In October 15, 2019, the Swiss Federal Patent Court held in Eli Lilly vs. Sandoz Pharmaceuticals that the Swiss part of Eli Lilly’s patent EP 1 313 508 B1 regarding the use of the anti-cancer drug pemetrexed in combination with a vitamin B12 is valid – almost to the day two years after the Swiss Federal Supreme Court handed down its decision that Actavis’ generic pemetrexed product is directly infringing EP 1 313 508 B1 (see here).

With regard to novelty, the Court found there was neither an explicit nor an implicit disclosure of an administration of pemetrexed in combination with vitamin B12 in Worzalla (Anticancer Res 1998, 18, 3235) as closest prior art. The Court also acknowledged inventive step with regard to each of the four documents Sandoz relied upon (Niyikiza (Annals of Oncology 1998, 9, 4, No. 609P), IBIS (IBIS Guide to Drug-Herb and Drug-Nutrient Interactions™, Copyright©1998-1999), Jackman (Antifolate Drugs in Cancer Therapy, ed. Ann. L. Jackman, 1999, ch. 8) and Calvert (Sem. in Onc. 1999, 26 (2), 3)).

The Court found that Niyikiza only discloses a correlation between toxicity and the non-specific marker homocysteine, but no correlation between toxicity and methylmalonic acid, the specific marker for vitamin B12. The Court concluded that a blockage of the DNA cycle by pemetrexed administration does not block the methylation cycle, in which vitamin B12 acts as a cofactor. Thus even in case of a possible administration of folic acid in the treatment with pemetrexed, the skilled person had no motivation to co-administer vitamin B12.

With regard to IBIS, the Court found that it discussed a different antifolate (methotrexate) regarding a different use (rheumatoid arthritis), which cannot be transferred to an anti-cancer treatment as claimed with the antifolate pemetrexed.

The Court found with regard to Jackman that the experimental results on the effect of folic acid administration in pemetrexed treatment showed that a folic acid administration reduced the antitumor efficacy of pemetrexed and thus would not have been considered. The Court also found that there was no reference to vitamin B12 in the chapter on pemetrexed and, that any such reference in a chapter regarding different antifolates would not be transferable to pemetrexed and thus not considered.

With regard to Calvert, the Court confirmed the decision of the Opposition Division of the EPO that not only is there no disclosure of vitamin B12 but in fact it references Niyikiza, which reports no correlation between toxicity and vitamin B12 (see above). The skilled person would thus have no incentive to turn to vitamin B12.

Finally, the Court dismissed Sandoz’s arguments regarding added matter.

A copy of the decision (in an informal English office translation) can be read here.
A copy of the decision (in German) can be read here.

Reported by: Christian Hilti, Demian Stauber, Andrea Carreira, RENTSCH PARTNER