PTAB

IPR2017-01923

Pfizer Inc v. Genentech Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Therapy of Autoimmune Disease in a Patient with an Inadequate Response to a TNFα-Inhibitor
  • Brief Description: The ’838 patent discloses methods for treating rheumatoid arthritis (RA) in patients who have an inadequate response to a TNFα-inhibitor. The claimed method involves administering an antibody that binds to CD20 (e.g., rituximab) as two intravenous doses of 1000mg.

3. Grounds for Unpatentability

Ground 1: Claims 1-5 and 7-14 are obvious over Edwards 2002 in view of Takemura, as evidenced by Klimiuk and Ulfgren.

  • Prior Art Relied Upon: Edwards 2002 (a 2002 clinical trial abstract), Takemura (a 2001 journal article), Klimiuk (a 1997 journal article), and Ulfgren (a 2000 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Edwards 2002 taught every element of the independent claims except for treating the specific patient population that has an inadequate response to a TNFα-inhibitor (a TNFi). Edwards 2002 disclosed a randomized trial that confirmed the efficacy of treating RA patients with two intravenous doses of 1000mg rituximab, often in combination with methotrexate and corticosteroids. The remaining references allegedly supplied the missing element. Klimiuk taught that RA synovitis is heterogeneous and that one subtype, diffuse synovitis, is characterized by the lowest levels of TNFα. Ulfgren taught that RA patients with low levels of TNFα respond poorly to TNFi therapy. Finally, Takemura taught that rituximab is effective in treating RA patients with diffuse synovitis, because its mechanism of depleting B-cells is independent of a patient’s TNFα levels.
    • Motivation to Combine: A POSITA would combine these teachings to address the known clinical problem of TNFi non-responders. Knowing from Klimiuk and Ulfgren that TNFi non-response was linked to low TNFα levels, and from Takemura that rituximab’s efficacy was independent of TNFα levels, a POSITA would be motivated to apply the known effective rituximab regimen from Edwards 2002 to this specific patient sub-population.
    • Expectation of Success: A POSITA would have a reasonable expectation of success because the prior art established that the mechanism of TNFi failure (low TNFα) was unrelated to rituximab’s mechanism of action (B-cell depletion). Therefore, the known effectiveness of the Edwards 2002 regimen would be expected to extend to patients who had failed TNFi therapy.

Ground 2: Claims 1-3 and 7-8 are obvious over Edwards 2001 in view of the Rituxan label and Takemura, as evidenced by Klimiuk and Ulfgren.

  • Prior Art Relied Upon: Edwards 2001 (a 2001 journal article), the Rituxan label (a 1999 PDR excerpt), Takemura, Klimiuk, and Ulfgren.
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented an independent pathway to the claimed invention starting from an earlier reference. Edwards 2001 taught treating severe RA with a monthly dose of approximately 2100mg of rituximab. Petitioner argued that the claimed regimen of two 1000mg doses was an obvious optimization of the Edwards 2001 regimen. The Rituxan label's pharmacokinetic data for treating non-Hodgkin's lymphoma (NHL) indicated that dosing was correlated with tumor burden. Because RA is not a cancer and has no "tumor burden" like NHL, a POSITA would have been motivated to reduce the dose and frequency of infusions for RA patients. Considering convenience, patient compliance, and the commercially available 500mg single-use vials, a POSITA would arrive at two 1000mg infusions as a routine optimization. The combination of Takemura, Klimiuk, and Ulfgren provided the same rationale as in Ground 1 for applying this optimized regimen to TNFi non-responders.
    • Motivation to Combine: A POSITA would be motivated to modify the regimen in Edwards 2001 to find an optimal dose for RA, a non-cancer indication. This would involve titrating down from the higher, more frequent NHL regimen, informed by the Rituxan label and practical considerations like cost and patient compliance, leading directly to the claimed dosing. The motivation to then apply this optimized dose to TNFi non-responders was based on the clear scientific rationale provided by Takemura, Klimiuk, and Ulfgren.
    • Expectation of Success: A POSITA would reasonably expect that a slightly lower total monthly dose administered in fewer infusions would be similarly effective to the regimen in Edwards 2001, especially for a non-cancer indication. There was a further reasonable expectation of success in the target patient population because rituximab's mechanism was known to be effective regardless of the patient's TNFα levels.
  • Additional Grounds: Petitioner asserted that claim 6 was obvious over the Ground 1 references in further view of Curd (WO 00/67796), which taught the use of specific corticosteroids (prednisone, methylprednisolone) with rituximab. Petitioner also asserted that claims 4-6 and 9-14 were obvious over the Ground 2 references in further view of Curd, which taught combining rituximab with agents like methotrexate and corticosteroids.

4. Key Claim Construction Positions

  • Intended Result Clauses: Petitioner argued that several claim phrases should be construed as non-limiting statements of intended results that add no patentable weight. These include limitations in claims 2-7 reciting an "amount that is effective to provide an ACR50 response," as well as "wherein" clauses in claims 10 and 12-14 reciting specific clinical outcomes (e.g., "wherein the patient has no erosive progression").
  • Preamble of Claim 11: Petitioner contended that the preamble of claim 11, which recites "[a] method of achieving a clinical response," merely states the intended effect of the claim's steps and is therefore non-limiting. Petitioner asserted that the claim body describes a complete method (administering rituximab and methotrexate) that does not depend on the preamble for meaning.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that the grounds asserted in this petition were substantially different from those in prior challenges to the ’838 patent (IPR2015-00417, IPR2015-01733, and IPR2016-01667). Specifically, this petition relied on key prior art references—Takemura, Klimiuk, and Ulfgren—that were not relied upon by previous petitioners or considered by the Examiner during prosecution. Petitioner contended these references provide the critical teaching that rituximab’s mechanism of action made it an ideal therapy for the specific sub-population of RA patients who did not respond to TNFis.

6. Relief Requested

  • Petitioner requests institution of inter partes review and cancellation of claims 1-14 of the ’838 patent as unpatentable.