In Hoffman-LaRoche, Inc. v. Apotex, Inc., the Federal Circuit affirmed the district court’s summary judgment that two Roche Boniva patents are invalid as obvious. The conclusion of obviousness is not particularly remarkable based on the Federal Circuit s recounting of the prior art, but the court’s willingness to affirm invalidity on summary judgment where the record included evidence of unexpected results demonstrates the difficulty of prevailing against obviousness challenges.
The Patents at Issue
The Roche Boniva® patents at issue were U.S. 7,718,634 and U.S. Patent No. 7,410,957, which were related as parent and continuation. The Federal Circuit identified claim 1 of the ’634 patent as representative:
1. A method for treating or inhibiting postmenopausal osteoporosis in a postmenopausal woman in need of treatment or inhibition of postmenopausal osteoporosis by administration of a pharmaceutically acceptable salt of ibandronic acid, comprising:
(a) commencing the administration of the pharmaceutically acceptable salt of ibandronic acid by orally administering to the postmenopausal woman, on a single day, a first dose in the form of a tablet, wherein the tablet comprises an amount of the pharmaceutically acceptable salt of ibandronic acid that is equivalent to about 150 mg of ibandronic acid; and
(b) continuing the administration by orally administering, once monthly on a single day, a tablet comprising an amount of the pharmaceutically acceptable salt of ibandronic acid that is equivalent to about 150 mg of ibandronic acid.
The District Court Proceedings
The district court proceedings stemmed from the defendants’ Abbreviated New Drug Applications (ANDAs) seeking FDA approval to market generic versions of Boniva®. The district court denied Roche’s motion for a preliminary injunction, finding that “Roche had failed to prove it was likely to succeed in defeating the defendants’ obviousness challenge.” (The Federal Circuit affirmed that ruling in a non-precedential decision issued in 2012). The district court granted the defendants’ motion for summary judgment of invalidity of claims 1-8 of the ’634 patent and then on its own motion under Federal Rule of Civil Procedure 56(f) raised the issue of summary judgment of invalidity of claims 1-10 of the ’957 patent, and held those claims invalid as well.
The Federal Circuit Decision
The Federal Circuit decision was authored by Judge Bryson and joined by Judge Lourie. Judge Newman filed a dissenting opinion.
The majority decision parsed the claims into two parts: (i) once monthly dosing and (ii) a monthly dose of 150 mg.
The majority found that several pieces of prior art taught “once monthly oral dosing of ibandronate or other bisphosphonates.” Roche argued that ”it was widely believed as of the date of invention that a bisphosphonate regimen with a dose-free interval longer than one or two weeks would not be effective,” but the Federal Circuit poked several holes in Roche’s arguments.
Therefore, even if Schnitzer’s interpretation of the Recker study were viewed as teaching away from monthly dosing, Riis’s contrary findings substantially undermined that interpretation.
Does this sound like a legal conclusion based on undisputed material facts?
With regard to the 150 mg dose, the majority found that dose to be obvious based on prior art teaching doses of 5 mg/day (x 30 days = 150 mg).
[T]he prior art pointed to a monthly treatment of 150 mg of ibandronate. At the very least, the 150 mg dose was obvious to try: There was a need to solve the problem of patient compliance by looking to less-frequent dosing regimens.
The majority rejected Roche’s arguments regarding the safety concerns of the 5 mg/day dose:
[A]lthough patients on the 5 mg daily dose dropped out of the study at a higher rate than patients on lower doses, Ravn did not conclude that the higher drop-out rate was statistically significant. Instead, the authors merely noted that a higher frequency of diarrhea was experienced with the 5 mg dose. A higher frequency of diarrhea does not necessarily teach away from the 5 mg daily dose or its equivalents, however, as the prior art indicated that modest gastrointestinal side effects must be weighed in light of the benefits of the drug. Indeed, Ravn itself concluded that “[i]n the present study, the side effect profile of ibandronate seemed to be safe” and that “[i]n general, the safety evaluation did not reveal any differences between ibandronate and placebo treated groups.”
Does this sound like a legal conclusion based on undisputed material facts?
The Federal Circuit majority also found:
[A]ny such teaching away would have been overcome by Riis’s finding that an oral administration of 20 mg of ibandronate every other day for 24 days, followed by a nine-week rest phase, resulted in the same rate of side effects as a 2.5 mg daily regimen.
Do the conclusions of one study “overcome” the conclusions of a different study?
On the record before it, the majority concluded that “[t]here is thus no genuine issue of fact concerning whether the prior art taught away from the 150 mg dose based on safety concerns.”
Unexpected Results Break Under the Strong Case of Obviousness
The majority recognized that Roche had presented evidence of unexpected results, but determined that it was not sufficient to overcome the prima facie case of obviousness.
The evidence of superior efficacy does nothing to undercut the showing that there was a reasonable expectation of success with the 150 mg monthly dose, even if the level of success may have turned out to be somewhat greater than would have been expected. For the same reasons, the nonlinear bioavailability of ibandronate does not rebut the prima facie showing of obviousness of a once monthly dose of 150 mg. The increased level of bioavailability has not been shown to be responsible for the improved osteoporosis treatment efficacy of the 150 mg dose.
Thus, the Federal Circuit affirmed the district court’s judgment of obviousness.
Judge Newman’s Dissent
Judge Newman’s dissenting opinion criticizes the majority on several grounds.
The unexpected results of the patented method are conceded by the panel majority. The evidence on summary judgment was that many others sought and failed to find an efficacious intermittent treatment schedule. The prior art relied on by my colleagues surrounded but missed the Roche method. The prior art shows that safety is likely to be compromised at high doses, and that efficacy is likely to be compromised at extended dosing intervals. Nonetheless, this court now holds that it was obvious to do what no one did or even suggested; my colleagues simply disregard the preferences and toxicity warnings and discard the procedures of the prior art.