PTAB

IPR2017-00804

Hospira Inc v. Genentech Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Dosages for treatment with anti-ErbB2 antibodies
  • Brief Description: The ’196 patent describes methods for treating cancers characterized by ErbB2 overexpression using a "front-loading" dosage regimen. The method involves administering an initial dose of an anti-ErbB2 antibody (trastuzumab, marketed as Herceptin) of at least approximately 5 mg/kg, followed by subsequent, lower or equal doses administered at intervals of at least two weeks.

3. Grounds for Unpatentability

Ground 1: 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 (1998 FDA Approved Label), Baselga ’96 (a 1996 clinical trial publication), and Pegram ’98 (a 1998 clinical trial publication).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of prior art taught or suggested every limitation of the challenged claims. The Herceptin Label, the FDA-approved package insert for the antibody (rhuMAb HER2), disclosed its use for treating HER2-overexpressing breast cancer. It taught that doses up to 500 mg had been safely administered weekly; Petitioner asserted that for an average-weight patient, this absolute dose corresponds to a weight-based dose greater than the claimed "at least approximately 5 mg/kg" initial dose. The Label also disclosed a front-loaded regimen (4 mg/kg initial dose followed by 2 mg/kg weekly maintenance doses), satisfying the limitation for subsequent doses being equal to or less than the initial dose. While the Label taught weekly administration, it also specified that Herceptin was approved for use in combination with paclitaxel, a chemotherapy agent administered tri-weekly (every 21 days). This discrepancy in schedules between the two combined drugs rendered the claimed two- or three-week interval for Herceptin obvious to a POSITA. Baselga ’96 and Pegram ’98, which described the clinical trials leading to Herceptin’s approval, established the target minimum trough serum concentration (10-20 µg/mL) needed for efficacy.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine these references because they all address the same problem: optimizing the treatment of HER2-positive breast cancer with the same antibody. The primary motivation to modify the weekly dosing schedule disclosed in the Herceptin Label was to align it with the tri-weekly schedule of co-administered chemotherapies like paclitaxel. Such alignment would significantly improve patient convenience by reducing the frequency of clinic visits, thereby enhancing patient compliance and quality of life, which were routine considerations in oncology.
    • Expectation of Success: A POSITA would have had a strong expectation of success in extending the dosing interval. The Herceptin Label itself disclosed a crucial pharmacokinetic parameter that was not before the Examiner during prosecution: an average half-life of 12.1 days for the antibody at the 500 mg dose. This long half-life directly indicated that the drug would remain at therapeutic concentrations well beyond the one-week dosing interval. Using this half-life, the target trough concentrations from Baselga ’96 and Pegram ’98, and standard pharmacokinetic models, a POSITA could readily calculate that a tri-weekly regimen would maintain serum levels safely above the minimum required for efficacy. The known safety of high doses further supported this expectation.
    • Key Aspects: Petitioner emphasized that during prosecution, the Patent Owner argued against the obviousness of a longer dosing interval by relying on prior art showing a shorter half-life, while failing to disclose the much longer 12-day half-life reported on its own FDA-approved Herceptin Label.

4. Key Technical Contentions (Beyond Claim Construction)

  • Pharmacokinetic Modeling was Routine: A central contention was that modifying a dosing regimen based on known pharmacokinetic (PK) parameters was a routine and predictable exercise for a POSITA at the time. Petitioner argued that a POSITA could use textbook, one-compartment PK equations to model Herceptin's serum concentration over time. By inputting the known half-life (~12 days) and volume of distribution from the Herceptin Label, and aiming to exceed the target trough concentration (10-20 µg/mL) from Baselga '96 and Pegram '98, a POSITA would have predictably arrived at an effective tri-weekly dosing regimen. The petition provided detailed calculations and figures to demonstrate that such a regimen would maintain drug levels well above the therapeutic minimum, making the claimed invention a product of routine optimization, not invention.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-3, 5, 7, 9-11, and 17-33 of Patent 6,627,196 as unpatentable under 35 U.S.C. §103.