PTAB

IPR2017-00731

Hospira, Inc. v. Genentech, Inc.

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1. Case Identification

2. Patent Overview

  • Title: Treatment with Anti-ErbB2 Antibodies
  • Brief Description: The ’441 patent is directed to a method for treating a human patient with a malignant tumor characterized by the overexpression of the ErbB2 protein. The claimed method involves administering a combination of an anti-ErbB2 antibody that binds to epitope 4D5 (such as Herceptin®/trastuzumab) and a taxoid chemotherapeutic agent (such as paclitaxel), specifically in the absence of an anthracycline derivative, to extend the time to disease progression.

3. Grounds for Unpatentability

Ground 1: Claims 1-14 are obvious over Baselga '97 in view of Baselga '94.

  • Prior Art Relied Upon: Baselga '97 (Baselga et al., a 1997 article in ONCOLOGY) and Baselga '94 (Baselga et al., a 1994 abstract in PROC. AM. SOC. CLIN. ONCOL.).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of these references taught every element of the challenged claims. Baselga '94 disclosed compelling preclinical data from mouse models where combining an anti-ErbB2 antibody (4D5) with paclitaxel resulted in synergistic tumor growth inhibition (93% inhibition vs. 35% for either agent alone) without increasing toxicity. Critically, Baselga '94 stated that human clinical trials of this combination were already underway. Three years later, Baselga '97 described the design of an ongoing Phase III multinational clinical trial in human patients using this exact combination therapy (rhuMAb HER2, a humanized 4D5 antibody, plus chemotherapy). This reference detailed the patient population (HER2-overexpressing breast cancer), the administration of a taxoid (paclitaxel), the explicit exclusion of concurrent anthracyclines due to their use in prior adjuvant settings, and the use of "time to disease progression" as a clinical endpoint.
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) would have been motivated to combine the teachings of these references. They document a clear and continuous line of research by the same lead author (Dr. Baselga) and overlapping co-authors. The combination was natural, as Baselga '97 described the human clinical trial that was a direct and logical progression from the promising preclinical results reported in Baselga '94.
    • Expectation of Success: A POSITA would have possessed a strong and reasonable expectation of success. The remarkable synergistic antitumor activity reported in the preclinical models of Baselga '94, coupled with the disclosure in both Baselga '94 and Baselga '97 that human clinical trials were not only planned but actively underway for several years, strongly suggested that the combination was proving to be safe and effective.

Ground 2: Claims 1-14 are obvious over Baselga '96 in view of Baselga '94.

  • Prior Art Relied Upon: Baselga '96 (Baselga et al., a 1996 article in J. CLIN. ONCOL.) and Baselga '94.
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented a very similar obviousness combination, substituting the 1996 publication for the 1997 one. Baselga '96 reported positive results from a Phase II clinical trial of the anti-ErbB2 antibody (rhuMAb HER2) as a monotherapy, establishing its safety ("remarkably well tolerated") and clinical activity in heavily pretreated patients. Crucially, Baselga '96 explicitly referenced the successful preclinical work, stating that rhuMAb HER2 "markedly potentiated the antitumor effects of several chemotherapeutic agents, including...paclitaxel, without increasing their toxicity." It then confirmed that "clinical trials of such combination therapy are currently in progress." When combined with the specific synergistic data from Baselga '94, this combination taught a method of treating human patients with the antibody and a taxoid.
    • Motivation to Combine: The motivation was identical to Ground 1. Baselga '96 cited the earlier preclinical work (including Baselga '94) and shared overlapping authors, demonstrating a clear research progression that would lead a POSITA to consider the references together.
    • Expectation of Success: A POSITA would have had a clear expectation of success. Baselga '96 confirmed the antibody's safety and efficacy in humans. This, combined with the powerful synergistic preclinical data from Baselga '94 and the explicit statement in Baselga '96 that human trials of the combination were already in progress, would lead a POSITA to reasonably expect the combination to be effective and safe. The known cardiotoxicity of anthracyclines, also mentioned in Baselga '96, would have further motivated a POSITA to pursue the superior paclitaxel combination in the absence of an anthracycline.

4. Key Technical Contentions (Beyond Claim Construction)

  • Refutation of No Expectation of Success: Petitioner's primary technical contention challenged the Patent Owner's arguments from prosecution that a POSITA would not have had a reasonable expectation of success. During prosecution, Patent Owner's expert (Sliwkowski) theorized that the combination would fail because the antibody (causing G1 cell cycle arrest) and paclitaxel (causing G2/M arrest) would be antagonistic. Petitioner argued this was hindsight speculation contradicted by the actual prior art. The Baselga '94 preclinical data showed strong synergy, not antagonism. Petitioner asserted that Genentech's own decision to proceed with a Phase III trial, as disclosed in the Baselga references, proved that those skilled in the art did, in fact, have an expectation of success at the time.
  • Inconsistent Positions on Prior Art: Petitioner argued that the Patent Owner took irreconcilable positions during prosecution. To swear behind the Baselga '97 reference, the inventor (Hellmann) relied on a clinical trial protocol and evidence of treating one patient as a reduction to practice. Yet, to argue against the obviousness of the claims over the Baselga '96 reference, the Patent Owner argued that Baselga '96's disclosure of a clinical trial in progress was insufficient to teach the invention. Petitioner contended it cannot be true that a mere plan for a trial proves invention while an actual trial in progress fails to even suggest it.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-14 of the ’441 patent as unpatentable under 35 U.S.C. §103.