In Valeant Pharmaceuticals Int’l, Inc. v. Mylan Pharmaceuticals Inc., No. 2018-2097 (Fed. Cir. April 8, 2020), the Federal Circuit was asked “whether prior art ranges for solutions of structurally and functionally similar compounds that overlap with a claimed range can establish a prima facie case of obviousness.” Concluding that they can, the Federal Circuit reversed and remanded the district court’s grant of summary judgment of non-obviousness of the sole claim at issue.
The claim at issue was directed to a stable pharmaceutical preparation comprising a solution of methylnaltrexone or a salt thereof, wherein the preparation comprises a pH between about 3.0 and about 4.0, the preparation being stable for storage for 24 months at about room temperature. The claimed pH range overlapped with a range of pH 3.0 to 7.0 in the art for structurally related compounds.
Relying on its body of case law that structurally similar chemical compounds can be expected to have similar properties, the court held that: “the principle established in these cases applies more broadly: a person of skill in the art can expect that compounds with common properties are likely to share other related properties as well.” Where “compounds share significant structural and functional similarity, those compounds are likely to share other properties, including optimal formulation for long term stability.” Reviewing the evidence of record, the court found that based on “the strong structural and functional similarity between the molecules, a person of skill could expect similar stability of the molecules at similar pH ranges in solution.”
The district court erred by rejecting this “inference” at the summary judgment stage. Because the three prior art molecules bore “significant structural and functionality similarity” and the prior art taught an overlapping pH range, defendant at least raised a prima facie obviousness argument sufficient to survive summary judgment.
The court did caution that its holding “should not be misconstrued to mean that molecules with similar structure and similar function can always be expected to exhibit similar properties for formulation,” an inquiry dependent upon the individual facts of each case. When tried to a factfinder, plaintiff might rebut that prima facie case, for example, by establishing the criticality of the claimed range, or that the structural differences between molecules yield unexpected results, or that the prior art teaches away from the claimed invention.
The court also faulted the district court for holding that as a matter of “basic math” the quantity of number ranges falling between pH 3 and 7 was infinite. Rather, the “bounded range of pH 3 to 4 presents a finite number of narrower pH ranges for a skilled artisan to try. As a matter of math, there may be an infinite potential number of ranges within the range 3 to 4, but only if the realities of pH values (and the limitations of commercially available pH meters) are ignored.”
The district court also erred in rejecting evidence regarding pH manipulation because no reference listed pH as the “first variable” that a skilled artist would try. “[T]here is no requirement that for a variable to be obvious to try, it must be the first variable a person of skill would alter.” It was also important that pH was the only variable in the claim, not one of many to be tried. Moreover, because the claim required only the compound and the claimed pH level, “it can be presumed, if the claim is valid, that the stability for up to 24 months must be due to the nature of the compound in the solution and the claimed pH level.”
Both prosecutors and litigators should be aware of the potential implications of the court’s decision. Opponents of formulation patents will certainly attempt to rely on the holding, and we will likely see attempts to broaden its application beyond claims directed to formulation stability. Claims directed to pharmacokinetic profiles, food effects, and other “functional” types of claiming for formulation or method of treatment claims will likely face challenge under the court’s rationale. It remains to be seen how broadly and to what “other related properties” that rationale might be extended.