Hoffman-La Roche Inc. and Genentech, Inc. v. Apotex Inc. et al.

Docket No. 2013-1128

April 11, 2014

Brief Summary: DC decision of invalidity for obviousness affirmed because prior art rendered claims “[a]t the very least…obvious to try.” Judge Newman’s dissent argued decision is wrong because, in part, it was not “obvious to do what no one did or even suggested”.

Summary: Hoffman-La Roche (Roche) appealed DC grant to Apotex et al. (Apotex) SJ of invalidity of US 7,718,634 and 7,410,957 (parent of ‘634) relating to methods for once monthly 150 mg dose of ibandronate (a bisphosphonate) for treatment of osteoporosis (Boniva®) as obvious. Difficult administration regimens associated with bisphosphonates were known to result in patient compliance problems that the once monthly dosing was designed to overcome. In a previous appeal (Hoffman-La Roch, FC 2012), the FC affirmed the DC’s denial of a preliminary injunction against Apotex because Roche had failed to prove it was likely to succeed. While that appeal was pending, the DC granted Apotex’s request for SJ of invalidity, finding “once monthly oral dosing of ibandronate was established in the prior art” that also “suggested a dosage level of about 150 mg per month, or at least indicated that a montly dose of 150 mg was obvious to try” (finding “Roche’s objective considerations evidence does not rise to the level of a mere scintilla” and “no evidence…that the skill artisan would have been surprised 150 mg once-monthly dose was superior to 2.5 mg daily dose”). The FC panel first reviewed the prior art and agreed with the DC that at least one of the references “along with other prior art that used BMD [bone mineral density] improvement as the primary efficacy marker for treating osteoporosis-established at least a reasonable expectation that once monthly dosing of ibandronate could successfully treat osteoporosis and reduce fracture risk” (e.g., no teaching away by one reference’s (Recker) failing to show statistical significance and statement by another “that dosing intervals longer than one or two weeks would be ineffective” due to contrary explanations in other references (Black speculating “that the doses in Recker were too low” and Riis conclusion that “it is the toal dose over a predefined period and not the dosing regimens that is the determining factor”)). Regarding the 150 mg dose, Riis was found to teach “one need only scale up a known-effective dose from a short-interval regimen-e.g., daily dosing-to achieve the same BMD and bone-loss efficacy with a long-interval regimen” and “[t]he prior art provided substantial guidance as to the total dose, within a given time period, that would produce effective results” (e.g., Ravn showed 2.5 mg dose was “most effective” and “‘virtually’ equal to the 5 mg dose” and, therefore, “someone scaling it to a single monthly dose of 150 mg (5 mg/day x 30 days/month) would have anticipated equivalent success in raising BMD and limiting bone turnover…At the very least, the 150 mg does was obvious to try” because “[t]here was a need to solve the problem of patient compliance” and a “finite number of identified, predictable solutions” (citing KSR, US 2007)). And the FC panel was not convinced by Roche’s arguments relating to lower side effects (e.g., the FDA’s refusal to approve a 5 mg dose “due to its toxic side effects” (see Judge Newman’s dissent)) or unexpected results (citing In re Merck, FC 1996 (evidence of superior efficacy may not overcome reasonable expectation of success, “even if the level of success may have turned out to be be somewhat greater than would have been expected”)). Thus, the DC decision was affirmed. Judge Newman’s dissent argued “[i]nvalidation of this patent is not supported by clear and convincing evidence” (e.g., “despite extensive exploration, this successful protocol was not discovered”, “this court now holds that it was obvious to do what no one did or even suggested…my colleagues simply disregard the preferencs and toxicity warnings and discard the procedures of the prior art”), thereby violating the “guidance of KSR”.

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