There is no requirement in patent law that the person of ordinary skill be motivated to develop the claimed invention based on a rationale that forms the basis for FDA approval.
On May 1, 2013, in Allergan, Inc. v. Sandoz Inc., the U.S. Court of Appeals for the Federal Circuit (Dyk, Prost,* O'Malley) affirmed-in-part and reversed-in-part the district court's judgment that U.S. Patents No. 7,642,258, No. 7,320,976, No. 7,323,463 and No. 7,030,149, which related to combination ophthalmic drug treatment such as Allergan's Combigan® for treating glaucoma using 0.2% brimonidine and 0.5% timolol, were not invalid under 35 U.S.C. § 103. The Federal Circuit stated:
The determination of obviousness under 35 U.S.C. § 103 is a legal conclusion based on underlying facts. . . . The underlying factual considerations in an obviousness analysis include the scope and content of the prior art, the differences between the prior art and the claimed invention, the level of ordinary skill in the art, and any relevant secondary considerations. Relevant secondary considerations include commercial success, long-felt but unsolved needs, failure of others, and unexpected results. Patents are presumed valid; accordingly, Sandoz was required to prove that the asserted claims were obvious by clear and convincing evidence.
Sandoz makes a strong case that the claims of the '463 patent would have been obvious. Both timolol and brimonidine were commercially available drugs used for opthamalic conditions at the time of the invention. Moreover, they were available in their claimed concentrations, contained the preservative BAK, and the commercially available form of brimonidine -- Alphagan® -- contained BAK in the claimed concentration. At the time of the invention, it was known that the serial administration of brimonidine and timolol reduced intraocular pressure greater than either timolol or brimonidine alone. . . . DeSantis provides an express motivation to combine alpha2-agonists and beta blockers in order to increase patient compliance. The district court, however, found that "while patient compliance may have created a need for fixed combination products, it did not motivate a person of skill in the art to develop fixed combinations with a reasonable expectation of success, because the FDA did not consider improving patient compliance as a factor in its approval decision." We agree with the district court that FDA approval may be relevant to the obviousness analysis, however, we find clear error in the court's conclusion that one of ordinary skill would not be motivated to develop fixed combinations with a reasonable expectation of success.
FDA approval may be relevant to the obviousness inquiry. The potential for FDA approval also may properly be considered, as it was here, in determining whether one of ordinary skill would be motivated to develop a drug product and whether there was skepticism regarding the efficacy of such a product. Nevertheless, we find the district court erred in concluding that one of ordinary skill would not be motivated to develop a fixed combination product to increase patient compliance because the FDA did not consider that particular motivation when evaluating drug applications. There is no requirement in patent law that the person of ordinary skill be motivated to develop the claimed invention based on a rationale that forms the basis for FDA approval. Motivation to combine may be found in many different places and forms; it cannot be limited to those reasons the FDA sees fit to consider in approving drug applications.
When viewed under the proper standard, the evidence of record establishes a motivation to combine brimonidine and timolol into a fixed combination product. Not only does DeSantis teach the fixed combination of timolol with an alpha2-agonist, numerous other references teach the fixed combination of other ophthalmic drugs. In fact, there were at least four other fixed combination products for the treatment of ocular hypertension and glaucoma on the market at the time of invention. Moreover, it was common at the time of the invention to provide brimonidine and timolol to a patient in serial fashion and DeSantis taught that by combining drugs in a fixed-combination formulation, patient compliance could be increased. Accordingly, we find clear error in the district court's finding that there was no motivation to develop a fixed combination brimonide/timolol product.
The district court found that unpredictability in the chemical arts also weighed in favor of nonobviousness. In reaching this conclusion, the district court relied both on general statements regarding the unpredictability associated with developing drug formulations and specific challenges associated with the development of Combigan®. While we agree that formulation science carries with it a degree of unpredictability, "obviousness cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success." Here, there was a reasonable expectation of success based upon the teachings of DeSantis. DeSantis showed that alpha2-agonists and beta blockers are complementary and should be used together. DeSantis further provided that BAK could be successfully used in the formulation. In view of DeSantis, one of ordinary skill would have a reasonable expectation of success in formulating a fixed combination product containing brimonidine, timolol, and BAK.
We find no error in the district court's factual finding that Allergan's formulators faced difficulties in developing Combigan®. However, these difficulties are not particularly probative with respect to obviousness for a number of reasons. For example, the claims are not drawn to the Combigan® formulation with any specificity given that Combigan® contains many elements in addition to those embodied in the claims. There is no requirement that one of ordinary skill have a reasonable expectation of success in developing Combigan®. Rather, the person of ordinary skill need only have a reasonable expectation of success of developing the claimed invention. More importantly, much of the formulators' struggles were associated with their attempts to utilize a proprietary preservative, rather than BAK. There is little evidence that once the formulators switched their focus to BAK they struggled to develop a formulation containing the claimed composition of brimonidine, timolol, and BAK. Accordingly, we find that the district court erred in finding that there was no reasonable expectation of success in view of the general unpredictability of the formulation arts and particularized, yet irrelevant, difficulties associated with the development of Combigan®.