Federal Circuit Affirms Non-Obviousness Summary Judgment for Novel Formulation of Prior Art Active Drug Compound

The U.S. Court of Appeals for the Federal Circuit affirmed a lower court’s grant of summary judgment that the Orange Book patent covering Fortical® was not obvious in view of more than 40 prior art references. Unigene Labs., Inc. v. Apotex, Inc., Case No. 10-1006 (Fed. Cir., Aug. 25, 2011) (Rader, C.J.).

Fortical® is a pharmaceutical composition of salmon calcitonin, the same active ingredient in another branded drug—Miacalcin®. In fact, both Fortical and Miacalcin contain the same concentration of salmon calcitonin and are pharmaceutical nasal sprays used to treat postmenopausal osteoporosis. Miacalcin was marketed almost five years before the earliest priority date claimed for the Fortical Orange Book-listed patent, U.S. Patent No. RE40,812E (the RE’812 patent).

At the lower court, both sides moved for summary judgment regarding whether a single claim of the RE’812 patent was obvious. Apotex, the defendant at the lower court arguing obviousness, based its arguments on more than 40 prior art references, all of which had also been considered by the U.S. Patent and Trademark Office (USPTO) during prosecution. The district court found that none of the cited prior art references taught the use of “about 20 mM citric acid” to increase “shelf stability and enhanced bioavailability” in a nasal salmon calcitonin formulation, as required by claim 19 of the RE’812 patent.

On appeal, the Federal Circuit affirmed the district court’s ruling of non-obviousness. Chief Judge Rader set forth the pertinent test: “The claimed invention is not obvious if a person of ordinary skill would not select and combine the prior art references to reach the claimed composition or formulation.” The Court found that one of skill in the art would have had ample motivation to try to create a competing formulation to the active ingredient found in the successful drug Miacalcin, the “reference composition” for purposes of the obviousness analysis, based on design need and market demand,

The Court, however, used the citric acid limitation to reject Apotex’s three main obviousness arguments. The Court distinguished the first reference because it called for much higher concentrations of citric acid to enhance bioavailability. The Court rejected the obviousness allegations relating to the second reference because, although it included a disclosure of 20.5 mM citric acid in a pharmaceutical nasal spray formulation of salmon calcitonin, it directly taught away from using this concentration of citric acid to either increase shelf stability or enhance bioavailability. Finally, the Court dismissed Apotex’s obviousness arguments with regard to the third reference because it only listed citric acid as a pH buffering agent, while other sections expressly listed absorption agents and preservatives for use in pharmaceutical formulations—none of which included citric acid, let alone at “about 20 mM” of that substance.

As a result, the Court found that the “about 20.0 mM citric acid” limitation alone supported the district court’s grant of summary judgment of non-obviousness.