Insite Vision Incorporated v. Sandoz, Inc.
783 F.3d 853
| Fed. Cir. | 2015Background
- Patents-in-suit: Pfizer’s ’411 patent (topical ocular azithromycin) and Insite’s ’113, ’443, ’893 patents (aqueous polymeric azithromycin ophthalmic formulations and methods). Inspire is licensee; Azasite® is the marketed product listed with the patents.
- Sandoz filed an ANDA with a Paragraph IV certification challenging the patents as invalid for obviousness; plaintiffs sued under 35 U.S.C. § 271(e).
- After claim construction, Sandoz stipulated infringement and litigated obviousness at a bench trial; district court found asserted claims not obvious and excluded late-proffered EPO file history evidence.
- Key factual findings credited by the district court: azithromycin had unfavorable properties for topical ocular delivery (high molecular weight, charge, poor solubility), numerous alternative ophthalmic antibiotics (e.g., fluoroquinolones) were known, and water-based azithromycin formulations raised stability concerns.
- District court also found persuasive secondary considerations (unexpected high topical concentrations and long-felt need) supporting nonobviousness.
- Sandoz appealed both the obviousness rulings and the exclusion of the EPO file history; the Federal Circuit affirmed.
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Proper framing of the obviousness problem | Frame broadly as whether developing a topical ophthalmic formulation containing azithromycin would have been obvious | Frame narrowly as whether topical azithromycin for conjunctivitis would have been obvious | Court upheld district court: framing is a fact-based inquiry; broad framing was not clear error and did not preclude Sandoz from proving narrower obviousness |
| Obviousness of the ’411 patent | Topical azithromycin would have been obvious by analogy to erythromycin topical (Ilotycin) and oral azithromycin (Zithromax); topical delivery is generally preferable | Prior art taught away: azithromycin’s properties made topical use uncertain; many superior alternatives existed; oral delivery relied partly on phagocytosis | Affirmed nonobvious: Sandoz failed to prove obviousness by clear and convincing evidence |
| Obviousness of the ISV patents (aqueous polymeric gel formulations) | Obvious to combine Insite’s DuraSite®/’535 patent polymer with azithromycin by substituting erythromycin for azithromycin; ’411 patent examples also disclose aqueous azithromycin | Prior art did not motivate use of aqueous polymers with azithromycin due to solubility/stability concerns; ’535 is a laundry list and does not teach azithromycin; ’411 examples insufficient | Affirmed nonobvious: district court’s factual findings supported; secondary considerations favored nonobviousness |
| Exclusion of EPO file history evidence | EPO file history shows contemporaneous proposals (Geneva meeting) supporting motivation to use topical azithromycin; exclusion was prejudicial | Exclusion justified as last-minute, prejudicial to plaintiffs, containing attorney argument and uncertain probative value under U.S. law | Affirmed exclusion: district court did not abuse discretion under Pennypack factors |
Key Cases Cited
- Graham v. John Deere Co., 383 U.S. 1 (setting the Graham obviousness framework)
- KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (obviousness: predictable solutions and motivation to combine)
- Microsoft Corp. v. i4i Ltd., 564 U.S. 91 (presumption of validity and clear-and-convincing evidentiary standard)
- Merck & Co. v. Biocraft Labs., 874 F.2d 804 (when a reference expressly teaches a combination or formulation)
- Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362 (motivation to combine need not match patentee’s stated motivation)
- Proctor & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989 (obviousness: motivation to combine and expectation of success)
- Tyco Healthcare Grp. LP v. Ethicon Endo-Surgery, Inc., 774 F.3d 968 (bench-trial review standards for obviousness)
- Novo Nordisk A/S v. Caraco Pharm. Labs., 719 F.3d 1346 (appellate review of factual findings)
- Muniauction, Inc. v. Thomson Corp., 532 F.3d 1318 (breadth of claims and obvious subject matter)
- Bayer Schering Pharma AG v. Barr Labs, 575 F.3d 1341 (motivation/expectation in obviousness analysis)