PTAB

IPR2017-00804

Hospira, Inc. v. Genentech, Inc.

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1. Case Identification

  • Case #: To Be Assigned
  • Patent #: 6,627,196
  • Filed: January 30, 2017
  • Petitioner(s): Hospira, Inc.
  • Patent Owner(s): Genentech, Inc.
  • Challenged Claims: 1-3, 5, 7, 9-11, and 17-33

2. Patent Overview

  • Title: Dosages for treatment with anti-ErbB2 antibodies
  • Brief Description: The ’196 patent relates to methods of treating cancer characterized by ErbB2 overexpression. The invention is a specific dosing regimen comprising a “front-loaded” initial dose of an anti-ErbB2 antibody (at least 5 mg/kg) followed by subsequent maintenance doses administered at least two weeks apart.

3. Grounds for Unpatentability

Ground 1: Obviousness over Herceptin Label, Baselga ’96, and Pegram ’98 - Claims 1-3, 5, 7, 9-11, and 17-33 are obvious over the Herceptin Label in view of Baselga ’96 and Pegram ’98.

  • Prior Art Relied Upon: Herceptin Label (the 1998 FDA Approved Label for rhuMAb HER2), Baselga ’96 (a 1996 Phase II clinical trial publication), and Pegram ’98 (a 1998 Phase II clinical trial publication).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combined references taught all limitations of the challenged claims. The Herceptin Label, the FDA-approved package insert for the antibody rhuMAb HER2 (trastuzumab), disclosed its use for treating HER2-overexpressing breast cancer, recommended front-loading doses (4 mg/kg initial dose, 2 mg/kg weekly maintenance), and provided critical pharmacokinetic data, including a 12.1-day half-life for a 500 mg dose. Petitioner asserted that converting the known safe 500 mg absolute dose to a weight-based dose for an average patient (e.g., 70 kg) resulted in a dose (7.14 mg/kg) that met the “at least approximately 5 mg/kg” limitation of independent claim 1. Baselga ’96 and Pegram ’98, which described the foundational clinical trials for Herceptin, established a target minimum trough serum concentration (10–20 µg/mL) required for efficacy and confirmed the antibody's favorable safety profile. The claim limitation requiring subsequent doses “separated in time... by at least two weeks” was allegedly obvious because the Herceptin Label also disclosed co-administration with paclitaxel, a chemotherapy agent dosed every three weeks.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine the references as they all address the same subject matter: treating HER2-overexpressing cancer with rhuMAb HER2. Baselga ’96 and Pegram ’98 provide the key clinical data that formed the scientific basis for the FDA-approved Herceptin Label. Petitioner argued a POSITA would be motivated to modify the weekly dosing regimen to improve patient convenience, compliance, and quality of life by aligning the antibody administration with the known tri-weekly schedule of co-administered chemotherapy. This modification would reduce the burden of frequent clinic visits, a routine and desirable goal in oncology.
    • Expectation of Success: A POSITA would have had a strong expectation of success in creating a less frequent dosing regimen. The long 12.1-day half-life disclosed in the Herceptin Label inherently suggested that a dosing interval longer than one week was feasible while maintaining therapeutic levels of the antibody. Further, the known safety of rhuMAb HER2 at high doses (up to 500 mg weekly) would have assured a POSITA that a modified schedule with a higher initial dose would be well-tolerated. The petition contended that routine pharmacokinetic calculations, using the data available in the prior art, would confirm that a tri-weekly regimen could safely maintain serum concentrations well above the established target trough levels, ensuring efficacy.

4. Key Claim Construction Positions

  • “ErbB2 receptor”: Petitioner submitted that the Broadest Reasonable Interpretation (BRI) of “ErbB2 receptor” in the ’196 patent claims is interchangeable with “HER2,” “ErbB2,” or “p185HER2.” This construction was based on the patent’s own specification, which used these terms synonymously to describe the human ErbB2 gene and its corresponding glycoprotein receptor.

5. Key Technical Contentions (Beyond Claim Construction)

  • A central technical contention was that modifying the rhuMAb HER2 dosing regimen from weekly to a less frequent schedule was a matter of routine optimization, not invention. Petitioner argued that a POSITA, defined as a team including an oncologist and a pharmacokineticist, could use standard, textbook pharmacokinetic equations to design an effective, non-weekly dosing schedule.
  • The petition provided detailed calculations to illustrate this point. It argued a POSITA would use the half-life and volume of distribution from the Herceptin Label, the target trough concentration from Baselga ’96 and Pegram ’98, and a one-compartment model (taught by Baselga ’96) to reliably calculate an appropriate loading dose and maintenance dose for a tri-weekly regimen. The provided calculations showed that a loading dose of ~712 mg followed by a maintenance dose of 500 mg every three weeks would be safe and effective, with the resulting weight-based doses (e.g., 10.2 mg/kg loading and 7.14 mg/kg maintenance for a 70 kg patient) falling squarely within the scope of the challenged claims.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and cancellation of claims 1-3, 5, 7, 9-11, and 17-33 of the ’196 patent as unpatentable under 35 U.S.C. §103.