PTAB

IPR2017-01122

Celltrion Inc v. Genentech Inc

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Petition
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1. Case Identification

2. Patent Overview

  • Title: Treatment with Anti-ErbB2 Antibodies
  • Brief Description: The ’549 patent claims methods for treating HER2-positive breast cancer by administering a three-drug combination: an anti-ErbB2 antibody (e.g., trastuzumab), a taxoid (e.g., paclitaxel), and a further growth inhibitory agent (e.g., a DNA alkylating agent like cisplatin).

3. Grounds for Unpatentability

Ground 1: Obviousness over Clinical Oncology References - Claims 1-11 and 14-17 are obvious over Baselga 1996, Seidman 1996, Pegram 1995, and the 1995 TAXOL PDR.

  • Prior Art Relied Upon: Baselga 1996 (a 1996 clinical oncology journal article), Seidman 1996 (a 1996 clinical oncology conference abstract), Pegram 1995 (a 1995 clinical oncology conference abstract), and the 1995 TAXOL PDR (a 1995 Physician’s Desk Reference entry for paclitaxel).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the independent claims require treating HER2-positive breast cancer with a combination of three agents: an anti-ErbB2 antibody, a taxoid, and a further growth inhibitory agent. The prior art allegedly disclosed the clinical efficacy of each component for this exact patient population. Specifically, Baselga 1996 taught that trastuzumab (an anti-ErbB2 antibody) was safe and effective as a monotherapy for metastatic HER2-positive breast cancer. Seidman 1996 taught that paclitaxel (a taxoid) was particularly effective in HER2-positive patients. Pegram 1995 taught that the two-drug combination of trastuzumab and cisplatin (a DNA alkylating agent, which is a species of "growth inhibitory agent") was clinically effective in this patient population with no apparent increase in toxicity. The 1995 PDR provided standard dosing information for paclitaxel and noted its use in combination therapies, including with cisplatin. Petitioner contended that these references collectively disclosed every element of the claimed three-drug combination.
    • Motivation to Combine (for §103 grounds): Petitioner asserted that a Person of Ordinary Skill in the Art (POSA) would have been motivated to combine the known trastuzumab/cisplatin therapy (from Pegram 1995) with paclitaxel based on well-established principles of cancer combination therapy. These principles encouraged combining drugs that (1) have single-agent activity in the target population, (2) have non-overlapping toxicities, (3) have different mechanisms of action, and (4) have different resistance mechanisms. The proposed trastuzumab/cisplatin/paclitaxel combination satisfied all four principles. The motivation was further strengthened by the dire need for effective treatments for the notoriously difficult-to-treat HER2-positive patient population and preclinical data showing synergy between trastuzumab and paclitaxel.
    • Expectation of Success (for §103 grounds): A POSA would have had a reasonable expectation of success because each component (trastuzumab, paclitaxel) and the sub-combination (trastuzumab/cisplatin) were already proven to be clinically effective and well-tolerated in the target patient population. The fact that clinical trials for a trastuzumab/paclitaxel combination were already underway, as noted in Baselga 1996, confirmed that skilled artisans already expected the combination to work safely and effectively.

4. Key Claim Construction Positions

  • "Extend the Time to Disease Progression in the Human Patient": Petitioner argued that, based on the patent’s specification and clinical trial examples, this relative term requires comparing the claimed combination treatment to treatment with a taxoid alone. This construction was central to framing the obviousness analysis, as the prior art allegedly demonstrated that adding trastuzumab and cisplatin to a taxoid regimen would have been an obvious path to improving efficacy.
  • "Therapeutic Agent" / "Growth Inhibitory Agent": Petitioner proposed that these terms mean "an agent with efficacy in the treatment of cancer," specifically including cisplatin as a DNA alkylating agent. This construction was necessary to map the cisplatin disclosures in the prior art (e.g., Pegram 1995) onto the claim limitations for the "further therapeutic agent" or "further growth inhibitory agent."

5. Key Technical Contentions (Beyond Claim Construction)

  • Rebuttal of Sliwkowski Declaration: During prosecution, the Patent Owner submitted a declaration from Dr. Sliwkowski arguing against a motivation to combine trastuzumab and paclitaxel. The declaration asserted a POSA would have expected an "antagonistic interaction" because trastuzumab arrests the cell cycle at the G1 phase, which would prevent paclitaxel from acting at its supposed G2/M phase. Petitioner countered that this was based on a flawed premise, arguing a POSA would have known that paclitaxel exhibits anticancer effects during all phases of the cell cycle, including the G1 phase.
  • Predictive Value of Xenograft Models: Dr. Sliwkowski also argued during prosecution that preclinical xenograft data showing synergy was not predictive of clinical success, relying on a non-prior art 2001 article. Petitioner contended that as of the patent's priority date, a POSA would have considered xenograft data highly relevant and predictive. Petitioner argued that the prior art established that POSAs commonly relied on such data to support clinical evaluation, and that Dr. Sliwkowski's own later publications contradicted his declaration by stating such models are rational for testing combinations in human trials.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-11 and 14-17 of Patent 7,892,549 as unpatentable.