PTAB

IPR2017-00737

Hospira Inc v. Genentech Inc

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Treatment with Anti-ErbB2 Antibodies
  • Brief Description: The ’549 patent describes methods for treating human patients with breast cancer that overexpresses the ErbB2 receptor. The claimed method comprises administering a three-drug combination of an anti-ErbB2 antibody, a taxoid, and a further growth inhibitory agent in an amount effective to extend the time to disease progression.

3. Grounds for Unpatentability

Ground 1: Obviousness over Baselga ’97 and Gelmon ’96 - Claims 1-11 and 14-17 are obvious over Baselga ’97 in view of Gelmon ’96.

  • Prior Art Relied Upon: Baselga ’97 (a 1997 oncology journal article) and Gelmon ’96 (a 1996 clinical oncology journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that every element of the claimed three-drug combination was known in the prior art. Baselga ’97 taught that the anti-ErbB2 antibody rhuMAb HER2 (trastuzumab) showed synergistic anti-tumor activity when combined with either paclitaxel (a taxoid) or cisplatin (a growth inhibitory agent). Separately, Gelmon ’96 taught a synergistic and effective combination of paclitaxel and cisplatin for treating metastatic breast cancer, noting their different mechanisms of action and non-overlapping toxicities. The combination of these references, Petitioner asserted, disclosed administering an anti-ErbB2 antibody, a taxoid, and a growth inhibitory agent to human breast cancer patients.
    • Motivation to Combine: Petitioner argued a person of ordinary skill in the art (POSITA) would combine the teachings because each two-drug permutation of the three components was already known to be synergistic and effective. With established synergistic pairs of (1) antibody + taxoid, (2) antibody + cisplatin, and (3) taxoid + cisplatin, combining all three was presented as the next logical step to further improve treatment efficacy for a disease that had not been eradicated.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success in achieving at least an additive, if not synergistic, effect. The known efficacy and acceptable toxicity profiles of the two-drug combinations would suggest that the three-drug regimen would be a viable and promising approach to extend the time to disease progression, a primary goal in cancer therapy.

Ground 2: Obviousness over Baselga ’97, Gelmon ’96, and Drebin ’88 - Claim 12 is obvious over Baselga ’97 in view of Gelmon ’96 and Drebin ’88.

  • Prior Art Relied Upon: Baselga ’97, Gelmon ’96, and Drebin ’88 (a 1988 oncogene journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground specifically addressed claim 12, which recites that the "further therapeutic agent" is another ErbB2 antibody. Petitioner argued that while Baselga ’97 and Gelmon ’96 provided the base combination of an antibody and chemotherapy, Drebin ’88 taught that combining antibodies reactive with two distinct regions of the ErbB2 receptor resulted in synergistic anti-tumor effects and complete tumor eradication in xenograft models.
    • Motivation to Combine: The motivation stemmed from the knowledge that treatment with a single anti-ErbB2 antibody (as in Baselga ’97) did not lead to complete tumor suppression. A POSITA, seeking to improve outcomes, would have been motivated to incorporate the strategy from Drebin ’88—using a second, complementary anti-ErbB2 antibody—to achieve a more complete receptor blockade and enhance sensitization to the chemotherapy combination taught by Baselga ’97 and Gelmon ’96.

Ground 3: Obviousness over Baselga ’96, Baselga ’94, and Gelmon ’96 - Claims 1-11 and 14-17 are obvious over Baselga ’96 in view of Baselga ’94 and Gelmon ’96.

  • Prior Art Relied Upon: Baselga ’96 (a 1996 clinical oncology journal article), Baselga ’94 (a 1994 clinical oncology proceedings abstract), and Gelmon ’96.
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented an alternative combination of references to argue the obviousness of the main set of claims. Petitioner argued that Baselga ’96 disclosed a Phase II clinical trial using rhuMAb HER2 and noted that preclinical studies showed it potentiated the effects of chemotherapeutic agents, including paclitaxel and cisplatin. Baselga ’96 cited Baselga ’94, which provided the underlying preclinical data showing a potent synergistic effect (93% growth inhibition) for the 4D5 antibody combined with paclitaxel. As in Ground 1, Gelmon ’96 was cited for its teaching of the synergistic paclitaxel and cisplatin combination.
    • Motivation to Combine: The motivation was similar to Ground 1. A POSITA, reading Baselga ’96 and its underlying support in Baselga ’94, would understand the powerful synergy between the antibody and taxoids. This knowledge, combined with the known synergistic paclitaxel-cisplatin regimen from Gelmon ’96, would provide a strong motivation to create a three-drug therapy to maximize anti-tumor effects.
  • Additional Grounds: Petitioner asserted additional obviousness challenges, including combinations incorporating Drebin ’88 (for claim 12) and Presta ’97 (a 1997 article on VEGF antibodies, for claim 13) with the Baselga ’96/’94/Gelmon ’96 base. The motivations relied on similar principles of combining known agents to achieve a more complete tumor blockade or to target unrelated oncogenic pathways.

4. Key Technical Contentions (Beyond Claim Construction)

  • Rebuttal of Prosecution Arguments on Expectation of Success: Petitioner directly challenged the arguments made by Patent Owner’s expert (Dr. Sliwkowski) during prosecution to overcome obviousness rejections.
    • Petitioner contended that the expert’s theory—that rhuMAb HER2 (causing G1 cell cycle arrest) would antagonize paclitaxel (causing G2/M arrest)—was speculative and contradicted by prior art. Specifically, Baselga ’94 reported strong in vivo synergistic data for the antibody-paclitaxel combination, which a POSITA would find more compelling than a theoretical cell-cycle conflict.
    • Petitioner also argued that the expert’s dismissal of preclinical models as not predictive of human success was unpersuasive. Petitioner pointed out that Genentech itself relied on the same preclinical data (e.g., Baselga ’94) and subsequent Phase II results (Baselga ’96 and ’97) to justify proceeding with a large-scale Phase III trial of the combination, demonstrating its own belief in the predictive value of the data.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-17 of Patent 7,892,549 as unpatentable.