PTAB

IPR2015-01733

Celltrion Inc v. Genentech Inc

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Petition
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1. Case Identification

2. Patent Overview

  • Title: Therapy of Autoimmune Disease in a Patient With an Inadequate Response to a TNF-α Inhibitor
  • Brief Description: The ’838 patent discloses methods for treating rheumatoid arthritis (RA) in patients who have an inadequate response to a tumor necrosis factor-alpha (TNF-α) inhibitor. The claimed method involves administering two 1000 mg intravenous doses of an anti-CD20 antibody, namely rituximab, sometimes in combination with methotrexate and/or corticosteroids.

3. Grounds for Unpatentability

Ground 1: Obviousness over Edwards VI and Tuscano - Claims 1-5 and 7-14 are obvious over Edwards VI in view of Tuscano.

  • Prior Art Relied Upon: Edwards VI (an abstract from the American College of Rheumatology 66th Annual Meeting, Oct. 2002) and Tuscano (an abstract from Arthritis Rheum 46: 3420, 2002).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Edwards VI disclosed a large, randomized, placebo-controlled clinical trial treating 161 RA patients with rituximab. Crucially, patients in the trial received the exact dosing regimen claimed in the ’838 patent: two intravenous doses of 1000 mg. Edwards VI further taught the co-administration of rituximab with methotrexate and corticosteroids. Petitioner contended that Tuscano explicitly addressed the specific patient population of the ’838 patent by describing the successful treatment of "Infliximab-Refractory" RA patients with rituximab. Infliximab is a known TNF-α inhibitor. Therefore, Petitioner asserted that the combination of Edwards VI's specific and effective dosing regimen with Tuscano's teaching of using rituximab for the claimed patient population rendered the claims obvious.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine Edwards VI and Tuscano to find an effective treatment for the known, difficult-to-treat population of TNF-α inhibitor non-responders. Tuscano established rituximab as a "promising agent" for these refractory patients, providing the direct motivation to apply the most current, effective dosing regimens, such as the one detailed in the large-scale Edwards VI study. The goal was to improve clinical outcomes for a patient group for whom a primary therapy had failed.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success. Tuscano demonstrated positive results for rituximab in TNF-α inhibitor non-responders, and Edwards VI reported "substantial clinical benefit" with the specific claimed dosage in a broader RA population. Combining a promising therapy with a proven effective dosage for the same disease would lead to a high expectation of a successful outcome.

Ground 2: Obviousness over Curd, De Vita, and Edwards IV - Claim 6 is obvious over Curd in view of De Vita and Edwards IV.

  • Prior Art Relied Upon: Curd (International Publication No. WO 00/67796), De Vita (an abstract from the Italian Society of Rheumatology, 2001), and Edwards IV (a 2001 journal article in Rheumatology).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground specifically targeted claim 6, which requires a corticosteroid regimen consisting of methylprednisolone and prednisone. Petitioner argued that Curd taught combination therapies for RA using rituximab with both methotrexate and corticosteroids, expressly listing prednisone and methylprednisolone as examples. De Vita disclosed treating RA patients non-responsive to TNF-α inhibitors with rituximab, and Edwards IV reported on a study treating refractory RA patients with rituximab in combination with the corticosteroid prednisolone.
    • Motivation to Combine: The motivation to combine these references stemmed from the well-established practice of using combination therapies to manage RA. Curd provided a general framework and specific examples of corticosteroids to use with rituximab. Edwards IV and De Vita provided real-world clinical evidence of the safety and efficacy of using rituximab with corticosteroids in refractory RA patients. A POSITA would have been motivated to combine the specific agents disclosed in Curd with the treatment protocols for refractory patients shown in Edwards IV and De Vita to optimize therapy.
    • Expectation of Success: Success was reasonably expected because corticosteroids were a long-established treatment for RA, and publications like Edwards IV had already demonstrated positive clinical outcomes (ACR50 and ACR70 responses) when combining rituximab with prednisolone. A POSITA would expect that applying Curd's disclosed corticosteroids to the patient population from De Vita would be a safe and effective treatment strategy.

4. Key Claim Construction Positions

  • Preamble Not Limiting: Petitioner argued that the preamble phrase "who experiences an inadequate response to a TNFα-inhibitor" should not be treated as a claim limitation. The petition contended that the claim body describes a structurally complete method of treatment (administering rituximab) and that deleting the preamble phrase would not affect the steps of the claimed invention. It further noted that the specification states an "inadequate response" could be determined even before a patient has been treated with a TNF-α inhibitor, reinforcing that it describes a patient characteristic rather than a mandatory process step.
  • "Wherein" Clauses Have No Patentable Weight: Petitioner asserted that the "wherein" clauses in claims 10 and 12-14, which recite specific clinical outcomes (e.g., "wherein the clinical response is ACR50 response at week 24"), are not entitled to patentable weight. The argument was that these clauses merely state the intended result of the administration steps already recited in the claims and do not add any further manipulative steps. The treatment administered is identical regardless of the patient's ultimate clinical response, which is a natural result of the treatment, not an inventive step.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-5 and 7-14 of Patent 7,976,838 as unpatentable under 35 U.S.C. §103.