Celltrion Inc v. Genentech Inc

1. Case Identification

• Case #: IPR2017-01140
• Patent #: 7,371,379
• Filed: March 24, 2017
• Petitioner(s): Celltrion, Inc.
• Patent Owner(s): Genentech, Inc.
• Challenged Claims: 1-3, 5, 7, 9-11, 13-28, and 30-40

2. Patent Overview

• Title: Dosages for Treatment with Anti-ErbB2 Antibodies
• Brief Description: The ’379 patent discloses methods for treating a human patient diagnosed with cancer characterized by overexpression of the ErbB2 receptor. The method involves co-administering an effective amount of an anti-ErbB2 antibody (trastuzumab) and a chemotherapeutic agent, wherein the antibody is given via an initial loading dose followed by subsequent doses separated by at least two weeks.

3. Grounds for Unpatentability

Ground 1: Claims 1-3, 5, 7, 9-11, 13-28, and 30-40 are obvious over Slamon and Watanabe, in view of Baselga and Pegram.

• Prior Art Relied Upon: Slamon (a 1998 clinical trial abstract, Ex. 1005), Watanabe (a 1998 dose escalation study abstract, Ex. 1006), Baselga (a 1996 Phase II clinical trial article, Ex. 1007), and Pegram (a 1998 Phase II clinical trial article, Ex. 1009).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the only material difference between the prior art and the challenged claims was the dosing regimen. Slamon taught the combination of trastuzumab and chemotherapy to treat HER2-overexpressing metastatic breast cancer, disclosing a regimen of a 4 mg/kg loading dose followed by weekly 2 mg/kg maintenance doses of trastuzumab, administered concurrently with chemotherapy given once every three weeks. Petitioner asserted that this prior art taught all elements of independent claims 1 and 30 except for the less frequent dosing interval (at least two weeks) and the specific higher doses. Watanabe taught that higher weekly doses of trastuzumab (up to 8 mg/kg) were safe and achieved the target serum trough concentration. Baselga and Pegram established the key pharmacokinetic (PK) parameters for trastuzumab, including a mean serum half-life of approximately 8-9 days and a target efficacious trough serum concentration of greater than 10 µg/ml.
  • Motivation to Combine (for §103 grounds): A Person of Ordinary Skill in the Art (POSA) would combine the teachings to improve patient convenience. Since Slamon’s chemotherapy was administered every three weeks, a POSA would be motivated to align the trastuzumab administration schedule with the chemotherapy schedule, thereby reducing the frequency of patient visits from weekly to every three weeks. This modification constituted a simple and predictable design choice based on known clinical practice principles.
  • Expectation of Success (for §103 grounds): A POSA would have a reasonable expectation of success in creating a safe and effective three-week dosing regimen. Based on the PK data from Baselga and Pegram, a POSA could perform routine calculations to determine an appropriate three-week dose that would maintain the serum concentration above the known 10 µg/ml efficacious threshold. Petitioner demonstrated that converting Slamon's weekly dose to a three-week dose intensity would result in an 8 mg/kg loading dose followed by 6 mg/kg maintenance doses—values within the safe range established by Watanabe. The known half-life of trastuzumab (approx. 8-9 days) would lead a POSA to predict that serum levels would remain therapeutic over a three-week interval.

4. Key Claim Construction Positions

• Petitioner stated that for the purposes of the IPR, it adopted the constructions for key terms as defined in the ’379 patent’s own specification. These included definitions for "ErbB2," "Antibody," and "Chemotherapeutic agent."
• Petitioner also noted that it would assume the claim preambles are limiting for the purposes of the proceeding. No specific terms were argued to have a construction different from their plain meaning or the specification's definition.

5. Key Technical Contentions (Beyond Claim Construction)

• Petitioner’s central technical contention was that the pharmacokinetics of trastuzumab were well-understood and predictable to a POSA before the patent's priority date. The prior art, particularly Baselga and Pegram, had already established a target efficacious serum trough concentration (>10 µg/ml) and the drug’s half-life.
• Petitioner contended that modifying a drug's dosing schedule to be less frequent while maintaining dose intensity was a routine and predictable optimization in oncology. A POSA could, and would, use standard PK principles to calculate an equivalent, less frequent dosing regimen with a high expectation of success, refuting any notion that such a modification would have been inventive.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate because the Examiner did not have the benefit of key prior art and arguments during the original prosecution.
• Specifically, Petitioner asserted that the primary reference, Slamon, was not before the Examiner. Slamon's disclosure of a combination therapy with mismatched dosing schedules (weekly trastuzumab vs. three-weekly chemotherapy) provided a powerful motivation for modification that the Examiner was unable to consider.
• Furthermore, Petitioner argued the Examiner was only presented with the applicant's conclusory assertion of a "fear" that less frequent dosing would be ineffective. The Examiner lacked the benefit of Petitioner's expert declaration, which provided detailed PK-based analysis from the prior art to show why a POSA would have had a reasonable expectation of success.

7. Relief Requested

• Petitioner requested the institution of an inter partes review and cancellation of claims 1-3, 5, 7, 9-11, 13-28, and 30-40 of Patent 7,371,379 as unpatentable for being obvious under 35 U.S.C. §103.