DCT

2:23-cv-01197

Catalyst Pharma Inc v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-01197, D.N.J., 03/01/2023
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendants maintaining regular and established places of business within the district, particularly a commercial manufacturing facility and U.S. sales and marketing operations in Somerset, New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiffs’ Firdapse® (amifampridine) tablets constitutes an act of infringement of six U.S. patents.
  • Technical Context: The dispute concerns amifampridine, a drug used to treat Lambert-Eaton Myasthenic Syndrome (LEMS), a rare autoimmune neuromuscular disorder that causes severe muscle weakness.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following a Notice Letter from Defendants, 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 Patent family
2016-06-10 Priority Date for ’088 Patent
2018-11-28 FDA approves Plaintiff's Firdapse® product
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
2023-01-26 Defendants send Notice Letter to Plaintiffs
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”

Issued April 21, 2020

The Invention Explained

  • Problem Addressed: Pharmaceutical products can contain impurities from synthesis or degradation, which may lead to adverse effects or reduced efficacy. The patent describes a need for highly sensitive methods to detect and quantify degradation products in samples of 3,4-diaminopyridine (’088 Patent, col. 1:16-35).
  • The Patented Solution: The invention identifies a specific degradation product of 3,4-diaminopyridine—a dimer—and claims methods for determining the purity of a drug sample by detecting or quantifying this dimer. The patent also claims the dimer compound itself, which can be used as a reference marker in quality control analyses like high-performance liquid chromatography (HPLC) (’088 Patent, Abstract; col. 5:56-6:11).
  • Technical Importance: The invention provides a method for quality control of pharmaceutical compositions containing 3,4-diaminopyridine, ensuring product purity and stability (Compl. ¶34).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’088 Patent without specifying particular claims (Compl. ¶51). Independent claim 1 is a composition of matter claim directed to the dimer.
  • 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 additional claims.

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

Issued October 6, 2020

The Invention Explained

  • Problem Addressed: The pharmacokinetic profile of orally administered 3,4-diaminopyridine (3,4-DAP) is highly variable between patients, with up to 10-fold differences in metrics like maximum plasma concentration (Cmax) and area under the curve (AUC). This variability complicates dosing, creating risks of side effects or lack of efficacy (’893 Patent, col. 2:12-26).
  • The Patented Solution: The inventors discovered this variability is explained by different rates of metabolism through N-acetyl transferase (NAT) enzymes. The patented solution is a method of personalized medicine: first determining a patient's "acetylator status" (e.g., slow or fast) based on their NAT2 genotype, and then administering a dose of 3,4-DAP that is adjusted to that status (’893 Patent, col. 2:32-49; Compl. ¶34).
  • Technical Importance: This approach allows for personalized dosing of 3,4-DAP, potentially maximizing therapeutic benefit while minimizing adverse events by accounting for a patient's individual genetic makeup (Compl. ¶34).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’893 Patent without specifying particular claims (Compl. ¶59). Independent claim 1 is a method of treatment claim.
  • 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 specific genetic mutations (a C282T mutation on both alleles, a T341C mutation on both alleles, or one of each)
  • The complaint reserves the right to assert additional claims.

Multi-Patent Capsule: U.S. Patent No. 11,060,128

  • Patent Identification: U.S. Patent No. 11060128, “Methods of Administering 3,4-Diaminopyridine,” issued July 13, 2021 (Compl. ¶37).
  • Technology Synopsis: The patent addresses the high inter-patient variability in the metabolism of 3,4-diaminopyridine. It claims methods for treating patients by adjusting the dosage of the drug based on the patient's genetically determined N-acetyl transferase 2 (NAT2) acetylator status (Compl. ¶34).
  • Asserted Claims: The complaint asserts infringement of one or more claims without specifying them (Compl. ¶¶66-67).
  • Accused Features: The accused features are the manufacturing, use, sale, and importation of Defendants' ANDA Product, and its administration to patients according to the proposed package insert, which allegedly instructs for infringing use (Compl. ¶¶65-67).

Multi-Patent Capsule: U.S. Patent No. 11,268,128

  • Patent Identification: U.S. Patent No. 11268128, “Methods of Administering 3,4-Diaminopyridine,” issued March 8, 2022 (Compl. ¶38).
  • Technology Synopsis: The patent addresses the high inter-patient variability in the metabolism of 3,4-diaminopyridine. It claims methods for treating patients by adjusting the dosage of the drug based on the patient's genetically determined N-acetyl transferase 2 (NAT2) acetylator status (Compl. ¶34).
  • Asserted Claims: The complaint asserts infringement of one or more claims without specifying them (Compl. ¶¶74-75).
  • Accused Features: The accused features are the manufacturing, use, sale, and importation of Defendants' ANDA Product, and its administration to patients according to the proposed package insert, which allegedly instructs for infringing use (Compl. ¶¶73-75).

Multi-Patent Capsule: U.S. Patent No. 11,274,331

  • Patent Identification: U.S. Patent No. 11274331, “Methods of Administering 3,4-Diaminopyridine,” issued March 15, 2022 (Compl. ¶39).
  • Technology Synopsis: The patent addresses the high inter-patient variability in the metabolism of 3,4-diaminopyridine. It claims methods for treating patients by adjusting the dosage of the drug based on the patient's genetically determined N-acetyl transferase 2 (NAT2) acetylator status (Compl. ¶34).
  • Asserted Claims: The complaint asserts infringement of one or more claims without specifying them (Compl. ¶¶82-83).
  • Accused Features: The accused features are the manufacturing, use, sale, and importation of Defendants' ANDA Product, and its administration to patients according to the proposed package insert, which allegedly instructs for infringing use (Compl. ¶¶81-83).

Multi-Patent Capsule: U.S. Patent No. 11,274,332

  • Patent Identification: U.S. Patent No. 11274332, “Methods of Administering 3,4-Diaminopyridine,” issued March 15, 2022 (Compl. ¶40).
  • Technology Synopsis: The patent addresses the high inter-patient variability in the metabolism of 3,4-diaminopyridine. It claims methods for treating patients by adjusting the dosage of the drug based on the patient's genetically determined N-acetyl transferase 2 (NAT2) acetylator status (Compl. ¶34).
  • Asserted Claims: The complaint asserts infringement of one or more claims without specifying them (Compl. ¶¶90-91).
  • Accused Features: The accused features are the manufacturing, use, sale, and importation of Defendants' ANDA Product, and its administration to patients according to the proposed package insert, which allegedly instructs for infringing use (Compl. ¶¶89-91).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendants' Abbreviated New Drug Application (ANDA) No. 217996, which seeks FDA approval to market a generic version of Catalyst's Firdapse® (amifampridine) 10 mg tablets ("Defendants' ANDA Product") (Compl. ¶1).
  • Functionality and Market Context: By filing the ANDA, Defendants have represented to the FDA that their proposed generic product will have the same active ingredient, method of administration, dosage form, and strength as Firdapse®, and will be bioequivalent to it (Compl. ¶46). The act of infringement alleged under 35 U.S.C. § 271(e)(2) is the submission of the ANDA itself for the purpose of obtaining approval to engage in the commercial manufacture, use, or sale of the drug before the expiration of the patents-in-suit (Compl. ¶1). Firdapse® is the first product approved by the FDA for the treatment of LEMS (Compl. ¶32).

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-chart analysis of any of the asserted patents. The allegations are pleaded generally, stating that the commercial manufacture, use, or sale of Defendants' ANDA Product, in accordance with its proposed package insert, would infringe one or more claims of each patent-in-suit (e.g., Compl. ¶¶51, 59).

For the ’088 Patent, a composition of matter patent, the infringement theory appears to be that Defendants' generic product will contain the claimed 3,4-diaminopyridine dimer as a degradation product, thereby infringing upon commercialization (Compl. ¶¶42, 51).

For the ’893 Patent and the other method of treatment patents, the infringement theory is based on inducement. The complaint alleges that Defendants' proposed package insert for the generic product will instruct and encourage medical practitioners and patients to administer the drug in a manner that practices the claimed methods of dosing based on acetylator status (Compl. ¶59).

  • Identified Points of Contention:
    • Evidentiary Question ('088 Patent): A primary question will be whether the ANDA itself, or other evidence, establishes that Defendants' proposed generic product will contain the specific dimer claimed in the ’088 patent. The complaint alleges that Firdapse® is covered by the patent and the generic will be bioequivalent, but does not present direct evidence that the dimer will be present in the accused product (Compl. ¶¶42, 46).
    • Inducement Question (Method Patents): A central point of contention for the five method patents will be whether Defendants' proposed label for the ANDA product instructs or encourages physicians to perform the claimed steps of determining a patient's NAT2 acetylator status and adjusting the dosage of amifampridine accordingly. The complaint makes this allegation but does not provide the specific language from the proposed label (Compl. ¶59).

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

  • The Term: "slow acetylator" (from ’893 Patent, Claim 1)
  • Context and Importance: The definition of this term is critical for the five asserted method patents, as it defines the specific patient population to whom the claimed method applies. Infringement will depend on whether the instructions in the Defendants' proposed label direct a course of treatment for patients falling within the patent's definition of a "slow acetylator."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discusses determining acetylator status through both genotyping and phenotyping methods, such as administering a probe drug like caffeine or isoniazid (’893 Patent, col. 5:50-65; col. 6:1-11). Parties seeking a broader construction might argue that any instruction to dose-adjust based on a recognized "slow metabolizer" status meets this limitation, regardless of the specific test used.
    • Evidence for a Narrower Interpretation: Independent claim 1 of the ’893 Patent explicitly defines a "slow acetylator" by reciting specific NAT2 gene mutations (e.g., "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"). This express recitation may support a narrower construction, limiting the claim's scope to only those patients and corresponding treatment instructions that rely on identifying these specific genetic markers.

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 Defendants' proposed package insert and instructions will actively encourage and aid physicians and patients to use the generic product in an infringing manner (Compl. ¶¶51, 59). Contributory infringement is based on the allegation that Defendants' ANDA Product is especially made or adapted for infringing the patents and is not suitable for substantial non-infringing use (Compl. ¶¶52, 60).
  • Willful Infringement: The complaint does not use the term "willful," but it alleges that Defendants have had knowledge of the patents-in-suit since at least the date they submitted their ANDA (Compl. ¶¶54, 62, 70, 78, 86, 94). The complaint also asserts that the case is "exceptional" and seeks an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶55, 63, 71, 79, 87, 95).

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

  • A core issue will be one of induced infringement: for the five method-of-treatment patents, the case will likely turn on the specific language of the Defendants' proposed product label. The central question for the court will be whether those instructions direct, encourage, or require prescribers to determine a patient's NAT2 acetylator status and adjust the dose of amifampridine based on that status, thereby practicing the patented methods.
  • A key evidentiary question will be one of product composition: for the '088 patent, the dispute may focus on whether Plaintiffs can prove that Defendants’ generic product, as defined in its ANDA, will necessarily contain the claimed 3,4-diaminopyridine dimer as an impurity or degradation product upon commercialization.