Opinion ID: 807367
Heading Depth: 2
Heading Rank: 1

Heading: The ’608 Compound

Text: We first address the ’608 Compound. Claim 3 of the ’608 patent recites the ’608 Compound, an antifolate that is structurally related to pemetrexed but never advanced to clinical use. As described, the ’608 patent issued in July 1991, more than three years before the ’932 patent issued with its claims covering pemetrexed. The question, then, is whether the asserted claims of the ’932 patent are (Stipulation and J. Order), ECF No. 10. We granted APP’s unopposed motion to consolidate that action with the related matters on appeal. Eli Lilly & Co. v. Teva Parenteral Meds. Inc., Nos. 2011-1561, -1562, 2012-1037 (Fed. Cir. Nov. 29, 2011) (Order Consolidating Appeals). 13 ELI LILLY v. APP PHARMA patentably distinct from Lilly’s earlier-issued claim to the ’608 Compound. On appeal, Teva contends that the district court erred by failing to invalidate the claims for obviousness-type double patenting. Teva’s primary argument concerns the appropriate legal standard for evaluating obviousnesstype double patenting. Relying on our decision in Amgen Inc. v. Hoffmann-La Roche Ltd., 580 F.3d 1340 (Fed. Cir. 2009), Teva contends that the correct analysis involves only the differences between the claims at issue, so that any features held in common between the claims—in this case, all but the aryl regions of the ’608 Compound and pemetrexed—would be excluded from consideration. In Amgen, we explained that once the differences between claims are established, the obviousness-type double patenting analysis entails determining “whether the differences in subject matter between the claims render the claims patentably distinct.” 580 F.3d at 1361. But those differences cannot be considered in isolation—the claims must be considered as a whole. Amgen expressly noted that “[t]his part of the obviousness-type double patenting analysis is analogous to an obviousness analysis under 35 U.S.C. § 103.” Id. And just as § 103(a) requires asking whether the claimed subject matter “as a whole” would have been obvious to one of skill in the art, so too must the subject matter of the ’932 claims be considered “as a whole” to determine whether the ’608 Compound would have made those claims obvious for purposes of obviousness-type double patenting. Gen. Foods Corp. v. Studiengesellschaft Kohle mbH, 972 F.2d 1272, 1278 (Fed. Cir. 1992) (“Claims must be read as a whole in analyzing a claim of double patenting.”). Thus, the district court did not err by examining whether one of ordinary skill in the art would have been motivated to modify the ’608 ComELI LILLY v. APP PHARMA 14 pound to create pemetrexed, considering the compounds as a whole. On the merits, Teva also disputes the district court’s findings and conclusions in view of the evidence presented. Specifically, Teva contends (1) that placing a phenyl group in the aryl position represented inescapable “conventional wisdom” in the field based on antifolate structures known at the time, (2) that the district court erred in finding that one of skill in the art would have considered a phenyl group undesirable within the structural context of the ’608 Compound, and (3) that the district court erred by discounting its theory that principles of bioisosterism 6 would have suggested replacing the ’608 Compound’s thienyl with phenyl. Lilly defends the district court’s findings, arguing that the evidence amply supported the court’s view that a person of ordinary skill would not have had reason to manipulate the ’608 Compound to produce pemetrexed. Lilly contended, and the district court found, that a chemist at the time seeking to develop TS inhibitors would have looked specifically to data from that emerging sub-discipline rather than attempting to emulate the “conventional” antifolates highlighted by Teva. In fact, according to Lilly, the contemporary experience and understanding in the TS field not only would have failed to suggest substituting a phenyl group into the ’608 Compound, but earlier reports of associated inefficacy and toxicity would have actively dissuaded one from doing so. Finally, Lilly maintains that bioisosterism provides no 6 Bioisosterism refers to a process that involves replacing one atom or functional group in a molecule with another of similar chemical, physical, or electronic properties in hopes that the substitution will result in similar or enhanced activity. 15 ELI LILLY v. APP PHARMA basis for predicting whether a substituted compound will prove more or less effective than the original. Based on the evidence presented at trial, we discern no error in the district court’s findings or its conclusion that the asserted claims are patentably distinct from the ’608 Compound. In the chemical context, we have held that an analysis of obviousness-type double patenting “requires identifying some reason that would have led a chemist to modify the earlier compound to make the later compound with a reasonable expectation of success.” Otsuka, 678 F.3d at 1297. Here, the district court considered the parties’ arguments and evidence, particularly their conflicting expert testimony as to how an ordinarily skilled chemist presented with the ’608 Compound would have been motivated to proceed at the time. In its decision, the court credited Lilly’s evidence to find that “the ways in which a person of ordinary skill in the art would modify [the ’608 Compound] would not result in pe- metrexed.” Eli Lilly, 2011 WL 3236037, at . We owe that finding considerable deference on appeal, and we see no clear error based on the record before us. Moreover, a complicated compound such as the ’608 Compound provides many opportunities for modification, but the district court did not find that substituting a phenyl group into the aryl position was the one, among all the possibilities, that would have been successfully pursued. Thus, absent any motivation to derive pemetrexed from the ’608 Compound or reason to expect success in doing so, the district court correctly concluded that the asserted claims were not invalid for obviousness-type double patenting over the ’608 Compound.