DCT

2:17-cv-13476

Impax Laboratories Inc v. Zydus Pharma USA Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: Impax Laboratories, Inc. v. Zydus Pharmaceuticals USA, Inc. and Cadila Healthcare Ltd., 2:17-cv-13476, D.N.J., 12/21/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Zydus Pharmaceuticals USA, Inc. is a New Jersey corporation with its principal place of business in the state. Defendant Cadila Healthcare Ltd. is an Indian corporation and not a resident of the United States, making venue proper in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's RYTARY® (carbidopa/levodopa) capsules constitutes an act of infringement of a patent covering a specific drug-release profile.
  • Technical Context: The technology concerns controlled-release oral formulations for Parkinson's disease treatment, aiming to provide steadier plasma concentrations of the drug levodopa to reduce motor fluctuations known as "on-off" periods.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act, triggered by Defendants' submission of ANDA No. 210911 and an accompanying Paragraph IV certification. The complaint alleges this certification notified Plaintiff that Defendants' generic product would not infringe certain claims of the patent-in-suit, but notably alleges the certification provided no non-infringement argument for asserted claim 21. The complaint also references other pending litigation by Plaintiff against different generic drug manufacturers concerning related patents.

Case Timeline

Date Event
2007-12-28 U.S. Patent 9,089,608 Priority Date
2015-07-28 U.S. Patent 9,089,608 Issue Date
2017-11-06 Plaintiff received Defendants' Paragraph IV Certification Letter
2017-12-21 Complaint Filing Date
2018-01-07 RYTARY® New Dosage Form Exclusivity End Date

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

U.S. Patent No. 9,089,608: "Controlled Release Formulations of Levodopa and Uses Thereof" (Issued July 28, 2015)

The Invention Explained

  • Problem Addressed: The patent describes the clinical challenge of treating Parkinson's disease with levodopa (LD), where conventional oral therapies cause fluctuating drug plasma levels. These fluctuations lead to debilitating "wearing off" periods and unpredictable swings from mobility to immobility, known as the "on-off" phenomenon (’608 Patent, col. 2:3-15). Existing controlled-release drugs are described as having their own issues, such as a long delay to take effect ('608 Patent, col. 2:16-27).
  • The Patented Solution: The invention claims to solve this problem with an oral solid formulation of levodopa, a decarboxylase inhibitor (e.g., carbidopa), and a carboxylic acid. This combination is designed to produce a steadier, more constant levodopa plasma concentration over a prolonged period, aiming to mimic the stable levels achieved by more invasive infusion therapies ('608 Patent, Abstract; col. 2:50-55). The claimed invention is not a composition of matter but a specific pharmacokinetic (PK) profile that a formulation achieves upon administration.
  • Technical Importance: The technology seeks to provide the clinical benefits of infusion therapy—reduced "off" time and fewer motor complications—in a more convenient oral dosage form, thereby improving the administration of LD to Parkinson's patients ('608 Patent, col. 2:41-55).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 21 (Compl. ¶41).
  • Independent Claim 21 requires a controlled-release oral solid formulation of levodopa that, when administered, results in a specific "median levodopa plasma or serum concentration profile" with the following essential elements:
    • A first concentration measured within one hour of administration.
    • A second, maximum concentration (Cmax) that occurs at a later time.
    • A third concentration that occurs at least four hours after the maximum concentration.
    • The first concentration must be "equal to about fifty percent" of the maximum concentration.
    • The third concentration must also be "equal to about fifty percent" of the maximum concentration.
  • The complaint uses general language ("at least one claim") suggesting it may assert other claims later in the litigation (Compl. ¶44).

III. The Accused Instrumentality

Product Identification

  • The accused product is Defendants' proposed generic carbidopa/levodopa extended-release capsules, for which they seek FDA approval via ANDA No. 210911 (the "Zydus ANDA Product") (Compl. ¶37).

Functionality and Market Context

  • The Zydus ANDA Product is designed as a generic equivalent to Plaintiff's RYTARY® drug, an extended-release treatment for Parkinson's disease (Compl. ¶32, ¶37).
  • The complaint alleges that Defendants' ANDA submission "refers to and relies upon the RYTARY® NDA and contains data that, according to Zydus, demonstrate the bioequivalence of the Zydus ANDA Product and RYTARY®" (Compl. ¶38). This allegation of bioequivalence is the central technical basis for the infringement claim, as it suggests the accused generic product is intended to produce the same plasma concentration profile as the branded drug.

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'608 Patent Infringement Allegations

Claim Element (from Independent Claim 21) Alleged Infringing Functionality Complaint Citation Patent Citation
A controlled release oral solid formulation of levodopa having a median levodopa plasma or serum concentration profile comprising: Defendants' Zydus ANDA Product is a controlled-release formulation of carbidopa/levodopa for which Defendants have submitted an ANDA asserting bioequivalence to Plaintiff's RYTARY® product. ¶37, ¶38 col. 46:50-52
a. a time of administration; b. a first concentration at a first time, that occurs within one hour of said time of administration; c. a second concentration at a second time, that occurs after said first time; d. a third concentration at a third time, that occurs at least four hours after said second time; Administration of the Zydus ANDA Product is alleged to produce a median plasma concentration profile that meets these specific temporal and concentration parameters. ¶38, ¶41 col. 46:53-61
wherein said second concentration is equal to the maximum concentration of said profile; said first concentration is equal to about fifty percent of said second concentration; said third concentration is equal to about fifty percent of said second concentration. The complaint alleges that due to the product's asserted bioequivalence with RYTARY®, its administration will result in a PK profile meeting the specific claimed ratios: an initial concentration at ~50% of the peak, followed by the peak (Cmax), followed by a later concentration also at ~50% of the peak. ¶38, ¶41 col. 46:62-68
  • Identified Points of Contention:
    • Technical Question: A primary issue will be whether the clinical data submitted in Defendants' ANDA actually demonstrates that the Zydus ANDA Product produces the specific pharmacokinetic profile defined by the limitations of claim 21. The case will likely involve detailed analysis of bioequivalence studies and expert testimony on data interpretation.
    • Scope Questions: A potential dispute may arise over the meaning of "median" concentration profile, as the choice of statistical measure (median vs. mean) can affect the outcome of comparisons. Furthermore, the term "about fifty percent" introduces ambiguity, raising the question of what degree of deviation from exactly 50% is permissible for a finding of infringement.
    • Procedural Question: The complaint's assertion that Defendants' Paragraph IV certification "does not include a non-infringement argument with respect to claim 21" (Compl. ¶42) raises a significant question about Defendants' litigation strategy. It suggests the possibility that Defendants may concede infringement if the patent is found valid and instead focus their defense primarily on challenging the patent's validity.

V. Key Claim Terms for Construction

  • The Term: "median levodopa plasma or serum concentration profile"

    • Context and Importance: This term defines the very subject matter of the claim. Infringement hinges entirely on whether the accused product's performance data, when analyzed, corresponds to this claimed profile. Practitioners may focus on this term because the specific choice of "median" over "mean" is a deliberate and potentially outcome-determinative technical distinction in how pharmacokinetic data is analyzed and compared.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent's specification describes a general goal of achieving "steadier" and "constant" plasma concentrations to mimic infusion therapy, which could support interpreting the claim as covering any profile that achieves this functional outcome, regardless of minor statistical variations ('608 Patent, col. 2:41-55).
      • Evidence for a Narrower Interpretation: The claim recites specific numerical relationships between points on the profile. The patent also provides specific graphical examples of profiles, such as the "IPX066" profile in Figure 1, which could be used to argue that the claimed "profile" is limited to one with a very similar shape and characteristics to those explicitly disclosed ('608 Patent, Fig. 1; col. 9:15-22).

  • The Term: "about fifty percent"

    • Context and Importance: The quantitative heart of the claim lies in this ratio. The infringement analysis will depend on whether the measured concentrations from the accused product fall within the range permitted by "about."
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of "about" generally signifies that exact numerical precision is not required. A party could argue the term should be interpreted functionally to encompass any concentration that achieves the patent's stated goal of a "flat" or "steady" profile.
      • Evidence for a Narrower Interpretation: The patent contains numerous tables with specific experimental data ('608 Patent, e.g., Tables 1-2). A party could argue that the scope of "about" should be limited by the range of experimental variability observed in the patent's own data, thereby preventing the patentee from claiming a scope broader than what was demonstrably achieved and disclosed.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement theory is based on the allegation that Defendants, with knowledge of the '608 patent, will provide promotional materials and package inserts instructing medical professionals and patients to administer the drug in a manner that directly infringes claim 21 (Compl. ¶48, ¶49). The contributory infringement allegation is based on the assertion that the Zydus ANDA Product is especially made for this infringing use and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶46, ¶47).
  • Willful Infringement: While the complaint does not use the word "willful," it pleads facts that could support such a claim. It alleges Defendants had pre-suit knowledge of the '608 patent via the ANDA process and their own Paragraph IV certification (Compl. ¶39, ¶48). It also requests an award of attorney fees, designating the case as "exceptional" under 35 U.S.C. § 285 (Compl. ¶51).

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

  • A core issue will be one of data interpretation: Does the clinical data in Defendants' ANDA, which asserts bioequivalence to RYTARY®, conclusively show that their product will generate the specific, multi-point "median" pharmacokinetic profile required by claim 21, or is there a statistical or functional mismatch?
  • A central strategic question will be the focus of the defense: Given the complaint’s allegation that Defendants did not contest infringement of claim 21 in their Paragraph IV notice, the case may pivot from an infringement dispute to a focused challenge on the patent's validity. Will Defendants attempt to prove claim 21 is invalid as obvious or not enabled in view of prior art drug formulations?
  • A key claim construction question will be the scope of numerical terms: How much variance does the term "about fifty percent" allow? The resolution of this issue will define the boundaries of infringement and will likely depend on expert testimony regarding what a person of ordinary skill in the art of pharmacokinetics would understand from the patent's specification and figures.