The U.S. Court of Appeals for the Federal Circuit recently affirmed a determination by a district court that Procter & Gamble’s patent covering its osteoporosis drug Actonel® was not invalid as obvious nor was it invalid for obviousness-type double patenting. Procter & Gamble Co. v. Teva Pharmaceuticals USA, Inc., Case Nos. 08-1404, -1405, -1406 (Fed. Cir., May 13, 2009) (Archer, J.; Newman, J. dissenting)

P&G’s osteoporosis drug Actonel reportedly has $1.5 billion in annual sales. The patent-in-suit claims the compound risedronate, the active ingredient in Actonel®. Risedronate is a member of a group of compounds referred to as bisphosphonates, which are active in inhibiting bone resorption. P&G sued Teva for infringement after Teva notified P&G that it planned to market risedronate as a generic equivalent of Actonel®. P&G alleged that Teva’s proposed drug infringed claims directed to the compound risedronate, pharmaceutical compositions containing risedronate and methods of treating diseases using risedronate. In its defense, Teva argued that the patent was invalid as obvious in light of P&G’s own expired prior art patent. Risedronate is neither claimed nor disclosed in the prior art patent. Instead, the prior art patent claims an intermittent dosing method for treating osteoporosis. The prior art patent lists 36 polyphosphonate molecules as treatment candidates and eight preferred compounds for intermittent dosing, including 2-pyr EHDP. Teva argued that the structural similarities between risedronate and 2-pyr EHDP render the challenged claims of the patent-in-suit obvious. In the alternative, Teva argued that the patent-in-suit was invalid for obviousness-type double patenting. The district court rejected Teva’s challenges. Teva appealed.

The Federal Circuit began its analysis by first noting that an obviousness argument based on structural similarity between claimed and prior art compounds requires a preliminary finding that one of ordinary skill in the art would have selected the prior art compound as a lead compound. The Court concluded that this inquiry was rendered irrelevant because, even if 2-pyr EHDP was a lead compound, the evidence did not establish that it would have been obvious to a person of ordinary skill at the time of the invention to modify 2-pyr EHDP to create risedronate. According to the Court, the issue of whether risedronate was obvious in light of the prior art turned on the question of whether, at the time of invention, a person of ordinary skill in the art would have had reason to attempt to make risedronate with a reasonable expectation of success. The Court next noted the importance to the obviousness determination of structural similarities and differences between the claimed compound and the prior art compound. In this case, risedronate and 2-pyr EHDP are positional isomers; they each contain the same atoms arranged in different ways leading to differences three dimensional shape, charge distribution and hydrogen bonding properties. The Court noted that P&G had presented expert testimony attesting that a person having ordinary skill in the art realized that the properties of bisphosphonates could not be anticipated based on their structure. In addition, the panel noted that P&G’s own testing had shown that another bisphosphonate was not active in inhibiting bone resorption despite its close relationship with potent compounds, evidencing the unpredictability of this class of compounds. The Court concluded that the lower court had not erred in finding that a person of ordinary skill would not have been motivated to synthesize and test risedronate and would not have had a reasonable expectation of success in synthesizing and testing risedronate. Moreover, the panel determined that there was no credible evidence that the structural modification of 2-pyr EHDP would have been routine. Overall, the Federal Circuit concluded that the District Court did not clearly err in finding that Teva had failed to establish a prima facie case of obviousness.

Regardless of the insufficiency of a prima facie case, the Court further determined that P&G had introduced sufficient evidence of unexpected results, including risedronate’s potency at low doses and lack of toxicity at higher doses than 2-pyr EHDP could be safely used. The Court also found no error in the district court’s consideration of evidence that risedronate had satisfied a long-felt but unmet need. Finally, having concluded that risedronate was not obvious under 35 U.S.C. § 103, the panel similarly concluded that the patent was not invalid for obviousness-type double patenting.