PTAB

IPR2017-02063

Pfizer Inc v. Genentech Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: TREATMENT WITH ANTI-ErbB2 ANTIBODIES
  • Brief Description: The ’441 patent describes methods for treating patients with cancer characterized by the overexpression of the ErbB2 receptor (HER2-positive cancer). The claimed method involves administering a combination of an anti-ErbB2 antibody (like trastuzumab) and a taxoid chemotherapeutic agent (like paclitaxel), specifically in the absence of an anthracycline derivative, to improve patient outcomes.

3. Grounds for Unpatentability

Ground 1: Claims 1-14 are obvious over Baselga 1996, Seidman 1996, and the 1995 TAXOL PDR.

  • Prior Art Relied Upon: Baselga 1996 (a clinical study on trastuzumab published in the Journal of Clinical Oncology), Seidman 1996 (a clinical study abstract on paclitaxel sensitivity in HER2-positive patients), and the 1995 TAXOL PDR (the official prescribing information for paclitaxel).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of prior art references taught all elements of the challenged claims. Baselga 1996 established the clinical efficacy and favorable safety profile of trastuzumab (an anti-ErbB2 antibody) as a monotherapy for metastatic HER2-positive breast cancer. Concurrently, Seidman 1996 demonstrated that paclitaxel (a taxoid) was particularly effective in the same patient population, showing a 58.8% response rate in HER2-positive patients. The 1995 TAXOL PDR provided standard, effective dosing regimens for paclitaxel. Petitioner contended that administering these two agents, both known to be effective for the same specific cancer, to achieve the claimed outcome of extending time to disease progression without a significant increase in adverse events, would have been obvious to a person of ordinary skill in the art (POSITA). The absence of an anthracycline derivative was also obvious due to its known cardiotoxicity, especially when combined with trastuzumab, which would lead a POSITA to prefer a non-anthracycline combination for safety.
    • Motivation to Combine: A POSITA would combine trastuzumab and paclitaxel based on bedrock principles of combination cancer therapy. The combination satisfied the four established criteria for selecting agents: (1) both drugs had proven single-agent activity in the target population; (2) they had non-overlapping toxicities (myelosuppression for paclitaxel vs. the generally well-tolerated profile of trastuzumab); (3) they employed different mechanisms of action (targeted antibody vs. broad chemotherapeutic); and (4) they had different resistance mechanisms. Most compellingly, Baselga 1996 explicitly stated that clinical trials combining trastuzumab with several chemotherapeutic agents, including paclitaxel, were "currently in progress," directly signaling to a POSITA that this specific combination was a logical and actively pursued next step in cancer treatment.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success. This expectation was founded on the strong, independent clinical efficacy shown by both trastuzumab (in Baselga 1996) and paclitaxel (in Seidman 1996) in the same specific patient group. Further bolstering this expectation were preclinical xenograft studies (cited in the prior art) that demonstrated clear synergy and a 93% tumor growth inhibition for the combination, far exceeding the additive effects of the monotherapies, without increasing toxicity.

4. Key Claim Construction Positions

  • Petitioner argued for a specific construction of the claim phrase "Extend the Time to Disease Progression in Said Human Patient, Without Increase in Overall Severe Adverse Events."
    • Petitioner asserted that this is a relative term and the proper baseline for comparison, based on the patent's own examples and the context of the field, is the efficacy and safety of treatment with the taxoid (paclitaxel) alone. The patent’s clinical data directly compares the T+H (Taxol + Herceptin) arm to the T (Taxol alone) arm. This construction is critical to defining the scope of the claimed invention and assessing whether the prior art rendered it obvious, as it frames the inventive concept as the improvement over an existing standard-of-care component, not just an effect relative to no treatment.

5. Key Technical Contentions (Beyond Claim Construction)

  • Petitioner's primary technical contention was that the Sliwkowski Declaration, submitted during prosecution to overcome a series of obviousness rejections, was fundamentally flawed and should be given no weight. This declaration was instrumental in the patent's allowance.
    • Refutation of Cell-Cycle Antagonism: Dr. Sliwkowski had argued that a POSITA would not combine the drugs due to a fear of "antagonistic interaction," theorizing that trastuzumab (arresting the cell cycle in the G1 phase) would prevent paclitaxel from working (as it purportedly only acts in the later G2/M phase). Petitioner countered that this was technically incorrect, as a POSITA would have known that paclitaxel also exerts anticancer effects during the G1 phase and, moreover, that tumors consist of a heterogeneous population of cells at all different stages of the cell cycle.
    • Refutation of Dismissal of Xenograft Data: Dr. Sliwkowski dismissed prior art xenograft data showing synergy by arguing, with support from a non-prior art reference, that such preclinical models are not predictive of clinical success. Petitioner argued this was contrary to the widespread reliance on xenograft data by POSAs at the time of the invention to guide clinical development. Furthermore, Petitioner noted that prior art for a similar combination (trastuzumab and cisplatin) showed synergy both preclinically and clinically, directly contradicting Sliwkowski's hypothesis and reinforcing the expectation of success for the claimed combination.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review (IPR) and the cancellation of claims 1-14 of Patent 7,846,441 as unpatentable for obviousness under 35 U.S.C. §103.