Mylan Laboratories Ltd v. Janssen Pharmaceutica NV

1. Case Identification

• Case #: IPR2020-00440
• Patent #: 9,439,906
• Filed: February 7, 2020
• Petitioner(s): Mylan Laboratories Ltd.
• Patent Owner(s): Janssen Pharmaceutica NV
• Challenged Claims: 1-21

2. Patent Overview

• Title: Dosing Regimen Associated with Long Acting Injectable Paliperidone Esters
• Brief Description: The ’906 patent discloses dosing regimens for administering paliperidone palmitate, a long-acting injectable antipsychotic, for the treatment of psychiatric disorders. The regimens generally involve administering two initial loading doses in close succession, followed by subsequent monthly maintenance doses.

3. Grounds for Unpatentability

Ground 1: Claims 1-7, 15, and 17-21 are obvious over Citrome, Cleton, and the ’544 patent.

• Prior Art Relied Upon: Citrome (a 2007 clinical practice article), Cleton (a 2008 pharmacology abstract), and the ’544 patent (Patent 6,555,544).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the key elements of the claimed dosing regimen were disclosed or suggested by the prior art. Citrome, a review of ongoing clinical trials, disclosed administering paliperidone palmitate in doses of 50, 100, or 150 mg-eq. on days 1, 8, 36, and 64. This schedule directly corresponds to the claimed regimen of a first loading dose (day 1), a second loading dose about a week later (day 8), and a first maintenance dose about a month later (day 36). The claimed dose amounts (e.g., 150 mg first loading dose, 100 mg second loading dose) fall within or overlap with the ranges tested in these publicly disclosed trials. Cleton provided pharmacokinetic data from a similar study and taught that deltoid muscle injection, a claimed site, resulted in higher peak plasma concentrations than gluteal injection. The ’544 patent, which is cited in the ’906 patent itself, described the underlying sustained-release aqueous nanoparticle formulation required by dependent claims.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) would combine these references to optimize a dosing regimen. A POSA would look to clinical trial data like that in Citrome and Cleton to establish a safe and effective dosing schedule. Since Citrome and Cleton described the "what" (dosing and schedule) but not the "how" (formulation), a POSA would have been motivated to look to the ’544 patent for the well-known aqueous nanoparticle formulation of paliperidone palmitate. The known objective of depot drug delivery—to rapidly achieve therapeutic levels with loading doses and then sustain them with maintenance doses—would have provided the framework for combining the specific values from the prior art.
  • Expectation of Success: A POSA would have had a high expectation of success. The art already established paliperidone palmitate as a treatment for schizophrenia, and the specific doses and schedules were being tested in Phase III clinical trials, which presupposes a strong likelihood of safety and efficacy. Combining these known dosing parameters with a known formulation from the ’544 patent would have been a routine optimization task.

Ground 2: Claims 8-14 and 16 are obvious over Citrome, Cleton, the Paliperidone Formulary, and the ’544 patent.

• Prior Art Relied Upon: Citrome (2007), Cleton (2008), the Paliperidone Formulary (2007), and the ’544 patent.
• Core Argument for this Ground:
  • Prior Art Mapping: This ground targets claims directed to treating "renally impaired" patients. The core argument builds upon Ground 1 by adding the teachings of the Paliperidone Formulary. Petitioner asserted that a POSA would start with the general dosing regimen established by Citrome and Cleton. The Paliperidone Formulary explicitly taught that "the dose of paliperidone should be reduced in patients with moderate or severe renal function impairment" and provided specific data on how total paliperidone clearance was reduced (e.g., by 32% in mild, 64% in moderate, and 71% in severe impairment). A POSA would apply these known reduction principles to the standard doses taught in Citrome to arrive at the lower dosage ranges claimed for renally impaired patients.
  • Motivation to Combine: The motivation was explicit. When treating a renally impaired patient, a POSA would be directly motivated to consult a reference like the Paliperidone Formulary for guidance on dose adjustments. This is a standard and necessary safety consideration in pharmacology. Combining this specific dose adjustment guidance with the general regimen from Citrome/Cleton and the formulation from the ’544 patent was a logical and predictable path.
  • Expectation of Success: The expectation of success was very high, as dose adjustment based on renal function is a fundamental, predictable aspect of clinical pharmacy. The ’906 patent itself acknowledged that a POSA could titrate doses based on a patient’s renal function. Therefore, applying the specific percentage reductions from the Formulary to the known effective doses from Citrome was a routine step with a predictable outcome.
• Additional Grounds: Petitioner asserted additional obviousness challenges against the same sets of claims based on subsets of the above references (e.g., Citrome and the ’544 patent alone), relying on similar design choice and routine optimization arguments.

4. Key Claim Construction Positions

• Petitioner argued that the challenged claims were not entitled to their claimed priority date of December 19, 2007 (the filing date of the ’918 provisional application).
• The argument centered on the limitation requiring a first maintenance dose "a month (±7 days)" after the second loading dose. Petitioner asserted that the ’918 provisional only disclosed administration "on between about the 34th and about the 38th day of treatment," a narrow 5-day window. The broader "month (±7 days)" limitation, which creates a much wider 20-day window, was first introduced in a later provisional.
• Petitioner contended this lack of written description support in the earliest provisional meant the claims' effective filing date was no earlier than December 5, 2008, making references like Cleton (Mar. 2008) available as prior art under §102(a).

5. Arguments Regarding Discretionary Denial

• §325(d) - Cumulative Art: Petitioner argued against discretionary denial based on cumulative art, stating that while the Examiner had considered the ’544 patent, the Examiner never considered it in combination with the other key references like Citrome or Cleton. Therefore, the petition raised new arguments and combinations not previously before the USPTO.
• §314(a) - Fintiv Factors: Petitioner argued against discretionary denial under Fintiv, asserting that the parallel district court litigation was in its infancy. As this was the first IPR filed against the ’906 patent, Petitioner contended it had not gained an unfair advantage from the co-pending litigation, and that considerations of efficiency and fairness favored instituting the IPR.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-21 of the ’906 patent as unpatentable.