DCT

1:17-cv-00672

Allergan Sales LLC v. Macleods Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00672, D. Del., 06/02/2017
  • Venue Allegations: Venue is alleged to be proper based on Defendant Macleods Pharma USA, Inc. being a Delaware corporation and on Defendants’ intent to market and sell the accused generic products within the district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for generic versions of Namenda XR® constitutes an act of infringement of four patents related to modified-release formulations of memantine.
  • Technical Context: The technology concerns pharmaceutical formulations that provide extended or modified release of memantine, a drug used to treat central nervous system disorders such as Alzheimer's disease, enabling once-daily administration.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Defendants’ submission of ANDA No. 206310, which seeks FDA approval to market generic memantine hydrochloride extended-release tablets. The patents-in-suit are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book") for Namenda XR®.

Case Timeline

Date Event
2004-06-17 U.S. Patent No. 8,039,009 Priority Date
2004-11-23 U.S. Patent Nos. 8,168,209, 8,173,708, & 8,283,379 Priority Date
2011-10-18 U.S. Patent No. 8,039,009 Issued
2012-05-01 U.S. Patent No. 8,168,209 Issued
2012-05-08 U.S. Patent No. 8,173,708 Issued
2012-10-09 U.S. Patent No. 8,283,379 Issued
2017-04-19 Alleged date on or before which Defendants submitted ANDA No. 206310
2017-04-21 Earliest date Plaintiffs allegedly received notification of ANDA filing
2017-06-02 Complaint Filing Date

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

U.S. Patent No. 8,039,009 - Modified Release Formulations Of Memantine Oral Dosage Forms

  • Patent Identification: U.S. Patent No. 8,039,009, "Modified Release Formulations Of Memantine Oral Dosage Forms," issued October 18, 2011 (Compl. ¶14).

The Invention Explained

  • Problem Addressed: The patent’s background section states that the then-current twice-daily dosing regimen for immediate-release memantine tablets was undesirable due to decreased patient compliance and could lead to a greater frequency of adverse events from a faster rate of drug absorption (’009 Patent, col. 2:64-3:9).
  • The Patented Solution: The invention is a once-daily, solid oral dosage form of memantine that provides sustained release of the active ingredient over an extended period of 4 to 24 hours (’009 Patent, Abstract). This is achieved by incorporating memantine into a pharmaceutically acceptable polymeric matrix, such as hydroxypropyl methylcellulose, which swells upon contact with gastric fluid and controls the rate of drug diffusion out of the matrix (’009 Patent, col. 3:56-61; col. 7:1-6).
  • Technical Importance: This once-daily formulation was designed to improve patient compliance and reduce side effects by maintaining more consistent therapeutic plasma levels of memantine over a 24-hour period (’009 Patent, col. 2:50-55).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 21 (Compl. ¶23).
  • The essential elements of independent claim 1 include:
    • A method for treating Alzheimer's disease comprising once daily administration of a modified release solid oral dosage form.
    • The dosage form comprises 28 mg ±5% of memantine or a pharmaceutically acceptable salt thereof.
    • The dosage form includes a pharmaceutically acceptable polymeric carrier that substantially contributes to modifying the release.
    • The dosage form sustains the release of memantine from about 4 to 24 hours.
    • The dosage form has a "single phase dissolution rate of less than about 80% after passage of about 6 hours" following entry into a use environment.
  • The complaint also asserts dependent claims 2, 22, and 23 (Compl. ¶23).

U.S. Patent No. 8,168,209 - Method And Composition For Administering An NMDA Receptor Antagonist To A Subject

  • Patent Identification: U.S. Patent No. 8,168,209, "Method And Composition For Administering An NMDA Receptor Antagonist To A Subject," issued May 1, 2012 (Compl. ¶15).

The Invention Explained

  • Problem Addressed: The patent identifies the difficulty of achieving patient compliance, which is "exacerbated by the complicated dosing schedules" for many neurological drugs (’209 Patent, col. 2:1-5). Specifically, many NMDAr antagonists require dose escalation at the start of therapy to avoid side effects, delaying the achievement of a therapeutically effective dose (’209 Patent, col. 2:62-3:2).
  • The Patented Solution: The invention provides a modified-release formulation of an NMDA receptor antagonist that can be administered at a therapeutically effective dose from the onset of therapy, avoiding the need for dose escalation (’209 Patent, col. 2:10-29). The formulation achieves this by controlling the initial rate of drug absorption to produce a plasma concentration profile (dC/dT) that is significantly less steep than that of an immediate-release formulation (’209 Patent, col. 4:38-54).
  • Technical Importance: This approach allows patients to begin treatment at a therapeutic dose, potentially reaching a beneficial steady-state plasma concentration more quickly and with fewer side effects compared to regimens requiring gradual dose titration (’209 Patent, col. 6:5-12).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶23).
  • The essential elements of independent claim 1 include:
    • A solid pharmaceutical composition in a unit dosage form for once daily oral administration.
    • The composition comprises an extended release formulation of 5 to 40 mg memantine or a pharmaceutically acceptable salt thereof.
    • Administration of the composition provides a plasma memantine concentration profile characterized by a rate of change (dC/dT) that is "less than 50% that of an immediate release dosage form comprising the same dose."
    • The dC/dT is measured between the time period of 0 to Tmax of the immediate release form.
  • The complaint also asserts dependent claims 2-4, 6, and 10-14 (Compl. ¶23).

U.S. Patent No. 8,173,708 - Method And Composition For Administering An NMDA Receptor Antagonist To A Subject

  • Patent Identification: U.S. Patent No. 8,173,708, "Method And Composition For Administering An NMDA Receptor Antagonist To A Subject," issued May 8, 2012 (Compl. ¶16).
  • Technology Synopsis: The ’708 Patent addresses the same technical problems as the ’209 Patent, namely the adverse effects and compliance challenges associated with immediate-release NMDAr antagonists that require dose escalation (’708 Patent, col. 2:1-5). The patented solution is a method of treatment using a once-daily, extended-release formulation that provides a less steep initial plasma concentration curve (dC/dT), thereby reducing the potential for adverse effects and enabling treatment to begin at a therapeutic dose (’708 Patent, col. 34:6-21).
  • Asserted Claims: Claims 1, 3-5, and 6-9 are asserted (Compl. ¶23).
  • Accused Features: The complaint accuses Defendants' proposed generic extended-release memantine tablets, and the methods of using them as detailed in the proposed package insert, of infringement (Compl. ¶21, 24).

U.S. Patent No. 8,283,379 - Methods And Compositions For The Treatment Of CNS-Related Conditions

  • Patent Identification: U.S. Patent No. 8,283,379, "Methods And Compositions For The Treatment Of CNS-Related Conditions," issued October 9, 2012 (Compl. ¶17).
  • Technology Synopsis: This patent is directed to methods and compositions for treating CNS-related conditions, such as Alzheimer's disease, by co-administering an NMDAr antagonist (like memantine) and an acetylcholinesterase inhibitor (AChEI) (’379 Patent, col. 1:49-54). The invention contemplates formulations, including extended-release versions, that are designed to optimize the pharmacokinetic profiles of the two drugs when used in combination to enhance efficacy and/or reduce side effects (’379 Patent, col. 6:1-8).
  • Asserted Claims: Claims 1-3 and 5 are asserted (Compl. ¶23).
  • Accused Features: The complaint accuses Defendants' proposed generic extended-release memantine tablets, and particularly the methods of using them as instructed on the proposed product label, of infringement (Compl. ¶21, 24, 27).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are "the Macleods Generic Products," identified as generic extended-release tablet products containing 7, 14, 21, and 28 milligrams of memantine hydrochloride as the active ingredient (Compl. ¶21). These products are the subject of Abbreviated New Drug Application (ANDA) No. 206310 submitted by Defendants to the FDA (Compl. ¶21).

Functionality and Market Context

The products are proposed generic equivalents of Plaintiffs' Namenda XR® brand extended-release capsules (Compl. ¶18, 21). Their intended function is to provide an extended release of memantine hydrochloride for once-daily administration (Compl. ¶21). The complaint alleges that by filing the ANDA, Defendants are seeking FDA approval to manufacture, use, and sell these generic products in the United States before the expiration of the patents-in-suit (Compl. ¶21).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element infringement analysis sufficient for the construction of a claim chart for any of the asserted patents. It alleges generally that the Macleods Generic Products and their methods of use will meet each and every element of the asserted claims, either literally or under the doctrine of equivalents (Compl. ¶24).

’009 Patent Infringement Allegations

  • Identified Points of Contention:
    • Scope Questions: Claim 1 requires a "single phase dissolution rate" that is "less than about 80% after passage of about 6 hours." An initial point of contention may be whether the dissolution profile of the accused generic product, as disclosed in its ANDA, meets this specific quantitative and qualitative limitation. The definition of "single phase" could be a central issue for claim construction.
    • Technical Questions: A key evidentiary question will be whether the actual dissolution performance of the Macleods Generic Product, when tested under the conditions specified by the patent or relevant FDA guidelines, falls within the claimed release profile.

’209 Patent Infringement Allegations

  • Identified Points of Contention:
    • Scope Questions: Claim 1 is defined by a comparative pharmacokinetic outcome: a rate of change in plasma concentration (dC/dT) that is "less than 50% that of an immediate release dosage form." A central legal question will be the proper standard for this comparison. This includes identifying the appropriate "immediate release dosage form" to be used as the benchmark and the clinical or laboratory conditions under which the comparison must be made.
    • Technical Questions: The infringement analysis will likely turn on bioequivalence and pharmacokinetic data. A key factual dispute will be whether the data in Defendants' ANDA, or new data generated during litigation, demonstrates that their product, when administered, actually produces the in-vivo plasma profile required by the claim.

V. Key Claim Terms for Construction

For the ’009 Patent

  • The Term: "single phase dissolution rate" (Claim 1)
  • Context and Importance: This term defines a core technical characteristic of the claimed invention's release profile. The infringement analysis will depend on whether the accused product's release mechanism can be characterized as having a "single phase" rate. Practitioners may focus on this term because formulations can be designed to have multiphasic releases (e.g., an initial immediate-release burst followed by a sustained-release phase), which might fall outside the scope of the claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent does not appear to provide an explicit definition. A party may argue that the term should be given its plain and ordinary meaning, referring to a generally continuous release curve without sharp inflection points, such as those depicted in the patent’s figures ('009 Patent, FIG. 1, 2).
    • Evidence for a Narrower Interpretation: The specification describes the invention as a swellable polymeric matrix where the drug is released by diffusion ('009 Patent, col. 7:1-6). A party could argue that "single phase" is limited to the specific type of diffusion-controlled release kinetics exhibited by such a matrix, potentially excluding other extended-release mechanisms.

For the ’209 Patent

  • The Term: "plasma memantine concentration profile" (Claim 1)
  • Context and Importance: Infringement of this claim hinges on a comparison between the "profile" of the accused product and that of a reference product. The definition of what constitutes the "profile"—whether it is a qualitative shape of the concentration-time curve or a set of specific quantitative pharmacokinetic parameters—is critical.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent illustrates concentration profiles as graphs of plasma concentration versus time ('209 Patent, FIG. 1A, 1B, 2D). A party may argue that the term refers to the overall characteristics of this curve, including its general shape and slope.
    • Evidence for a Narrower Interpretation: The detailed description extensively discusses specific pharmacokinetic parameters such as Cmax (maximum plasma concentration) and Tmax (time of maximum concentration) ('209 Patent, col. 15:37-40). A party could argue that the "profile" must be defined by these specific, measurable parameters rather than a more general curve shape, requiring a comparison of discrete data points rather than overall curve morphology.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce infringement by doctors, pharmacists, and patients through the proposed product label and instructions for use (Compl. ¶27). It also alleges contributory infringement, stating that the Macleods Generic Products are not staple articles of commerce and are especially made for use in an infringing manner (Compl. ¶26).
  • Willful Infringement: While the complaint does not explicitly allege "willful infringement," it does allege that Macleods was aware of the patents-in-suit prior to filing its ANDA (Compl. ¶27). It further requests that the case be found "exceptional under 35 U.S.C. § 285," which is the statutory basis for an award of attorney's fees, often predicated on findings of willful infringement or litigation misconduct (Compl. ¶28).

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

  • A core issue will be one of comparative performance: does the accused generic product, as described in its ANDA filing, exhibit the specific dissolution and in-vivo pharmacokinetic profiles required by the asserted claims when compared to the relevant benchmarks (e.g., the dissolution of 80% at 6 hours for the ’009 patent, or the dC/dT relative to an immediate-release form for the ’209 patent)? The case will likely involve a significant dispute between technical experts over bioequivalence data and dissolution testing results.
  • A second central question will be one of induced infringement, particularly for the method claims. The analysis will focus on whether the specific language in the proposed product label for the Macleods Generic Products actively encourages, recommends, or instructs physicians and patients to use the drug in a manner that would directly infringe the patented methods of treatment.