Par Pharmaceutical, Inc. v. Twi Pharmaceuticals, Inc.
773 F.3d 1186
| Fed. Cir. | 2014Background
- Par Pharma developed and obtained FDA approval for a nanosized megestrol acetate oral suspension (Megace ES) that reduced the fed/fasted (food) effect observed in the older micronized product (Megace OS); Par later pled guilty to certain misbranding charges unrelated to patentability.
- Par obtained U.S. Patent No. 7,101,576 claiming methods of treating anorexia/cachexia using nanosized megestrol with specific particle-size, dosing, and pharmacokinetic "no substantial difference" (food effect) limitations.
- TWi filed an ANDA to market a generic nanosized megestrol and asserted the ’576 patent was invalid; the parties litigated in the D. Md., where the bench trial found the asserted claims obvious and invalid.
- The district court found prior art disclosed micronized megestrol and nanoparticle (NanoCrystal) technology and concluded the reduced food effect limitation was inherent in the obvious combination, supporting invalidity; it also found motivation to combine (viscosity/interpatient variability) and reasonable expectation of success.
- On appeal, the Federal Circuit vacated and remanded because the district court applied an incorrect, overly broad inherency standard in the obviousness analysis — remanding for findings whether the food-effect limitation is necessarily present (i.e., the natural result) of the prior-art combination.
Issues
| Issue | Par's Argument | TWi's Argument | Held |
|---|---|---|---|
| Whether the claimed "no substantial difference" fed/fasted Cmax limitation is disclosed by prior art (inherency) | The food-effect limitation was not known in the prior art and thus not disclosed; inherency cannot be presumed from possible benefits of nanosizing | The limitation is an inherent result of combining known megestrol formulations with nanoparticle technology (reduced particle size => improved bioavailability => reduced food effect) | Vacated and remanded: district court used an incorrect inherency standard; remand required to determine if the limitation is necessarily present in the prior-art combination |
| Whether the asserted claims are obvious based on prior art (motivation to combine) | No motivation to combine since food effect was not known; thus no reason to nanosize megestrol for that purpose | Multiple motivations existed (reduce viscosity, improve bioavailability, reduce interpatient variability); NanoCrystal tech taught these benefits | Affirmed factual findings: motivation to combine existed (viscosity/interpatient variability) |
| Whether there was a reasonable expectation of success in using nanoparticle technology with megestrol | Nanoparticle technology was new, unpredictable in 2002; no reasonable expectation of success | Prior art (Liversidge patents, publications, marketing) showed predictable improvements across BCS Class II drugs and touted simplicity/reliability | Affirmed: reasonable expectation of success existed based on prior art disclosures |
| Role of objective indicia (unexpected results, long-felt need) in obviousness | Unexpected reduction in food effect and improved weight gain show nonobviousness; long-felt need supports patentability | Even if unexpected, other motivations (viscosity/variability) and strength of prior art outweigh these indicia | District court properly considered objective indicia; affirmed that the evidence did not overcome the showing of obviousness on the record, but remand on inherency required |
Key Cases Cited
- Graham v. John Deere, 383 U.S. 1 (establishes the Graham factual framework for obviousness)
- KSR Int’l Co. v. Teleflex, 550 U.S. 398 (adopted an expansive, flexible approach to obviousness)
- In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litig., 676 F.3d 1063 (standard for motivation to combine and reasonable expectation of success)
- Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989 (burden and proof regarding unexpected results in rebutting obviousness)
- In re Oelrich, 666 F.2d 578 (inherency requires the natural result, not mere possibility)
- Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344 (limitations that are merely inherent serum concentrations cannot render an obvious formulation patentable)
- Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362 (inherency in obviousness when the limitation is necessarily present)
- In re Napier, 55 F.3d 610 (inherency is a question of fact)
- In re Rijckaert, 9 F.3d 1531 (inherency cannot be established by probabilities or possibilities)