Subset patent prevents generics from entering cardiovascular market.

In a recent decision from the District of Delaware involving dronedarone tablets, 400 mg, marketed by Sanofi Aventis (“Sanofi”) as Multaq®, the trial court found that the defendant generic drug companies would induce doctors to infringe Sanofi’s method of treatment patent based on their FDA-approved labeling.  See Sanofi & Sanofi Aventis United States Llc v. Lupin Atl. Holdings S.A., 2017 U.S. Dist. LEXIS 174931 (D. Del. Oct. 23 2017).

The decision demonstrates how a generic will induce infringement of a method of treatment patent when it republishes the clinical trials section of an innovator’s label, even when the patent covers only a subset of the patients enrolled in the trial. To succeed, the innovator must prove that a medical doctor would conclude from the clinical studies section that the treatment is effective in the patented subset. 

Dronedarone is a cardiovascular antiarrhythmic drug approved in the United States for reducing:

“the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation.” 

The patent at issue, US Patent No. 9,107,900 (the ‘900 patent), claims in relevant part:

“1. A method of reducing a risk of cardiovascular hospitalization in a patient, said method comprising administering to said patient an effective amount of dronedarone … (iii) wherein said patient has … coronary heart disease; and (iv) wherein the patient has (a) an age greater than or equal to 75 or (b) an age greater than or equal to 70 and at least one cardiovascular risk factor … .”

As can be seen, the claim requires the use of dronedarone to treat patients with coronary heart disease that meet specified age criteria. 

Because generic drug companies do not market their drugs to doctors, the focus for method of treatment patents is nearly always on the FDA-approved label for the generic drug, and whether the label will induce doctors to infringe the patent.  As the Federal Circuit has explained, “The pertinent question is whether the proposed label instructs users to perform the patented method.” AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060 (Fed. Cir. 2010). A generic generally cannot be liable for “off-label” patented uses of a drug, even if those uses make up a substantial portion of the drug’s sales, because its label does not instruct users to perform the patented method.  Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348 (Fed. Cir. 2003).

In this case, the generic defendants argued that their labels did not induce infringement because their labels did not affirmatively instruct doctors to administer dronedarone to patients with coronary heart disease that met the age criteria in the claim. They relied primarily on the FDA-approved indication which did not mention coronary heart disease or restrict the age of the patient who could take the drug. 

The court rejected this argument based on the clinical trials section of the generic labeling, and expert testimony of how a cardiologist would interpret and apply the clinical trials to his or her practice. The primary clinical study described in the generic labels, the ATHENA study, did not specifically refer to coronary heart disease, but the court concluded that 20-25% of the patients who met the inclusion criteria of the ATHENA study had coronary heart disease, and that a cardiologist reviewing the label would understand that 20-25% of the patients had coronary heart disease.  The label’s reference to two subsidiary studies, the EURIDIS and ADONIS studies, which made specific reference to coronary heart disease, supported the court’s conclusion.

The ATHENA study also did not correlate precisely to the age criteria recited in the claims. The inclusion criteria for the ATHENA study initially allowed patients less than 70 years old, but the criteria were subsequently amended to require an age greater than 75 or greater than 70 with at least one risk factor.  Even under the original inclusion criteria, which enrolled patients ranging from 23 to 97 years old, 42% were 75 years old or older.

Based on these facts, and other evidence presented at trial, the court concluded that FDA had determined when it approved dronedarone that dronedarone was effective in patients with coronary heart disease that met the claimed age criteria, and that FDA’s determination would guide doctors to use dronedarone in this claimed subset.  The court stated:

“In sum, while the Indications and Usage section does not expressly instruct the administration of dronedarone to patients with coronary heart disease who meet the Age Criteria, it directs a [cardiologist] to review, and a [cardiologist] would review, the Clinical Studies section. From the Clinical Studies section, it would be readily apparent to a [cardiologist] that the use of dronedarone for patients with coronary heart disease and who meet the Age Criteria would reduce the risk of cardiovascular hospitalization.”

Stay tuned for further posts on this case.  We are particularly interested to see how the Federal Circuit applies the Supreme Court’s 2011 decision that “liability for induced infringement can only attach if the defendant knew of the patent and knew as well that the induced acts constitute patent infringement.” Global-Tech Appliances, Inc. v. SEB S.A., 563 U.S. 754 (2011). We saw no evidence in the decision that the generic defendants actually understood that their labels would induce infringement of the ‘900 patent.  It appears that the court imputed this knowledge to the defendants based on its belief that any other result would constitute “willful blindness.” See Global-tech, supra (knowledge requirement for induced infringement may be satisfied by actual knowledge or willful blindness).