Pfizer Inc v. Genentech Inc

1. Case Identification

• Case #: IPR2018-00373
• Patent #: 9,795,672
• Filed: January 5, 2018
• Petitioner(s): Pfizer Inc.
• Patent Owner(s): Genentech, Inc.
• Challenged Claims: 1-18

2. Patent Overview

• Title: Treatment with Anti-VEGF Antibodies
• Brief Description: The ’672 patent is directed to methods of treating cancer with the anti-VEGF antibody bevacizumab. The claims cover a method of managing a known side effect, grade III hypertension, by administering an antihypertensive agent while continuing the bevacizumab treatment without altering the original dosage regimen.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-18 by Kabbinavar

• Prior Art Relied Upon: Kabbinavar (Fairooz Kabbinavar et al., a 2003 clinical oncology journal article). For an alternative obviousness argument, the petition also references Harrison's (a 2001 internal medicine textbook).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Kabbinavar, a published Phase II clinical trial summary, anticipates every limitation of the claims. Kabbinavar taught treating colorectal cancer with bevacizumab and disclosed that patients experiencing hypertension required oral antihypertensive therapy, which meets the patent's definition of a "grade III hypertensive event." Critically, Kabbinavar reported that treatment was continued for six cycles and that only one patient discontinued bevacizumab therapy, leading to the direct inference that the dosage regimen was not altered for the other hypertensive patients, thus anticipating the core limitation of the claims.
  • Motivation to Combine (for §103 alternative): In the alternative, if any element was found missing from Kabbinavar, a person of ordinary skill in the art (POSA) would have been motivated to combine its teachings with standard clinical practice for managing hypertension, as detailed in authoritative texts like Harrison's. This would have led to the same claimed method.
  • Expectation of Success: Kabbinavar's own conclusion that bevacizumab-related hypertension was generally "manageable" would have provided a POSA with a strong expectation of success in treating the side effect with standard antihypertensives without needing to alter the primary cancer therapy.

Ground 2: Obviousness of Claims 1-18 over PCT’360 and Presta

• Prior Art Relied Upon: PCT’360 (WO 01/74360) and Presta (a 1997 cancer research article).

• Core Argument for this Ground:

  • Prior Art Mapping: Petitioner asserted this is a classic case where a method of treatment claim is obvious because it merely confirms in humans a result observed and predicted from animal testing. PCT’360 taught, based on preclinical rat studies, that anti-VEGF agents cause hypertension and that this side effect can be managed by co-administering an antihypertensive agent while continuing the anti-VEGF agent at its original dose. Presta explicitly taught the humanization of the murine antibody A.4.6.1 (the subject of PCT’360’s teachings) into bevacizumab, making it suitable for human clinical trials.
  • Motivation to Combine: A POSA, knowing from Presta how to create humanized bevacizumab, would have been directly motivated to apply the method taught in PCT’360 for managing the known side effects of the antibody class during human treatment. The combination directly teaches all elements of claim 1.
  • Expectation of Success: The preclinical data in PCT’360, which demonstrated the successful reversal of hypertension with an antihypertensive drug while maintaining the anti-VEGF inhibitor dose, provided a POSA with a reasonable expectation of success for applying the same strategy in human patients.

• Additional Grounds: Petitioner asserted additional challenges, including that claims 1-18 are anticipated by Chen (a 2001 clinical trials review) and Yang (a 2003 clinical trial publication). These grounds argued that Chen's disclosure of hypertension being "controllable with medication" and Yang's protocol of only withholding bevacizumab for a higher grade of toxicity inherently taught the claimed method.

4. Key Claim Construction Positions

• The petition argued for a specific construction of the term "grade III hypertensive event" to mean "hypertension requiring therapy or more intensive therapy than previously."
• This proposed construction was based on the National Cancer Institute's Common Toxicity Criteria (CTC), which the ’672 patent's specification explicitly references when describing the clinical trials in its examples. Petitioner noted that the Patent Owner also adopted this definition during prosecution, making it a binding interpretation. This construction is central to the argument that prior art describing hypertension as "requiring" or being "controllable with" medication inherently discloses this claim limitation.

5. Key Technical Contentions (Beyond Claim Construction)

• A central contention was that the ’672 patent is not entitled to its claimed May 30, 2003 priority date. Petitioner argued that the 2003 Provisional Application lacks sufficient written description to support the key claim limitation: "continuing to treat the patient with bevacizumab... without altering the dosage regimen."
• The provisional's simple statement that hypertension was "easily managed with oral medications" was argued to be a bare assertion that fails to show the inventors possessed the complete invention. This argument, if successful, would make references like Yang (published July 2003) prior art under §102(a) and §102(b), invalidating the patent.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that the Examiner's decision to allow the claims over Kabbinavar during prosecution should not be given deference under §325(d).
• The argument was twofold: First, the Examiner was never presented with the priority date challenge, a key issue that changes the landscape of available prior art. Second, the Examiner's rejection was overcome only by an inventor declaration (the Novotny Declaration) that Petitioner argued was conclusory, uncorroborated, and insufficient to disqualify Kabbinavar as prior art under the standards of In re Katz.

7. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-18 of the ’672 patent as unpatentable under 35 U.S.C. §102 and/or §103.