Spectrum Pharmas. V. Sandoz Inc., (Fed. Cir. October 2, 2015)

Addressing an unusual twist on an obviousness case, the U.S. Court of Appeals for the Federal Circuit held a substantially pure isomer obvious in view prior art disclosing both a completely pure isomer and an impure mixture. Spectrum Pharmas. V. Sandoz Inc., 15-1407(Oct. 2, 2015) (Lourie, J.). The court also held that Spectrum surrendered any doctrine of equivalents arguments related to different dosages during prosecution.

The case related to the drug leucovorin, and a patent covering a mixture of its isomers. Leucovorin has a chiral sixth carbon, so it exists in two enantiomers, 6R and 6S. The 6S enatiomer has a variety of therapeutic uses including counteracting the toxic effects of methotrexate, a cancer treatment, and treating folate deficiency. The 6R enantiomer lacks any relevant therapeutic effects.

Spectrum’s patent covered substantially pure mixtures of the two enantiomers with at least 92 percent or 95 percent 6S enantiomer, depending on the claim. The prior art disclosed two relevant formulations, a 50/50 mixture of both enantiomers and a completely pure 6S formulation. Sandoz argued those two pieces of prior art rendered the Spectrum patent obvious. Spectrum countered that a person of skill in the art lacked motivation to pursue a substantially pure 6S isomer since the completely pure isomer already existed in the art. The court sided with Sandoz, invalidating the patent.

For the motivation argument, the court focused on the 50/50 mixture. It found that a person of skill in the art had the motivation to purify the 50/50 mixture, regardless of the already existing completely pure isomer. The court also held the patent invalid over the completely pure isomer. It reasoned that the substantially pure isomer worked identically to the completely pure isomer for treatment purposes, so no unexpected result justified finding the substantially pure isomer non-obvious.

The court also addressed five claims related to the dosage amount. The Spectrum patent’s claims limited it to “a quantity sufficient to provide multiple doses . . . in an amount of 2000mg per dose.” Sandoz’s abbreviated new drug application (ANDA) covered a product distributed in vials of 175 milligrams or 250 milligrams. Spectrum argued that because Sandoz would import those vials in aggregate amounts beyond the 2,000 milligram doses, they infringed under the doctrine of equivalents. The court held the Sandoz vials did not infringe because Spectrum repeatedly emphasized the importance of their dosage size during prosecution to ensure that their patent issued over another prior art reference that disclosed a different amount of leucovorin. As such, Spectrum surrendered equivalents arguments based on other dosage sizes.

This case provides a road map to patent defendants seeking to invalidate formulation patents that stress purity as their novel aspect, and it also highlights the litigation importance of arguments and interpretations made during a patent’s prosecution.