By Jason Rantanen
Otsuka Pharmaceutical Co., Ltd. v. Sandoz, Inc. (Fed. Cir. 2012) Download 11-1126
Panel: Lourie (author), Moore, Reyna
This opinion addresses the appropriateness of using a "lead compound" analytical framework for evaluating the obviousness of chemical compounds, reaffirming and refining the approach taken in Takeda Chemical Industries, Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350 (Fed. Cir. 2007).
The defendants in Otsuka consist of a group of ANDA applicants who contended that the compound claimed in Patent No. 5,006,528, aripiprazole (marketed under the brand name Abilify®), was obvious in light of three prior art carbostyril derivative compounds. Prior to aripiprazole (itself a carbostyril derivative), the only atypical antipsychotic compounds approved by the FDA for the treament of schizophrenia were those that possessed structures related to the antipsychotics clozapine and risperidone, neither of which were the basis for the obviousness challenge. Following a bench trial, the district court concluded that the asserted claims were not obvious in light of the three "lead compounds" identified by defendants, nor was the patent invalid due to nonstatutory double patenting.
Obviousness: In rejecting defendants' appeal of the district court's determination of nonobviousness, the CAFC endorsed the two-step framework of Takeda (also authored by Judge Lourie). In Takeda, the CAFC addressed the defendant's argument that "the prior art would have led one of ordinary skill in the art to select compound b as a lead compound," with "lead compound" referring "to a compound in the prior art that would be most promising to modify in order to improve upon its antidiabetic activity and obtain a compound with better activity." Takeda, 492 F.3d at 1357. The court then analyzed whether a PHOSITA would have both selected and modified the prior art compounds identified by the defendant, an approach applied by the district court in Otsuka and challenged by the defendants on appeal as the type of rigid analysis precluded by KSR.
The CAFC disagreed, holding that the Takeda approach was permissible:
Our case law demonstrates that whether a new chemical compound would have been prima facie obvious over particular prior art compounds ordinarily follows a two-part inquiry. First, the court determines whether a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds, or starting points, for further development efforts....The second inquiry in the analysis is whether the prior art would have supplied one of ordinary skill in the art with a reason or motivation to modify a lead com-pound to make the claimed compound with a reasonable expectation of success.
Slip Op. at 17, 19.
Of course, aspects of KSR do impact this conclusion. For example, the reason or motivation for a PHOSITA to modify a lead compound may come from a variety of sources, or not even be explicit in the prior art. Slip Op. at 19-20. And the CAFC's approval of the Takeda approach may have been guided in part by the parties' decision to focus their arguments on selecting and modifying particular prior art compounds, rather than approaching obviousness from another direction. Id. at 17.
Examining the two steps, the CAFC concluded that the district court did not err when it found that a PHOSITA would not have selected the prior art compounds for use as lead compounds for further antipsychotic research or made the modifications necessary to arrive at the claimed compound.
Obviousness-type double patenting: The CAFC also rejected defendants' nonstatutory obviousness-type double patenting argument, using the opportunity to clear up an apparent ambiguity about the differences between obviousness and obviousness-type double patenting. Although analogous, the two differ in several respects. The patent principally underlying the double patenting rejection need not be prior art (which makes sense given that the purpose of the double patenting doctrine is to prevent one person from obtaining more than one valid patent for the same invention or an obvious modification of the same invention). More notably, "when analyzing obviousness-type double patenting in cases involving claimed chemical compounds, the issue is not whether a skilled artisan would have selected the earlier compound as a lead compound." Slip Op. at 28 (emphasis added). Rather, selection of the earlier compound as a lead compound is presumably automatic under the court's language. However, it is still necessary to identify some reason that would have led the PHOSITA "to modify the earlier compound to make the later compound with a reasonable expectation of success." Id. at 29. This is mandatory: "There is no other way to consider the obviousness of compound B over compound A without considering whether one of ordinary skill would have had reason to modify A to make B. That is traditional obviousness analysis." Id. at 30 (emphasis added).
As with the obviousness inquiry generally, the CAFC declined to find clear error in the district court's determination that no such reason existed in this case.
WARNING: Appellate lawyers often feel compelled to make sub-arguments in footnotes, as Otsuka's counsel did here in contending that a PHOSITA would not have consulted an unindexed file history of a patent. Although Otsuka ultimately prevailed, this practice is strongly discouraged by the court: "Arguments raised only in footnotes, however, are waived...Although we may exercise our discretion to consider improperly raised arguments, we decline to do so here." Slip Op. at 22.