PTAB

IPR2018-00186

Pfizer Inc v. Biogen Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Combination Therapies for B-Cell Lymphomas Comprising Administration of Anti-CD20 Antibodies
  • Brief Description: The ’821 patent is directed to methods of treating low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). The claimed methods involve administering the anti-CD20 monoclonal antibody rituximab in combination with a CVP chemotherapy regimen (cyclophosphamide, vincristine, and prednisone).

3. Grounds for Unpatentability

Ground I: Claims 1-6 are obvious over Steward, Czuczman, and Maloney

  • Prior Art Relied Upon: Steward (a 1988 journal article on CVP therapy), Czuczman (a 1995 journal abstract on rituximab with CHOP chemotherapy), and Maloney (a 1997 journal article on rituximab monotherapy).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that as of the August 1999 priority date for claims 1-3, the combination of these references rendered all claims obvious. Steward established that CVP chemotherapy administered in three-week cycles was a preferred, standard therapy for low-grade NHL but that better therapies were needed. Maloney demonstrated that administering 375 mg/m² of rituximab was safe and effective for treating the same condition. Czuczman, which studied rituximab with the similar CHOP chemotherapy, provided explicit rationales for such combinations, including "single agent efficacy, non cross-resistant mechanism of action, synergy with chemotherapeutic agents and non-overlapping toxicities."
    • Motivation to Combine: A person of ordinary skill in the art (POSA) would have been motivated to combine the standard CVP therapy from Steward with the safe and effective rituximab dose from Maloney to address the need for improved NHL treatments. The rationale for combination provided by Czuczman (synergy, non-overlapping toxicities) would apply equally to a combination with CVP. Maloney further suggested investigating rituximab in "combination with or after standard chemotherapy," which a POSA would understand to include CVP.
    • Expectation of Success: Because rituximab was known to be safe, effective as a single agent, and demonstrated synergy with CHOP chemotherapy, a POSA would have had a reasonable expectation of success in combining it with the less toxic, preferred CVP regimen to achieve a beneficial, synergistic effect.

Ground II: Claims 4-6 are anticipated by Marcus

  • Prior Art Relied Upon: Marcus (a 2005 journal article on CVP plus rituximab).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that claims 4-6 are entitled to a priority date no earlier than June 15, 2012, making the 2005 Marcus reference prior art. Marcus disclosed a clinical trial that directly taught the method of claims 4-6: treating follicular NHL by administering 375 mg/m² of rituximab in combination with CVP once every three weeks for a maximum of eight cycles. Petitioner argued that Marcus disclosed all limitations of claims 4-6, including the "beneficial synergistic effect" of claim 4, which Petitioner contended is a non-limiting statement of intended result that is inherently met by the disclosed regimen.

Ground III: Claims 4-6 are obvious over Marcus, Czuczman, and Pinter-Brown

  • Prior Art Relied Upon: Marcus (2005 journal article), Czuczman (1995 journal abstract), and Pinter-Brown (a 2009 textbook chapter).

  • Core Argument for this Ground:

    • Prior Art Mapping: As an alternative to anticipation, Petitioner argued that even if the "beneficial synergistic effect" limitation in claim 4 were considered limiting, the claim would have been obvious. Marcus disclosed the complete treatment regimen (375 mg/m² rituximab with CVP every three weeks for eight doses) and further taught that "a synergistic effect between rituximab and various cytotoxic agents has been demonstrated."
    • Motivation to Combine: This ground assumes the combination taught by Marcus. The motivation was to achieve a synergistic effect.
    • Expectation of Success: A POSA would have had a reasonable expectation of synergy based on Marcus's own disclosure. This expectation would have been reinforced by Czuczman's teaching of synergy between rituximab and chemotherapy generally, and by Pinter-Brown, a 2009 textbook that stated combinations of rituximab with chemotherapy regimens "are believed to be synergistic" and that rituximab was "the first-line therapy [for low-grade NHL] when combined with CVP."

  • Additional Grounds: Petitioner asserted an additional obviousness challenge against claims 1-3 over Czuczman, Foon, and Dana, arguing a POSA would have been motivated to substitute the CVP chemotherapy taught by Foon and Dana for the CHOP regimen in Czuczman's rituximab combination therapy.

4. Key Claim Construction Positions

  • "beneficial synergistic effect": Petitioner argued this term, as recited in claims 1 and 4, is a non-limiting statement of the intended result of administering the claimed dosage regimen. Because the claims recite express dosage amounts and frequencies, Petitioner contended this phrase merely describes the expected outcome and does not add a separate patentable limitation to the method. This position was critical to the anticipation argument under Ground II.
  • "the chimeric anti-CD20 antibody is produced from [particular nucleic acid]": Petitioner argued this limitation in claims 3 and 6, which recites specific amino acid sequences, is merely a description of the known antibody rituximab. Petitioner asserted that this recitation is a non-limiting "identification and characterization of a prior art material" and does not impart patentability to the method claims.

5. Relief Requested

  • Petitioner requests institution of IPR and cancellation of claims 1-6 of the ’821 patent as unpatentable.