Acorda Therapeutics, Inc. v. Roxane Laboratories, Inc.
903 F.3d 1310
| Fed. Cir. | 2018Background
- Acorda markets Ampyra® (10 mg sustained‑release 4‑aminopyridine (4‑AP) tablets, twice daily) approved by FDA to improve walking in MS patients; Acorda listed several patents (the Acorda patents) plus an earlier Elan patent in the Orange Book.
- The Elan patent claims sustained‑release formulations of 4‑AP for neurological diseases generally; Acorda patents claim a narrower regimen: 10 mg twice daily, stable dosing (≥2 weeks), serum levels ~15–35 ng/ml, with improved walking.
- Multiple prior studies (Stefoski, Davis, Van Diemen, Polman, Bever, Schwid, Goodman, Hayes) explored 4‑AP (mostly immediate‑release), some showing improvements in motor function/walking at various doses and some showing dose‑related toxicity (seizures); Elan developed and tested a sustained‑release formulation but had mixed/unpublished large‑trial results.
- Acorda ran dose‑finding and Phase II/III trials, ultimately showing efficacy for 10 mg twice daily; Acorda filed patent applications with a 2004 priority date and obtained FDA approval in 2010.
- Generic manufacturers filed ANDAs; defendants in the district court conceded infringement but challenged validity. The district court found the Acorda patent claims obvious and the Elan patent valid; appeal followed.
Issues
| Issue | Plaintiff's Argument (Acorda) | Defendant's Argument (Generics) | Held |
|---|---|---|---|
| Obviousness (motivation/expectation to combine prior art to yield 10 mg BID SR 4‑AP improving walking) | Prior art did not teach/stable‑dose 10 mg BID as effective; prior work taught titration and suggested higher doses needed; no reasonable expectation of success. | Schwid and Goodman (and other studies) taught efficacy of SR 4‑AP on walking or motor function at doses in/near the claimed range and warned of toxicity at higher doses, motivating lower stable dosing with reasonable expectation of success. | Court affirmed obviousness: skilled artisan would be motivated to test 10–20 mg BID SR 4‑AP with a reasonable expectation of success; 10 mg BID was an attractive, low‑end choice. |
| Pharmacokinetic limitation (serum 15–35 ng/ml) | Serum‑level limitation is not taught as tied to efficacy for MS walking; not suggested by prior art. | Hayes (Hayes et al.) disclosed steady‑state Cav for 10 mg BID SR ≈20.8 ng/ml; those PK results were inherent to the formulation/dosing and known to skilled artisans. | Held that Hayes disclosed the PK results and that the claimed plasma range was inherent in the known 10 mg BID SR dosing, so PK limits do not negate obviousness. |
| Objective indicia (commercial success, long‑felt need, failure of others) | Strong objective indicia: Ampyra’s commercial success, long‑felt unmet need, and past failures support nonobviousness. | The Elan patent acted as a blocking patent/licensing regime that deterred others, diminishing probative force of those indicia. | Court affirmed discounting of indicia in context: blocking patent evidence reduced weight of commercial success/failure‑of‑others; overall evidence still established obviousness. |
| Mootness of cross‑appeal re: Elan patent validity/injunction | (Acorda as appellee) | Defendants cross‑appealed Elan validity and injunction. | Cross‑appeal dismissed as moot because injunction expired with Elan patent and no prospective relief remained. |
Key Cases Cited
- KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007) (framework for motivation to combine and obvious‑to‑try analysis)
- Graham v. John Deere Co. of Kansas City, 383 U.S. 1 (1966) (Graham factors for obviousness including objective indicia)
- Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344 (Fed. Cir. 2012) (recognizing that claiming inherent PK parameters of a known dosage form does not necessarily impart nonobviousness)
- In re Cyclobenzaprine Hydrochloride Extended‑Release Capsule Patent Litig., 676 F.3d 1063 (Fed. Cir. 2012) (standard for reasonable expectation of success and evaluation of PK‑based claims)
- Merck & Co. v. Teva Pharm. USA, Inc., 395 F.3d 1364 (Fed. Cir. 2005) (blocking patent may reduce probative value of commercial success)
- Merck Sharp & Dohme Corp. v. Hospira, Inc., 874 F.3d 724 (Fed. Cir. 2017) (blocking patents affect but do not automatically negate objective indicia; fact‑specific inquiry)