Developing a pharmaceutical product can take on the order of a decade from research (first inventing the drug) to development, and finally to FDA approval. While Patent Term Extension can restore some time lost due to the regulatory approval process, the traditional strategy of relying on patents based on the drug itself or its general method of use will necessarily start – and stop – the protection clock much earlier. This limits the potential return on investment prior to generic copyists. But, if one is creative and coordinated, additional strategies can be used to advance business growth with longer and stronger patents.

While each and every product presents new and unique facts that must be separately evaluated, creative strategies such as coordinating patent claims with the product label, claiming unexpected discoveries from later product development, and using the oft-overlooked “means plus function” claiming format have each been shown to provide opportunities for valuable patent protection.

Coordinating the Claims and the Label

With some exceptions, a generic or bio-similar manufacturer must copy the innovator’s FDA-approved package insert (“label”). This makes innovations reflected in and recommended on the label – such as from pivotal Phase III clinical trials – a potentially valuable source for additional patent protection. The successful use of clinical trial results in this way was affirmed in Sanofi v. Watson, 875 F.3d 636 (Fed. Cir. 2017), in relation to Sanofi’s antiarrhythmic dronedarone product, marketed as Multaq®. The net result for Sanofi was achieving 10 more years of patent exclusivity for Multaq® compared to the dronedarone composition of matter patent.

Prior to the approval of Multaq®, a Phase III clinical trial conducted by Sanofi showed decreased cardiovascular hospitalisation and death in a particular high-risk patient population, specifically patients at least age 75 or those having hypertension, diabetes, or other cardiovascular risk factors. Sanofi’s patent in the case relied on the Phase III data to claim a method of administering dronedarone to decrease the risk of cardiovascular hospitalisation in these patients. Once approved, the Multaq® label included the same Phase III results with all the relevant details in its “Clinical Studies” section, which was also cross-referenced from the label’s “Indications and Usage” section. The generic party (Watson) copied the Multaq® label, including the “Clinical Studies” section with the Phase III results and the “Indications and Usage” section. Watson argued, however, that this did not induce the claimed method in part because its “Indications and Usage” did not specify treating the claimed high-risk patients. The courts – district court and Federal Circuit – disagreed. They found that the generic label induced infringement by encouraging the claimed treatment of the claimed high-risk patients. Id. at 646. Relying in part on the fact Watson’s “Indications and Usage” section also cross-referenced to the “Clinical Studies” section, the courts found that Watson’s label “directs medical providers to information identifying the desired benefit for only patients with the patent-claimed risk factors.” Id. at 645. The strategy of protecting non-obvious innovations developed from late-phase clinical trials included on the product label has proved successful in other cases as well. For instance, Vanda Pharmaceuticals obtained stronger patent exclusivity by developing, claiming, and including on its product label a method of using iloperidone to treat patients suffering from schizophrenia, where the dose was adjusted based on determining whether the patient was a poor CYP2D6 metaboliser.1 There are several key considerations to successfully rely on late-developed clinical innovations included in the label. For example, a patent application based on later clinical trials is best filed before the product is approved and before such results are published. Otherwise, the product label or publication could become prior art, as set out under 35 U.S.C. § 102(a)(1), in the absence of any 35 U.S.C. § 102(b)(1) exceptions. Importantly, with timing being everything, IP teams should coordinate early and frequently with clinical and regulatory teams to implement this strategy. Another important consideration is whether the specific information included in the label and covered by the claims can be carved out by the generic or biosimilar manufacturer. In general, label information related to safety, dosage adjustments, and references to the clinical studies section in the “Indication and Usage” section must be copied, such that they are particularly suitable when considering how to best protect the product. In addition, the relied-upon clinical trial results should be recommended or encouraged by the label, such as the population to be treated or the dose to be used to minimise the effect of drug-drug interactions.