PTAB

IPR2017-01958

Samsung Bioepis Co., Ltd. v. Genentech, Inc.

Log In

1. Case Identification

2. Patent Overview

  • Title: Dosages for Treatment with Anti-ErbB2 Antibodies
  • Brief Description: The ’196 patent is directed to methods of treating disorders characterized by ErbB2 overexpression, such as breast cancer, by administering an anti-ErbB2 antibody using a "front-loading" dose. The claimed methods involve an initial dose of at least 5 mg/kg followed by subsequent doses separated by at least two weeks.

3. Grounds for Unpatentability

Ground 1: Obviousness over Herceptin Label, Baselga, and Pegram - Claims 1-3, 5, 7, 9-11, and 17-33 are obvious over the Herceptin Label in view of Baselga ’96, Pegram ’98, and the knowledge of a Person of Ordinary Skill in the Art (POSA).

  • Prior Art Relied Upon: Herceptin Label (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 combination of prior art taught or suggested every limitation of the challenged claims.
      • Anti-ErbB2 Antibody Treatment (Preamble, Claim 1): The Herceptin Label explicitly taught using rhuMAb HER2 (an anti-ErbB2 antibody, also known as Herceptin) to treat patients with metastatic breast cancer characterized by overexpression of the HER2 protein (ErbB2).
      • Initial Dose ≥ 5 mg/kg (Claim 1[a]): The Herceptin Label disclosed that doses up to 500 mg were safely administered weekly. Petitioner asserted that a POSA would understand that this absolute dose could be converted to a weight-based dose. For a standard 70 kg patient, a 500 mg dose is equivalent to 7.14 mg/kg, which is greater than the claimed "at least approximately 5 mg/kg." For a reasonable patient weight range of 55-85 kg, this 500 mg dose converts to a range of 9.09 mg/kg down to 5.88 mg/kg, meeting the claim limitation.
      • Subsequent Doses ≤ Initial Dose (Claim 1[b]): The Herceptin Label taught a front-loaded regimen (4 mg/kg loading dose, 2 mg/kg weekly maintenance dose). Baselga ’96 and Pegram ’98 confirmed this front-loading approach. This established that using a subsequent dose equal to or less than the initial dose was a known and conventional practice for rhuMAb HER2.
      • Dosing Interval ≥ 2 weeks (Claim 1[c]): The Herceptin Label taught weekly dosing but also provided key pharmacokinetic data. It disclosed a half-life of 12.1 days for a 500 mg dose, which is significantly longer than the 7-day weekly interval. This long half-life would suggest to a POSA that less frequent dosing was feasible. Furthermore, the Herceptin Label taught co-administration of rhuMAb HER2 with chemotherapies like paclitaxel, which were administered on a tri-weekly (every 21 days) schedule. This provided a strong rationale to modify the rhuMAb HER2 schedule to align with the chemotherapy schedule, which would inherently satisfy the "at least two weeks" limitation.
      • Dependent Claims: Petitioner asserted that the specific dose ranges and intervals in dependent claims (e.g., initial dose of 8 mg/kg, subsequent doses of 6 mg/kg, three-week interval) were obvious results of routine optimization. Using standard pharmacokinetic equations, a POSA could calculate appropriate loading and maintenance doses for a tri-weekly schedule that would fall squarely within the claimed ranges.
    • Motivation to Combine: A POSA would combine these references as they address the same subject matter: the treatment of HER2-positive cancer with rhuMAb HER2. Baselga ’96 and Pegram ’98 were pivotal clinical trials that supported the FDA approval and labeling of Herceptin. A POSA seeking to optimize the Herceptin regimen would naturally consult the foundational clinical data. The primary motivation was to create a more convenient dosing regimen for patients (especially terminally ill ones) by reducing the frequency of hospital visits and to align the antibody administration schedule with the tri-weekly schedule of co-administered chemotherapy, thereby improving patient compliance and quality of life.
    • Expectation of Success: A POSA would have a reasonable expectation of success in extending the dosing interval. The drug's known 12-day half-life and established safety profile at high doses indicated that it would remain at therapeutic levels even with less frequent administration. Routine pharmacokinetic calculations—using the one-compartment model from Baselga ’96 and data from the Herceptin Label—would confirm that a tri-weekly schedule would maintain serum concentrations well above the target trough levels (10-20 µg/mL) established by Baselga and Pegram.

4. Key Claim Construction Positions

  • Petitioner submitted that the Broadest Reasonable Interpretation (BRI) of “ErbB2 receptor” in the ’196 patent claims is, interchangeably, “HER2,” “ErbB2,” or “p185HER2.” This construction is supported by the patent’s specification, which uses the terms interchangeably.

5. Key Technical Contentions (Beyond Claim Construction)

  • The petition’s central technical contention was that determining the claimed dosing regimen was a matter of routine optimization using well-known pharmacokinetic principles, not an inventive act.
  • Petitioner argued a POSA could use standard, textbook equations to model a tri-weekly dosing schedule for rhuMAb HER2. Using the half-life (12.1 days) and volume of distribution (44 mL/kg) from the Herceptin Label, and applying a one-compartment model (taught by Baselga ’96), a POSA could calculate that a 500 mg maintenance dose every three weeks would keep serum trough concentrations well above the effective target.
  • Further, a POSA could use established formulas to calculate an appropriate loading dose (approx. 712 mg) to achieve steady-state kinetics immediately with a 500 mg tri-weekly maintenance dose. When converted to weight-based doses for typical patients, these calculated loading (e.g., 8-12 mg/kg) and maintenance (e.g., 6-9 mg/kg) doses directly correspond to the ranges recited in the challenged dependent claims, demonstrating their obviousness.

6. Relief Requested

  • Petitioner requested 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.