Opinion ID: 799379
Heading Depth: 3
Heading Rank: 2

Heading: The Unsubstituted Butoxy Compound

Text: In evaluating the differences between the claimed invention and the prior art, the district court first considered the unsubstituted butoxy compound disclosed in the prior art '416 patent and the Nakagawa declaration. The Defendants contend that the court erred by finding that a skilled artisan would not have selected the unsubstituted butoxy as a lead compound for antipsychotic drug discovery. We disagree. As the court noted, the claims of the prior art '416 patent explicitly disclose the unsubstituted butoxy as producing an antihistaminic effect. This clear teaching controls over the far more nebulous disclosure that the trillions of carbostyril compounds encompassed by the '416 patent have antihistaminic and central nervous controlling effects. '416 patent col.2 ll.50-51. As explained by Dr. Bryan Roth, whom the court credited as an expert in schizophrenia, antipsychotic drug discovery, and psychopharmacology, one of ordinary skill in the art would not have understood the '416 patent's laundry list of potential central nervous system controlling effects to mean that every carbostyril derivative disclosed in the '416 patent is a potential antipsychotic. Otsuka, 2010 WL 4596324, at , , 2010 U.S. Dist. LEXIS 132595, at , . The Nakagawa declaration similarly fails to support the Defendants' contentions. As an initial matter, Otsuka argues in a footnote to its brief that the Nakagawa declaration is not eligible as prior art because the Defendants failed to prove that a chemist seeking to develop a new antipsychotic drug would have consulted the unindexed file history of the prior art '416 patent in the course of his or her research. Br. Pl.-Appellee Otsuka, at 24 n. 1. Arguments raised only in footnotes, however, are waived. SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1320 (Fed.Cir.2006). Although we may exercise our discretion to consider improperly raised arguments, we decline to do so here. See Becton Dickinson & Co. v. C.R. Bard, Inc., 922 F.2d 792, 800 (Fed.Cir. 1990). We therefore assume, without deciding, that the Nakagawa declaration qualifies as prior art. Although Nakagawa's mouse jumping data could be indicative of potential antipsychotic activity to the skilled artisan, Otsuka, 2010 WL 4596324, at , 2010 U.S. Dist. LEXIS 132595, at , that alone does not resolve the matter. Rather, we must consider the contents of the declaration as a whole, as the district court correctly did. In doing so, we focus in particular on the compounds' disclosed properties because, as the district court found, [g]enerally, a skilled artisan would be attracted to the most potent compounds in selecting a lead compound for development. Id. at , 2010 U.S. Dist. LEXIS 132595 at ; see also Daiichi, 619 F.3d at 1354. Of the nine carbostyril test compounds for which the Nakagawa declaration supplied mouse jumping data, the unsubstituted butoxy was inferior to four other test compounds and thus was only of middling potency. Otsuka, 2010 WL 4596324, at , 2010 U.S. Dist. LEXIS 132595, at . Significantly, the four more potent test compounds were all propoxy-linked, including Compound 44, which, with an ED50 of 0.53 milligrams per kilogram, was by far the most potent of the compounds tested. Id. at , 2010 U.S. Dist. LEXIS 132595 at . One of the Defendants' own experts conceded that the activity of Compound 44 was striking, and Dr. Roth testified that if a skilled artisan were to select any compound from the Nakagawa declaration, it would be Compound 44. Id. at , -18, 2010 U.S. Dist. LEXIS 132595 at , . The Defendants do not allege obviousness over the structurally dissimilar Compound 44, which, unlike aripiprazole, has a propoxy linker connected at the 5-position of its carbostyril core and a 2-ethoxy substituent on its phenyl ring. As the district court found, the Nakagawa declaration would, if anything, have taught one of ordinary skill to select a 5-linked propoxy carbostyril derivative as a lead compound. See id. at , 2010 U.S. Dist. LEXIS 132595 at  (comparing the ED50 value of 2.1 for a 5-linked unsubstituted propoxy and the ED50 value of 9.3 for a 7-linked unsubstituted propoxy and finding that this significant difference would teach the skilled artisan the superiority of 5-linked propoxy compounds over 7-linked propoxy compounds). Thus, neither the '416 patent nor the Nakagawa declaration supports the Defendants' position that one of ordinary skill would have selected the prior art unsubstituted butoxy compound as a lead compound for further antipsychotic research.