Eli Lilly Co v. Teva Pharmaceuticals Intl GmbH

1. Case Identification

• Case #: IPR2018-01426
• Patent #: 9,890,211
• Filed: August 8, 2018
• Petitioner(s): Eli Lilly and Company
• Patent Owner(s): Teva Pharmaceuticals International GMBH
• Challenged Claims: 1-15

2. Patent Overview

• Title: Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide
• Brief Description: The ’211 patent relates to humanized monoclonal antagonist antibodies that bind to Calcitonin Gene-Related Peptide (CGRP). The patent discloses the use of these antibodies for the prevention and treatment of CGRP-related conditions, such as migraines and other vasomotor symptoms.

3. Grounds for Unpatentability

Ground 1: Obviousness over Tan, Wimalawansa, and Queen - Claims 1-15 are obvious over Tan 1995 in view of Wimalawansa and Queen.

• Prior Art Relied Upon: Tan 1995 (a 1995 journal article), Wimalawansa (a 1996 review article), and Queen (Patent 6,180,370).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the claimed invention represents a predictable combination of known elements. Tan 1995 disclosed a murine monoclonal anti-CGRP antagonist antibody (MAb C4.19) that binds both human and rat CGRP with high affinity (e.g., 1.9 nM), demonstrating in vivo efficacy. This provided a suitable starting antibody. Wimalawansa, a comprehensive review article, expressly proposed evaluating "humanized anti-CGRP monoclonal antibodies" as therapeutic agents for CGRP-related diseases like migraine. This supplied the explicit reason to modify Tan's antibody. Queen described the "gold standard" methods for humanizing non-human antibodies by grafting their complementarity-determining regions (CDRs) onto a human IgG scaffold, a process known to preserve or improve the donor antibody's binding affinity to levels well within the claimed range (<10 nM). Petitioner asserted that the measurement of binding affinity via surface plasmon resonance (SPR) at 37° C was a routine, standard technique by 2005 for antibodies intended for human therapeutic use.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) would combine these references to create a safer, more effective therapeutic for known CGRP-mediated conditions. The demonstrated in vivo efficacy of the murine antibody in Tan provided a strong incentive to develop it for human use. The known problem of immunogenicity with murine antibodies in humans would have motivated a POSA to apply the well-established humanization techniques taught by Queen. Wimalawansa confirmed this motivation by specifically identifying humanized anti-CGRP antibodies as a promising therapeutic avenue that "should be explored" for treating conditions like migraine. The combination was thus a straightforward pursuit of a known therapeutic goal using standard tools.
  • Expectation of Success: A POSA would have had a reasonable expectation of successfully producing the claimed antibody. The generation of murine anti-CGRP antibodies was a known and conventional technique, as shown by Tan. Furthermore, the humanization methods described in Queen were routine by 2005 and were known to predictably maintain the specificity and affinity of the original murine antibody. Queen explicitly teaches that its humanized antibodies could achieve binding affinities of 10 nM to 0.1 nM or less. Given that humanization was a "clinically well-validated technology," a POSA would reasonably expect that applying Queen's methods to an antibody like Tan's would result in a humanized anti-CGRP antibody with the claimed structural and functional properties.

4. Key Claim Construction Positions

• "specific binding": Petitioner argued that, consistent with the patent's own definition, this term should be construed broadly. The specification states that an antibody that "specifically or preferentially binds to a first target may or may not specifically or preferentially bind to a second target." Petitioner contended this means the claims do not require exclusive binding to CGRP. This construction is important because the prior art antibody from Tan (MAb C4.19) was shown to bind both α and β forms of CGRP and was not precluded from binding other peptides, aligning it with the claim language under this interpretation.

5. Key Technical Contentions (Beyond Claim Construction)

• Secondary Considerations of Non-obviousness are Lacking: Petitioner preemptively argued against any potential secondary considerations arguments from the Patent Owner.
  • Lack of Nexus: Petitioner asserted that the challenged claims are directed broadly to a genus of humanized anti-CGRP antibodies, yet the ’211 patent's specification only discloses a single specific antibody (G1) and its close derivatives. Petitioner argued this narrow disclosure is insufficient to establish the required nexus between the full scope of the claimed genus and any alleged unexpected results.
  • Near-Simultaneous Invention: Petitioner provided evidence that it (Eli Lilly) and researchers at Stanford University independently and nearly simultaneously developed humanized anti-CGRP antagonist antibodies for treating migraines around the same time as the ’211 patent's priority date. This near-simultaneous development by multiple independent entities was presented as strong objective evidence that the claimed invention was merely the product of ordinary skill in the art at the time.

6. Arguments Regarding Discretionary Denial

• Denial under §325(d) is Inappropriate: Petitioner argued that discretionary denial would be improper because the core prior art and arguments were not previously considered by the USPTO. While the Tan, Wimalawansa, and Queen references were listed in an Information Disclosure Statement (IDS) during prosecution, they were part of a submission containing over 450 references. Petitioner contended the Examiner did not cite or substantively analyze this specific combination in any Office Action, and therefore did not have the opportunity to appreciate its significance, which is further illuminated by the expert declarations submitted with the petition.

7. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-15 of the ’211 patent as unpatentable.