Takeda Pharms. U.S.A., Inc. v. West-Ward Pharm. Corp.

Case Name: Takeda Pharms. U.S.A., Inc. v. West-Ward Pharm. Corp., 785 F.3d 625 (Fed. Cir. May 6, 2015) (Circuit Judges Newman, Dyk, and Hughes presiding; Opinion by Dyk, J.; Dissent by Newman, J.) (Appeal from D. Del., Robinson, J.)

Drug Product and Patent(s)-in-Suit: Colcrys^® (colchicine); U.S. Patents Nos. 7,964,648 ("the '648 patent"), 7,981,938 ("the '938 patent"), 8,097,655 ("the '655 patent"), 8,440,722 ("the '722 patent"), and 7,964,647 ("the '647 patent")   

Nature of the Case and Issue(s) Presented: Colchicine itself has been used for centuries. But Takeda owns several patents that cover methods of administering colchicine products to treat gout. Specifically, the ’647 and ’938 patents are directed toward methods of treating acute gout flares. The ’655, ’648 and ’722 patents are directed toward methods for administering colchicine for prophylaxis of gout in patients who are concomitantly taking certain drug inhibitors known as “CYP3A4” and “P-gp” inhibitors.
Defendants sought FDA approval of a colchicine product for prophylaxis of gout flares by submitting a § 505(b)(2) application. Defendants’ application was approved by the FDA on September 26, 2014, and it prepared to begin marketing the drug which is commercially known as Mitigare®. On October 3, 2014, Defendants launched Mitigare and Takeda sued for patent infringement, based on language contained in the Mitigare product labelling. The district court granted Takeda’s request for a temporary restraining order on October 9, 2014, which prevented Defendants from releasing a generic version of its drug. Takeda was also prevented from launching a generic version of its drug while the temporary restraining order was in place, and was also required to provide Defendants with at least 10 business days of notice before the launch of any authorized generic version of Colcrys. On November 14, 2014, the district court denied Takeda’s motion for a preliminary injunction, finding that the Plaintiff did not meet its burden of showing a likelihood of success on the merits for its induced infringement claims or irreparable injury. Takeda immediately appealed the district court’s denial of the preliminary injunction to the Federal Circuit, which affirmed the denial of injunctive relief.

Why Hikma Prevailed: The issue here concerns whether statements contained in Defendants’ drug product labelling were sufficient to establish allegations of induced infringement. Review of a denial of a preliminary injunction is subject to an abuse of discretion standard. In order to obtain a preliminary injunction, the moving party must establish that it is likely to succeed on the merits, that it is likely to suffer irreparable harm in the absence of relief, that the balance of equities is in its favor, and that an injunction is in the public interest. The Federal Circuit limited its analysis to reviewing Takeda’s evidence of induced infringement to determine whether it had established a likelihood of success on the merits.

Defendants’ 505(b)(2) application was not filed in conjunction with a Paragraph IV certification, because Defendants did not seek FDA approval for a use covered by one of Takeda’s asserted patents. Specifically, Defendants’ product labelling indicated that it should be used for prophylaxis of gout flares, which was a use that was not covered by any of Takeda’s patents. The court noted that a generic manufacturer can avoid infringement by proposing a label that does not claim a patented method of use. It was undisputed by Takeda that the labelling for Mitigare stated that it was “indicated for prophylaxis” and that “safety and effectiveness of [it] for acute treatment of gout flares during prophylaxis has not been studied.” Additionally, the product labelling indicated that in the event of a flare, the patient should “tell [her/his] healthcare provider.”

Takeda argued that these instructions were sufficient to establish induced infringement because the instruction to consult a healthcare provider in the event of a flare likely would have led the provider to tell the patient to administer Mitigare in a manner that would infringe Takeda’s patents. The Federal Circuit held that vague label language could not be combined with speculation about how physicians may act in order to find inducement. To support its conclusion, the Federal Circuit noted that there were a variety of ways to treat a gout flare that did not necessarily implicate Takeda’s patented treatment methods. Alternative treatments included the administration of non-steroidal anti-inflammatory drugs such as indomethacin or naproxen and systemic and intra-articular corticosteroids. The Federal Circuit pointed out the fact that Takeda failed to produce evidence that physicians would necessarily forego these alternative treatments in favor of Takeda’s patented methods.

Takeda also argued that it would make little sense for a doctor not to tell a patient to use the Mitigare in an infringing manner, since the patient already presumably had a supply, and it would not make sense for the doctor to also provide the patient with Colcrys. The Federal Circuit rejected the argument that it was “common knowledge” in the field that physicians routinely prescribe approved drugs for off-label uses, that information regarding the off-label prescriptions was “readily available” to the public, and that generic drugs are “commonly substitute[d]” for branded drugs. To support its position, Takeda submitted a physician’s affidavit stating that the physician typically would not prescribe two very similar colchicine products, and that he was aware that Colcrys or Mitigare could be used with equal effectiveness. The Federal Circuit found that proof that doctors would prescribe Mitigare for acute flares was not evidence of inevitability.

Next the Federal Circuit addressed Takeda’s drug-drug interaction patents. Mitigare’s labelling warns patients that co-administration of colchicine and certain inhibitors “have been reported to lead to colchicine toxicity,” that drug-drug interactions must thus “be considered prior to and during therapy,” and that concomitant use “should be avoided if possible.” The label also warns that if co-administration “is necessary, the dose of Mitigare should be reduced and the patient should be monitored carefully for colchicine toxicity.” The label also suggests that if co-administration is necessary, “the dose…should be adjusted by either reducing the daily dose or reducing the dose frequency.” Takeda argued that this language would necessarily lead to induced infringement because a physician would be required to determine whether co-administration was necessary, and if it was, the physician would then follow the patented drug-drug interaction methods. Takeda again introduced a physician’s affidavit indicating that he would typically follow Takeda’s patented methods if it were necessary to co-administer colchicine and the relevant inhibitors. The Federal Circuit rejected this evidence, noting that the language failed to recommend or suggest to physicians that the patented methods should be followed. Additionally, the Federal Circuit found no evidence of any direct infringement of the drug-drug interaction methods by any physician. Finally, the Federal Circuit rejected Takeda’s arguments in relation to the ’655 and ’648 patents. These patents claimed the use of a dose of 0.3 mg of colchicine. The court determined that these patents were unlikely to be infringed, because Defendants’ Mitigare drug was sold in doses of 0.6 mg, and its dosing directions would have been unlikely to lead a patient to get down to the 0.3 mg dose that would have been necessary for infringement.

Judge Newman, in dissent, disagreed with the majority’s opinion that a label that instructs a patient to seek a physician rather than explicitly describing an infringing method of treatment could never rise to the level of induced infringement. Instead, Judge Newman argued that evidence of a physician’s likelihood to prescribe a drug in an infringing manner should be taken into consideration. Such situations are fact-specific, and were not well-served by applying the oversimplified bright-line rule proposed by the majority.