The general lesson is that obviousness involves a weighing of the evidence and that it may be the case that no issue alone is dispositive. More specific lessons are that motivation to combine in drug applications “cannot be limited to those reasons the FDA sees fit to consider in approving drug applications,” and that “the person of ordinary skill need only have a reasonable expectation of success of developing the claimed invention” itself, not of achieving any particular or preferred embodiment.
Background / Facts: This action concerns a combination ophthalmic drug treatment and arises under the Hatch-Waxman Act, which enables the approval and marketing of generic drugs. Each of the Appellants in this case submitted to the U.S. Food and Drug Administration (“FDA”) an Abbreviated New Drug Application (“ANDA”) seeking approval to market a generic version of Allergan’s glaucoma drug Combigan, a combination of the well-known alpha2-agonist Alphagan (0.2% brimonidine) and the well-known beta-blocker Timoptic (0.5% timolol), both of which are also used to treat glaucoma.
Issue(s): Whether the combination comprising 0.2% brimonidine and 0.5% timolol was as a whole obvious.
Holding(s): Yes. This was a true weighing of the evidence decision. The court found in the prior art that “[b]oth 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. Moreover, [the reference] DeSantis expressly provided a motivation to formulate fixed combinations of alpha2-agonists and beta blockers, including timolol, in order to increase patient compliance.” Ultimately, the court acknowledged the district court’s factual findings with regard to motivation to combine, reasonable expectations of success, and secondary considerations of non-obviousness, but found them to be insufficient. With regard to motivation to combine, while the court acknowledged that likelihood of “FDA approval may be relevant to the obviousness inquiry” and that “the FDA did not consider improving patient compliance [as in this case] as a factor in its approval decision,” it concluded that “[m]otivation 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.” With regard to reasonable expectation of success, the court cautioned that any problems associated with achieving the claimed invention must be to the broadest scope of the claimed invention and not any particular embodiment. “There is no requirement that one of ordinary skill have a reasonable expectation of success in developing [the preferred commercial embodiment] Combigan. Rather, the person of ordinary skill need only have a reasonable expectation of success of developing the claimed invention.” With regard to the secondary considerations of non-obviousness, the court was simply unimpressed by the unexpected results. “We agree with the [district] court’s finding that this result was unexpected. However, we do not find that these unexpected results are sufficient to outweigh the other evidence of obviousness as to these formulation claims.”