DCT

2:17-cv-03295

Impax Laboratories Inc v. Actavis Laboratories FL Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:17-cv-03295, D.N.J., 05/09/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey as both defendants maintain principal places of business in the state and have previously consented to jurisdiction in the district in related litigation.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to obtain FDA approval for a generic version of Plaintiff’s Parkinson’s disease drug RYTARY® constitutes an act of infringement of a patent covering controlled-release formulations of Levodopa/Carbidopa.
  • Technical Context: The technology concerns oral pharmaceutical formulations for treating Parkinson's disease designed to provide steadier plasma concentrations of the active ingredient, levodopa, thereby reducing motor fluctuations common with conventional treatments.
  • Key Procedural History: The complaint notes prior, related litigation between the parties in the same judicial district. It also states that this action was triggered by Plaintiff's receipt of a Paragraph IV Certification letter from Defendants, in which Defendants asserted that the patent-in-suit is invalid or would not be infringed by their proposed generic product.

Case Timeline

Date Event
2007-12-28 '046 Patent Priority Date
2016-03-27 Plaintiff receives Defendants' Paragraph IV Certification
2017-01-03 U.S. Patent No. 9,533,046 Issues
2017-05-09 Complaint Filing Date
2018-01-07 RYTARY® New Dosage Form Exclusivity Expiration Date

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

U.S. Patent No. 9,533,046 - "Controlled Release Formulations of Levodopa and Uses Thereof"

  • Patent Identification: U.S. Patent No. 9,533,046 ("the '046 Patent"), "Controlled Release Formulations of Levodopa and Uses Thereof," issued January 3, 2017. (Compl. ¶20).

The Invention Explained

  • Problem Addressed: The patent describes the clinical challenge in treating Parkinson's disease (PD) with levodopa (LD). Conventional oral LD treatments can lead to fluctuating drug levels in the blood, causing periods of poor mobility ("off" time) and involuntary movements (dyskinesia). Existing controlled-release formulations, while an improvement, often have a delayed onset of action, leaving patients immobile for extended periods after a dose, particularly in the morning. ('046 Patent, col. 2:5-24).
  • The Patented Solution: The invention is a pharmaceutical formulation that combines immediate-release and controlled-release components of levodopa and a decarboxylase inhibitor (carbidopa). A key feature is the inclusion of a carboxylic acid, such as tartaric acid, which is claimed to enhance absorption and help achieve a more stable, infusion-like plasma concentration profile over approximately six hours. This dual-action approach aims to provide both rapid symptom relief and sustained effectiveness, reducing the "peak-to-trough" fluctuations. ('046 Patent, Abstract; col. 2:41-54).
  • Technical Importance: This formulation seeks to provide the steady-state pharmacokinetic benefits of a continuous-infusion therapy, which is highly effective but invasive and inconvenient, in the form of a conventional oral dosage form. ('046 Patent, col. 2:35-44).

Key Claims at a Glance

  • The complaint asserts infringement of "at least one claim" of the '046 Patent. (Compl. ¶28). Independent method of treatment claim 1 is representative.
  • Essential elements of Independent Claim 1 include:
    • A method for treating Parkinson's disease by orally administering a multiparticulate formulation containing specified amounts of carbidopa and levodopa.
    • The formulation comprises an "immediate release component" with carbidopa and levodopa.
    • The formulation also comprises a "controlled release component" that releases carbidopa, levodopa, and a "carboxylic acid" over a period of about 6 hours.
    • The molar ratio of the carboxylic acid to levodopa must be within a specified range (greater than 1:4 and less than 4:1).
    • Administration of the formulation results in a specific, multi-part levodopa plasma concentration profile, defined by concentrations at specific time points and a peak-to-trough ratio of about 1.5 to 2.5. ('046 Patent, col. 51:1-52:1).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "Actavis ANDA Product": proposed generic carbidopa/levodopa extended-release capsules in 23.75 mg/95 mg, 36.25 mg/145 mg, 48.75 mg/195 mg, and 61.25 mg/245 mg dosages. (Compl. ¶25).

Functionality and Market Context

  • The complaint alleges that Actavis submitted ANDA No. 208522 seeking FDA approval to market a generic version of Impax's branded drug, RYTARY®. (Compl. ¶¶1, 25).
  • The infringement theory is predicated on the allegation that Actavis's ANDA "refers to and relies upon the RYTARY® NDA and contains data that, according to Actavis, demonstrate the bioequivalence of the Actavis ANDA Product and RYTARY®." (Compl. ¶26). This suggests the accused product is designed to have the same active ingredients, dosage form, and pharmacokinetic performance as the branded product which allegedly practices the patent.
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or a detailed, element-by-element analysis of infringement. The infringement allegations are based on the statutory act of filing an ANDA under 35 U.S.C. § 271(e)(2). The underlying theory is that because the Actavis ANDA Product is intended to be bioequivalent to RYTARY®, its administration to a patient would necessarily result in the pharmacokinetic profile claimed in the '046 Patent, thereby directly infringing method claims such as claim 1. (Compl. ¶¶26, 28, 31).

  • Identified Points of Contention:
    • Technical Questions: A primary factual dispute will be whether the formulation detailed in Actavis’s confidential ANDA submission, and the resulting pharmacokinetic data, meets every limitation of the asserted claims. This includes not only the compositional elements (e.g., immediate-release component, controlled-release component, carboxylic acid) but also the specific, multi-part plasma concentration profile recited in claims like claim 1.
    • Scope Questions: The case raises the question of whether data demonstrating "bioequivalence" for FDA regulatory purposes is legally sufficient to prove infringement of the patent's more granular pharmacokinetic limitations. Further, a dispute may arise over whether any acidic excipients in the accused product function as the claimed "carboxylic acid" to achieve the patented effect, or if they are present for other, non-infringing purposes.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for a full analysis of claim construction disputes. However, based on the technology and the nature of the claims, the following terms may be central to the case.

  • The Term: "...a carboxylic acid that is not carbidopa or levodopa..." (Claim 1)

    • Context and Importance: The inclusion of a separate carboxylic acid is presented as a key inventive concept for achieving the desired stable plasma profile. Practitioners may focus on this term because the infringement analysis will depend on whether the accused formulation contains such an acid and whether that acid performs the function described in the patent.
    • Intrinsic Evidence for a Broader Interpretation: The specification provides a long list of suitable acids, including "tartaric acid, adipic acid, succinic acid, citric acid, benzoic acid, acetic acid, ascorbic acid..." suggesting the term is not limited to a single type of acid. ('046 Patent, col. 5:16-20).
    • Evidence for a Narrower Interpretation: The patent’s examples and figures focus heavily on tartaric acid. ('046 Patent, Example 1, col. 16:3-4). A defendant could argue that the term should be limited to acids that are demonstrated in the patent to achieve the specific claimed pharmacokinetic results.

  • The Term: "...the peak-to-trough ratio of the second concentration to the third concentration is about 1.5 to about 2.5..." (Claim 1)

    • Context and Importance: This pharmacokinetic (PK) parameter is a critical limitation defining the "flatter plasma profile" that is a core objective of the invention. Infringement will require proof that the accused product meets this numerical constraint.
    • Intrinsic Evidence for a Broader Interpretation: The use of the word "about" suggests the patentees did not intend to be bound by the precise numerical endpoints. Plaintiff may argue that this term encompasses any profile that is bioequivalent to the profile generated by its own RYTARY® product.
    • Evidence for a Narrower Interpretation: A defendant may argue that the term "about" does not rescue a claim from indefiniteness if the specification fails to provide an objective standard for its scope. The defendant will likely contend that its product's PK profile, while potentially "bioequivalent" for regulatory purposes, does not fall within a properly construed (i.e., narrow) range for this limitation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce infringement by providing promotional materials and package inserts that instruct physicians and patients to administer the accused product in a manner that directly infringes the method claims of the '046 Patent. (Compl. ¶¶34-35). Contributory infringement is also alleged, on the basis that the accused product is especially adapted for infringing use and is not a staple article of commerce. (Compl. ¶¶32-33).
  • Willful Infringement: The complaint does not contain a separate count for willful infringement but alleges that Actavis had "knowledge of the '046 patent" and that the case is "exceptional" under 35 U.S.C. § 285, which forms a basis for seeking enhanced damages and/or attorney fees. (Compl. ¶¶34, 37).

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

  • A central issue will be one of evidentiary sufficiency: Is the data submitted in Actavis's ANDA to establish "bioequivalence" with RYTARY® for regulatory approval sufficient to also prove, by a preponderance of the evidence, that the accused product meets the specific, multi-part pharmacokinetic limitations recited in the asserted method claims?
  • The case will also present a key technical question of infringement: Does the specific formulation of the Actavis ANDA product, as confidentially disclosed to the plaintiff, contain the elements of the asserted claims, particularly a "carboxylic acid" that functions to produce the claimed stable plasma profile?
  • Finally, a core validity question will be one of non-obviousness: In light of the state of the art in controlled-release drug formulations, was it obvious to combine an immediate-release/controlled-release levodopa formulation with a carboxylic acid to achieve the specific, stable pharmacokinetic profile claimed in the '046 Patent?