PTAB

IPR2016-00188

Coherus Biosciences Inc v. AbbVie Biotechnology Ltd

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Key Events
Petition

1. Case Identification

2. Patent Overview

  • Title: METHODS OF ADMINISTERING ANTI-TNFα ANTIBODIES
  • Brief Description: The ’680 patent claims methods for treating moderately to severely active rheumatoid arthritis (RA) by subcutaneously administering a 40 mg dose of a specific human anti-TNFα antibody, D2E7 (adalimumab), every 13-15 days in combination with methotrexate.

3. Grounds for Unpatentability

Ground 1: Obviousness over van de Putte and Kempeni - Claims 1-4 are obvious over van de Putte 1999 in view of Kempeni.

  • Prior Art Relied Upon: van de Putte (a 1999 clinical trial abstract, EX. 1004) and Kempeni (a 1999 review article, EX. 1003).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of van de Putte and Kempeni taught all elements of the challenged claims. Independent claim 1 requires a method of treating RA by administering 40 mg of the D2E7 antibody subcutaneously every 13-15 days in combination with methotrexate. Petitioner asserted that van de Putte 1999 disclosed treating RA with subcutaneous injections of 20, 40, and 80 mg weekly doses of D2E7, concluding that all doses were "statistically significantly superior to placebo" and "nearly equally efficacious." This established the core elements of the specific antibody (D2E7), the 40 mg dose, the subcutaneous route of administration, and its efficacy for RA.
    • Petitioner argued Kempeni supplied the remaining claim elements. Kempeni, a review article summarizing early D2E7 trials, explicitly disclosed that D2E7 was "safe and effective as monotherapy or in combination with methotrexate." Furthermore, Kempeni taught that the terminal half-life of D2E7 was 11.6 to 13.7 days, which strongly suggests a biweekly (every 14 days) dosing interval. Kempeni also reported on other clinical trials where D2E7 was successfully administered on a biweekly basis, establishing the claimed "every 13-15 days" frequency as known and effective in the art. Dependent claims 2-4 add limitations related to specific antibody sequences and the use of a "dosage unit form," which Petitioner contended were inherent properties of the D2E7 antibody and administration methods already described in the prior art.
    • Motivation to Combine: Petitioner argued a person of ordinary skill in the art (POSITA) would have been motivated to modify the weekly dosing regimen in van de Putte to a biweekly one based on the pharmacokinetic data in Kempeni. Kempeni’s disclosure of an 11.6 to 13.7-day half-life for D2E7 would have directly suggested to a POSITA that a less frequent dosing interval, such as biweekly, was not only possible but pharmacologically logical. Such a modification represented a routine optimization to improve patient convenience and compliance, a well-known goal in drug development. The motivation to combine D2E7 with methotrexate was explicitly provided by Kempeni, which reported that D2E7 was safe and effective when used in combination with methotrexate and noted that such combination therapies were already standard for other anti-TNFα antibodies. Kempeni expressly stated that "additional studies are underway to further define optimal use," directly inviting the type of routine optimization claimed in the ’680 patent.
    • Expectation of Success: Petitioner asserted a POSITA would have had a strong and reasonable expectation of success. Van de Putte had already demonstrated that a 40 mg weekly subcutaneous dose was safe and effective for treating RA. Given Kempeni's disclosure that D2E7's half-life was approximately 14 days, a POSITA would reasonably expect that a 40 mg dose administered every 14 days would maintain sufficient therapeutic concentrations to be effective. This was not a case of unpredictable trial and error, but a logical adjustment based on known pharmacokinetic principles. The expectation of success for the combination with methotrexate was also high, as Kempeni explicitly reported successful trials using this combination and it was a common practice for similar drugs. Therefore, combining these known, effective elements was highly predictable.

4. Key Claim Construction Positions

  • "Method of reducing signs and symptoms": Petitioner proposed that this phrase, found in the preamble of all challenged claims, should be interpreted under its plain meaning and does not require any particular level of efficacy (e.g., a level required for regulatory approval). It merely requires that a patient's signs and symptoms are reduced relative to their pre-treatment state. This construction is important because the prior art demonstrated a statistically significant, but not necessarily superior, reduction in symptoms, which Petitioner argued was sufficient to meet the claim limitation.
  • "Every 13-15 days": Petitioner argued that under the broadest reasonable interpretation, this phrase would encompass a biweekly (i.e., every 14 days) dosing regimen. This was critical for connecting the claims to prior art in Kempeni that disclosed biweekly dosing trials and a half-life that supported a 14-day interval.
  • "Dosage unit form": Recited in claim 3, Petitioner asserted this term, as defined in the patent's specification, would encompass a standard delivery device like a syringe pre-filled with 40 mg of D2E7.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-4 of the ’680 patent as unpatentable under 35 U.S.C. §103.