PTAB

IPR2018-01712

Eli Lilly Co v. Teva Pharmaceuticals Intl GmbH

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods for Treating Headache Using Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide
  • Brief Description: The ’908 patent discloses methods for treating headaches, including migraines, by administering a humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist antibody. The claims recite general structural features of an IgG antibody and a specific binding affinity to human CGRP.

3. Grounds for Unpatentability

Ground 1: Claims 1-18 are obvious over Olesen, Tan, and Queen.

  • Prior Art Relied Upon: Olesen (a 2004 clinical trial publication), Tan (a 1995 journal article on anti-CGRP antibodies), and Queen (Patent 6,180,370).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Olesen, Tan, and Queen taught or suggested every limitation of the challenged claims. Olesen provided the clinical proof-of-concept that blocking the CGRP pathway is an effective treatment for migraine in humans, validating it as a therapeutic target. Tan described a murine monoclonal IgG anti-CGRP antagonist antibody (MAb C4.19) that blocked the biological effects of CGRP in vivo and possessed a binding affinity (KD of 1.9 nM) within the range required by claim 1 (about 10 nM or less). Queen disclosed the "gold standard" methods for humanizing non-human antibodies, such as the one in Tan, by grafting their complementarity-determining regions (CDRs) onto a human antibody framework. Queen’s methods were designed to reduce immunogenicity for therapeutic use in humans while retaining the original antibody's binding affinity and specificity.
    • Motivation to Combine (for §103 grounds): Petitioner asserted that a person of ordinary skill in the art (POSA), armed with Olesen's clinical validation of the CGRP pathway as a migraine target, would be motivated to develop a CGRP antagonist for treatment. A POSA would have looked to anti-CGRP antibodies, such as the one described in Tan, as a known and promising class of CGRP antagonists with demonstrated in vivo efficacy and inherent advantages over small molecules (e.g., longer half-life, higher specificity). Because Tan's antibody was murine, a POSA intending to create a therapeutic for humans would have been motivated to humanize it to reduce immunogenicity, a routine and necessary step for which Queen provided the well-established and predictable methodology.
    • Expectation of Success (for §103 grounds): Petitioner contended that a POSA would have had a reasonable expectation of success. Olesen’s clinical success provided a strong expectation that other CGRP antagonists would be effective. Tan’s in vivo data confirmed that anti-CGRP antibodies could successfully block CGRP activity. Furthermore, humanization technology as taught by Queen was a "clinically well-validated technology" by 2005, providing a POSA with a high degree of confidence that a murine antibody's key functional properties—its specific binding to CGRP with high affinity—would be preserved in the resulting humanized antibody.
    • Key Aspects: The petition emphasized that the dependent claims add only conventional features. For example, claims to specific IgG isotypes (IgG1, IgG2, IgG4) represented a simple choice from a limited number of known options, and claims to C-terminal binding were directed to a known functional region of CGRP.

4. Key Claim Construction Positions

  • "treating": Petitioner argued that based on the specification's express definition, "treating" should be construed as "an approach for obtaining a beneficial or desired clinical result," which does not require the actual achievement of a clinical response. This broad construction lowers the burden for showing a reasonable expectation of success.
  • "effective amount": Petitioner argued this term should not be construed to require a clinical response. Further, based on the doctrine of claim differentiation with dependent claim 7 (reciting a dose of "at least 3 µg/kg"), the term in independent claim 1 must be broader and encompass doses lower than 3 µg/kg.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. § 325(d) would be improper because the core prior art references—Olesen, Tan, and Queen—were not cited or substantively considered by the Examiner during prosecution. Although the references were listed in Information Disclosure Statements containing over 450 documents, Petitioner asserted they were not the basis of any rejection, and the Examiner did not have the benefit of the expert declarations explaining their significance.

6. Relief Requested

  • Petitioner requests institution of an inter partes review (IPR) and cancellation of claims 1-18 of the ’908 patent as unpatentable.