A recent Federal Circuit decision has clarified the scope of “direction or control” necessary to support attribution of one party’s actions to another in divided infringement contexts. The decision has particular relevance for the pharmaceutical industry, as the court discussed the direction or control standard as applied to doctor/patient relationships and highlighted the importance of Abbreviated New Drug Application (ANDA) product labeling in the analysis.

Eli Lilly & Co. (Eli Lilly) markets the chemotherapy drug pemetrexed disodium (pemetrexed) under the brand name ALIMTA®. Eli Lilly also owns U.S. Patent No. 7,772,209 (the ’209 patent), which claims methods of administering pemetrexed after pretreatment with two common vitamins – folic acid and vitamin B12. The dual-vitamin pretreatment reduces pemetrexed toxicity in patients. 

Asserted independent claim 12 of the ’209 patent is provided below:

12. An improved method for administering pemetrexed to a patient in need of chemotherapeutic treatment, wherein the improvement comprises:

a)  administration of between about 350 µg and about 1000 µg of folic acid prior to the first administration of pemetrexed;

b) administration of about 500 µg to about 1500 µg of vitamin B12, prior to the first administration of pemetrexed ; and

c) administration of pemetrexed.

The defendants submitted ANDAs seeking U.S. Food and Drug Administration approval to market generic versions of ALIMTA®, including Paragraph IV certifications declaring that the ’209 patent was invalid, unenforceable, or not infringed. Eli Lilly responded by bringing a consolidated action against the defendants for infringement under 35 U.S.C. § 271(e)(2). Specifically, Eli Lilly argued that the sale of defendants’ generic drugs would induce infringement of treatment methods claimed in the ’209 patent. The defendants raised a number of noninfringement and invalidity defenses. 

The defendants’ proposed product labeling would materially match that of ALIMTA®, which contained two documents: (1) the Physician Prescribing Information; and (2) the Patient Information. Both documents detailed procedures by which a physician would administer pemetrexed and vitamin B12, but the patient would be responsible for self-administering prescribed doses of folic acid.

Accordingly, the parties agreed that under the defendants’ proposed labeling, no single actor performed all steps of the asserted claims.  To establish direct infringement by the physician (as a predicate for establishing inducement by the defendants), Eli Lilly argued that a prescribing physician sufficiently directed or controlled the patient actions such that the folic acid administration step should be attributed to the physician for infringement purposes.

The district court agreed and held that the defendants would induce infringement of the ’209 patent based on the attribution standard announced in the Federal Circuit’s 2015 Akamai V decision, which broadened the circumstances in which others’ acts can be attributed to a single actor to support direct-infringement liability to include instances where the accused infringer (i) conditions another’s participation or receipt of a benefit upon performance of a patented step, and (ii) establishes the manner and timing of that performance.  Defendants appealed. 

The Federal Circuit affirmed. Specifically, the Court focused on the defendants’ proposed product labeling to determine whether prescribing physicians would sufficiently direct or control their patients’ self-administration of folic acid to merit attributing those actions to the physician under the Akamai V standard.

Under the first prong of the Akamai V direction or control test, the court agreed with the defendants that pemetrexed treatment qualified as the relevant benefit that might be conditioned upon folic acid pretreatment, rather than the inherent benefit of reduced pemetrexed toxicity associated with such pretreatment. Regarding whether pemetrexed treatment had in fact been conditioned on folic acid pretreatment, the court highlighted the defendants’ proposed Physician Prescribing Information, which defined folic acid pretreatment as a “requirement” and repeatedly directed physicians to instruct patients accordingly. In addition, expert witnesses and the Patient Information indicated that physicians would withhold pemetrexed if a patient failed to comply with pretreatment. Accordingly, the court held that the evidence supported a conclusion that the pemetrexed treatment would be conditioned upon the patient’s compliance with prescribed folic acid pretreatment. The court rejected the defendants’ arguments that conditioning a benefit must go so far as affirmative testing for compliance or imposing a legal obligation.

The court also concluded that the product labeling showed that physicians sufficiently established the manner and timing of patients’ pretreatment steps to qualify as exerting direction or control. In particular, the labeling set forth folic acid administration schedules that matched the dosage and timing recited in the asserted claims.

Importantly, the court noted that its decision turned on the particular facts of the case, emphasizing that the physician-patient relationship was not alone sufficient to attribute patient action to a prescribing physician.

The decision provides key guidance regarding the divided infringement analysis in the ANDA context. In particular, the product labeling provided the touchstone for the court’s analysis, and in this case, the label provisions were explicit in defining patient actions as a requirement for treatment. It remains for future cases, however, to further define the boundary separating physician control from mere guidance or suggestion, such as cases addressing less explicitly conditional labeling or allegedly infringing off-label uses.