PTAB

IPR2018-00943

Amneal Pharmaceuticals LLC v. Alkermes Pharma Ireland Ltd

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Naltrexone Long Acting Formulations and Methods of Use
  • Brief Description: The ’499 patent discloses methods for treating conditions like alcohol or opioid dependence by administering a long-acting, injectable formulation of naltrexone. The formulation uses a biocompatible polymer (PLGA) to provide sustained release, allegedly resulting in a serum Area Under the Curve (AUC) approximately three times greater than that of standard daily oral naltrexone administration.

3. Grounds for Unpatentability

Ground 1: Anticipation over Comer - Claims 1, 3-5, and 10-12 are anticipated by Comer.

  • Prior Art Relied Upon: Comer (a 2002 journal article), interpreted with reference to Nuwayser (Patent 7,157,102) to define a term.
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued Comer discloses every element of claim 1. Comer describes a clinical study treating opioid-dependent patients by parenterally administering a 384 mg depot injection of naltrexone, which falls within the claimed dose range of 310-480 mg. A person of ordinary skill in the art (POSA) would understand Comer’s reference to "Depotrex®" to be the PLGA-based formulation detailed in Nuwayser. Comer shows the formulation is long-acting, providing therapeutic blood levels for about four weeks. The core of the argument is that Comer inherently discloses the claimed AUC differential of "about three" times greater than 50 mg/day oral dosing when Comer's pharmacokinetic data is compared against the same oral dosing data the patent owner used during prosecution.
    • Key Aspects: Petitioner contended that since the dose (384 mg) and formulation (PLGA) in Comer are identical to that used in the patent’s underlying study, the resulting dose-dependent AUC must also be the same and is therefore anticipated.

Ground 2: Obviousness over Comer and Nuwayser - Claims 1-13 are obvious over Comer in view of Nuwayser, Rubio, and Wright.

  • Prior Art Relied Upon: Comer (journal article), Nuwayser (Patent 7,157,102), Rubio (a 2001 journal article), and Wright (Patent 6,264,987).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that even if Comer does not explicitly define the formulation used, a POSA would look to related art like Nuwayser for a suitable long-acting naltrexone/PLGA formulation. Comer teaches the method and dose (384 mg), while Nuwayser provides a detailed description of the "Depotrex" PLGA microparticle formulation and confirms its month-long release profile. The pharmacokinetic plots in Comer and Nuwayser are superimposable, confirming they describe the same product. Rubio teaches long-term (12-month) treatment protocols for alcoholics, and Wright teaches PLGA microparticle drug loadings (30-75%) that encompass the claimed concentration.
    • Motivation to Combine: A POSA, seeking to implement the treatment protocol in Comer, would be motivated to use the specific PLGA formulation for "Depotrex" described in Nuwayser to achieve the reported results. Both references address the same problem of improving patient compliance via depot injection.
    • Expectation of Success: A POSA would have a high expectation of success because both references report successful therapeutic outcomes with nearly identical release profiles from a formulation made by the same manufacturer. The combination merely applies a known formulation (Nuwayser) to a known method of use (Comer).

Ground 3: Obviousness over Nuwayser and Kranzler - Claims 1-13 are obvious over Nuwayser in view of Kranzler, Rubio, and Wright.

  • Prior Art Relied Upon: Nuwayser (Patent 7,157,102), Kranzler (a 1998 journal article), Rubio (a 2001 journal article), and Wright (Patent 6,264,987).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground starts with Nuwayser, which describes the long-acting naltrexone/PLGA formulation and its pharmacokinetic profile but does not explicitly state the exact dose that produced its results. Petitioner argued that determining this dose would be an act of routine optimization for a POSA.
    • Motivation to Combine: A POSA would be motivated to determine the appropriate dose for the Nuwayser formulation to achieve the disclosed 30-day therapeutic effect. Kranzler provides a known data point, teaching that a 206 mg naltrexone depot injection provided three weeks of therapeutic blood levels. This would motivate a POSA to generate a standard dose-response curve to find the dose required for a four-week effect, an exercise of routine experimentation.
    • Expectation of Success: A POSA would expect success in determining the dose, as generating a dose-response curve to match a desired pharmacokinetic endpoint (like the AUC in Nuwayser's Figure 7) is a standard and predictable practice in pharmaceutical formulation. The resulting dose would inherently fall within the claimed range and produce the claimed AUC differential.

  • Additional Grounds: Petitioner asserted anticipation of claims 1, 3-5, 11, and 12 over Nuwayser alone (Ground 2), arguing the dose is inherently disclosed by integrating the AUC plot. Petitioner also asserted obviousness over Nuwayser in view of Comer (Ground 4), reversing the primary and secondary references from Ground 2, and obviousness over Patent Owner's own prior art, including its 10-K filing and Vivitrex trademark specimen (Ground 6).

4. Key Claim Construction Positions

  • "the serum AUC of naltrexone...than that achieved by 50 mg/day oral administration": Petitioner argued this term is critically undefined in the patent specification. The patent fails to provide any data for either the claimed formulation's AUC or the comparator oral dosing AUC, making the claimed "about three times greater" relationship unsubstantiated.
  • Petitioner contended that under the broadest reasonable interpretation, a POSA is invited to use any available prior art data set for the comparison. Using the same oral data as the patent owner's expert during prosecution, prior art like Comer and Nuwayser meets the "about three times" limitation. However, using other available oral data sets from the art would not, rendering the claim indefinite and subject to manipulation. This ambiguity was central to Petitioner's argument that the AUC limitation carries little patentable weight.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-13 of the ’499 patent as unpatentable.