PTAB

IPR2018-01710

Eli Lilly Co v. Teva Pharmaceuticals Intl GmbH

Log In
Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods of Using Anti-CGRP Antagonist Antibodies
  • Brief Description: The ’045 patent claims methods for reducing the incidence of or treating CGRP-associated disorders, such as headaches and migraines, by administering an effective amount of a human or humanized monoclonal anti-CGRP antagonist antibody.

3. Grounds for Unpatentability

Ground 1: Claims 1, 3-4, 8-17, 19-20, and 24-31 are obvious over Olesen, Tan, and Queen.

  • Prior Art Relied Upon: Olesen (a 2004 clinical trial publication), Tan (a 1995 in vivo antibody study), and Queen (Patent 6,180,370).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the prior art collectively disclosed all elements of the challenged claims. Olesen provided clinical proof-of-concept that blocking the Calcitonin Gene-Related Peptide (CGRP) pathway with a CGRP antagonist effectively treats migraine in humans. Tan disclosed murine anti-CGRP antagonist antibodies that demonstrated in vivo efficacy in blocking CGRP activity in a rat model relevant to migraine (vasodilation). Queen taught the "gold standard" methods for humanizing non-human (e.g., murine) antibodies to make them suitable for therapeutic use in humans by reducing immunogenicity while retaining antigen-binding affinity. Petitioner contended that a person of ordinary skill in the art (POSITA) would have found it obvious to apply the routine humanization techniques of Queen to an anti-CGRP antibody like that described in Tan for the clinically validated purpose taught by Olesen—treating migraine.
    • Motivation to Combine: Petitioner asserted that Olesen's successful clinical trial provided a strong motivation to develop CGRP antagonists for treating migraine. A POSITA would have recognized anti-CGRP antibodies, as disclosed by Tan, as a known alternative to the small-molecule antagonist used in Olesen, offering potential advantages such as longer half-life and greater specificity, which are desirable for treating a chronic condition like migraine. Since Tan's antibodies were murine, a POSITA would have been further motivated to humanize them using the well-established methods of Queen to avoid immunogenic responses in human patients requiring repeated administration. The prior art explicitly suggested exploring humanized monoclonal antibodies for diseases linked to CGRP.
    • Expectation of Success: Petitioner argued a POSITA would have had a high expectation of success. Olesen clinically validated the CGRP pathway as a therapeutic target. Tan demonstrated that anti-CGRP antibodies were effective in vivo in a relevant animal model. By 2005, the antibody humanization techniques taught by Queen were considered a "clinically well-validated technology" routinely used to create therapeutic antibodies that successfully retained their biological function. The ’045 patent’s own specification admitted that methods for making and humanizing antibodies were "known" and "conventional," reinforcing the predictability of the outcome.

4. Key Claim Construction Positions

  • "reducing incidence of or treating": Petitioner argued this phrase does not require achieving an actual clinical response. Based on the patent’s express definitions, "treatment" is defined as "an approach for obtaining a beneficial or desired clinical result," meaning the claim is directed to the attempt, not the successful outcome. This construction broadens the scope of the claims and lowers the burden for proving obviousness.
  • "effective amount": Petitioner argued this term also does not require a clinical response and, based on the doctrine of claim differentiation from dependent claims 16 and 31 (which recite a dose of "at least about 3 µg/kg"), must encompass doses lower than 3 µg/kg. Petitioner asserted that such low doses would not be expected to generate a clinical response anyway, further supporting that the claim is directed to an approach rather than a guaranteed result.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under §325(d) would be inappropriate because the core prior art references central to its petition—Olesen and Queen—were never submitted to or considered by the USPTO examiner during the original prosecution of the ’045 patent. As the examiner did not have the opportunity to evaluate the patentability of the claims in light of this specific and highly material combination of prior art, Petitioner asserted that the arguments raised in the petition were new and substantial.

6. Relief Requested

  • Petitioner requests institution of an inter partes review (IPR) and cancellation of claims 1, 3-4, 8-17, 19-20, and 24-31 of the ’045 patent as unpatentable.