Eli Lilly Co v. Teva Pharmaceuticals Intl GmbH

1. Case Identification

• Case #: IPR2018-01711
• Patent #: 9,884,907
• Filed: October 1, 2018
• Petitioner(s): Eli Lilly and Company
• Patent Owner(s): Teva Pharmaceuticals International GMBH
• Challenged Claims: 1-18

2. Patent Overview

• Title: Methods for Treating Headache Using Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide
• Brief Description: The ’907 patent claims methods for treating headache, including migraine, by administering an effective amount of a humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist antibody. The claims recite general structural features of a human IgG antibody that specifically binds to human CGRP.

3. Grounds for Unpatentability

Ground 1: Claims 1-18 are obvious over Olesen, Tan, and Queen under 35 U.S.C. §103.

• Prior Art Relied Upon: Olesen (a 2004 clinical trial publication in New Engl. J. Med.), Tan (a 1995 in vivo study publication in Clin. Sci.), 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 all limitations of the challenged claims. Olesen established that blocking the CGRP pathway was a clinically proven method for treating migraine in humans. Tan disclosed a specific tool for blocking this pathway: a murine monoclonal IgG antibody (MAb C4.19) that acted as an anti-CGRP antagonist and demonstrated in vivo efficacy. Queen taught the "gold standard" methods for converting a non-human (e.g., murine) antibody into a humanized version suitable for therapeutic use in humans, which would possess the generic IgG structure (heavy/light chains, CDRs, FRs, Fc region) recited in claim 1.
  • Motivation to Combine: Petitioner contended a person of ordinary skill in the art (POSITA), motivated by Olesen's clinical success, would seek an effective CGRP antagonist to treat migraine. A POSITA would find Tan's disclosure of an anti-CGRP antagonist antibody to be an obvious and promising candidate. Because Tan's antibody was murine, and migraine is a chronic condition often requiring repeated administration, a POSITA would have been further motivated to reduce the antibody's immunogenicity for human use. Queen provided the well-known and routine solution of humanizing the antibody by grafting its CDRs onto a human IgG scaffold.
  • Expectation of Success: Petitioner asserted a strong expectation of success. Olesen's clinical proof-of-concept demonstrated that blocking the CGRP pathway was a viable therapeutic strategy. Tan’s in vivo data confirmed that anti-CGRP antibodies were effective at blocking CGRP activity. Finally, by 2005, the humanization techniques taught by Queen were considered a well-validated and routine technology known to preserve the binding affinity and specificity of the original donor antibody, providing a high probability of creating a functional therapeutic.

4. Key Claim Construction Positions

• "treating": Petitioner proposed this term should be construed as "an approach for obtaining a beneficial or desired clinical result," consistent with the patent's express definition. This construction does not require the achievement of a specific clinical response, thereby broadening the claim scope.
• "effective amount": Petitioner argued this term does not require a clinical response and must encompass doses lower than 3 µg/kg. This construction was based on the doctrine of claim differentiation, as dependent claim 7 recites a specific dose of "at least 3 µg/kg," meaning the broader term in independent claim 1 must cover a different, lower range.
• "specific binding": Petitioner contended this term, as used in the patent, does not require exclusive binding to a single CGRP isoform and does not preclude binding to other peptides, such as amylin.

5. Key Technical Contentions (Beyond Claim Construction)

• Petitioner dedicated significant argument to refuting a potential "teaching away" argument regarding the Tan reference, which Patent Owner had asserted during prosecution of a related application. Petitioner argued that Tan does not teach away from using full-length antibodies for CGRP blockade. While Tan's data showed a Fab' fragment outperformed the full-length antibody under the specific, short-term experimental conditions used, Tan explicitly explained this result was expected due to slower distribution of the larger molecule and provided express guidance for improving the in vivo efficacy of the full-length antibody, such as by increasing the dose or using repeated administration. Petitioner argued this constituted a teaching toward the use and optimization of full-length antibodies, not away from them.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate because the evidence submitted was not previously considered by the USPTO. While the Olesen, Tan, and Queen references were listed in an Information Disclosure Statement (IDS) during prosecution, that IDS contained over 450 references. Petitioner asserted the Examiner did not, and could not have been expected to, fully appreciate the significance of this specific combination of references from such a voluminous list. Therefore, the core obviousness argument presented in the petition was not substantively evaluated during examination.

7. Relief Requested

• Petitioner requested the institution of an inter partes review (IPR) and the cancellation of claims 1-18 of the ’907 patent as unpatentable.