DCT

2:23-cv-01190

Catalyst Pharma Inc v. Teva Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-01190, D.N.J., 03/01/2023
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on the Defendants having a regular and established physical place of business in the district, systematically conducting business there, and having previously availed themselves of New Jersey courts.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff’s Firdapse® (amifampridine) tablets infringes six patents related to methods of determining drug degradation and methods of administering the drug based on patient genetics.
  • Technical Context: The technology concerns amifampridine, a treatment for Lambert-Eaton Myasthenic Syndrome (LEMS), a rare and debilitating neuromuscular disorder.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Teva’s submission of ANDA No. 218029 and its associated notification letter, dated January 17, 2023, which asserted via a Paragraph IV certification that the patents-in-suit are invalid, unenforceable, or will not be infringed by Teva’s 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
2023-01-17 Defendant sends Notice Letter regarding its ANDA filing
2023-03-01 Complaint for Patent Infringement 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 describes a need for reliable methods to ascertain whether the active pharmaceutical ingredient 3,4-diaminopyridine has degraded, as impurities in drug products can lead to increased toxicity or decreased efficacy (’088 Patent, col. 1:20-35).
  • The Patented Solution: The invention provides methods for determining the purity of a 3,4-diaminopyridine sample by detecting the presence, absence, or amount of a specific degradation product—a dimer of 3,4-diaminopyridine. This dimer serves as a reference marker for degradation, which can be quantified using high-performance liquid chromatography (HPLC) (’088 Patent, Abstract; col. 2:42-54).
  • Technical Importance: The invention provides a method for quality control in pharmaceutical manufacturing, ensuring that dosage forms of 3,4-diaminopyridine are free from potentially harmful degradation products and contain the proper amount of active ingredient (’088 Patent, col. 3:50-58).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’088 patent (Compl. ¶55). Independent claim 1 is analyzed as representative.
  • Essential elements of Claim 1:
    • 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.
  • The complaint reserves the right to assert other claims.

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

The Invention Explained

  • Problem Addressed: The patent notes that the pharmacokinetic profile of orally administered 3,4-diaminopyridine (3,4-DAP) is “highly variable between patients,” leading to inconsistent drug exposure and potential side effects or lack of efficacy (’893 Patent, col. 2:12-25).
  • The Patented Solution: The invention is based on the discovery that this variability is due to genetic polymorphisms in N-acetyl transferase (NAT) enzymes, which metabolize 3,4-DAP into a major 3-N-acetyl metabolite (’893 Patent, col. 5:26-41). The patent claims methods of administering specific dose ranges of 3,4-DAP to patients identified as "slow acetylators" based on their specific NAT2 genetic makeup, thereby tailoring the treatment to the individual's metabolic profile.
  • Technical Importance: The claimed method enables a personalized medicine approach to treating LEMS, allowing physicians to select drug dosages based on a patient's genetic profile to maximize efficacy and safety (’893 Patent, col. 7:36-41).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’893 patent (Compl. ¶63). Independent claim 1 is analyzed as representative.
  • Essential elements of Claim 1:
    • A method of treating a human patient diagnosed with a 3,4-DAP sensitive disease;
    • 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 a C282T mutation on both alleles, a T341C mutation on both alleles, or a C282T mutation on one allele and a T341C mutation on the other allele.
  • The complaint reserves the right to assert other claims.

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

  • Issued: July 13, 2021
  • Technology Synopsis: This patent, part of the same family as the ’893 patent, addresses the high inter-patient variability in 3,4-DAP pharmacokinetics (’128A Patent, col. 2:12-25). It provides methods for administering the drug based on a patient's genetically determined N-acetyl transferase 2 (NAT2) acetylator status to improve safety and efficacy (’128A Patent, col. 5:26-41).
  • Asserted Claims: One or more claims (Compl. ¶71).
  • Accused Features: Teva's ANDA Product, which will allegedly be administered according to directions in its proposed package insert (Compl. ¶71).

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

  • Issued: March 8, 2022
  • Technology Synopsis: Continuing the '893 patent family, this patent addresses the high inter-patient variability in 3,4-DAP pharmacokinetics (’128B Patent, col. 2:12-25). It provides methods for administering the drug based on a patient's genetically determined NAT2 acetylator status to improve safety and efficacy (’128B Patent, col. 5:26-41).
  • Asserted Claims: One or more claims (Compl. ¶79).
  • Accused Features: Teva's ANDA Product, which will allegedly be administered according to directions in its proposed package insert (Compl. ¶79).

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

  • Issued: March 15, 2022
  • Technology Synopsis: Continuing the '893 patent family, this patent addresses the high inter-patient variability in 3,4-DAP pharmacokinetics (’331 Patent, col. 2:12-25). It provides methods for administering the drug based on a patient's genetically determined NAT2 acetylator status to improve safety and efficacy (’331 Patent, col. 5:26-41).
  • Asserted Claims: At least one claim (Compl. ¶87).
  • Accused Features: Teva's ANDA Product, which will allegedly be administered according to directions in its proposed package insert (Compl. ¶87).

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

  • Issued: March 15, 2022
  • Technology Synopsis: Continuing the '893 patent family, this patent addresses the high inter-patient variability in 3,4-DAP pharmacokinetics (’332 Patent, col. 2:12-25). It provides methods for administering the drug based on a patient's genetically determined NAT2 acetylator status to improve safety and efficacy (’332 Patent, col. 5:26-41).
  • Asserted Claims: One or more claims (Compl. ¶95).
  • Accused Features: Teva's ANDA Product, which will allegedly be administered according to directions in its proposed package insert (Compl. ¶95).

III. The Accused Instrumentality

Product Identification

Defendant’s Abbreviated New Drug Application (“ANDA”) No. 218029 product (“Teva’s ANDA Product”), a generic version of Catalyst’s Firdapse® (amifampridine) 10 mg tablets (Compl. ¶1).

Functionality and Market Context

  • The accused product contains amifampridine, a voltage-dependent potassium channel blocker used for the treatment of Lambert-Eaton Myasthenic Syndrome (LEMS) (Compl. ¶¶33, 35). The complaint alleges that upon approval, Teva's product will have the same active ingredient, method of administration, dosage form, and strength as Firdapse®, and will be bioequivalent to it (Compl. ¶50).
  • The complaint alleges that Teva is one of the "leading generic pharmaceutical companies in the United States" and intends to engage in the commercial manufacture, use, and sale of the accused product upon FDA approval (Compl. ¶¶1, 17).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or sufficient technical detail to construct one. The infringement allegations are based on the filing of the ANDA under 35 U.S.C. § 271(e)(2), which constitutes a technical act of infringement, and future commercial activity that will allegedly induce infringement by end-users.

For the ’088 Patent, the complaint alleges that administration of Teva's ANDA Product by patients and medical practitioners according to the proposed package insert will constitute infringement of one or more claims (Compl. ¶55). The complaint does not allege that Teva's ANDA Product itself contains the claimed dimer.

For the ’893 Patent (and the related ’128A, ’128B, ’331, and ’332 patents), the complaint alleges that Teva will induce infringement because its proposed package insert will instruct patients and practitioners to administer the generic product in a manner that directly infringes the method claims (Compl. ¶63). The complaint does not specify what Teva's proposed label instructs regarding administration to specific patient populations defined by genetic markers.

Identified Points of Contention

  • Technical Questions: A principal question for the ’088 patent is how the administration of an amifampridine drug product, as instructed by a package insert, could infringe a claim directed to a distinct chemical compound (a dimer) (’088 Patent, Claim 1). The complaint does not provide facts to support a theory that Teva’s product contains the claimed dimer or that administration results in its formation in an infringing manner.
  • Scope Questions: For the ’893 patent and its family, a central question will be whether Teva's proposed label for its generic product will instruct or encourage administration to the specific patient population of "slow acetylators" as narrowly defined by the genetic mutations recited in the independent claims (e.g., ’893 Patent, Claim 1). The infringement case may depend on whether the label’s instructions, even if not explicitly mentioning genetic tests, will inevitably lead to use by the claimed patient population.

V. Key Claim Terms for Construction

  • The Term: "3,4-Diaminopyridine dimer" (’088 Patent, Claim 1)
  • Context and Importance: The construction of this term is critical because the infringement theory for the ’088 patent is not detailed in the complaint. Practitioners may focus on whether this term is limited to the specific chemical compound disclosed or if it can be construed more broadly to be implicated in the method of administering the non-dimer drug product.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The complaint does not provide a basis for a broad interpretation.
    • Evidence for a Narrower Interpretation: Claim 1 of the ’088 patent recites a specific chemical structure for the dimer, and the specification repeatedly describes it as a distinct compound that is a degradation product of 3,4-diaminopyridine (’088 Patent, Abstract; col. 3:59-61). This evidence suggests the term refers to a specific chemical entity, not a process.
  • The Term: "slow acetylator" (’893 Patent, Claim 1)
  • Context and Importance: This term defines the specific patient population to whom the claimed method is directed. The dispute may turn on whether Teva’s proposed label, even if facially neutral, encourages use in a way that satisfies this limitation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discusses "slow acetylator" in a functional sense, noting that the phenotype is present in 50-59% of Caucasians and that such individuals exhibit higher plasma levels of 3,4-DAP (’893 Patent, col. 6:58-65; col. 7:26-34).
    • Evidence for a Narrower Interpretation: Claim 1 itself provides a precise and limiting definition of "slow acetylator," requiring the patient to have specific genetic mutations in the NAT2 gene (a C282T mutation, a T341C mutation, or one of each) (’893 Patent, col. 90:7-12). This explicit definition within the claim itself may be seen as controlling the scope of the term for infringement purposes.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all six patents-in-suit. Inducement is based on the allegation that Teva’s proposed package insert will instruct and encourage medical practitioners and patients to administer the drug in an infringing manner (e.g., Compl. ¶¶ 55, 63). Contributory infringement is based on the allegation that Teva’s product is especially made or adapted for use in infringing the patents and is not suitable for substantial non-infringing use (e.g., Compl. ¶¶ 56, 64).
  • Willful Infringement: The complaint does not use the word "willful" but alleges that Teva has had knowledge of the patents-in-suit since at least the date it submitted its ANDA and that the submission itself constitutes an act of infringement, thereby alleging pre-suit knowledge (e.g., Compl. ¶¶ 58, 66). The complaint seeks a finding that the case is “exceptional,” which is the standard for an award of attorneys' fees under 35 U.S.C. § 285 (e.g., Compl. ¶¶ 59, 67).

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

  • A core issue will be one of infringement theory: What is the factual and legal basis for the allegation that administering amifampridine infringes the ’088 patent, which claims a specific chemical dimer? The viability of this claim may depend on evidence, not present in the complaint, that Teva's product contains the dimer as an impurity.
  • A key evidentiary question will be one of inducement: What instructions and representations are contained in Teva's proposed product labeling and marketing materials? The infringement case for the five method patents (’893 family) will likely depend on whether this evidence shows specific intent to encourage administration of the generic product to the narrowly-defined "slow acetylator" patient population recited in the claims.
  • A central question of claim scope will be whether the term "slow acetylator" is limited to the explicit genetic definitions provided in the claims of the '893 patent family, or if it can be construed more broadly to cover a functional pharmacokinetic profile, which could alter the infringement analysis.