Challenges to new molecule patents frequently hinge on the question of obviousness in view of a prior art “lead compound.” More often than not, patentees fend off these challenges by successfully arguing against selection or modification of the asserted lead compound, and/or by showing unexpected properties. But when the skilled person had at least some reason to select and appropriately modify a lead compound, and unexpected results fail, can “no reasonable expectation of success” save the day?
The Patent Trial and Appeal Board (PTAB) did not think so in its April 8, 2019 Final Written Decision in Incyte Corp. v. Concert Pharm., Inc., IPR2017-01256. The patent at issue in Incyte claimed deuterated ruxolitinib, which possessed improved metabolic stability relative to non-deuterated ruxolitinib, a myelofibrosis drug. The PTAB found that the prior art provided a reason to deuterate ruxolitinib to achieve potential improvements in safety, tolerability, and efficacy, or at the very least to achieve properties similar to the non-deuterated ruxolitinib. The PTAB dismissed the improved metabolic stability as a mere difference in degree, not kind, and therefore not probative of non-obviousness.
The patentee argued that the unpredictable effects of deuteration defeated any reasonable expectation of success in achieving the additional advantageous property of improved metabolic stability. The PTAB disagreed, citing Petitioner’s arguments that “the challenged claims do not recite any of those features” and emphasizing that reasonable expectations of success turn on the “claimed invention.” IPR2017-01256 Final Written Decision at p. 31. The PTAB also noted that it need not address whether proposed substitute claims encompassed the advantageous properties because the claims did not recite them. Id. at p. 48. Although the PTAB found a reasonable expectation that deuterated ruxolitinib may display improved metabolism, it stopped short of equating this with “expected success.”
But, was the PTAB correct to apparently disregard whether the prior art supplied a reasonable expectation of achieving the full spectrum of properties, because those properties were not claimed? Typically new compound claims do not recite properties, as courts have long considered a compound claim “as a whole” to include the compound and all its properties. See In re Papesch, 315 F.2d 381, 391 (C.C.P.A. 1963) (“a compound and all of its properties are inseparable; they are one and the same thing.”) Thus, the absence of compound properties from a claim should not, by itself, eliminate those properties from the analysis of reasonable expectations of success.
Even so, should a reasonable expectation of successfully achieving something less than all of a compound’s properties satisfy this part of an obviousness analysis? In one CAFC decision, an expectation of mere baseline activity similar to the prior art sufficed to establish a reasonable expectation of success. Bristol-Myers Squibb v. Teva Pharms. USA, 752 F.3d 967, 976-77 (Fed. Cir. 2014) (additional properties relegated to the analysis of secondary indicia of non-obviousness), reh’g and reh’g en banc denied, 769 F.3d 1339 (2014). Other decisions have included the full spectrum of a compound’s activity in the evaluation of reasonable expectations of success. See Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc., 231 F.3d 1339, 1345 (Fed. Cir. 2000) (“success” defined not as a compound with baseline activity, but “a compound that had high activity, few side effects, and lacked toxicity”); Eli Lilly & Co. v. Zenith Goldline Pharm., 364 F. Supp. 2d 820, 905 (S.D. Ind. 2005) (“success” required not just activity in animal or in vitro tests but activity without adverse side effects or other toxicities), aff’d, 471 F.3d 1369 (Fed. Cir. 2006).
So although the PTAB’s Incyte decision may have erred in focusing on the absence of certain properties from the claims, the courts have yet to entirely resolve the meaning of reasonable expectations of success for pharmaceutical compounds. See Bristol-Myers, 769 F.3d at 1358-59 (Taranto, J., dissenting from denial of rehearing en banc). Beyond the facts in Incyte, factoring all known properties into expectations of success would provide patentees with an avenue for proving non-obviousness in cases where actual unexpected differences over a lead compound could only be shown with costly side-by-side clinical testing. The patentee has vowed to appeal the Incyte decision, so stay tuned for further developments that hopefully can shed more light on these issues.