Spectrum Pharms., Inc. v. Sandoz Inc.

Many prior cases have addressed whether a pure stereoisomer is obvious when the corresponding 50/50 mixture is known in the prior art. In upholding a finding of summary judgment, however, the U.S. Court of Appeals for the Federal Circuit has for the first time addressed whether a substantially pure chemical enantiomer is obvious when both the 50/50 mixture and the pure stereoisomer are in the prior art. It is Spectrum Pharms., Inc. v. Sandoz Inc., Case No. 15-1407 (Fed. Cir., Oct. 2, 2015) (Lourie, J.).

Spectrum Pharmaceuticals markets leucovorin, a drug that helps alleviate the toxic effects of certain chemotherapy drugs. Leucovorin naturally exists as a mixture of two stereoisomers, which can be thought of in simple terms as mirror images—or “left hand” and “right hand” versions—of the same molecule. The patent at issue claims a pharmaceutical composition of leucovorin consisting of “at least 92%” or “at least 95%” by weight of the (6S) diastereoisomer. After the district court held certain claim invalid as obvious, Spectrum appealed.

The Federal Circuit agreed, finding the subject claims obvious over the prior art, which disclosed: the 50/50 mixture of leucovorin diastereoisomers, the pure (6S) diastereoisomer, a process for purifying the pure (6S) isomer from the 50/50 mixture and that the (6S) isomer was the particular isomer responsible for leucovorin’s therapeutic activity. In particular, the Court agreed with the district court that a person of skill in the art would have been motivated to modify the 50/50 prior art mixture to arrive at the claimed mixtures, which are substantially (but not completely) pure. Because it was known in the art that the biologic activity of leucovorin resides in the (6S) isomer, “surely, it is better, and there is generally motivation, to try and obtain the purest compound possible.”

The Court further noted that there was no evidence in the record to indicate that the 92 percent to 95 percent pure (6S) isomer possessed any unexpected advantages over the either the completely pure compound or the 50/50 mixture. For example, the Court agreed that a person of skill in the art “would not have expected there to be any differences in the biological properties between purified (6S) leucovorin with or without a small amount of (6R) impurity . . . because small amounts of the inactive isomer would not be noticeable in terms of therapeutic effects.”

The only objective indicium of non-obviousness at issue on appeal was long-felt but unmet need, and the Federal Circuit upheld the district court’s conclusion that no such long-felt need existed. Interestingly, the same factual findings that helped to defeat Spectrum’s non-obviousness arguments also served to defeat Spectrum’s long-felt need argument. In particular, the Court noted that even if there were a long-felt need, the substantially pure (6S) isomer could not have met that need because it was found to be clinically interchangeable with the 50/50 mixture and, similarly, did not show “any meaningful difference” from the completely pure (6S) isomer.