On Jan 16, 2019, Court of The Hague dismissed Sandoz invalidity argument & found Alimta® combination patent valid.
Lilly is the proprietor of EP 1313508 B1 (expiring on Jun 15, 2021), entitled, “Combination containing an antifolate and methylmalonic acid lowering agent “. EP’508 contains two independent claims (1 and 12) which relate to use of pemetrexed disodium & vitamin B12 combination therapy for inhibiting tumor growth. Dependent claims further require addition of folic acid to the therapy. Lilly markets the Alimta® for the treatment of certain lung cancers which contains pemetrexed disodium as active substance. Sandoz intends to market generic medicine of Alimta®. Sandoz put forth invalidity attack on EP’508.
Court in summary held that prior arts mainly starting point for inventive step attack did not show that it was belonging to the general professional knowledge at the time of priority. Specifically, the combination of pemetrexed & folic disclosed in prior arts did not teach that the said combination would be helpful in treating cancers. Though prior arts disclosed role of folic acid in reducing the toxicity of antifolate drugs such as pemetrexed but it did not teach the possible effect of this combination on efficacy. Person skill in the art would have recognized that folic acid decreases the toxicity associated with pemetrexed but at the same time the efficacy of pemetrexed would have been decreased. To counteract this decreased efficacy skilled person would have increased the dose of pemetrexed but again it would have detrimental effect of body organs such as kidney leading to renal toxicity as known from the prior arts. The District Court also took into account that the documents discussed concerning the combination of pemetrexed and folic acid date back to 1998 and that if these (potentially) show a successful combination therapy for cancer, it would be expected that this combination on the priority date in the treatment of cancer was applied, at least that further studies for that application would have taken place. Sandoz neither stated nor proved that this was the case.
Now that the combination therapy of pemetrexed and folic acid cannot be regarded as a given for the person skilled in the art on the priority date, Sandoz’ arguments were rejected. Therefore, the court also rejected the arguments regarding the combination with vitamin B12 based on additional prior arts.
The said EP’508 patent also litigated in many EU countries with respect to infringement issues. Few had reached to the Supreme Court in countries like UK, Germany. Most of the decisions across many jurisdictions are on same page & they found infringement whether generic uses same or different salts. See my previous post of “May 2018 here”. There might be few updates /changes happened after this post, which I might not have captured.