Case Name: Vanda Pharms., Inc. v. Teva Pharms. USA, Inc., Civ. No. 18-651-CFC, 2022 WL 17593282 (Dec. 13, 2022) (Connolly, J.)
Drug Product and Patent(s)-in-Suit: Hetlioz® (tasimelteon); U.S. Patents Nos. RE46,604 (“the ’604 patent”), 10,149,829 (“the ’829 patent”), 9,730,910 (“the ’910 patent”), and 10,376,487 (“the ’487 patent”)
Nature of the Case and Issue(s) Presented: Defendants Teva and Apotex filed ANDAs seeking to market generic tasimelteon capsules. Hetlioz is the only FDA-approved drug indicated for the treatment of Non-24-hour sleep-wake disorder, a circadian rhythm sleep disorder suffered by individuals whose biological clocks do not synchronize to a 24-hour day. Vanda asserted the four patents-in-suit. Defendants have stipulated to infringement of the ’487 patent. Otherwise, Defendants deny infringement and asserted invalidity defenses. After a four-day bench trial, the court found that Defendants do not infringe the ’604 patent, and that claim 3 of the ’604 patent, claim 4 of the ’829 patent, claim 14 of the ’910 patent, and claim 5 of the ’487 patent are invalid.
Why Defendants Prevailed: Vanda contended that Defendants’ ANDA products would induce infringement of claim 3 of the ’604 patent. Because Defendants disputed that they infringe claim 3’s “entraining” and “daily sleep period of approximately 7 to 9 hours” limitations. Because the court found that the ANDA labels did not instruct, recommend, encourage, teach, or promote the use of Defendants’ tasimelteon drug products to treat Non-24 by entraining a patient to a 24-hours sleep-wake cycle, Vanda failed to meet its burden and the court did not address the “daily sleep period” limitation. Moreover, claim 3 was found invalid for obviousness because each element of the claimed method was taught or suggested by two different combinations of prior art references and a skilled artisan would have been motivated to combine the teachings and suggestions of those references to entrain a blind Non-24 patient with the claimed method and would have had a reasonable expectation of success in doing so.
Claim 14 of the ’829 patent was also found to be invalid as obvious. The referenced prior art combinations taught the treatment of patients with 20 milligrams of tasimelteon once daily, that tasimelteon is primarily metabolized by CYP1A2, and that tasimelteon should not be co-administered with any drug that inhibits CYP1A2. A skilled artisan intending to administer tasimelteon to a patient who was already taking a CYP1A2 inhibitor would have expected that tasimelteon should not be co-administered with a CYP1A2 inhibitor and would have heeded the prior art’s warning against co-administering tasimelteon and CYP1A2 inhibitors, especially in light of the well-known drug-drug interaction between ramelteon and fluvoxamine. Therefore, a skilled artisan would have found it obvious to discontinue treatment of a patient with a strong CYP1A2 inhibitor such as fluvoxamine before treating that patient with tasimelteon.
Additionally, claim 4 of the ’910 was found invalid as obvious. The prior art taught the treatment of light perception impaired (i.e. blind) Non-24 patients with 20 milligrams of tasimelteon once daily before a target bedtime; that ramelteon is metabolized by CYP3A4 and should not be used in combination with fluvoxamine or ciprofloxacin; that the CYP inducer rifampin has been shown to considerably decrease levels of both ramelteon and its metabolite M-II; and that to avoid losses in efficacy, relevant CYP enzymes should be avoided when administering ramelteon. A skilled artisan would have looked to ramelteon to predict tasimelteon’s drug-drug interactions because of the many known similarities between ramelteon and tasimelteon, including the fact that ramelteon and tasimelteon have similar structures, half-life durations, and affinities for melatonin receptors (MT1 and MT2). And in light of the well-known similarities between ramelteon and tasimelteon, if a skilled artisan would have intended to administer tasimelteon to a patient who was already taking the CYP3A4 inducer rifampin, then the artisan would have expected that tasimelteon should not be co-administered with rifampin and would have thought it necessary and obvious to stop treating the patient with rifampin before treating the patient with tasimelteon.
Finally, the court found claim 5 of the ’487 patent invalid as obvious. The prior art combinations taught the treatment of Non-24 patients with 20 milligrams of tasimelteon once daily 30 minutes before bedtime. The court also found it is more likely than not that an skilled artisan who was administering tasimelteon within 30 minutes of the patient’s bedtime would do so without food. Therefore, it would have been obvious to a skilled artisan to administer tasimelteon without food 30 minutes before bedtime. Whether to administer tasimelteon with food is a binary choice, and “when two equally viable options are available, as here, then, without more, either one would seem to have been obvious.”
