Drug manufacturers cannot avoid infringement by dividing method between physicians and patients

On January 12 2017 the Federal Circuit in Eli Lilly v Teva Parenteral Meds, Inc stated that a physician may directly infringe a patented method for drug administration, even when the infringing steps are divided between the physician and patient. Specifically, the court held that infringement cannot be avoided when the physician "directs or controls" the patient to perform at least one step of the patented method.

Facts
Eli Lilly owned Patent 7,772,209 (the '209 patent'), which covers a method of administering the chemotherapy drug pemetrexed disodium. The toxicity of pemetrexed is potentially life threatening; however, the '209 patent teaches that folic acid and vitamin B12, when used in combination, synergistically reduce these highly toxic side effects. Therefore, a critical step of the '209 method patent requires treatment with folic acid and vitamin B12 before a patient receives pemetrexed.

During the pendency of the '209 patent, Teva requested Food and Drug Administration (FDA) approval to market generic versions of pemetrexed using dosing instructions that were substantially identical to the methods taught in Eli Lilly's patent application. According to the dosing documentation, physicians administer both the pre-dose of vitamin B12 and the ultimate dose of pemetrexed; however, part of the dosing regimen requires that patients, under the physician's direction, self-administer folic acid daily during the week before pemetrexed administration. Soon after the '209 patent issued, Eli Lilly sued Teva for Teva's proposed marketing, claiming that administration of generic versions of pemetrexed following folic acid and vitamin B12 pre-treatment infringes the '209 patent.

Although Teva manufactured the proposed generic drug and provided dosing instructions, it never directly administered the drug to patients; hence, Teva could not directly infringe Eli Lilly's patented method. Consequently, Eli Lilly claimed that Teva, by instructing physicians and patients to carry out infringing methods, was liable for inducing others to infringe the '209 patent. According to the Supreme Court, there can be no finding of induced infringement in the absence of an underlying direct infringement by a single party. Therefore, to have a viable argument that Teva induced infringement, Eli Lilly had to show that an actor had directly infringed the '209 patent by following Teva's dosing instructions.

Importantly, when the steps of the patented method are divided between more than one actor, a finding of direct infringement requires that the collective steps of each actor be attributed to a single entity. Using the case at hand as an example, in order to support direct infringement Eli Lilly had to show that the patient's self-administration of folic acid, a required step of the '209 patent, could be attributed to the physician, making the physician responsible for all of the patented steps (ie, pre-treatment of vitamin B12, pre-treatment of folic acid and administration of pemetrexed).

The Federal Circuit recently expanded the reach of divided infringement, holding that infringing steps can be attributed to a single entity when one actor "directs or controls" the activity of other actors (Akamai Technologies, Inc v Limelight Networks, Inc (Akamai V)). According to Akamai V, one actor "directs or controls" another if the actor:

• "conditions participation in an activity or receipt of a benefit upon performance of at least one step of a patented method"; and
• "establishes the manner or timing of that performance". 

Using this case law, Eli Lilly claimed that the patient's act of self-administering folic acid should be attributed to the physician because the physician directed and controlled the patient to perform the act.

Decision
The Federal Circuit agreed with Eli Lilly and held that physicians meet both of the requirements for directing or controlling patients. First, physicians require their patients to self-administer folic acid before receiving the benefit of pemetrexed administration, which satisfies the first condition. In so reasoning, the court relied on Teva's product labeling that required patients to take folic acid to prevent the potentially devastating toxicity of the chemotherapy drug. The court also relied on Eli Lilly and Teva's expert witnesses, both of whom stated that the standard practice of physicians is to withhold pemetrexed administration if the patients fail to comply with self-administration of folic acid.

Physicians also meet the second prong of the Akamai V test. According to the court, physicians establish the time and manner of performance by delineating the time frame (once daily for seven days) and dosage of the patients' self-administration of folic acid.

Having shown that physicians direct or control patients' activity, all of the steps of Eli Lilly's patent can be attributed to physicians (ie, pre-treatment of vitamin B12, pre-treatment of folic acid and administration of pemetrexed). Therefore, physicians directly infringed the patented method. Since direct infringement can be shown, Teva was guilty of induced infringement of the patented method by providing physicians with instructions to administer Teva's generic drug in an infringing manner.

Thus, the Federal Circuit removed any doubt as to whether drug manufacturers may avoid infringement by dividing the steps of a patented method for drug administration between physicians and patients. Under such circumstances, infringement cannot be circumvented by instructing physicians to require that patients perform a step of the method before administration of the generic drug. Accordingly, entities seeking FDA approval to market generic versions of patented drugs should take caution and ensure that any instructions for administration of the drug do not merely divide the steps of a patented method between two or more parties. This case should come as welcome news to many existing patent holders, providing another tool for more effective exclusion of market competitors and potentially increasing the value of patented methods for drug administration.