Eli Lilly and Company v. Teva Pharmaceuticals International 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 relates to methods for treating headaches, including migraine, by administering a humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist antibody. The claims broadly cover humanized IgG antibodies that specifically bind to human CGRP.

3. Grounds for Unpatentability

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

• Prior Art Relied Upon: Olesen (J. et al., New Engl. J. Med. 350:1104-1110 (2004)), Tan (K.K.C. et al., Clin. Sci. 89:565-573 (1995)), and Queen (Patent 6,180,370).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the combination of Olesen, Tan, and Queen rendered all challenged claims obvious. Olesen’s clinical trial established clinical proof-of-concept that blocking the CGRP pathway with an antagonist effectively treats migraine in humans. Tan disclosed using a murine monoclonal anti-CGRP IgG antibody (MAb C4.19) to block CGRP activity in vivo and confirmed its effectiveness in a rat saphenous nerve model relevant to migraine. Queen taught the "gold standard" and routine methods for humanizing murine antibodies by grafting their complementarity-determining regions (CDRs) onto a human IgG framework to reduce immunogenicity for therapeutic use in humans, while retaining the original binding affinity. Independent claim 1’s limitations—reciting a humanized monoclonal IgG antibody with standard heavy and light chain structures (CDRs, framework regions, Fc region) that binds to CGRP—were argued to be a predictable result of applying Queen's routine humanization techniques to an antibody like Tan's for the purpose established by Olesen.
  • Motivation to Combine (for §103 grounds): A POSITA, aware of Olesen’s clinical validation of the CGRP pathway as a therapeutic target for migraine, would be motivated to find effective CGRP antagonists. Tan provided a known alternative to small-molecule receptor antagonists: using an anti-CGRP antibody for immunoblockade. To make Tan's murine antibody suitable for human use, particularly for a chronic condition like migraine requiring repeat administration, a POSITA would have been motivated to use the well-established humanization methods taught by Queen to minimize immunogenicity.
  • Expectation of Success (for §103 grounds): A POSA would have had a reasonable expectation of success because each step was based on well-validated technology. Olesen provided clinical evidence that the therapeutic strategy worked, Tan showed that anti-CGRP antibodies were biologically active in vivo, and Queen provided a routine, predictable process for humanizing antibodies that was known to preserve binding affinity.
  • Key Aspects: Petitioner contended that the combination represents a classic case of combining known elements for their predictable results: applying a routine optimization technique (humanization via Queen) to a known biological tool (anti-CGRP antibody from Tan) to address a clinically validated target (CGRP pathway for migraine from Olesen).

4. Key Claim Construction Positions

• "treating": Petitioner argued this term should be construed as "an approach for obtaining a beneficial or desired clinical result," without requiring the actual achievement of a clinical response. This construction is based on the patent's own definition and is critical because the patent lacks human clinical data.
• "effective amount": Petitioner asserted this term does not require a clinical response and must encompass doses lower than 3 µg/kg. This argument relies on the doctrine of claim differentiation, as dependent claim 7 explicitly recites a dose of "at least 3 µg/kg," meaning the broader term in independent claim 1 must cover a different, wider range.
• "specific binding": Petitioner contended this term is broad, allowing for binding to multiple CGRP isoforms (e.g., α and β) and not precluding binding to other peptides. This construction is based on language in the specification and broadens the scope of the prior art that meets the limitation.

5. Key Technical Contentions (Beyond Claim Construction)

• Tan Does Not Teach Away: The petition preemptively rebutted an argument that the Patent Owner made during prosecution, asserting that Tan teaches away from using full-length antibodies. Petitioner argued that while Tan showed a Fab' fragment was more effective than a full-length antibody in one specific in vivo model with a short timeframe, Tan did not discredit the full-length antibody. Instead, Tan explained the result was consistent with known antibody pharmacokinetics (larger molecules take longer to distribute) and expressly recommended strategies to improve efficacy, such as increasing the dose and using repeated administration—guidance the ’907 patent itself allegedly followed.

6. Arguments Regarding Discretionary Denial

• Prior Art Not Previously Considered: Petitioner argued that discretionary denial under §325(d) would be inappropriate because the core prior art references—Olesen, Tan, and Queen—were not substantively considered by the Examiner during prosecution. Although the references were listed in an Information Disclosure Statement containing over 450 references, they were never cited in an Office Action or used as the basis for a rejection.

7. Relief Requested

• Petitioner requested the Board institute an inter partes review and find all challenged claims (1-18) of the ’907 patent unpatentable.