PTAB

IPR2017-02127

Pfizer Inc v. Genentech Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Treatment of Chronic Lymphocytic Leukemia Using Anti-CD20 Antibodies
  • Brief Description: The ’711 patent is directed to methods of treating chronic lymphocytic leukemia (CLL) by administering the monoclonal antibody rituximab at a specific dosage of 500 mg/m², either alone or in combination with chemotherapy drugs such as fludarabine and cyclophosphamide.

3. Grounds for Unpatentability

Ground I: Obviousness of Claims 1, 5-8 over Maloney 1994, Maloney (Sept.) 1997, and Genentech Press Release

  • Prior Art Relied Upon: Maloney 1994 (a 1994 clinical trial article in Blood), Maloney (Sept.) 1997 (a 1997 article in Blood), and the Genentech Press Release (a 1995 press release).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of these references rendered the core method of claim 1 obvious. Maloney 1994 taught that rituximab was a promising therapy for both Non-Hodgkin's Lymphoma (NHL) and CLL, disclosing a safe and dose-dependent dose range of 10 mg/m² to 500 mg/m² for depleting B-cells in NHL patients. The Genentech Press Release, issued by the Patent Owner, explicitly announced plans for clinical trials to study rituximab for treating CLL, based on encouraging results in NHL. Maloney (Sept.) 1997 confirmed that weekly doses of rituximab were safe and effective for NHL. For dependent claims 5-7, Petitioner asserted these weekly, bi-weekly, and monthly dosing frequencies fall within a known, safe range established by the Maloney references. For claim 8, Maloney 1994 expressly taught the advantages of using a "naked" antibody (without a radiolabel) over radiolabeled antibodies, thus teaching the negative limitation.
    • Motivation to Combine: A person of ordinary skill in the art (POSA) would be motivated to apply the teachings from successful rituximab treatment in NHL to the closely related B-cell cancer, CLL. This was reinforced by the Patent Owner's own public statements in the Genentech Press Release. A POSA would have been motivated to select the 500 mg/m² dose because CLL patients have a significantly higher tumor burden than NHL patients, and Maloney 1994 taught that B-cell depletion was dose-dependent, making the highest tested safe dose a logical choice.
    • Expectation of Success: The Genentech Press Release, which announced planned clinical trials for rituximab in CLL based on prior success, would have provided a POSA with a strong, reasonable expectation of success.

Ground II: Obviousness of Claim 2 over the Maloney References and Genentech Press Release

  • Prior Art Relied Upon: Maloney 1994, Maloney (Sept.) 1997, Maloney (Oct.) 1997 (a 1997 article in J. Clinical Oncology), and the Genentech Press Release.
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built upon Ground I to challenge claim 2, which adds the administration of a "chemotherapeutic regimen." The incremental teachings came from the additional Maloney references from 1997. Maloney (Oct.) 1997 taught that rituximab "increases sensitivity to the cytotoxic effect of chemotherapy/toxins." Maloney (Sept.) 1997 explicitly suggested that future research should include rituximab in "combination with or after standard chemotherapy" for B-cell histologies like CLL.
    • Motivation to Combine: The motivation was to improve efficacy by combining two treatments with different and complementary mechanisms of action, a common strategy in oncology. A POSA would combine rituximab with chemotherapy because the higher tumor burden and lower CD20 expression in CLL made it potentially difficult to treat with rituximab alone. The prior art's suggestion that rituximab sensitizes cancer cells to chemotherapy provided a clear scientific rationale for the combination.
    • Expectation of Success: A POSA would reasonably expect the combination to be effective, as it represented one of a finite number of predictable solutions for improving CLL treatment, leveraging the known benefits of both rituximab and standard chemotherapy.

Ground III: Obviousness of Claims 3, 4, and 9 over the Maloney References, Genentech Press Release, and O'Brien

  • Prior Art Relied Upon: The Maloney References (1994, Sept. 1997, Oct. 1997), the Genentech Press Release, and O'Brien 1996 (a 1996 abstract from Blood).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground challenged the claims specifying the chemotherapeutic agents fludarabine and cyclophosphamide (claims 3, 4, and 9). The key additional reference, O'Brien, disclosed that the combination of fludarabine and cyclophosphamide was already known by 1996 to be an "extremely active regimen in CLL" with very high response rates. Claim 9, which recites the full combination of rituximab at 500 mg/m² with fludarabine and cyclophosphamide, was alleged to be a simple combination of these known elements.
    • Motivation to Combine: A POSA would be motivated to combine the obvious rituximab therapy (from Grounds I and II) with the known standard-of-care chemotherapy combination for CLL (taught by O'Brien). This combination represented a logical next step to further improve patient outcomes by integrating a promising new targeted therapy with the best available conventional therapy.
    • Expectation of Success: Given that O'Brien taught high efficacy for the fludarabine/cyclophosphamide combination in CLL, and the Maloney references and Genentech Press Release provided a reasonable expectation of success for rituximab in CLL, a POSA would have a reasonable expectation of success for the three-drug combination.

4. Key Claim Construction Positions

  • "amount effective to treat the CLL": Petitioner contended this term, as used in the claims, is a non-limiting statement of intended result that adds nothing to the express dosage limitation of "500 mg/m²." Petitioner argued that even if the term were limiting, it should be construed as achieving "a reduction in the number of the small lymphocytic tumor cells." This construction is supported by the patent's specification and prosecution history. Petitioner asserted this construction is critical because the prior art clearly teaches that rituximab reduces circulating tumor cells, making obviousness clear under this interpretation.

5. Key Technical Contentions (Beyond Claim Construction)

  • Applicability of NHL Data to CLL: A central technical contention was that a POSA would have readily extrapolated findings from rituximab studies in NHL to CLL. Petitioner argued that both are B-cell malignancies expressing the CD20 antigen. Key differences, such as CLL's higher tumor burden and lower CD20 density, would not have taught away from using rituximab. Instead, these differences would have motivated a POSA to use a higher dose within the known safe range (i.e., 500 mg/m²) to overcome these challenges, directly supporting the obviousness of the claimed dose.

6. Relief Requested

  • Petitioner requested the Board to institute an inter partes review and cancel claims 1-9 of the ’711 patent as unpatentable.