Docket No. 2015-1407
LOURIE, WALLACH, HUGHES
October 2, 2015
Brief Summary: DC finding that Spectrum’s claims to a “substantially pure” compound (at least 92%) would have been obvious in view of prior art to 50/50 mixture and pure compound (no unexpected advantages). DOE not applicable because of applicants’ “clear and unmistakable surrender of” less than “2000 mg per dose of the mixture”.
Summary: Spectrum (exclusive licensee from Univ. Strathclyde) appealed DC decision that claims 1-2 of US 6,500,829 are obvious and claims 5-9 are not infringed by Sandoz’s ANDA regarding leucovorin used to ameliorate the toxic effects of methotrexate (MTX) used to treate folate deficiency during chemotherapy and enhance 5-fluorouracil (FU) treatment. Leucovorin can exist as a 50/50 mixture of R and S diastereoisomers. Claim 1 of the ‘829 patent encompasses composoitions “which consist essentially of” 6S or 6S/6R mixture with at least 92% by weight (“substantially pure”) 6S “for the treatment of human beings for methotrexate rescue or folate deficiency”. The DC found claims 1-2 obvious since prior art processes “would have ‘invariably’ produced a mixture containing the 6R isomer as an impurity, and…a highly pure (6S) isomer” and that Spectrum could not rebut the prima facie case with secondary factors because it failed to prove any nexus [to] what was claimed”. The question here was, given that the 50/50 mixture and the pure compound were known, would there have been a motivation to produce the claimed “substantially pure” (“at least 92%”) mixture? The FC panel acknowledged that “there is always [where “the desired acitivity all lies in one isomer”] a motivation to aim for a pure, resolved material” and that “no reason had been shown why one would want to have an impure material” but still found no error with the DC findings because “the desirable properties of the prior art 50/50 mixture are attributable to only one component, and the slightly impure mixture…has not been shown to possess unexpected advantages” (and the compounds “are described as ‘substantially pure’ and…not patentably different from pure material”; DC found “a purified (6S) isomer compound…was shown to be clinically interchangeable with the 50/50 mixture”). Claim 5 encompasses the composition with a pharmaceutically acceptable carrier and being “of a quantity at least sufficient to provide multiple doses…in an amount of 2000 mg per dose.” The DC granted SJ of no literal (Sandoz’s vials would only contain up to 250 mg) or DOE infringement of claims 5-9. Regarding DOE, it found a “clear and unmistakable surrender of…composition quantities less than what is required to provide two or more doses of, at minimum, 2000 mg per dose of the mixture”. Spectrum argued “the applicants did not surrender covering aggregate quantities of the mixture” (Sandoz stipulated to future importations of more than 10 grams) but the FC panel agreed with the DC (“The product that is likely to be sold..is what Sandoz’s ANDA describes…single-use vials with 175 mg or 250 mg…far less than at least two doses of 2000 mg each.”) It found that during prosecution “the applicants asserted that newly added [claims 5-9] ‘include specific limitations as to quantities of materials’, and distinguished the prior art by pointing to the ‘quantitites of these specific mixtures specified in the claims.’” Thus, it found no error with the DC decision.