Adele Critchley | February 16, 2017
Eli Lilly and Company, v. Teva Parenteral Medicines, Inc., APP Pharmaceuticals LLC., Pliva Hrvatska D.O.O., Teva Pharmaceuticals USA, Inc., Barr Laborites, Inc.
January 12, 2017
Before Prost, Newman and Dyk. Opinion by Prost.
The case centered on Eli Lilly’s patent directed to methods of administering a chemotherapy drug after pretreatment with two common vitamins. The drug was marketed under the brand name ALIMTA®. The Defendants had submitted ANDAs seeking approval of a generic version of ALIMTA®. The CAFC upheld the district counts findings, in favor of Eli Lilly’s patent, in full. The issues addressed were induced infringement, and invalidity issues of indefiniteness, obviousness and obvious-type double patenting.
Eli Lilly is the owner of U.S. Patent No., 7,772,209 (patent ‘209), directed to methods of administering the chemotherapy drug “pemetrexed’ after pretreatment with two common vitamins (folic acid and vitamin B12). The purpose of the dual vitamin pretreatments is to reduce the toxicity of the pemetrexed to the patients. The drug was marketed under the brand name ALIMTA®.
The Defendants notified Eli Lilly that they had submitted ANDAs seeking approval of a generic version of ALIMTA®. After the ‘209 patent issued, Defendants sent Eli Lilly notices that they had filed Paragraph IV certifications under 21 U.S.C. §355(j)(2)(A)(vii)(IV), declaring that the patent was invalid, unenforceable or would not be infringed. Eli Lilly subsequently brought a consolidated action against the Defendants for infringement, alleging that the generic drug would be administered with folic acid and vitamin B12 pretreatments.
Eli Lilly asserted a number of claims at trial, all of which required patient pretreatment by ‘administering’ or ‘administration of’ folic acid, and a number of dependent claims which defined dosage restrictions.
The parties agreed for the purpose of appeal that no single actor performs all steps, rather they are divided between patient and physician. Specifically, physicians administered vitamin B12 and pemetrexed, while the patient folic acid.
Initially, in June 2013, Defendants conditionally conceded induced infringement under the then-current law set forth in Akamai II (Akamai II held that “induced infringement can be found even if there is no single party who would be liable for direct infringement”). At the time, Akamai was subject of a petition to the Supreme Court for a writ of certiorari. The parties’ stipulation included a provision reserving Defendants right to litigate infringement if the Supreme Court reversed or vacated Akamai II. While an appeal on invalidity was pending (district court had held the claims were not invalid), the Supreme Court reversed Akamai II, holding the liability for inducement cannot be found without direct infringement. In view of this, the parties in this case filed a joint motion to remand the matter to the district court for the limited propose of litigating infringement. CAFC granted the motion. The district court held a second bench trial and concluded that Defendants would induce infringement of the ‘209 patent. The court had applied the intervening Akamai V decision, which had broadened the circumstances in which others’ acts may be attributed to a single actor to support direct infringement liability.
Defendants timely appealed. The CAFC upheld the district courts findings, addressing each issue in turn.
(I) “Whoever actively induces infringement of a patent shall be liable as an infringer.” Importantly, liability for induced infringement “must be predicated on direct infringement.” (Akamai III). The patentee must also show that the alleged infringer “knew or should have known his actions would induce actual infringements.” A patentee seeking relief under §271(e)(2) bears the burden of prove.
The district court relied in part on the Defendants’ proposed product labeling as evidence of infringement. The labeling consisted of two documents: the Physician Prescribing Information and the Patient Information. Amongst other things, the information provides the following:
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…
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 of folic acid every day for at least 5 days out of the 7 days before your first dose of [pemetrexed].
The CAFC held that where, as here, no single actor performs all the steps of the method claim, direct infringement only occurs if “the acts of one are attributable to the other such that a single entity is responsible for the infringement.” Akamai V. In Akamai V, the CAFC held that directing or controlling other’s performance includes circumstances in which an actor (1) conditions participation in an activity or receipt of a benefit upon another’s performance of one or more steps of a patented method, and (2) establishes the manner or timing of that performance. The district court applied this two-point prong test to the subject case.
With respect to the first prong – the CAFC agreed with the district court’s findings. Specifically, the labeling information repeatedly instructs the patients to take folic acid and provides information about the dosage range and schedule. The labeling information explains that the folic acid is a “requirement for premedication” in order to “reduce the treatment-related hematologic and gastrointestinal toxicity” of pemetrexed. Eli Lilly’s expert testified that it is “the physician’s responsibility to initiate the supplementation of folic acid.” The patient information also informs patients that a physician may withhold pemetrexed treatment based on blood tests. Eli Lilly’s expert testified that a physician would withhold treatment if the patient had not taken their required dosage of folic acid to avoid toxicity.
The Defendants argued that the product labeling was mere guidance and insufficient to show conditioning. The Defendants also argued there is no evidence that physicians go further to “verify compliance” with their instructions. The CAFC replied that conditioning does not necessarily require double checking.
Next, the Defendants argued that an actor can only condition the performance of a step by imposing a legal obligation to do so. The CAFC rejected this argument, stating that infringement is not limited solely to contractual arrangements, and the like.
With respect to the second prong – the CAFC agreed with the district court’s findings. Specifically, the Physician Prescribing Information instructs physicians to tell patients to take folic acid at specific dosages and at a specific schedule. Moreover, the testimony of a Dr. Chabner was highlighted in part affirming that “it is the doctor” who “decided how much” the patient takes.
Defendants argued that patients are able to seek additional outside assistance regarding folic acid administration, but the CAFC held this was immaterial.
Thus, the two-point prong test of Akamai V was met. However, the mere existence of direct infringement by physicians is not sufficient to find liability for induced infringement. Eli Lilly carried this burden.
The district court held that the administration of folic acid before pemetrexed administration was ‘not merely a suggestion or recommendation, but a critical step,’ in light of the Defendants proposed labeling.
Defendants argued that Eli Lilly has not offered any evidence of what physicians do in general but only speculation about how they may act. They argued that physicians must go beyond labeling. The CAFC found this argument unavailing. For the purpose of inducement “it is irrelevant that some users may ignore the warnings in the proposed label,” if the label “encourage(s), recommend(s) or promote(s) infringement.” The product labeling included repeat instructions and warning regarding the importance of folic acid.
(II) Indefiniteness of “vitamin B12” – the Defendants argued in view of Nautilius that vitamin B12 is indefinite as the term is used in two different ways in the intrinsic record (vitamin B12 and Cyanocobalamin).
The district count accepted the testimony of Eli Lilly’s expert that one of ordinary skill in the art would understand in the context of the patent claims vitamin B12 to mean Cyanocobalamin. The CAFC saw no error in the districts court findings, holding that vitamin B12 has a plain meaning to one of skill in this particular art.
In addition, it was noted that claim 1 required administering a “methylmalonic acid lowering agent…” and claim 2 “vitamin B12.” Therefore, if vitamin B12 was to refer to a whole class of compounds it would be the same scope as claim 1. However, the doctrine of claim differentiation presumes that dependent claims are of narrower scope, and so reading the claims as to require ‘vitamin B12’ of claim 2 to be a specific compound within the scope of “methylmalonic acid lowering agent” avoids this problem.
The Defendants argued that if vitamin B12 means Cyanocobalamin, the given Markush group in claim 1 of the “methylmalonic acid lowering agent,” lists the same compound twice. The CAFC held that the mere fact that a compound may be embraced by more than one member of a Markush group recited in the claim does not necessarily render the scope unclear. The CAFC held the redundancy is support by the prosecution history (the Examiner had stated they were the same, in response the patentee removed Cyanocobalamin, but later put the term back into the claim).
(III) Obviousness – the CAFC agreed with the district counts finding that a skilled artisan would have concluded that vitamin B12 deficiency was not the problem in pemetrexed toxicity.
In brief, the Defendant had relied upon an Abstract published from an Eli Lilly scientist that showed homocysteine levels served as an indicator of either a folic acid or vitamin B12 deficiency and that such levels were elevated with increased pemetrexed toxicities. However, the levels of another marker methylmalonic acid (MMA), which more specifically is an indicator of just vitamin B12 deficiency, showed no correlation. The CAFC indicated this was sufficient for the claims not to be rendered obvious.
(V) Obviousness-type double patenting – the Defendants argued that the claims are not valid over an Eli Lilly’s earlier patent (US 5,271,974 – ‘974). The district court disagreed, and the CAFC upheld.
In brief, the ‘974 patent more broadly claimed a much greater amount of folic acid with an antifolate agent administrated to a mammal. The claims of the subject patent are much more specific with regards to the amount of folic acid and the administration of a specific antifolate agent to a patient. The CAFC held this was sufficient for the claims to be patentably distinct.
Method claims drafted to encompass actions of a single entity are still preferable, in order to reduce burden of proving infringement. However, where no single entity performs all the steps, direct infringement can be found if the steps of the method claim are performed under the control or direction by a single entity.
Naturally, patent specification drafters should always endeavor to be careful in their use of claim terminology. Even so, where claim terms are have a specific meaning in their relevant arts, the courts tend to not apply those terms contrary to their common understanding, unless the applicant clearly intended to redefine the term.