By Jason Rantanen
In re Brimonidine Patent Litigation (Fed. Cir. 2011) Download 10-1102-1103
Panel: Bryson (author), Dyk (dissenting in part), Prost
Appellate review of obviousness assessments is highly fact-intensive. Although there are several viable legal approaches that can be applied, from the Graham framework to the "obvious to try" analysis, the Federal Circuit's review of this issue largely boils down to an evaluation of the district court's express or implied factual determinations. The CAFC's recent opinion in the Brimonidine patent litigation is no exception, and it highlights the degree to which Federal Circuit judges are willing to dig into the factual record to serve as the ultimate arbiters of obviousness.
In the mid-1990's, Allergan introduced ALPHAGAN, an optically administered solution containing 0.2% brimonidine, a drug that reduces an eye problem associated with glaucoma. An allergic reaction to brimoninidine among some patients led to the introduction of ALPHAGAN P, a formulation with a lower concentration of brimonidine, higher pH, and solubility-enhancing component. ALPHAGAN P also uses stabilized chlorine dioxide (SCD) as a preservative instead of benzalkonium chloride, which was known to be an eye irritant. Although the formulators initially expressed concern that the SCD would oxidize brimonidine, they later found the two were compatible.
Following Apotex and Exela's submission of Abbreviated New Drug Applications seeking permission to market a generic version of ALPHAGAN P, Allergan sued them for infringement of five patents under 35 U.S.C. § 271(e)(2): Patent No. 5,024,078, covering a buffered, aqueous ophthalmic solution generally, and four patents (referred to as the "related patents") more specific to its brominidine-containing product. The district court found all the patents nonobvious following a bench trial and Apotex stipulated to infringement. The district subsequently found that Exela infringed one of the related patents and entered an injunction against both defendants.
Buffered Solution Patent: Obvious
The panel first addressed Apotex's challenge to the district court's nonobviousness ruling on the '078 patent. After analyzing the content of the two prior art patents cited by Apotex, the panel unanimously concluded that the district court was wrong. "Based on the evidence presented at trial, we are convinced that it would have been obvious to one of skilled in the art to adjust the SCD solution disclosed in Ratcliff to approximate physiologic pH, to include a buffer component to maintain that pH, and to include a tonicity component to approximate physiologic osmoloality." Slip Op. at 8. Although a re-evaluation of the evidence is inherent in the panel's analysis, the opinion frames the court's conclusion as one of law: "We therefore hold that the district court committed legal error in concluding that it would not have been obvious to one skilled in the art." Slip Op. at 9.
"Related" Patents: Nonobvious
The majority reached a different result on the four "related patents," concluding that the district court correctly found the narrowest claims to be nonobvious. Here, too, the panel engaged in a detailed analysis of the factual determinations made by the district court. With respect to the "related patents," however, Judges Bryson and Prost agreed that the district court had reached the correct conclusions, giving particular deference to the district judge's weighting of the testimony. The opposite conclusion was reached by Judge Dyk, who dug deeply into the factual record before concluding that the district court had clearly erred.
Reviewing Prior Art Patents vs Other Evidence of Obviousness
Although neither the majority nor dissent explicitly discussed the standard of review, the different ways in which the court handled the two groups of patents perhaps hints at the manner in which the Federal Circuit reviews obviousness determinations. The prior art asserted against the '078 patent consisted of two earlier patents. Although likely not intended by the panel, the opinion's discussion of the '078 patent reads like a de novo review. The analysis of the "related patents" differs significantly. Here, the majority explicitly defers to the district court's factual findings in places, while the dissent concludes that the district court made "clearly erroneous findings of fact," Dissent at 3, implicitly referencing the standard of review. Although somewhat of a subjective assessment, it certainly seems plausible that the CAFC may be much more willing to engage in de novo review on the question of obviousness when the prior art consists of patents as opposed to other forms of evidence
Exela's Noninfringement Appeal
The panel also reversed the district court's determination that Exela's product would infringe one of Allergan's patents. This section of the opinion is largely noteworthy for its discussion of the effects of statements made in ANDAs and the extent to which companies are bound by those statements. The CAFC concluded that the statement in Exela's ANDA that its product would be manufactured with a pH of between 6.5 and 6.7 (the claims required a minimum pH of 7.0) overrode Allergan's argument that Exela might produce its product with a higher pH to account for a fall in the pH that occurs over time. "Here, neither party disputes that if Exela complies with its ANDA, it will never manufacture or sell a product at a pH above 6.7. We cannot assume that Exela will not act in full compliance with its representations to the FDA, and we accordingly reverse the district court's judgment [of infringement]." Slip Op. at 22.