U.S. Pat. No. 8,889,135B2
May 17, 2017
Final Written Decision (IPR granted May 17, 2016)
Update: See summary of May 16, 2017 FWD finding claims 1-5 unpatenable. See also July 6, 2017 FWD in IPR2016-00408 and IPR2016-00409 (both requested by Boehringer Ingelheim) finding claims 1-5 of the ‘135 patent unpatentable (408: obvious over van de Putte 2000 and Rau 2000; 409: obvious over Kempeni and van de Putte; Rau, Shattendkirchner and van de Putte). Also note IPR2016-00188 found claims 1-4 of US 9,017,680 obvious over van de Putte and Kempeni (June 9, 2017 FWD); and IPR2016-00189 found claims 1 and 2 US 9,073,987 obvious over Kempeni and van de Putte (June 9, 2017 FWD).
Brief Summary: Final Written Decision after IPR finds claims 1-5 of Abbvie’s US 8,889,135B2 relating to Humira® unpatentable for obviousness.
Summary: Coherus requested IPR of claims 1-5 of Abbvie’s US 8,889,135B2 relating to methods for treating rheumatoid arthritis (RA) using a human anti-TNF[alpha] antibody having particular complementarity determining regions (CDRs) and the “heavy chain constant region of D2E7, a known recombinant human anti-TNF[alpha] antibody” (encompassing Humira® (adalimumab)). The claims require “administering subcutaneously…a total body does of 40 mg…once every 13-15 days for time period sufficient to treat” RA. The Petition alleged unpatentability for obviousness (§ 103) in view of the Kempeni (cited as anticipatory and for obviousness by the examiner during prosecution) and van de Putte (cited by the applicant during prosecution and by the examiner for anticipation and obviousness) references, and included 16 background technology references as well as three expert declarations (Drs. Baughman, O’Dell and Reisetter). As noted previously in the summary of the decision to institute IPR, but not in either decision, Kempeni and van de Putte were cited in combination in an obviousness rejection during prosecution, but only with several other references. The Board first determined the level of ordinary skill in the art as one possessing “the skill sets of both a physician treating RA patients and a pharmacokineticist with experience in monoclonal antibodies”. Under the broadest reasonable construction standard (BRC), the Board confirmed its determination in the Institution Decision that the preamble phrase “A method for treating” RA is not limiting. In its Institution Decision, the Board determined “for a time period sufficient to treat” RA as that which “reduce[s] the signs, symptoms, and/or progression of RA” (not meaning “significantly”). AbbVie argued this phrase would be “understood…to require meaningful therapeutic efficacy” but the Board disagreed because, e.g., “the specification uses the word ‘treat’ in its customary and ordinary way.” It did not address “every 13-15 days” or “pharmaceutically acceptable composition” as requested by Coherus.
As in the Institution Decision, Kempeni was found to teach a fully human anti-TNF[alpha] antibody (D2E7) used in RA clinical trials, finding it to be “safe and effective as monotherapy”. And van de Putte was found to “compare three dose levels of D2E7 to placebo over three months in patients with long-standing active RA”, showing it to be “statistically significantly superior to placebo”. The Board concluded that these references “collectively disclose each limitation of the challenged claims”. It also noted that “[e]ven ‘[i]f all elements of the claims are found in a combination of prior art references,’ ‘the factfinder should consider whether a person of ordinary skill in the art would [have been] motivated to combine those references, and whether in making that combination…would have [had] a reasonabl expectation of success” (Merck, FC 2015; Pfizer, FC 2007). The Board agreed with Coherus that “the ordinary skilled artisan would have had a reason to select subcutaneous, including that van de Putte used subcutaneous dosing and Kempeni referred to it as a “promising approach”, but also that it would have been “more convenient and less expensive”. The Board found Coherus did not show “a reason to modify van de Putte’s 20 mg weekly dose to a 40 mg biweekly dose” (this argument “appear[ing] to be a shift from the position taken in the Petition” (Wasica Fin., FC 2017 (“[s]uch a shift in position…‘is forclosed’”)) and AbbVie persuasively argued half-life is not the sole determining factor in dose modeling. The Board also concluded Kempeni did not teach away “from the fixed dosing regimen of the claims” or “administering low doses” (In re Gurley, FC 2004; In re Mouttet, FC 2012 (“mere disclosure of alternative designs…does not teach away”)), “the difference in bioavailability between an intravenous and subcutaneous dose would have counseled against a subcutaneous 40 mg dose of D2E7 biweekly”, “[n]othing in the record…suggests that D2E7 has a narrow therapeutic range”, and that disease elimination or “reduc[ing] it to the fullest extent possible” would not have been “the goal of a skilled artisan in June 2001”. Regarding secondary considerations, the Board agreed Humira® is commercially successful but did not find a nexus between that success and the claims (In re Huai-Hung Kao, FC 2011), was not persuaded “the claimed dosing regimen satisfied a long-felt, but unmet need”, and did not find sufficient evidence…the efficacy…would have been unexpected.” Thus, the claims 1-5 were concluded to be unpatentable.