Takeda Pharmaceuticals U.S.A., Inc. v. West-Ward Pharmaceutical Corp.
Docket: Civ. No. 14-1268-SLR
Court: District Court, D. Delaware; May 18, 2016; Federal District Court
On October 3, 2014, Takeda Pharmaceuticals U.S.A. Inc. initiated a lawsuit against West-Ward Pharmaceutical Corporation and its affiliates, claiming induced infringement of five patents under 35 U.S.C. § 271(b) related to its colchicine product, Colcrys®, which is used for gout flare treatment. Hikma's product, Mitigare, also contains colchicine and is indicated for gout prophylaxis but was submitted to the FDA via a New Drug Application (NDA) rather than an Abbreviated New Drug Application (ANDA). Notably, Hikma's proposed labeling omits references to the patented uses of Colcrys®.
Takeda sought a temporary restraining order (TRO) on October 5, 2014, which the court granted on October 9, 2014, extending it through November 4, 2014. However, the court later denied Takeda's motion for a preliminary injunction, concluding that Takeda did not sufficiently demonstrate a likelihood of success on the merits or imminent irreparable harm. The court allowed for the maintenance of the status quo pending appeal if Takeda promptly appealed and requested expedited review. Takeda filed an appeal on November 5, 2014, with Hikma cross-appealing shortly thereafter. The Federal Circuit ultimately upheld the denial of the preliminary injunction.
On September 10, 2015, Takeda submitted its first amended complaint, which alleges Hikma’s Mitigare™ products induce infringement of both the Acute Flare Patents and the DDI Patents based on the product labels, FDA correspondence, and Hikma's marketing efforts. Hikma has since filed a motion to dismiss this amended complaint under Federal Rule of Civil Procedure 12(b)(6). The court maintains jurisdiction under 28 U.S.C. §§ 1331 and 1338(a).
Hikma is accused by Takeda of infringing its Acute Flare Patents through various aspects of Hikma’s Mitigare™ product. Takeda highlights that while Colcrys® is approved for both prophylaxis and treatment of acute gout flares, Mitigare™ is approved solely for prophylaxis, although the same colchicine dosage is used for both purposes. Takeda interprets the Mitigare™ label's instruction to inform healthcare providers of gout flares as an indication that Hikma intends for its product to be prescribed for acute treatment, following Colcrys® labeling and guidelines from the American College of Rheumatology. Takeda notes that the Mitigare™ label does not provide guidance against using the product for acute treatment nor does it specify the appropriate dosage.
Takeda cites FDA correspondence that acknowledged a high likelihood of Mitigare™ being prescribed for acute treatment, suggesting Hikma's intent to facilitate this use in line with Takeda’s patented methods. Furthermore, Takeda claims that Hikma's marketing and sales efforts, including its product launches and communications with prescribers about the prolonged use of Mitigare™, demonstrate a direct competition with Colcrys. Hikma's sales representatives reportedly informed prescribers that Mitigare™ could be used for treating acute gout flares, and Hikma has secured contracts with insurance providers that ensure Mitigare™ is the sole oral colchicine option for covered patients. Takeda concludes that Hikma's actions indicate a willful blindness or intent to induce infringement of its patent claims.
Takeda accuses Hikma of infringing the DDI Patents by focusing on the labeling of the Mitigare™ product and Hikma's communications with the FDA. Takeda claims that the Mitigare labels instruct healthcare providers to adjust dosages when coadministering with CYP3A4 or P-gp inhibitors but do not detail how to implement these adjustments. Takeda argues that Hikma is aware of existing guidance from Mutual and the Colcrys product label regarding colchicine dosing adjustments and therefore should recognize that some doctors and patients might rely on Colcrys instructions for dosage modifications.
Additionally, Takeda points out that the FDA rejected several of Hikma's proposed product labels and deemed Hikma's drug-drug interaction studies inconclusive. Takeda asserts that the only specific dosage reduction instructions are found in the Colcrys label, which is considered the standard of care by the American College of Rheumatology. This indicates that Hikma was either aware of or willfully blind to the potential reliance of healthcare professionals on the Colcrys label for proper dosing guidelines.
Regarding standards of review for motions to dismiss under Federal Rule of Civil Procedure 12(b)(6), a complaint must present sufficient factual allegations to provide fair notice to the defendant of the claims. The court conducts a two-part analysis: first, distinguishing factual from legal elements, and second, assessing whether the well-pled facts support a plausible claim for relief. Courts must accept all factual allegations as true and view them favorably toward the plaintiff, while also considering pleadings, public records, and relevant documents. The analysis does not evaluate the likelihood of the non-moving party's success but rather whether they are entitled to present evidence supporting their claims. This approach requires enough facts to create a reasonable expectation that discovery will yield necessary evidence.
Indirect infringement can be established through two theories: active inducement and contributory infringement, as outlined in 35 U.S.C. § 271(b) and (c). Indirect infringement liability is contingent on the existence of direct infringement, as affirmed in Limelight Networks, Inc. v. Akamai Technologies, Inc. Under active inducement, a patent owner must demonstrate that the alleged infringer knowingly induced infringement with specific intent, requiring evidence of deliberate actions aimed at encouraging infringement. Knowledge of the infringing acts can be proven through actual knowledge or willful blindness, where the defendant intentionally avoids confirming wrongdoing.
For contributory infringement, the patent owner must prove: (1) an offer to sell, sale, or import; (2) a component or material that is a material part of the patented invention; (3) the defendant's knowledge that the component is specially made for infringing use; and (4) that the component is not suitable for substantial non-infringing use. The defendant must be aware that the combination for which the component was designed is patented and infringing.
The Federal Circuit in Takeda highlighted that inducement can be evidenced by active steps to encourage direct infringement, such as advertising or providing instructions for infringing use. However, mere awareness of potential infringement does not suffice; specific intent and actions to induce infringement must be established.
The analytical framework is informed by the Federal Circuit’s ruling in Warner-Lambert Co. v. Apotex Corp., where Warner-Lambert's patent for gabapentin’s use in treating epilepsy had expired, yet they held a valid patent for its use in treating neurodegenerative diseases, which lacked FDA approval. Apotex sought approval to market a generic version of gabapentin for the approved epilepsy treatment after the expiration of the relevant patent.
Apotex filed an Abbreviated New Drug Application (ANDA) with a Paragraph IV certification for gabapentin, prompting Warner-Lambert to sue for patent infringement in the Northern District of Illinois under 35 U.S.C. § 271(e)(2). The court ruled in favor of Apotex, granting summary judgment of non-infringement due to a lack of evidence showing that Apotex induced physicians to prescribe its product for neurodegenerative diseases. The Federal Circuit upheld this ruling, emphasizing that allowing a § 271(e)(2) action for off-label method of use patents would grant undue rights to patent owners contrary to Congressional intent. The court noted Warner-Lambert needed to show a genuine issue of material fact regarding Apotex's inducement of infringement, which was not established. The Federal Circuit affirmed that a method of use patent holder cannot bring an infringement action under § 271(e)(2) for methods lacking FDA-approved uses. The document also references a similar case involving AstraZeneca, where the Federal Circuit examined method patents related to rosuvastatin calcium, concluding that generic applicants could not be liable under § 271(e)(2) for seeking FDA approval for treatments not covered by the patents, despite the existence of other approved uses. AstraZeneca claimed the ANDA filings infringed its patents, arguing that if approved, they would induce infringement, and anticipated that the FDA would require labeling changes that included the patented indications.
AstraZeneca’s infringement claims were dismissed by the district court due to lack of subject matter jurisdiction, as AstraZeneca failed to present a valid claim under § 271(e)(2) concerning ANDA filings. The court also ruled that AstraZeneca's claims were not ripe regarding potential future labeling amendments. On appeal, the Federal Circuit rejected AstraZeneca's distinction between patents for unapproved versus approved uses, emphasizing that under § 271(e)(2), the focus should be on the scope of regulatory approval sought in the ANDA. The Court noted that the Hatch-Waxman Act permits generic manufacturers to limit their approval scope, allowing them to avoid infringement claims by excluding patented indications from their ANDAs through a Section viii statement. Furthermore, the Federal Circuit dismissed AstraZeneca's argument that generic substitution by pharmacists or doctors could lead to infringement, highlighting that speculative prescribing practices could undermine the intent of Section viii statements. Concerns were raised about a pioneer drug manufacturer potentially achieving indefinite exclusivity through serial patents and misuse of § 271(e)(2) against competitors. Ultimately, the Federal Circuit affirmed the district court’s dismissal of AstraZeneca's complaint.
Takeda’s Colcrys® is approved for treating and preventing acute gout flares, while Hikma’s Mitigare is only approved for prevention, explicitly stating that its safety and effectiveness for treating acute flares has not been studied. The Mitigare label does not suggest that it can be used for acute treatment, which parallels the findings in AstraZeneca regarding the scope of exclusivity. The Federal Circuit has emphasized that induced infringement requires the proposed label to teach an infringing use, not just a possibility of infringement from following the label. Since the Mitigare label directs patients to consult healthcare providers, it does not actively encourage infringement, failing to establish induced infringement. Takeda’s burden to demonstrate plausible claims is unmet, as it has not provided concrete factual allegations regarding Hikma’s marketing or sales activities. Allegations based on "information and belief" regarding Mitigare sales representatives and contracts with insurers are deemed too vague and lack the necessary specificity to support Takeda's claims. Furthermore, merely stating that Mitigare can be used for acute flares does not equate to instructing patients to use it in an infringing manner.
Hikma's allegations against third-party insurance providers are insufficient as they only acknowledge potential infringement without demonstrating that Hikma has taken "active steps" to encourage direct infringement. Established legal precedent dictates that mere awareness of possible infringement does not equate to inducement; specific intent and actions must be proven. The court finds that Takeda fails to adequately allege direct or induced infringement of the DDI Patents, which require a 0.3 mg daily dose of colchicine, while Mitigare is a 0.6 mg capsule. Takeda's amended complaint lacks factual allegations of actual infringement despite Mitigare's marketing for over ten months, relying instead on speculative assertions about potential doctor and patient behavior regarding colchicine dosing. The court views these claims as insufficient to establish a reasonable inference of infringement, paralleling previous discussions about the Acute Flare Patents. Speculative future infringement does not suffice, and hypothetical instances do not establish indirect infringement. Liability for inducement arises only if actual infringement occurs, and there is no basis for asserting attempted patent infringement. The court cannot find a "plausible claim for relief" from Takeda due to the absence of factual allegations of infringement, leading to the granting of Hikma’s motion to dismiss. The relevant patents are categorized into groups, including DDI Patents and Acute Flare Patents, with Takeda referencing these patents as Acute Gout Treatment Patents. Takeda's claims regarding Hikma's intent to infringe are supported solely by Hikma’s agreement with Kaiser Permanente, which contains dosing instructions for acute treatment but lacks instructions for prophylactic use, the only FDA-approved use for Mitigare.
Takeda asserts that Hikma was aware of the medication guide for MITIGARE™ and that this awareness indicates Hikma's intent or willful blindness to the fact that healthcare providers will use MITIGARE™ for treating acute gout flares as outlined in the Acute Flare Patents. Takeda's amended complaint highlights that the medication labels list clarithromycin, ketoconazole, and verapamil as CYP3A4 inhibitors but do not indicate the necessary reduction in colchicine dosage. The court notes that Hikma applied for MITIGARE™ approval through the NDA pathway under the Hatch-Waxman Act's 505(b)(2) clause, leading Takeda to base its induced infringement claims under § 271(b) rather than § 271(e)(2). The court finds the precedent set by Warner-Lambert relevant, particularly as the Federal Circuit supported the denial of a preliminary injunction regarding Takeda's induced infringement claim's likelihood of success. The Hatch-Waxman Act requires ANDA applicants to certify the status of patents listed in the Orange Book, including certifications that there are no relevant patents, the patents have expired, or that the applicant believes the patents are invalid or non-infringed. Filing an ANDA with a Paragraph IV certification is considered an act of infringement. The court references that an applicant may submit a Section viii statement to exclude uses claimed in a method of use patent and that the Federal Circuit has determined that alleging infringement through the filing of an ANDA is sufficient for establishing subject matter jurisdiction.
Instructions on the Mitigare™ label mandate consultation with a physician and do not provide specific usage guidelines, differing from the AstraZeneca label which adhered to FDA standards. Takeda asserts that MITIGARE™ sales representatives informed prescribers that thirty capsules could last a patient up to one year, indicating an intent by Hikma and West-Ward to market MITIGARE™ products for treating acute gout flares. Additionally, representatives communicated that MITIGARE™ and MITIGARE™ AG can be used for such treatment. Takeda alleges that Hikma has secured at least two sole-source contracts with insurance providers, ensuring that Mitigare™ or its AG product is the sole oral colchicine option for patients covered under these plans. Evidence includes Hikma’s agreement with Kaiser Permanente, which offers dosing instructions for acute treatment based on Takeda’s patented method but lacks guidance for prophylactic use, the only FDA-approved indication for MITIGARE™. The court and Federal Circuit have previously rejected Takeda’s claim that a 0.3 mg dosage could be achieved by adjusting the frequency of a 0.6 mg dosage.
