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

1. Case Identification

• Case #: IPR2021-01336
• Patent #: 10,874,677
• Filed: August 18, 2021
• Petitioner(s): Fresenius Kabi USA, LLC and Fresenius Kabi SwissBioSim GmbH
• Patent Owner(s): Chugai Seiyaku Kabushiki Kaisha and Hoffmann-La Roche Inc.
• Challenged Claims: 1-8

2. Patent Overview

• Title: Subcutaneously Administered Anti-IL-6 Receptor Antibody
• Brief Description: The ’677 patent is directed to an article of manufacture, such as a pre-filled syringe or autoinjector, that contains and delivers a 162 mg fixed dose of the anti-IL-6R antibody tocilizumab for subcutaneous administration to a patient.

3. Grounds for Unpatentability

Ground 1: Anticipation Over NCT00965653 - Claims 1 and 5 are anticipated by NCT00965653.

• Prior Art Relied Upon: NCT00965653 (a clinical trial protocol publicly posted on ClinicalTrials.gov on August 25, 2009).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that NCT00965653, a protocol for a study of subcutaneously administered tocilizumab, expressly disclosed administering a fixed dose of "tocilizumab 162 mg sc either weekly or every other week." This directly taught the fixed 162 mg dose of tocilizumab required by claim 1. For claim 5, Petitioner asserted that the specific amino acid sequences of the antibody are inherent properties of tocilizumab, as confirmed by the patent specification and admissions during prosecution. The "subcutaneous administration device" was argued to be implicitly disclosed, as one is necessary to perform the disclosed subcutaneous administration.
  • Key Aspects: Petitioner emphasized that NCT00965653 was publicly available more than one year prior to the patent's earliest priority date, making it a statutory bar under pre-AIA 35 U.S.C. §102(b).

Ground 2: Obviousness Over Maini 2006 and Kivitz in view of Bonilla and Wang - Claims 1-8 are obvious.

• Prior Art Relied Upon: Maini 2006 (a 2006 clinical trial publication), Kivitz (a 2007 journal article), Bonilla (a 2008 journal article), and Wang (a 2009 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued the only difference between the claims and Maini 2006—which taught safe and effective intravenous (IV) administration of tocilizumab at 4 and 8 mg/kg—was the claimed subcutaneous fixed dose of 162 mg and the delivery device. Bonilla taught that subcutaneous administration of immunoglobulins was preferable to IV for maintaining more stable serum levels. Wang taught that fixed dosing was preferable to weight-based dosing for monoclonal antibodies with a wide therapeutic window, like tocilizumab, due to convenience and reduced error risk. Kivitz disclosed that several other biologics for rheumatoid arthritis were successfully delivered subcutaneously via pre-filled syringes and autoinjectors.
  • Motivation to Combine: A POSITA would combine these references to improve on the known IV therapy in Maini 2006. The known advantages of subcutaneous delivery (convenience, stability) and fixed dosing (safety, convenience), as taught by Bonilla and Wang, would motivate a POSITA to develop a subcutaneous fixed-dose version of tocilizumab. Kivitz demonstrated that the necessary delivery devices (syringes, autoinjectors) were well-known and successfully used for similar antibody drugs.
  • Expectation of Success: A POSITA would have a reasonable expectation of success. Bonilla taught how to convert an IV dose to an equivalent subcutaneous dose, suggesting a dose between 100% and 139% of the IV dose. Petitioner calculated that the known 4 mg/kg IV dose for a typical 70 kg patient converts to a subcutaneous range of 140-195 mg every other week. The claimed 162 mg falls squarely within this predictable range, making its selection a matter of routine optimization. The success of other biologics in autoinjectors, as shown by Kivitz, confirmed the viability of the claimed administration device.

Ground 3: Anticipation Over Georgy - Claims 1 and 5 are anticipated by Georgy.

• Prior Art Relied Upon: Georgy (a clinical study abstract published in February 2010).

• Core Argument for this Ground:

  • Prior Art Mapping: Petitioner asserted that Georgy disclosed a clinical study in which twelve patients received a "162 mg subcutaneous dose of tocilizumab." This explicitly teaches the administration of a 162 mg fixed dose of the antibody. As with the NCT00965653 ground, Petitioner argued that the use of a subcutaneous administration device is inherent to performing the disclosed administration, and the claimed amino acid sequences are inherent to the disclosed tocilizumab.

• Additional Grounds: Petitioner asserted additional obviousness challenges for claims 1-8 over NCT00965653 in view of Kivitz, and over Georgy in view of Kivitz. These arguments relied on the same core disclosures from NCT00965653 and Georgy, adding Kivitz to explicitly teach the use of specific devices like syringes and autoinjectors (recited in dependent claims 2-4 and 6-8), which were well-known options for subcutaneous antibody delivery.

4. Key Claim Construction Positions

• "fixed dose": Petitioner adopted the definition from the ’677 patent specification: "a dosage of a drug, such as an anti-IL-6R antibody which is administered without regard to the patient's weight or body surface area (BSE), i.e., it is not administered as either a mg/kg or mg/m² dose."
• "subcutaneous administration device": Petitioner adopted the definition from the ’677 patent specification: "a device, such as syringe, injection device, infusion pump, injector pen, needleless device, patch delivery system, etc, which is adapted or designed to administer a drug or pharmaceutical formulation by the subcutaneous route."

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate. Although the NCT00965653 and Georgy references were listed on an Information Disclosure Statement (IDS) during prosecution, they were never substantively evaluated by the Examiner. Petitioner contended it presented new evidence and arguments, including expert testimony establishing the public availability date of NCT00965653, which the applicant had omitted from the IDS. Furthermore, the primary obviousness combination (Maini 2006, Kivitz, Bonilla, and Wang) presented entirely new art and arguments that were not before the Examiner.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-8 of Patent 10,874,677 as unpatentable.