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

Nos. 2013-1128, 1161-64 (Fed. Cir. April 11, 2014)

Despite a prolonged period of research for the patented inventions and evidence of unexpected efficacy, the Federal Circuit, in Hoffman-La Roche Inc. and Genentech Inc. v. Apotex Inc. and Apotex Corp., recently affirmed summary judgment of obviousness for two patents directed to drug administration.

Appellant Hoffman-La Roche (“Roche”) alleged that the defendants infringed two patents, (U.S. Patent No. 7,718,634 (“the ’634 patent”) and its parent, U.S. Patent No. 7,410,957 (“the ’957 patent”), under 35 U.S.C. § 271(e)(2), based on the defendants’ ANDA filings.  The ’634 patent related to a method of treating osteoporosis through the once-monthly administration of an oral tablet comprising a salt (ibandronate) equivalent to about 150 mg of ibandronic acid.  At trial, the U.S. District Court for the District of New Jersey granted summary judgment of invalidity of the ’634 patent under 35 U.S.C. § 103, finding that once-monthly oral dosing was established in the prior art, and that a drug dosage level of 150 mg was obvious to try at the time of invention.  The district court then raised, on its own motion, summary judgment of the ’957 patent, finding its claims invalid as obvious for the same reasons as in the ’634 patent.  These determinations were appealed to the Federal Circuit for de novo review.

The Federal Circuit affirmed the lower court’s decision. In its affirmance, the court pointed to several prior art documents which, either explicitly or generally, referenced oral once-monthly formulations of bisphosphonates (the larger class of compounds including ibandronate).

The court then turned to the question of dosage.  In its analysis, the court focused on a “total- dose concept” set forth in a 2001 article, establishing that the efficacy of ibandronate depended on the total oral dose given rather than the particular dosing schedule.  The court also relied on a prior art patent proposing a 5 mg daily dose (which, multiplied by 30 days, would amount to 150 mg per month).  Slip Op at 12-13.  The court found that “[t]he prior art provided substantial guidance as to the total dose, within a given time period, that would produce effective results,” leaving a person skilled in the art with a very limited set of dosage possibilities.  Id.  From these limited options, the court held that a 150 mg monthly dose was obvious to try, and that one could have anticipated success therefrom.  Slip Op. at 13.  The court, discarding Roche’s argument that application of simple multiplication was a misinterpretation of the total-dose concept, found that the total-dose concept can reliably predict efficacy of a treatment within a given period, regardless of the amount administered at any single time.  Slip Op. 14-15.

Having reached this conclusion, the Federal Circuit dismissed Roche’s arguments regarding the prior art’s safety concerns for higher dosages as unsupported by the facts. Slip Op. at 15-16.  The court also discarded Roche’s argument of unexpected results based on superior efficacy, stating that while such may find support in the evidence, it was nonetheless insufficient to rebut a  finding that one of skill in the art would have had a reasonable expectation of success. Slip Op. at 16-17.  Accordingly, the court upheld the district’s court’s judgment of the asserted claims as obvious and therefore invalid.

Dissenting, Judge Newman focused on the fact that Roche’s commercial drug took twelve years of research and clinical testing to demonstrate efficacy, and that, despite the extensiveness of the prior art, no prior art source had found Roche’s successful dosage protocol.  Dissent at 3.  The dissent also took issue with the majority’s reduction of the “total dosing concept” to that of multiplication, finding prior art concern with toxicity levels at odds with the idea that a dosage 30 times larger would be obvious.  Dissent at 5. Finally, Judge Newman opined that the prior art’s extensive experimentation with other dosing regimens, coupled with its failure to find Roche’s regimen, weighed heavily against the conclusion that the regimen was obvious to try. Dissent at 13.