PTAB Invalidates Patent for Blockbuster Drug HUMIRA®

| David Schmidt, Ph.D.Kerry S. Taylor, Ph.D.

The PTAB issued a Final Written Decision in Coherus BioSciences Inc. v. AbbVie Biotechnology Ltd., IPR2016-00172 (P.T.A.B. May 16, 2017) finding claims 1-5 of U.S. Patent No. 8,889,135 (“the ‘135 patent”) unpatentable.

Biosimilars petitioner Coherus filed an IPR petition against claims 1-5 of AbbVie’s ’135 patent, one of many patents owned by AbbVie purportedly covering AbbVie’s blockbuster autoimmune disease drug HUMIRA®, the world’s top-selling pharmaceutical. The PTAB instituted the IPR proceeding on all five claims.

Both independent claims include the language “for a time period sufficient to treat rheumatoid arthritis…” In its final written decision, the PTAB determined that under the broadest reasonable interpretation, the phrase means “for a time sufficient to reduce the signs, symptoms, and/or progression of rheumatoid arthritis.” Relying on this construction, the PTAB held that all claims were obvious over two published journal articles, “van de Putte” and “Kempeni.”

van de Putte describes the results of a dose-finding phase II study that compared the inflammatory response to an antibody termed D2E7, the human anti-TNFα monoclonal antibody used in AbbVie’s HUMIRA® product, at three subcutaneous doses:  20 mg/week, 40 mg/week, and 80 mg/week. Coherus argued that one of ordinary skill would extend van de Putte’s dosing regimen to two weeks, simply based upon optimization of drug efficacy using half-lives. Coherus also argued in the alternative that that one of skill would be motivated to modify van de Putte’s dosing regimen to the biweekly regime of Kempeni, because Kempeni demonstrated that biweekly dosing is safe and effective. Kempeni describes the results of several clinical studies investigating the use of D2E7. Kempeni intravenously dosed patients once every two weeks (“biweekly”) with 0.5-1 mg/kg D2E7 and evaluated the therapeutic response using standard testing criteria associated with rheumatid arthritis.

AbbVie did not dispute that the prior art discloses each element of the claims. Instead, according to the Board, AbbVie “‘hotly contest[ed]’ whether the ordinary skilled artisan would have had a reason to select the claimed dosing regimen, and also contest[ed] whether one of ordinary skill would have expected success in treating rheumatoid arthritis using that regimen.” AbbVie made several arguments related to both the available data and the prior art teaching away from the combination of van de Putte and Kempeni, including that the prior art as a whole teaches away from administering low doses. AbbVie further argued multiple secondary indicia of nonobviousness, including the commercial success of HUMIRA®, long-felt need, and unexpected results.

The PTAB disagreed with Coherus’ argument of optimization of van de Putte’s dosing regimen, noting that Coherus failed to show evidence of skilled artisans routinely using half-lives to develop a dosing schedule. The PTAB did agree, however, with Coherus’ alternative argument that one of skill would be motivated to modify van de Putte’s dosing regimen to the biweekly regime of Kempeni, because Kempeni demonstrated that biweekly dosing is safe and effective. Further, the PTAB was not swayed by AbbVie’s various assertions of “teaching away,” noting that the disclosure of alternatives does not teach away from the claims. The PTAB was also not swayed by AbbVie’s indicia of nonobviousness, holding that the evidence did not establish that the commercial success of HUMIRA® was due to the merits of the claimed invention.

It will be interesting to monitor any appeal of this case to the Federal Circuit.  In the meantime, this successful petition by a biosimilars company provides a roadmap for invalidating a biotechnology patent through the use of published journal articles.