The Patent Trial and Appeal Board (“PTAB”) recently denied Sandoz’s petition for inter partes review (“IPR”) of claims 1-30 of AbbVie’s patent, U.S. Patent No. 9,187,559 (“the ’559 patent”). The ’559 patent is directed towards a multiple-variable dose regimen for treating idiopathic inflammatory bowel disease. The patent discloses administering a high dose of a TNFα inhibitor in an induction phase and following up with a second administration of the inhibitor during a maintenance or treatment phase. Claim 1 specifically recites administering a first dose of 160 mg of adalimumab and two weeks after administration of the first dose, administering a second dose of 80mg of adalimumab. In its petition, Sandoz asserted that the ’559 patent claims were unpatentable under 35 U.S.C. §103(A) over the combination of a 2003 Humira Package Insert, WO 02/100330 A2 (“WO ’330”), Goodman & Gilman’s The Pharmaceutical Basis of Therapeutics, a 2002 Remicade Package Insert, and Hanauer’s Evolving Treatment Strategies for Inflammatory Bowel Disease. The PTAB denied institution, concluding that Sandoz failed to demonstrate that the 160mg/80mg dosing regimen of the ’559 patent claims would have been obvious. See Sandoz Inc. v. AbbVie Biotechnology LTD., IPR2018-00156 (PTAB June 5, 2018) (Paper 11).

Sandoz argued that the asserted prior art references disclosed all of the elements of the claims except the 160mg/80mg induction dosing regimen. Id. at 17. However, Sandoz argued that the dosing regimen would have been obvious because WO ’330 disclosed using higher doses of adalimumab, such as 80 mg every other week, to treat TNFα related disorders. Id. at 18. Sandoz argued that a person of ordinary skill in the art (“POSITA”) would have expected an 80 mg every other week dosing regimen to serve as good baseline for determining an induction or loading dose. Id. at 18. Sandoz also argued that a POSITA would have modified the 80mg every other week induction dose to arrive at the claimed 160mg/80mg dosing scheme based on several teachings in the prior art. Id. at 18. For example, Sandoz argued that the prior art taught that an “80 mg dose administered 2 weeks after the 160 mg dose would maintain heightened blood levels for 4 weeks, at which time the 40 mg every other week maintenance dosing would begin.” Id. at 18-19 (citing Petition at 22-23).

The PTAB held that Sandoz failed to show, without the use of hindsight, that a POSITA would have been motivated to use 160 mg as an induction dose or to select an intermediate dose to serve as a base for determining an induction dose. The PTAB agreed with Sandoz that the prior art disclosed that an induction/loading dose “is twice the size of the maintenance dose, if the maintenance dosing interval corresponds to the biological half-life of the drug.” Id. at 19. However, the PTAB concluded that “[a]pplying the general rules for determining an appropriate loading dose…results in an adalimumab loading dose of 80mg (i.e. a doubling of the 40 mg dose that Petitioner identifies as the maintenance dose), not a dose of 160 mg as recited in the claims.” Id. at 20. The PTAB stated that the prior art does not show how a POSITA would thus have arrived at the recited dosing regimen.

The PTAB also rejected Sandoz’s argument that the prior art discloses using a baseline dose to select an induction dose for a dosing regimen. The PTAB stated that instead, an induction dose is determined based on the maintenance dose. Thus, the PTAB denied institution of Sandoz’s petition, finding that the claims of the ’559 patent were not obvious over the cited prior art.

This is not the first time the PTAB has denied Sandoz’s petitions for IPR of AbbVie’s patents relating to the treatment of diseases using adalimumab. As discussed in a previous blog post, the PTAB recently denied Sandoz’s petition for IPR of AbbVie’s patent, U.S. Patent No. 9,512,216, directed towards a method of treating moderate to severe chronic plaque psoriasis using adalimumab.