July 2013
Synthesizing and Screening Tens of Thousands of Candidate Compounds Constitutes Undue Experimentation
| Judges: Moore (author), Bryson, Wallach |
| [Appealed from D.N.J., Judge Pisano] |
In Wyeth v. Abbott Laboratories, Nos. 12-1223, -1224 (Fed. Cir. June 26, 2013), the Federal Circuit affirmed the district court’s SJ of invalidity for nonenablement, holding that there was no genuine issue of material fact that the specification does not enable one of ordinary skill to practice the asserted claims without undue experimentation.
U.S. Patent Nos. 5,516,781 and 5,563,146 (collectively “the patents-in-suit”) relate to methods of treating or preventing restenosis—the renarrowing of an artery—by administering rapamycin. Generally, “rapamycin” may refer to a class of compounds; however, the parties agreed that the shared specification of the patents-in-suit discloses only one rapamycin species called sirolimus.
In two separate actions, Wyeth and Cordis Corporation (collectively “Wyeth”) sued Abbott Laboratories, Abbott Cardiovascular Systems, Inc., Abbott Laboratories, Inc., Medtronic Inc., Medtronic Vascular, Inc., Medtronic USA, Inc., Boston Scientific Corporation, and Boston Scientific Scimed, Inc. (collectively “Defendants”) for infringement of the patents-in-suit. Defendants market stent products that elute everolimus and zotarolimus, two drugs that have the same macrocyclic ring as sirolimus but different substituents at the C–42 position. The district court adopted Wyeth’s proposed construction of “rapamycin” as “a compound containing a macrocyclic triene ring structure produced by Streptomyces hygroscopicus, having immunosuppressive and anti-restenotic effects,” and based in part on that construction, granted Defendants’ joint motions for SJ of invalidity for nonenablement and lack of written description. Slip op. at 4-5 (citation omitted).
The central issue on appeal, as articulated by the Court, was whether practicing the full scope of the claims requires excessive—and thus undue—experimentation. Agreeing with the district court, the Court concluded that there was no genuine dispute that practicing the full scope of the claims, measured at the time of filing, would require excessive experimentation. The Court noted that the scope of the claims-at-issue was broad and, “[u]nder the district court’s unchallenged construction of ‘rapamycin,’ the invention is a new method of use of a known compound (sirolimus) and any other compounds that meet the construction’s structural and functional requirements.” Id. at 7. The Court further agreed that there was no genuine dispute that the specification’s guidance was limited to disclosures of the immunosuppressive and antirestenotic properties of sirolimus and assays to screen for those properties.
“In sum, there is no genuine dispute that practicing the full scope of the claims would require synthesizing and screening each of at least tens of thousands of compounds.” Slip op. at 8.
For purposes of SJ, the Court accepted as true Wyeth’s claims about the state of the art and Wyeth’s expert testimony that one of ordinary skill in the art would have understood that potential rapamycin compounds should have molecular weights below 1,200 Daltons in order to be permeable across cell membranes. The Court also accepted as true that one of ordinary skill could routinely use the assays disclosed in the specification to determine immunosuppressive and antirestenotic effects in candidate compounds. Even accepting all of this as true, the Court found no genuine dispute that practicing the full scope of the claims would require more than routine experimentation for two reasons. “First, there is no dispute that, even if potential rapamycin compounds must have a molecular weight below 1,200 Daltons, there are still at least tens of thousands of candidates.” Id. at 8. Specifically, the Court noted, the specification is silent about how to structurally modify sirolimus, let alone in a way that would preserve the recited utility. “Second, there is no genuine dispute that it would be necessary to first synthesize and then screen each candidate compound using the assays disclosed in the specification to determine whether it has immunosuppressive and antirestenotic effects.” Id. The Court noted there was no evidence in the record that any particular substitutions outside of the macrocyclic ring are preferable.
The Court then addressed whether having to synthesize and screen each of at least tens of thousands of candidate compounds constitutes undue experimentation. The Court concluded that in this instance, it did, stating that “[u]ndue experimentation is a matter of degree.” Id. at 8-9 (citing Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1253 (Fed. Cir. 2004)). Relying on its precedent describing limits on permissible experimentation in the context of enablement, the Court found that the specification here disclosed only a starting point for further iterative research in an unpredictable and poorly understood field. The Court reasoned that synthesizing candidate compounds derived from sirolimus could, itself, require a complicated and lengthy series of experiments in synthetic organic chemistry. Specifically, the Court determined that, “[e]ven putting the challenges of synthesis aside, one of ordinary skill would need to assay each of at least tens of thousands of candidates,” each of which Wyeth’s expert conceded would take weeks to complete. Id. at 10. Accordingly, the Court affirmed the district court’s grant of SJ of invalidity, concluding that “[t]he resulting need to engage in a systematic screening process for each of the many rapamycin candidate compounds is excessive experimentation.” Id.
The Federal Circuit noted that because it found the patents-in-suit invalid for lack of enablement, it need not address the written description issues raised in Wyeth’s appeal.
