time, which is critical for quality control.
    • Technical Importance: Assessing dosage forms for impurities and degradation products is a fundamental requirement for ensuring the safety, efficacy, and quality control of pharmaceutical products (Compl. ¶42; ’088 Patent, col. 3:54-58).
  • Key Claims at a Glance:
    • The complaint asserts infringement of at least one claim (Compl. ¶59). Independent claim 1 is representative:
      • 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"

  • The Invention Explained:
    • Problem Addressed: The patent background describes that the pharmacokinetic profile of orally administered 3,4-diaminopyridine (3,4-DAP) is "highly variable between patients," but that "no rationale has been provided previously for this variability" (’893 Patent, col. 2:12-22).
    • The Patented Solution: The inventors discovered that this variability is explained by a patient's genetic makeup, specifically polymorphisms in N-acetyl transferase (NAT) enzymes that metabolize the drug (’893 Patent, col. 5:30-41). The invention provides a method of treating patients by first determining if they are a "slow acetylator" based on their specific NAT2 genotype and then administering a corresponding dose of 3,4-DAP (’893 Patent, Abstract).
    • Technical Importance: This discovery allows for personalized medicine, tailoring drug dosages to a patient's specific metabolic profile to optimize efficacy and safety (Compl. ¶42).
  • Key Claims at a Glance:
    • The complaint asserts infringement of at least one claim (Compl. ¶67). Independent claim 1 is representative:
      • A method of treating a human patient diagnosed with a 3,4-diaminopyridine (3,4-DAP) sensitive disease in need of treatment thereof comprising administering a dose of about 2.5 mg to about 30 mg of 3,4-DAP or a pharmaceutically acceptable salt thereof to a human patient;
      • who is a slow acetylator having an N-acetyl transferase 2 (NAT2) gene comprising one of three specific combinations of C282T and T341C mutations.

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

  • Technology Synopsis: This patent is part of the same family as the ’893 Patent and is also directed to methods of administering 3,4-DAP based on a patient's NAT2 acetylator status (Compl. ¶45). It claims methods of treating "slow acetylators" with a specific dose range of the drug (’128A Patent, Abstract).
  • Asserted Claims: At least one claim is asserted (Compl. ¶75).
  • Accused Features: The accused feature is the proposed method of use for the generic product as will be described in its package insert, which is alleged to instruct infringing administration (Compl. ¶75).

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

  • Technology Synopsis: This patent, also in the ’893 Patent family, is directed to methods of administering 3,4-DAP (Compl. ¶46). Its claims cover methods of treating a patient population having two NAT2 slow alleles with a specified dose range (’128B Patent, Abstract).
  • Asserted Claims: At least one claim is asserted (Compl. ¶83).
  • Accused Features: The accused feature is the proposed method of use for the generic product as will be described in its package insert, which is alleged to instruct infringing administration (Compl. ¶83).

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

  • Technology Synopsis: This patent, also in the ’893 Patent family, is directed to methods of administering 3,4-DAP (Compl. ¶47). Its claims cover methods of treating a patient having two NAT2 fast alleles with a specified dose range (’331 Patent, Abstract).
  • Asserted Claims: At least one claim is asserted (Compl. ¶91).
  • Accused Features: The accused feature is the proposed method of use for the generic product as will be described in its package insert, which is alleged to instruct infringing administration (Compl. ¶91).

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

  • Technology Synopsis: This patent, also in the ’893 Patent family, is directed to methods of administering 3,4-DAP (Compl. ¶48). Its claims cover methods of treating a patient having two NAT2 fast alleles with a total daily dose of about 30 mg to 100 mg, provided as a series of divided doses (’332 Patent, Abstract).
  • Asserted Claims: At least one claim is asserted (Compl. ¶99).
  • Accused Features: The accused feature is the proposed method of use for the generic product as will be described in its package insert, which is alleged to instruct infringing administration (Compl. ¶99).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendants' Abbreviated New Drug Application No. 218007 and the generic amifampridine 10 mg tablet product that will be commercially manufactured, used, or sold upon its approval ("Defendants' ANDA Product") (Compl. ¶1).
  • Functionality and Market Context: As a generic version of Firdapse®, the ANDA Product is represented to the FDA as having the same active ingredient, method of administration, dosage form, and strength, and as being bioequivalent to Firdapse® (Compl. ¶54). The complaint alleges that upon FDA approval, the product will be manufactured and sold in the United States, with its proposed package insert instructing patients and medical practitioners on its administration (Compl. ¶¶59, 67).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for analysis of infringement on a claim-by-claim basis, as it does not include a claim chart or the text of the Defendants' proposed product label. The infringement allegations are based on the future, intended use of the ANDA product.

  • ’088 Patent Infringement Allegations

    • Identified Points of Contention:
      • Factual Question: The complaint alleges that Defendants' "manufacturing, use, offer for sale, sale, and/or importation" of the ANDA Product will infringe claims of the ’088 patent (Compl. ¶60). Since the patent claims a method of determining purity, a central question will be evidentiary: What are the specific quality control and manufacturing processes Defendants will use for their generic amifampridine product, and do those processes include the step of determining the presence or amount of the claimed dimer?

  • ’893 Patent Infringement Allegations

    • Identified Points of Contention:
      • Scope and Inducement Question: The complaint alleges that administration of the ANDA Product "according to the directions and instructions in the proposed package insert" will constitute infringement (Compl. ¶67). A key dispute will concern induced infringement: Does the language of the Defendants' proposed product label instruct or encourage medical practitioners to administer the specified dose range ("about 2.5 mg to about 30 mg") specifically to patients identified as "slow acetylators" based on the claimed NAT2 genetic mutations? The outcome may depend on whether the label's instructions are specific enough to map onto the claim elements and establish the requisite intent for inducement.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of key claim terms for the ’088 Patent.

For the ’893 Patent:

  • The Term: "slow acetylator"
  • Context and Importance: This term is the lynchpin of independent claim 1 and related claims, as it defines the specific patient population to whom the patented method applies. Its construction will determine the scope of infringing conduct. Practitioners may focus on this term because the claim itself provides an explicit, narrow definition tied to specific genetic mutations, which could be a focal point for non-infringement arguments if the accused label's instructions are more general.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discusses determining acetylator status through phenotyping (e.g., via a caffeine test) in addition to genotyping, stating that an "individual's acetylator phenotype can be determined by using procedures described in Example 15 and Example 15a" (’893 Patent, col. 5:65-67). A party might argue this supports a broader meaning not strictly limited to the specific mutations recited in the claim.
    • Evidence for a Narrower Interpretation: Claim 1 itself contains what appears to be an explicit definition, limiting a "slow acetylator" to a patient "having an N-acetyl transferase 2 (NAT2) gene comprising" one of three specific combinations of C282T and T341C mutations (’893 Patent, col. 89:7-14). This express language provides strong evidence that the term should be narrowly construed as being defined by the claim itself.

VI. Other Allegations

  • Indirect Infringement: For the method patents (’893, ’128A, ’128B, ’331, and ’332), the complaint alleges induced infringement based on the contention that Defendants’ user instructions and proposed package insert will actively encourage and instruct patients and medical practitioners to perform the claimed methods of administration (e.g., Compl. ¶¶67, 75, 83, 91, 99). For the ’088 patent, contributory infringement is alleged on the basis that the ANDA product is "especially made or adapted for use in infringing" the patent (Compl. ¶60).
  • Willful Infringement: The complaint does not use the word "willful," but alleges that "Defendants have had knowledge of the [asserted patents] since at least the date Defendants submitted Defendants' ANDA" (e.g., Compl. ¶¶62, 70). It also seeks a finding that the case is "exceptional" under 35 U.S.C. § 285, which may entitle Plaintiffs to an award of attorneys' fees (e.g., Compl. ¶¶63, 71).

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

  • A central issue for the method-of-use patents (’893 and its family) will be one of induced infringement: What are the precise instructions and recommendations in the Defendants' proposed product label? Can the Plaintiffs demonstrate that this label will lead physicians to prescribe, and patients to take, the generic drug in a manner that directly infringes the patented methods, thereby establishing the specific intent required for inducement?
  • A key evidentiary question for the ’088 patent will be one of direct infringement: What are the specific quality control and manufacturing procedures that Defendants will employ for their ANDA product? Will those procedures include the step of detecting the claimed 3,4-diaminopyridine dimer as a method of assessing product degradation, as required by the patent's claims?
  • A foundational question of claim construction will be the definition of "slow acetylator" and "fast acetylator" in the method-of-use patents. The dispute may center on whether these terms are strictly limited to the specific genetic mutations recited in the claims or if they can be interpreted more broadly to include other methods of classification, such as phenotyping, as described elsewhere in the specification.