In Eli Lilly & Co. v. Teva Parenteral Medicines, Inc., the Federal Circuit affirmed the district court decision finding infringement under Akamai of a two-step method of treatment when the prescribing information for the prescription drug component required coadministration of the other active agent. The appeal arose from ANDA litigation surrounding Eli Lilly’s ALIMTA® product, which is to be taken with folic acid and vitamin B12 to reduce side effects. Although pharmaceutical companies may welcome this decision, they should be aware of the emphasis the court place on the specific guidance and instructions provided in the product labeling.
The Patent At Issue
The patent at issue was Eli Lilly’s U.S. Patent No. 7,772,209. The court focused on independent claims 1 and 12:
1. A method for administering pemetrexed disodium to a patient in need thereof comprising administering an effective amount of folic acid and an effective amount of a methylmalonic acid lowering agent followed by administering an effective amount of pemetrexed disodium,
wherein the methylmalonic acid lowering agent is selected from the group consisting of vitamin B12, hydroxycobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo-10-cobalamin perchlorate, azidocobalamin, cobalamin, cyanocobalamin, or chlorocobalamin.
12. An improved method for administering pemetrexed disodium to a patient in need of chemotherapeutic treatment, wherein the improvement comprises
a) administration of between about 350 mg and about 1000 mg of folic acid prior to the first administration of pemetrexed disodium;
b) administration of about 500 mg to about 1500 mg of vitamin B12, prior to the first administration of pemetrexed disodium; and
c) administration of pemetrexed disodium.
The ALIMTA® Labeling
As noted above, this case arose from ANDA litigation surrounding Eli Lilly’s ALIMTA® product. As such, Teva’s s proposed product labeling, which was based on Eli Lilly’s label for ALIMTA®, was relied on as evidence of infringement. In this context, both the district court and the Federal Circuit considered the Physician Prescribing Information and the Patient Information.
The Federal Circuit noted these instructions in the Physician Prescribing Information:
Instruct patients to initiate folic acid 400 [m]g to 1000 [m]g orally once daily beginning 7 days before the first dose of [pemetrexed]…
Instruct patients on the need for folic acid and vitamin B12 supplementation to reduce treatment-related hematologic and gastrointestinal toxicity…
The Federal Circuit noted similar guidance in the Patient Information document:
To lower your chances of side effects of [pemetrexed], you must also take folic acid and vitamin B12 prior to and during your treatment with [pemetrexed].
It is very important to take folic acid and vitamin B12 during your treatment with [pemetrexed]to lower your chances of harmful side effects. You must start taking 400-1000 micrograms