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

1. Case Identification

• Case #: IPR2021-01542
• Patent #: 8,580,264
• Filed: September 24, 2021
• Petitioner(s): Fresenius Kabi USA, LLC and Fresenius Kabi Swissbiosim GmbH
• Patent Owner(s): Chugai Seiyaku Kabushiki Kaisa, Genentech, Inc., and Hoffmann-La Roche Inc.
• Challenged Claims: 4, 5, and 12

2. Patent Overview

• Title: Subcutaneously Administered Anti-IL-6 Receptor Antibody
• Brief Description: The ’264 patent is directed to methods of treating rheumatoid arthritis (RA) by subcutaneously administering a 162 mg fixed dose of the anti-IL-6R antibody tocilizumab every week or every two weeks.

3. Grounds for Unpatentability

Ground 1: Obviousness of Claim 4 - Claim 4 is obvious over NCT00965653 in view of Emery.

• Prior Art Relied Upon: NCT00965653 (a 2009 clinical trial protocol) and Emery (a 2008 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that NCT00965653, a publicly available clinical trial protocol, disclosed every element of base claim 1: a method of treating RA by subcutaneously administering a 162 mg fixed dose of tocilizumab weekly or bi-weekly. Emery taught that intravenous (IV) administration of tocilizumab was safe and effective for treating RA patients who were "TNF-inhibitor-inadequate responders," the specific patient population recited in dependent claim 4.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine these references because Emery established the efficacy of tocilizumab in the claimed patient population, and NCT00965653 provided a specific, known subcutaneous (SC) dosing regimen for tocilizumab. A POSA would be motivated to apply the more convenient and patient-preferred SC regimen from NCT to the patient population in Emery, where tocilizumab was already known to be effective.
  • Expectation of Success: A POSA would have a reasonable expectation of success. The efficacy of tocilizumab in TNF-inhibitor-inadequate responders was already established by Emery. The prior art taught that SC administration of antibodies was a well-known and predictable alternative to IV administration, and the 162 mg SC dose was understood to be bioequivalent to the proven IV doses.

Ground 2: Anticipation of Claim 12 - Claim 12 is anticipated by Ohta 2010.

• Prior Art Relied Upon: Ohta 2010 (a 2010 journal abstract).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Ohta 2010 disclosed a clinical study evaluating a 162 mg fixed dose of SC tocilizumab administered weekly and every two weeks (Q2W) in RA patients, which resulted in a "good clinical response." This directly taught the administration of a fixed 162 mg dose of tocilizumab every two weeks. Petitioner argued the final limitation—"wherein structural joint damage at week 24 or week 48 is found to be inhibited"—is an inherent result of the administered regimen.
  • Key Aspects: The core of the argument was that inhibiting joint damage is a known, ultimate goal of RA treatment with tocilizumab. Because the ’264 patent provided no additional steps to achieve this inhibition beyond administering the drug, the "wherein" clause merely stated the natural result of the method disclosed in Ohta. Therefore, the functional limitation was inherently disclosed by Ohta's teaching of the same administration regimen.

Ground 3: Obviousness of Claim 12 - Claim 12 is obvious over Maini 2006 and Nishimoto 2007 in view of Bonilla and Wang.

• Prior Art Relied Upon: Maini 2006 (journal article), Nishimoto 2007 (journal article), Bonilla (a 2008 journal article), and Wang (a 2009 journal article).

• Core Argument for this Ground:

  • Prior Art Mapping: Petitioner argued that this combination taught every element of claim 12 by starting from a known effective IV therapy and modifying it in a predictable way. Maini 2006 taught effective RA treatment with IV tocilizumab (4-8 mg/kg every four weeks). Nishimoto 2007 taught that this IV therapy inhibits structural joint damage by week 48.
  • Motivation to Combine: A POSA would be motivated to convert the known effective IV therapy from Maini into a more desirable SC fixed-dose regimen. Bonilla taught that SC administration of immunoglobulins is preferable to IV, allowing for bi-weekly dosing with more stable serum concentrations. Wang taught that fixed dosing is preferable to weight-based dosing for drugs like tocilizumab with a wide therapeutic window, as it improves convenience, compliance, and safety. A POSA would therefore combine these teachings to create a 162 mg bi-weekly fixed SC dose and would be motivated by Nishimoto to confirm the known effect of inhibiting joint damage.
  • Expectation of Success: A POSA would have expected success because the conversion from an IV, weight-based dose to an SC, fixed dose was a routine optimization for monoclonal antibodies. Petitioner argued that routine calculations, accounting for bioavailability, would lead a POSA to a bi-weekly SC dose range of 140-195 mg, which squarely contains the claimed 162 mg dose. Because Nishimoto showed IV tocilizumab inhibits joint damage, a POSA would expect the bioequivalent SC dose to do the same.

• Additional Grounds: Petitioner asserted seven additional grounds, including that claim 5 (for methotrexate naïve or discontinued patients) is obvious over NCT00965653/Ohta in view of Maini 2006. Further grounds relied on the same combination of Emery/Maini/Nishimoto with Bonilla and Wang to challenge claims 4 and 5.

4. Key Claim Construction Positions

• "a method of treating rheumatoid arthritis in a patient" (preamble of claim 1, from which claims 4 and 5 depend): Petitioner argued this phrase is a non-limiting preamble that merely states an intended purpose.
• "treating": Alternatively, if the preamble were found to be limiting, Petitioner argued the term "treating" should be construed to mean attempting to provide a therapeutic benefit, not necessarily achieving an effective result in any particular patient. This construction is based on the term's plain meaning and usage within the patent's specification, which describes treating patients who had an "inadequate response" to prior treatments.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be inappropriate because the key prior art and arguments were not properly considered during prosecution.
• For grounds relying on NCT00965653, the Examiner was presented with the reference on an IDS but was not provided with evidence of its public availability date, and thus never substantively evaluated it as prior art.
• For grounds relying on Ohta 2010, the Examiner made a material error by allowing the applicant to overcome the rejection based on an uncorroborated inventor declaration that failed to properly establish a prior invention date.
• For grounds relying on Bonilla and Wang, these references were never before the Examiner at all.

6. Relief Requested

• Petitioner requests institution of an IPR and cancellation of claims 4, 5, and 12 of the ’264 patent as unpatentable.