PTAB

IPR2017-00737

Hospira, Inc. v. Genentech, Inc.

Log In

1. Case Identification

2. Patent Overview

  • Title: Treatment with Anti-ErbB2 Antibodies
  • Brief Description: The ’549 patent describes methods for treating a human patient with breast cancer that overexpresses the ErbB2 receptor. The claimed method involves administering a combination therapy comprising an anti-ErbB2 antibody, a taxoid, and a further growth inhibitory or therapeutic agent.

3. Grounds for Unpatentability

Ground 1: Claims 1-11 and 14-17 are obvious over Baselga '97 and Gelmon '96.

  • Prior Art Relied Upon: Baselga '97 (a 1997 journal article on HER2 overexpression and paclitaxel sensitivity) and Gelmon '96 (a 1996 clinical trial report on paclitaxel and cisplatin).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that every element of the claimed three-drug combination was well-known in the prior art for treating breast cancer. Baselga '97 taught using the anti-ErbB2 antibody rhuMAb HER2 (trastuzumab) with the taxoid paclitaxel to treat HER2-overexpressing breast cancer, noting synergistic anti-tumor activity. Gelmon '96 taught the synergistic combination of paclitaxel with cisplatin (a growth inhibitory agent) for metastatic breast cancer, noting their different mechanisms of resistance and non-overlapping toxicities made them an appropriate combination.
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) would be motivated to combine the teachings of these references to find more effective therapies for HER2-positive breast cancer. A POSITA would have understood from Gelmon '96 that a paclitaxel/cisplatin combination was a promising therapy, and from Baselga '97 that rhuMAb HER2 could sensitize HER2-positive tumors to such chemotherapies. The combination represented a logical next step to improve treatment outcomes for a patient population known to be resistant to certain chemotherapies.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success. Each two-drug permutation of the claimed three-drug therapy (antibody + taxoid; antibody + cisplatin; taxoid + cisplatin) was already known to be synergistic and had been used in human clinical trials. Combining them was a predictable, common-sense approach to further improving efficacy without an unreasonable risk of new or increased toxicity.

Ground 2: Claim 12 is obvious over Baselga '97, Gelmon '96, and Drebin '88.

  • Prior Art Relied Upon: Baselga '97, Gelmon '96, and Drebin '88 (a 1988 journal article on synergistic anti-tumor effects of combining antibodies against distinct ErbB2 domains).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground specifically challenges claim 12, where the "further therapeutic agent" is "another ErbB2 antibody." The core combination of an anti-ErbB2 antibody (from Baselga '97) and a taxoid (from Baselga '97 and Gelmon '96) is established as in Ground 1. Drebin '88 was cited for its teaching that combining antibodies reactive with two distinct regions of the p185 (ErbB2) molecule resulted in synergistic anti-tumor effects and even complete tumor eradication.
    • Motivation to Combine: Since the prior art, including Baselga '97, showed that blockade of a single ErbB2 domain (the 4D5 epitope) did not result in complete tumor suppression, a POSITA would be motivated to enhance the therapy. Drebin '88 provided the solution: use a second anti-ErbB2 antibody targeting a different epitope to achieve greater, synergistic anti-tumor effects. A POSITA would combine this teaching with the established antibody-plus-chemotherapy backbone to further improve tumor suppression.
    • Expectation of Success: The expectation of success was high, as Drebin '88 explicitly demonstrated the synergistic benefit of using multiple anti-ErbB2 antibodies.

Ground 3: Claims 1-11 and 14-17 are obvious over Baselga '96, Baselga '94, and Gelmon '96.

  • Prior Art Relied Upon: Baselga '96 (a 1996 Phase II clinical trial report), Baselga '94 (a 1994 xenograft study report), and Gelmon '96.

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground presented an alternative, but conceptually identical, argument to Ground 1. Baselga '96 and Baselga '94 taught the synergistic combination of an anti-ErbB2 antibody (4D5/rhuMAb HER2) and paclitaxel, reporting marked potentiation of antitumor effects in preclinical models and disclosing that clinical trials were in progress. As in Ground 1, Gelmon '96 supplied the teaching of combining paclitaxel with cisplatin. The combination of these references disclosed all elements of the claimed three-drug therapy.
    • Motivation to Combine: The motivation was identical to Ground 1: the ongoing and unmet need for more effective breast cancer treatments. The synergistic results reported in Baselga '94 and the human clinical trial data from Baselga '96 would strongly motivate a POSITA to combine the antibody-taxoid therapy with another known synergistic agent like cisplatin (from Gelmon '96) to further enhance efficacy.
    • Expectation of Success: The expectation of success was based on the same logic as Ground 1. The established synergistic effects of the various two-drug combinations, the use of all components in humans, and the non-overlapping toxicity profiles provided a strong scientific basis to expect the three-drug combination would be safe and effective.

  • Additional Grounds: Petitioner asserted additional obviousness challenges, including for claim 13 over Baselga '97, Gelmon '96, and Presta '97 (adding a VEGF antibody), and for claim 12 over the Baselga '96/'94 combination plus Drebin '88. These grounds relied on the same core logic of combining a known antibody-chemotherapy backbone with another known anti-cancer agent acting via a complementary mechanism.

4. Key Technical Contentions (Beyond Claim Construction)

  • Rebuttal of Prosecution-History Arguments: Petitioner's arguments centered on refuting the Sliwkowski Declaration, which Patent Owner used to overcome obviousness rejections during prosecution.
    • Petitioner contended that Sliwkowski's argument—that rhuMAb HER2 (causing G1 cell cycle arrest) and paclitaxel (causing G2/M arrest) would be expected to be antagonistic—was flawed. Petitioner argued this hypothesis was directly contradicted by the in vivo data in the Baselga '94 prior art, which showed a strong synergistic effect, not antagonism.
    • Petitioner also argued that Sliwkowski's declaration was irrelevant as it only addressed a two-drug combination (antibody + taxoid), not the three-drug combinations of the challenged claims.
    • Petitioner asserted that any purported controversy over the predictive value of preclinical models was a red herring, as Patent Owner itself relied on such models (e.g., in Baselga '94) to proceed to human clinical trials.

5. Relief Requested

  • Petitioner requests that the PTAB institute an inter partes review and cancel claims 1-17 of the ’549 patent as unpatentable.