PTAB

IPR2021-01025

Fresenius Kabi USA LLC v. Chugai Seiyaku Kabushiki Kaisha Chugai Pharmaceutical Co Ltd

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Method for Treating Rheumatoid Arthritis with a Human IL-6 Receptor Antibody and Methotrexate
  • Brief Description: The ’201 patent discloses a method for treating rheumatoid arthritis (RA) by administering a specific combination therapy. The method involves intravenously administering 8 mg/kg of a humanized anti-interleukin-6 receptor (anti-IL-6R) antibody, MRA (tocilizumab), every four weeks in combination with orally administering 10 to 25 mg of methotrexate (MTX) once per week to achieve or increase the likelihood of achieving a significant clinical improvement (an ACR70 response).

3. Grounds for Unpatentability

Ground 1: Anticipation over Nishimoto - Claims 1-15 are anticipated by Nishimoto

  • Prior Art Relied Upon: Nishimoto (a journal article titled "Anti-IL-6 Receptor Antibodies, Usefulness and Issues in Rheumatoid Arthritis," published December 2002).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Nishimoto discloses every element of the claimed method. Nishimoto explicitly taught that the recommended dosage regimen for MRA in treating RA is 8 mg/kg administered intravenously every four weeks. It also disclosed an ongoing phase II clinical study where MRA was co-administered with MTX. Petitioner asserted that although Nishimoto does not specify the MTX dosage in that study, a person of ordinary skill in the art (POSA) would have understood that the standard, well-known oral dose of MTX for RA patients was between 7.5 mg and 25 mg per week. This established range overlaps with and teaches the claimed range of 10 to 25 mg. The result-based limitations in the claims (e.g., achieving an ACR70 response) were argued to be the inherent and natural result of administering the disclosed combination therapy, and therefore are also disclosed by Nishimoto.
    • Key Aspects: The core of the anticipation argument rested on the assertion that the specific MRA dosing regimen was expressly disclosed and that the MTX dosing regimen was inherently disclosed, as a POSA would have known the standard-of-care dosage to use in the described clinical trial.

Ground 2: Obviousness over Nishimoto and Weinblatt 2003 - Claims 1-15 are obvious over Nishimoto in view of Weinblatt 2003

  • Prior Art Relied Upon: Nishimoto (2002 journal article) and Weinblatt 2003 (a journal article on the use of adalimumab with MTX).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner contended that Nishimoto established MRA as a safe and effective treatment for RA, recommending an optimal dose of 8 mg/kg intravenously every four weeks and disclosing ongoing trials combining MRA with MTX. Weinblatt 2003 exemplified the standard clinical practice for RA patients who inadequately responded to MTX monotherapy. It taught that these patients were maintained on a stable weekly oral dose of MTX between 10 and 25 mg when a new biologic drug (adalimumab, another anti-cytokine agent) was added to their regimen. The combination of Nishimoto's MRA regimen and Weinblatt's MTX regimen for non-responders maps directly onto the claimed method.
    • Motivation to Combine: A POSA would combine the teachings because it was the standard of care to treat RA patients who were inadequately responding to MTX alone by adding a new biologic agent to their existing, stable MTX therapy. Nishimoto identified MRA as a promising new anti-cytokine agent, and Weinblatt 2003 provided the well-established protocol for adding such an agent to an MTX regimen (i.e., maintaining the 10-25 mg weekly dose). A POSA would have been motivated to apply this standard protocol to the new MRA biologic disclosed in Nishimoto to improve patient outcomes.
    • Expectation of Success: A POSA would have had a reasonable expectation of success. Both MRA and MTX were known to be individually effective for RA. Furthermore, the strategy of combining MTX with other anti-cytokine biologics (e.g., anti-TNF agents like adalimumab) was a well-established and successful treatment paradigm. A POSA would reasonably expect that combining another anti-cytokine agent, MRA, with the "anchor therapy" of MTX would likewise be safe and effective.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. § 325(d) would be inappropriate because the Examiner made a material error by overlooking the most pertinent teachings of the prior art. Although Nishimoto was listed on an Information Disclosure Statement (IDS), it was never substantively evaluated or used as the basis for a rejection. Petitioner contended that the Examiner's cited references were deficient because they did not teach the claimed 8 mg/kg MRA dose every four weeks combined with MTX, a critical gap that Nishimoto's express disclosures fill. Therefore, the arguments and art presented in the petition were substantially different from what the Examiner considered and remedy a clear error in the original examination.

5. Relief Requested

  • Petitioner requests institution of an IPR and cancellation of claims 1-15 of Patent 10,744,201 as unpatentable.