Amerigen Pharmaceuticals v. Ucb Pharma Gmbh
913 F.3d 1076
Fed. Cir.2019Background
- UCB owns U.S. Patent No. 6,858,650 covering fesoterodine, a prodrug of the active metabolite 5‑HMT used to treat urinary incontinence (Toviaz®).
- Mylan (and joined parties including Amerigen) petitioned for inter partes review (IPR) of claims 1–5 and 21–24 of the ’650 patent on obviousness grounds relying on prior art about tolterodine/5‑HMT metabolism (Detrol label, Brynne, Postlind), prodrug design (Bundgaard), and salts (Berge, Johansson).
- The Patent Trial and Appeal Board instituted review but concluded petitioners failed to prove claims unpatentable as obvious, primarily finding no motivation to make a 5‑HMT prodrug or to make the specific claimed alkyl esters (including fesoterodine).
- Amerigen appealed the Board’s decision; UCB moved to dismiss for lack of standing. The Federal Circuit found Amerigen had Article III standing because the Orange Book listing of the ’650 patent blocks Amerigen’s tentatively approved ANDA launch and invalidation/delisting would redress the injury.
- On the merits the Board’s factual findings were upheld: skilled artisans would not have been motivated to prodrug 5‑HMT to solve a bioavailability problem (Lipinski analysis showed no predicted absorption issues), no persuasive evidence that 5‑HMT esters would be inactive, and many prodrug alternatives meant arriving at the claimed monoester (isobutyryl at 2‑position) was not routine.
Issues
| Issue | Plaintiff's Argument (Amerigen) | Defendant's Argument (UCB) | Held |
|---|---|---|---|
| Standing to appeal Board decision | Listing of the ’650 patent in Orange Book delays Amerigen’s ANDA launch; invalidation would enable earlier approval — concrete economic injury | No cognizable injury because Amerigen is a Paragraph III filer and cannot be sued for infringement before patent expiry; prior district litigation forecloses injury | Amerigen has Article III standing: Orange Book listing blocks launch; invalidation/delisting would likely redress injury |
| Motivation to modify 5‑HMT (increase lipophilicity/prodrug) | A skilled artisan would have sought to increase lipophilicity of 5‑HMT (to improve absorption) or otherwise modify it | Prior art and expert (Dr. Roush) show 5‑HMT did not predictably suffer bioavailability problems (Lipinski Rule of 5); no demonstrated need to prodrug | No motivation shown: substantial evidence supports Board’s finding that a skilled artisan would not be motivated to prodrug 5‑HMT to solve an undefined problem |
| Obviousness of the specific claimed monoesters (including fesoterodine) | Bundgaard teaches ester prodrugs; esterifying the 2‑position to short alkyl esters would have been obvious/routine optimization | Bundgaard teaches many prodrug options and artisans would have considered multiple positions and moieties; large space of candidate esters (many choices) and no teaching of the specific isobutyryl 2‑ester; no evidence prodrugs would be inactive or preferable | Held not obvious: substantial evidence supports Board’s conclusion that prior art did not suggest making the specific claimed compounds and it would not have been routine to narrow to those monoesters |
| Dependent claims (R‑enantiomer, fumarate salt) | These variants would have been obvious to try or follow from routine optimization | No reasoned teaching would have led to those specific choices; lack of analogous examples and routine-selection rationale | Court affirmed Board’s adverse findings (though it considered them unnecessary to outcome) |
Key Cases Cited
- Lujan v. Defenders of Wildlife, 504 U.S. 555 (standing requires injury‑in‑fact, traceability, redressability)
- MedImmune, Inc. v. Genentech, Inc., 549 U.S. 118 (declaratory‑judgment standing where patent listing creates concrete controversy)
- Apotex, Inc. v. Daiichi Sankyo, Inc., 781 F.3d 1356 (Fed. Cir.) (Orange Book listing can create cognizable injury independent of infringement risk)
- Janssen Pharmaceutica, N.V. v. Apotex, Inc., 540 F.3d 1353 (Fed. Cir.) (contrast re: pre‑MMA Hatch‑Waxman framework and standing implications)
- Graham v. John Deere Co., 383 U.S. 1 (obviousness is a legal determination based on underlying factual inquiries)