522 F.Supp.3d 200
N.D.W. Va.2021Background:
- AstraZeneca sued Mylan under the Hatch–Waxman framework after Mylan filed an ANDA to market generic versions of Symbicort®; the dispute concerned validity of specific claims in U.S. Patents 7,759,328; 8,143,239; and 8,575,137 covering a pMDI suspension formulation and related treatment methods.
- The asserted claims recite a suspension comprising budesonide and formoterol fumarate dihydrate in HFA‑227 with excipients PVP K25 at 0.001% w/w and PEG‑1000 at 0.3% w/w (and specified dose per actuation for certain claims).
- Mylan argued the claims were obvious: a person of ordinary skill (POSA) would have been motivated to convert the marketed Symbicort® DPI to a pMDI and to use HFA‑227, PVP, and PEG at routine grades/concentrations through ordinary optimization.
- AstraZeneca argued the prior art (notably Rogueda and Mistry) taught away, presented stability/adhesion problems with the closest formulations, left enormous ‘‘design‑space’’ choices, and that the claimed low PVP concentration produced unexpected stability demonstrated in prosecution and testing.
- The Court found key prior art controls discouraged the claimed combination, that the number of plausible combinations made routine optimization unlikely to yield the claimed formulation with a reasonable expectation of success, and credited AstraZeneca’s unexpected‑stability evidence.
- Holding: The Court concluded Mylan failed to prove invalidity by clear and convincing evidence; the asserted claims are valid and enforceable.
Issues:
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Whether the asserted claims are invalid for obviousness | AstraZeneca: prior art teaches away; no motivation to combine elements; unexpected stability supports validity | Mylan: obvious to reformulate DPI to pMDI and to select HFA‑227, PVP K25, PEG‑1000; routine optimization would reach claimed concentrations | Court: Mylan failed to meet clear and convincing burden; claims not obvious |
| Motivation to select and combine claimed elements | AstraZeneca: many viable alternatives; no clear path; PTO found claims nonobvious based on stability data | Mylan: market pressure and known prior art would motivate a POSA to try available options and grades | Court: While motivated to make some pMDI, there was no reasoned motivation to select the specific claimed combination from the vast design space |
| Whether the prior art (Rogueda controls) teaches away | AstraZeneca: Rogueda controls showed adhesion/instability for similar formulations—discouraging a POSA | Mylan: Rogueda shows feasibility of similar formulations | Court: Rogueda taught away; its data would have discouraged pursuing the claimed combination |
| Reasonable expectation of success / unexpected properties | AstraZeneca: POSA would not reasonably expect a stable, dose‑uniform product; claimed formulation showed unexpected superior stability | Mylan: routine screening/optimization of known excipients and propellants would have produced the invention | Court: No reasonable expectation of success; evidence of unexpected stability further supports validity (court reached this as supportive even though not strictly necessary) |
Key Cases Cited
- KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007) (articulates an expansive, flexible obviousness inquiry and the ‘‘obvious to try’’ framework)
- Graham v. John Deere Co., 383 U.S. 1 (1966) (sets out factual inquiries for obviousness analysis)
- Microsoft Corp. v. I4i Ltd. P'ship, 564 U.S. 91 (2011) (patent claims are presumed valid; invalidity must be shown by clear and convincing evidence)
- In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003) (overlapping ranges in prior art can motivate optimization)
- Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352 (Fed. Cir. 2011) (prior art must guide a POSA to a particular solution to render it obvious)
- Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280 (Fed. Cir. 2012) (focus on the path a POSA would have followed, not the inventor’s actual path)
- WBIP, LLC v. Kohler Co., 829 F.3d 1317 (Fed. Cir. 2016) (analysis of whether a POSA would select particular references to combine)
- Leo Pharm. Products, Ltd. v. Rea, 726 F.3d 1346 (Fed. Cir. 2013) (absence of ‘‘clues’’ pointing to promising combinations undercuts obviousness)
- Institut Pasteur & Universite Pierre et Marie Curie v. Focarino, 738 F.3d 1337 (Fed. Cir. 2013) (assessing reasonable expectation of success in obviousness inquiry)
- Allergan, Inc. v. Sandoz, Inc., 796 F.3d 1293 (Fed. Cir. 2015) (claimed ingredient amounts can unpredictably and materially alter formulation properties)