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

1. Case Identification

• Case #: IPR2021-01024
• Patent #: 7,521,052
• Filed: June 28, 2021
• Petitioner(s): Fresenius Kabi USA, LLC and Fresenius Kabi Swissbiosim GmbH
• Patent Owner(s): Chugai Seiyaku Kabushiki Kaisha
• Challenged Claims: 1

2. Patent Overview

• Title: Methods for Treating Interleukin-6 Related Diseases
• Brief Description: The ’052 patent is directed to a method for treating rheumatoid arthritis (RA) by co-administering an effective amount of an anti-interleukin-6 (IL-6) receptor antibody and an effective amount of methotrexate (MTX). The sole claim specifies the antibody is a humanized PM-1 antibody.

3. Grounds for Unpatentability

Ground 1: Anticipation over Yoshizaki - Claim 1 is anticipated under 35 U.S.C. §102 by Yoshizaki.

• Prior Art Relied Upon: Yoshizaki (a 1998 journal article titled "Therapy of Rheumatoid Arthritis by Blocking IL-6 Signal Transduction with a Humanized Anti-IL-6 Receptor Antibody").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued Yoshizaki expressly discloses every limitation of claim 1. Yoshizaki described treating a 67-year-old patient with severe RA who was on "conventional therapy," which included MTX. This patient was then administered 50 mg of rhPM-1 (explicitly identified as a reshaped human anti-IL-6R antibody generated from mouse PM-1) once or twice weekly "combined with the conventional treatment." Petitioner asserted that the disclosed 50 mg dose of rhPM-1 constituted an "effective amount," as Yoshizaki reported the patient's "clinical and laboratory abnormalities improved." Similarly, Petitioner contended that a person of ordinary skill in the art (POSA) would understand that "conventional therapy" with MTX for RA implies an "effective amount" based on well-established dosing parameters at the time.

Ground 2: Anticipation over Nishimoto - Claim 1 is anticipated under §102 by Nishimoto.

• Prior Art Relied Upon: Nishimoto (a 2002 journal article titled "Anti-IL-6 Receptor Antibodies, Usefulness and Issues in Rheumatoid Arthritis").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Nishimoto, a printed publication from December 2002, anticipates claim 1 by disclosing an ongoing clinical trial that necessarily practiced the claimed method. Nishimoto identifies MRA as a humanized anti-IL-receptor antibody (reshaped human PM-1) and recommends a dose of 8 mg/kg every four weeks as having "excellent treatment efficacy" for RA. The article then explicitly stated that "a phase II study of coadministration with methotrexate is currently underway." Petitioner argued a POSA would reasonably infer that this disclosed study used an effective amount of MRA (the recommended 8 mg/kg dose) and a standard effective amount of MTX (e.g., 7.5-25 mg weekly), thereby disclosing the complete claimed method.

Ground 3: Obviousness over Nishimoto and Weinblatt 2003 - Claim 1 is obvious over Nishimoto in view of Weinblatt 2003.

• Prior Art Relied Upon: Nishimoto (the 2002 journal article) and Weinblatt 2003 (a 2003 journal article on the use of adalimumab with MTX).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Nishimoto established MRA (a humanized PM-1 antibody) as a safe and effective treatment for RA at a recommended dose of 8 mg/kg every four weeks and expressly disclosed an ongoing study combining it with MTX. Weinblatt 2003 was presented as evidence of the standard clinical practice for treating RA patients who inadequately responded to MTX monotherapy. This practice involved adding a new biologic agent (in Weinblatt's case, the anti-TNF antibody adalimumab) to the patient's existing, stable, and effective MTX regimen (10 to 25 mg/week).
  • Motivation to Combine: A POSA would combine Nishimoto's disclosure of MRA with a standard MTX regimen as taught by Weinblatt 2003. The motivation stemmed from the established "treatment of choice" paradigm in which MTX served as an "anchor therapy," and new biologics were routinely added to improve clinical response in patients with persistent disease activity. Nishimoto itself taught co-administration, and other art, including FDA guidance, suggested it was "inevitable" that new RA agents like MRA would be used in combination with MTX.
  • Expectation of Success: A POSA would have a reasonable expectation of success. Both MRA and MTX were known to be individually effective for treating RA. Furthermore, the successful track record of combining other anti-cytokine drugs (e.g., anti-TNF therapies like adalimumab) with MTX would have led a POSA to reasonably expect that combining an anti-IL-6R antibody with MTX would also be safe and effective.

4. Key Claim Construction Positions

• "A method of treating rheumatoid arthritis ... in a patient": Petitioner proposed this phrase means "a method attempting to cause a therapeutic improvement," arguing it does not require that a therapeutic benefit is actually achieved in the specific patient.
• "administering an ... antibody .. and methotrexate": Petitioner contended this term should be construed to include either simultaneous or sequential administration of the two drugs, citing the patent's specification and prosecution history where broader claims to administration schedule were pursued.
• "an effective amount": For both the antibody and MTX, Petitioner argued this term should be construed to include amounts known in the art to be effective for treating RA in a patient population, regardless of the effect on a particular patient. Petitioner identified specific dosage ranges from the prior art, such as 8 mg/kg every four weeks for MRA and 7.5 to 25 mg weekly for MTX, as falling within this construction.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) should not apply. The petition asserted that none of the primary prior art references relied upon (Yoshizaki, Nishimoto, Weinblatt 2003) were before the Examiner during the original prosecution of the ’052 patent.

6. Relief Requested

• Petitioner requested the institution of an inter partes review and the cancellation of claim 1 of Patent 7,521,052 as unpatentable.