Case Name: Taiho Pharm. Co., Ltd. v. Eugia Pharma Specialties Ltd., Civil Nos. 19-2309-CFC, 19-2321-CFC, 19-2342-CFC-JLH, 19-2368-JLH, 2023 WL 5218125 (D. Del. Aug. 15, 2023) (Connolly, J.)

Drug Product and Patent(s)-in-Suit: Lonsurf® (trifluorothymidine / tipiracil); U.S. Patent No. RE46,284 (“the ’284 patent”)

Nature of the Case and Issue(s) Presented: Lonsurf is an oral combination therapy indicated to treat metastatic colorectal cancer in adults that have failed on previous treatments. Lonsurf contains two active ingredients: trifluorothymidine (FTD) and tipiracil. Plaintiff asserted claim 13 of the ’284 patent, which recited a method of treating patients with colorectal cancer by orally administering a specific dosage and molar ratio of FTD and tipiracil in two divided portions per day for a period of five days followed by two days without treatment. Defendants did not dispute infringement, but instead argued that the ’284 patent was invalid for obviousness and lack of written description. Following a two-day bench trial, the court found that Defendants have not proven claim 13 invalid.

Why Plaintiffs prevailed: Regarding the issue of obviousness, the parties agreed that every element of the asserted claim was in the prior art, except for the twice-daily dosing limitation. The court concluded that a skilled artisan would have been motived to administer the combination therapy in divided doses, but that a skilled artisan would not have been motivated to administer in twice-daily doses. In particular, the closest prior art examined three-times daily dosing compared to once-daily dosing, and, as such, a skilled artisan would not have been motivated to administer twice-daily doses.

The court also addressed secondary indicia of non-obviousness. As to unexpected results, the court found that the inventor’s testimony “sounded mystical” and that he “had a really hard time accepting that … was a scientific approach” to twice-a-day dosing. As to long-felt need, the court agreed that a need existed for treatment options that would extend the length and quality of life of patients with advanced colorectal cancer, but found that because of its complicated dosing schedule, Lonsurf failed to satisfy this need. With respect to industry praise, the court agreed that the industry praised Lonsurf as a product, but found that there was no record evidence that the industry praised the dosing schedule in claim 13 of the ’284 patent. Finally, as to commercial success, the court agreed that Lonsurf was a financial success, but did not find that this factor weighed in favor of non-obviousness because Taiho’s other patents barred others from commercially testing the features of the asserted claim. Despite concluding that no secondary indicia of non-obviousness were present, the court still found that the patent was not invalid as obvious.

Regarding inadequate written description, Defendants argued that the ’284 patent specification did not adequately describe a study in which colorectal or digestive cancer patients were orally administered the recited combination therapy in twice-daily doses for a period of five days followed by two days of rest. The examples in the patent did, though, describe clinical trials where breast cancer patients received the combination therapy by oral administration twice-daily. Defendants argued that the studies in the specification were run on different diseases—breast cancer—and that any conclusions would not apply equally to colorectal cancer. The court disagreed, finding that both breast and colorectal cancer are solid tumors that commonly respond to cytotoxic agents.