Hoffmann-La Roche Inc. v. Apotex Inc. (Fed. Cir.)

Finding of obviousness affirmed when it would have been obvious to select a once-monthly oral dosing regimen of ibandronate to treat osteoporosis and to set that dose at 150 mg.

Summer 2014

GENERICally Speaking

Case Name: Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326 (Fed. Cir. Apr. 11, 2014) (Circuit Judges Newman, Lourie, and Bryson presiding; Opinion by Bryson, J.; Dissent by Newman, J.) (Appeal from D.N.J., Chesler, J.)

Drug Product and Patent(s)-in-Suit: Boniva® (ibandronate sodium); U.S. Patents Nos. 7,718,634 (“the ’634 patent”) and 7,410,957 (“the ’957 patent”)

Nature of the Case and Issue(s) Presented: Hoffman-La Roche (“Roche”) appeals from the decision of the district court granting defendants summary judgment of invalidity as to claims 1-8 of the ’634 patent and claims 1-10 of the ’957 patent. The asserted claims describe a method of treating osteoporosis consisting of orally administering about 150 mg of ibandronic acid once monthly on a single day. As to the frequency of dosing, the district court found that once-monthly oral dosing of ibandronate was established in the prior art. As to the amount of the monthly dose, the district court found that the combination of several prior art references suggested a dosage level of about 150 mg per month, or at least indicated that a monthly dose of 150 mg was obvious to try. The Federal Circuit affirmed.

Why Apotex Prevailed: The Federal Circuit framed the issue on appeal as “whether it would have been obvious at the time of invention to select a once monthly oral dosing regimen of ibandronate to treat osteoporosis and to set that dose at 150 mg.” In answering the preceding question in the affirmative, the Federal Circuit found that a relatively infrequent dosing schedule “has long been viewed as a potential solution to the problem of patient compliance stemming from the inconvenience of oral bisphosphonate (the class of compounds to which ibandronate belongs) regimens.” Several prior-art references, including the Chen ’559 patent, which discloses coated dosage forms of bisphosphonic acids, explicitly disclosed a preferred embodiment in which “a dosage form of the invention is administered to a patient…preferably once a month.” In response, Roche relies on prior art that it contends teaches away from once monthly dosing because it was widely believed that a bisphosphonate regimen with a dose-free interval longer than one or two weeks would not be effective. Relying on the 2001 reference authored by Riis, the Federal Circuit stated that “[a]ny doubt about the efficacy of oral ibandronate dosing that may have been created by [Roche’s prior art’s] speculation was put to rest by [Riis].” Moreover, the Federal Circuit held that conclusive proof of efficacy is not necessary to show obviousness because all that is required is a “reasonable expectation of success.”

The Federal Circuit next found that a person of ordinary skill in the art looking to scale to a monthly dose was faced with a very limited set of possibilities as taught in the prior art: 2.5 mg or 5 mg. Multiplying the 5 mg/day dose to a monthly regimen (i.e., 30 days) results in the 150 mg dose that is contemplated by the asserted patents. “Accordingly, the prior art pointed to a monthly treatment of 150 mg of ibandronate. At the very least, the 150 mg dose was obvious to try….” Roche argued that there were disputed issues of fact as to whether it would have been obvious to administer once monthly doses of 150 mg in light of alleged safety concerns about the adverse gastrointestinal effects of ibandronate and other bisphosphonates. But the Federal Circuit found otherwise. Relying on the prior art Moekel ’326 patent, which disclosed single-dose units up to 250 mg, the Federal Circuit found that there was no significant side effects in clinical studies using ibandronate “even at high dosages.”

In her dissent, Judge Newman takes issue with the majority’s “invoking judicial hindsight to reconstruct the patented subject matter.” According to Judge Newman, nowhere amid the many studies of bisphosphonate osteoporosis treatments over a wide range of dosages and conditions, did any reference show or suggest the combination of a single 150 mg dose and once-a-month administration. “No reference suggested the effectiveness and safety of this combination. Nonetheless, my colleagues declare this treatment obvious to them. My colleagues’ primary reason, that 150 mg is thirty times the daily dose of 5 mg, does not mention that the FDA refused to approve the 5 mg dose due to its toxic side effects. Surely this leads away from the obviousness of a single dose thirty times larger.”

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