Docket No. 2017-2596 (IPR2016-01665)
LOURIE, CHEN, STOLL
January 11, 2019
Brief summary: Board decision finding UCB’s ‘650 patent relating to Pfizer’s Toviaz product was not shown invalid for obviousness affirmed. UCB’s motion to dismiss for lack of standing since Amerigen’s ANDA was filed under Paragraph III denied since this dispute arose from an IPR and not Hatch-Waxman.
Summary: Amerigen (which with Alembic joined Mylan’s original Petition after institution) appealed Board IPR final written decision (FWD) holding that claims 1-5 and 21-24 of UCB’s US 6,858,650 relating to Pfizer’s antimusarinic fesoterodine (Toviaz (fesoterodine fumarate)) not to be unpatentable on two different obviousness grounds (Detrol Label, Postlind, Bundgaard, Bundgaard PCT, and Berge; or Brynne, Bundgaard, Bundgaard PCT, and Johansson). The FC panel opinion explains that “[f]esoterodine is a prodrug of the active compound 5-hydroxymethyl tolterodine (‘5-HMT’)” which is “a metabolite of the compound tolterodine, an older antimusarinic drug sold under the trade name Detrol to treat overactive bladder.” “Fesoterodine”, the FC panel opinion explains, “differs from 5-HMT at the 2-position” (an isobutyl ester and a hydroxy group, respectively), and the question here was whether it would have been obvious to modify the 2-position. Claim 1 of the ‘650 patent “encompasses a genus of esters including ‘C1-C6 alkyl, C3-C10-cycloalkyl, [and] substituted or unsubstituted phenyl’” (see FN1). The Detrol Label, Postlind, and Brynne references relate to tolterodine and its metabolites, Bundgaard and Bundgaard PCT references relate to prodrug design principles, and Berge and Johansson relate to fumarate salts. The Board agreed that 5-HMT would have been selected “as a lead compound…in order to reduce the number of potential metabolic steps and to avoid CYP2D6-related drug-drug interactions” but, based on expert testimony, found no motivation to replace “the 2-position hydroxy group with an alkyl ester of six or fewer carbons” as in the ‘650 claims (e.g., the Board “credited Dr. Roush and determined that a person of ordinary skill would not have been motivated to modify 5-HMT because of bioavailability concerns…would not have made a 5-HMT prodrug to solve a bioavailability problem that did not exist”) and “that the prior art did not suggest modifying 5-HMT to make the specific claimed compounds.” The FC panel agreed with the Board’s conclusion that obviousness was not shown by a preponderance of the evidence (e.g., “Amerigen’s conclusory argument is not sufficient to overcome the substantial evidence to the contrary” and it “does not explain why a skilled artisan would modify a drug to increase its lipophilicity independent of bioavailability…it would not have been routine to make the claimed molecular modifications”.) The Board also rejected Amerigen’s argument “that a skilled artisan would have been motivated to modify 5-HMT because 5-HMT was patented” but the FC panel found that such “[a] general motivation” is insufficient (Takeda, FC 2007, citing In re Deuel, FC 1995).
UCB’s motion to dismiss for lack of standing was previously denied, appealed here, and again denied. The FC panel found that Amerigen, which filed under paragraph III (i.e., FDA approval withheld under expiration of the ‘650 patent in 2022), “has standing…because the launch of its tentatively approved drug is blocked by the ‘650 patent” and the NDA holder must notify the FDA “if the ‘650 patent is held unpatentable trough reversal of the Board’s decision, meaning that Amerigen’s ANDA could be finally approved by the FDA (also, the other Orange Book-listed patents expire in 2019) (Medimmune, US 2007; E.I. DuPont, FC 2018). UCB argued that only a paragraph IV filer has standing under Hatch-Waxman (Daiichi, FC 2015 (“listing a patent in the Orange Book may create a cognizable injury independent of the prospect of infringement liability; Jannsen, FC 2008), but the FC panel explained that “this case does not arise under” Hatch-Waxman and Amerigen has Article III standing with respect to the IPR decision “even though it may be incapable (as a Paragraph III filer) of maintaining a parallel Hatch-Waxman suit.”