On Aug. 15, 2023, Delaware district court found Lonsurf®patent valid and infringed.

 

This is an Hatch-Waxman litigation related to Lonsurf® [combination of trifluorothymidine (FTD) & tipiracil – called TAS-102 therapy] product, marketed by Taiho pharmaceuticals. USFDA approved Lonsurf® for treating adult patients with metastatic colorectal cancer who have already received certain other prior treatments. Defendants (Aurobindo / Accord / MSN Pharma / Natco) filed ANDAs with the FDA to market generic version. Taiho alleged that Defendants’ ANDA submissions constitute infringement of claim 13 of U.S. Patent No. RE46,284.  Claim 13 is directed towards 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 of treatment followed by two days off treatment. Defendants do not dispute that they infringe the #284 patent, but they argue that the #284 patent is invalid for obviousness and for lack of an adequate written description.

 

Obviousness:

Defendants argued that TAS-102 and its oral administration; dosage; molar ratio; and five days on, two days off administration schedule are all explicitly disclosed in the prior arts. Prior arts did not disclose specifically, twice-daily doses but defendants argued that it would have been “common sense,” based on the relevant prior art, to administer TAS-102 in twice-daily doses. Court said that the prior arts would have motivated an artisan of ordinary skill in January 2005 to administer TAS-102 in divided doses. However, defendants did not adduce clear and convincing evidence that a skilled artisan would have been motivated administer TAS-102 in twice-daily doses. Emura II’s authors “concluded that multiple daily dosing may result in better clinical benefits of TAS-102 when compared with single daily dosing.” But Emura II compared only the results of thrice-daily and once-daily
T AS-102 dosing. Emura II did not report any results about twice-daily TAS-102 dosing. Defendants also did adduce evidence that “other oral chemotherapy combinations were known to be given two times a day in the relative time frame.” Court gave little weights to secondary considerations.

 

Written Description Requirement:

Defendants argued that the #284 patent’s specification does not show that the inventors were in possession of all of claim 13’s inventive aspects-namely, twice-daily administration of TAS-102 to a patient with colorectal cancer. Although the #284 patent’s written description describes a study in which TAS-102 was administered twice-daily to
breast cancer patients, Defendants said that breast and colorectal cancer are too distinct to compare helpfully. Court said that the #284 patent’s written description does include “Example 3” and “Example 4,” which respectively describe the study 9805 (digestive cancer with thrice-daily dosing) and study 9804 (breast cancer with twice-daily dosing) that Taiho conducted. In both Example 3 and Example 4, TAS-102 was administered every five days followed by two days off treatment. Court found Dr. Goldberg’s testimony credible that “Phase I studies are often” conducted with a “collection of patients with many types of primary, including breast and GI cancers,” and breast and colorectal cancer are both solid tumors that “commonly respond to cytotoxic agents.” Based on this record, Court found that Defendants have not adduced clear and convincing evidence that the #284 patent lacks written description support.