Last week, in Eli Lilly and Company v. Teva Parenteral Medicines, Inc., Judge Tanya Walton Pratt of the U.S. District Court for the Southern District of Indiana determined that Eli Lilly and Company had shown by a preponderance of the evidence that U.S. Patent No. 7,772,209, owned by Lilly, would be infringed by the ANDA products for which Defendants Teva Parenteral Medicines, Inc.; Teva Pharmaceuticals USA, Inc.; APP Pharmaceuticals, LLC; Barr Laboratories, Inc.; and Pliva Hrvatska D.O.O. sought approval to market (opinion). The District Court indicated that its finding of infringement was "based upon inducement of infringement by a single actor, the physician administering pemetrexed disodium in accordance with the claimed methods" of the '209 patent.
Claims 1 and 12 of the '209 patent recite:
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 μg and about 1000 μg of folic acid prior to the first administration of pemetrexed disodium; b) administration of about 500 μg to about 1500 μg of vitamin B12, prior to the first administration of pemetrexed disodium; and c) administration of pemetrexed disodium.
Claims 9, 10, 12, 15, 18, 19, and 21 of the '209 patent were asserted by Lilly with respect to Defendants' ANDA products. Claims 9 and 10 depend indirectly from claim 1 and claims 15, 18, 19, and 21 depend indirectly or directly from claim 12.
The District Court noted that the '209 patent covers the method of administering a chemotherapy drug, pemetrexed disodium, with vitamins, which Lilly markets under the trade name ALIMTA®. The Court also noted that Defendants' product labeling for their proposed generic versions of ALIMTA® instructs physicians to follow exactly the claimed regimen, since Defendants' ANDA products will be required to be distributed with identical labeling as that for ALITMA®. Experts for both Lilly and the Defendants agreed that following the labels, physicians would administer vitamin B12 by injection and administer pemetrexed disodium by infusion, but that patients, at the instruction of the physician, would obtain and take the folic acid. Thus, the issue at trial was whether the steps of the claimed methods could be attributed to a single actor, the physician, thus supporting a finding that Defendants would induce infringement of the asserted claims.
In a separate trial on validity, the Defendants had failed to show by clear and convincing evidence that the asserted claims were invalid. Although the Defendants had appealed that ruling to the Federal Circuit, both parties jointly moved to remand the appeal in order to litigate the issue of infringement in light of the Supreme Court's decision in Limelight Networks, Inc. v. Akamai Techs., Inc., in which the Supreme Court reversed the Federal Circuit's decision, and remanded the case to the Federal Circuit. In an en banc per curiam opinion, the Federal Circuit set forth the law of divided infringement under 35 U.S.C. § 271(a). The District Court noted that "for purposes of this case, the Court must apply this most current articulation of the law of divided infringement as stated by the Federal Circuit in its most recent ruling."
In finding for Lilly, the District Court observed that "[a]lthough the instant case involves the administration of a medical treatment, the factual circumstances are sufficiently analogous to those in Akamai to support a finding of direct infringement by physicians under § 271(a), and thus inducement of infringement by Defendants under § 271(b), under the legal standard recently set forth by the Federal Circuit." The Court was not persuaded by the Defendants' argument that the actions of the patient in taking folic acid prior to pemetrexed treatment cannot be attributed to the physician because the physician does not physically place the folic acid into the patients' mouth, and because patients are instructed to obtain folic acid, either by prescription or over the counter, and take it on their own. According to the Court, whether patients actually take the folic acid was irrelevant to the issue of infringement, and "the only relevant question is whether the actions of the patient in taking folic acid as instructed may be attributable to the physician as a single actor." With respect to this question, the Court pointed out that "[t]he physician, based upon the patented method, directs the manner and timing of the patient’s ingestion of folic acid -- 400 to 1000 μg of folic acid for at least five days out of the seven days prior to and during pemetrexed administration -- and the patient is required to do so to receive the full benefit of the treatment." The Court therefore concluded that:
Lilly has shown, by a preponderance of the evidence that, in accordance with Defendants' proposed labeling, the physician directs or controls the patient's administration of folic acid such that the performance of all the claimed steps, including the administration of folic acid, can be attributed to a single person, i.e. the physician. The evidence showed that physicians specify both the "manner and timing" in detail, including prescribing an exact dose of folic acid and directing that it be ingested daily.