Apotex Inc v. Alkermes Pharma Ireland Ltd

1. Case Identification

• Case #: IPR2025-00514
• Patent #: 7,919,499
• Filed: January 30, 2025
• Petitioner(s): Apotex Inc.
• Patent Owner(s): Alkermes Pharma Ireland Limited
• Challenged Claims: 1-13

2. Patent Overview

• Title: Method of Using Naltrexone Formulations
• Brief Description: The ’499 patent describes methods for treating individuals in need of naltrexone by parenterally administering a long-acting formulation containing naltrexone and a polylactide-co-glycolide (PLGA) polymer. The claimed method results in a serum Area Under the Curve (AUC) for naltrexone that is about three times greater than that achieved by a standard 50 mg/day oral administration, aiming to improve patient compliance.

3. Grounds for Unpatentability

Ground 1: Claims 1, 3-5, and 12 are anticipated by Comer as evidenced by Nuwayser.

• Prior Art Relied Upon: Comer (a 2002 clinical study) and Nuwayser (Patent 7,157,102).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Comer, a study on a depot formulation of naltrexone called "Depotrex®," disclosed every limitation of the challenged claims. Comer taught parenterally administering a "high dose" of 384 mg of naltrexone, which falls within the claimed range of 310-480 mg. Petitioner asserted that Nuwayser, which describes the composition of Depotrex®, serves as evidence that a Person of Ordinary Skill in the Art (POSITA) would have understood Comer’s Depotrex® to contain the claimed PLGA polymer. Petitioner's expert calculated the AUC from Comer’s published data and argued it was approximately 2.9 times greater than the oral dose data used during prosecution of the ’499 patent, thereby meeting the "about three times greater" AUC limitation. Comer also disclosed a release period of at least four weeks (claims 3-4), a dose of about 380 mg (claim 5), and administration by injection (claim 12).

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

• Prior Art Relied Upon: Comer (2002 study), Nuwayser (’102 patent), Rubio (2001 study), and Wright (Patent 6,264,987).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner contended that, even if Comer does not inherently disclose a PLGA formulation, a POSITA would have found it obvious to use the PLGA-based naltrexone formulation from Nuwayser in the treatment method taught by Comer. Both references describe long-acting depot naltrexone formulations ("Depotrex®") and present nearly identical pharmacokinetic plots, indicating their interchangeability. Rubio was cited to show that treating alcohol dependency with naltrexone was well-known (claim 10). Wright was cited to teach that naltrexone drug loading concentrations of 30-75% by weight were conventional, rendering the "about 35% by weight" limitation of claim 13 obvious.
  • Motivation to Combine: A POSITA implementing the treatment protocol in Comer would have looked to references like Nuwayser for specific, suitable long-acting naltrexone formulations. The shared trade name (Depotrex®), similar therapeutic goals, and superimposable release profiles provided a strong motivation to use Nuwayser’s formulation to practice Comer’s method.
  • Expectation of Success: A POSITA would have had a high expectation of success because both Comer and Nuwayser demonstrated successful therapeutic outcomes with similar formulations over a one-month period. The predictable nature of combining a known drug carrier (Nuwayser's PLGA) with a known drug administration method (Comer's protocol) would lead to the expected pharmacokinetic profile.

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

• Prior Art Relied Upon: Nuwayser (’102 patent), Comer (2002 study), Rubio (2001 study), and Wright (’987 patent).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground inverted the primary references from Ground 2. Petitioner argued a POSITA starting with Nuwayser’s disclosure of a long-acting PLGA naltrexone formulation would be motivated to administer it at the 384 mg dose taught by Comer. While Nuwayser provides the formulation and a resulting pharmacokinetic plot, it does not explicitly state the dose used to generate that plot.
  • Motivation to Combine: A POSITA seeking to determine the appropriate dose for Nuwayser's formulation would consult related art. Comer, which used the same Depotrex® product from the same manufacturer and produced a virtually identical pharmacokinetic plot, explicitly disclosed a 384 mg dose. This would have motivated a POSITA to apply Comer’s dosage to Nuwayser’s formulation.
  • Expectation of Success: Given that the references describe the same product from the same manufacturer and show nearly identical performance, a POSITA would reasonably expect that combining Nuwayser’s formulation with Comer’s dose would successfully replicate the reported therapeutic effects and pharmacokinetic results.

4. Key Claim Construction Positions

• "the step of parenterally administering a long acting formulation comprising about 310 mg to about 480 mg of naltrexone": Petitioner argued this term should be given its plain and ordinary meaning, which does not preclude administration via multiple injections. This construction allows Comer's "high dose," administered as two separate 192 mg injections to deliver a total of 384 mg, to meet the claim limitation. Petitioner noted that the Patent Owner previously argued for a "single injection" construction, which Petitioner contended is an improper limitation unsupported by the claims or specification.
• "serum AUC of naltrexone is about three times greater than that achieved by 50 mg/day oral administration": Petitioner adopted the Board’s understanding from a prior IPR ('943 IPR), arguing that "about three" encompasses a range including at least 2.7 to 3.3. The baseline for comparison is the oral AUC data from the Ehrich Declaration, which was submitted during the original prosecution of the ’499 patent.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial would be improper. It contended that denial under General Plastic is unwarranted because Petitioner (Apotex Inc.) is a different entity from the petitioner in a prior terminated IPR ('943 IPR) and shares no "significant relationship" with it. Denial under Fintiv was argued to be inapplicable as there is no parallel district court litigation involving Petitioner. Finally, Petitioner asserted that denial under 35 U.S.C. §325(d) is inappropriate because the primary references (Comer and Nuwayser) were not substantively evaluated by the Examiner during prosecution, who instead incorrectly focused on a different reference as the closest prior art.

6. Relief Requested

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