In Re Brimonidine Patent Litigation
643 F.3d 1366
Fed. Cir.2011Background
- Allergan markets Alphagan P (0.1% and 0.15% brimonidine) for glaucoma; Alphagan (0.2%) caused allergic conjunctivitis.
- Alphagan P uses higher pH (7.15–7.8) and includes CMC and SCD to improve solubility and stability.
- Allergan sought FDA Orange Book patents covering Alphagan P formulations; five related patents and the '078 patent are at issue.
- Apotex and Exela each filed ANDAs seeking generics; Allergan sued for infringement in separate district courts, consolidated in multistate litigation.
- District Court found the '078 patent invalid as obvious and upheld validity of related patents; it issued injunctions against Apotex and Exela.
- On appeal, the Federal Circuit (majority) affirmed-in-part and reversed-in-part regarding Apotex; Exela’s infringement claim was reversed.
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Obviousness of the '078 patent | Apotex contends Ratcliff/Stockel render obviousness. | Allergan argues enhancements (pH, buffer, tonicity) were non-trivial. | Yes: '078 claims were obvious. |
| Validity of the four related patents | All asserted claims non-obvious in light of Alphagan/Refresh Tears. | Obvious to try due to combination with routine modifications. | No: related patents not obvious; injunction upheld as to Apotex. |
| Solubility and CMC as solubility enhancer (related patents) | CMC enhances brimonidine solubility at high pH. | Loftsson references do not teach brimonidine with CMC at relevant conditions. | No clear error; no obviousness finding based on those references. |
| SCD as preservative and oxidation concerns (related patents) | Purite® less oxidizing; oxidation concerns not limiting. | Articulated oxidative concerns would deter mixing Alphagan with Refresh Tears. | Not clearly erroneous; no reversible error; claims survive as non-obvious. |
| Post-trial references and obviousness evidence | Certain admitted references should support obviousness arguments. | No supporting expert testimony; not properly considered. | District court did not abuse discretion in not considering them. |
Key Cases Cited
- Abbott Labs. v. Sandoz, Inc., 544 F.3d 1339 (Fed. Cir. 2008) (obvious-to-try analysis; focus on motivation and reasonable expectation of success)
- Bayer AG v. Elan Pharm. Res. Corp., 212 F.3d 1241 (Fed. Cir. 2000) (ANDA-based infringement; controlling description in infringement inquiry)
- Rolls-Royce v. United Techs. Corp., 603 F.3d 1325 (Fed. Cir. 2010) (obvious-to-try analysis; blocking factors and non-anticipated combinations)
- In re Kubin, 561 F.3d 1351 (Fed. Cir. 2009) ("obvious to try" standard; reasonable expectation of success suffices)
- Wyers v. Master Lock Co., 616 F.3d 1231 (Fed. Cir. 2010) (evidentiary standards for reliance on references; expert testimony context)