Eli Lilly & Co. v. Teva Parenteral Medicines, Inc. (Fed. Cir. 2017)

By Kevin E. Noonan --

From the nadir of the Supreme Court's allegations that the Federal Circuit "fundamentally misunderstood" the law of inducing infringement in Limelight Networks, Inc. v. Akamai Technologies, Inc., the nation's specialized patent appellate court has crafted a two-prong test for assessing when the actions of more than a single actor amount to literal infringement sufficient to support a determination of inducement.  Akamai Technologies, Inc. v. Limelight Networks, Inc. (Fed. Cir. 2015) (en banc).

The case came to the Court from ANDA litigation between Eli Lilly and Teva and other ANDA filers over infringement under 35 U.S.C. § 271(e)(2) of U.S. Patent No. 7,772,209.  The claims were directed to methods for administering pemetrexed disodium (sold by Eli Lilly as Alimta^®) after pretreatment with folic acid and vitamin B12.  Claims 1 and 12 are representative as set forth in the opinion:

1.  A method of 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, cyanoco- balamin, 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.

(Where the italicized limitations were specifically at issue.)  Here, the patient practices the step of the claim involving administering folic acid (which is available as a pill), and the physician administers B12 and pemetrexed by injection.  The question of whether the existence of two actors (patients and physicians) practicing the claims creates a divided infringement situation that would vitiate literal infringement was clearly contemplated throughout the litigation, during the course of which the Federal Circuit and Supreme Court were considering the question.  That both actors performed their individual steps of the claimed method was not disputed, but its effects on infringement liability, and whether Teva could be liable for inducing infringement was central to the dispute between the parties.

As the litigation progressed, defendants conditionally stipulated to induced infringement subject to being able to litigate the issue if (as it turned out) the Supreme Court reversed the Federal Circuit's contemporaneous standard.  The District Court proceeded on the invalidity issues and held Eli Lilly's claims not to be invalid on obviousness and obviousness-type double patenting grounds nor were indefinite.  After the Supreme Court's Akamai decision, the parties relitigated the infringement issues.  The District Court used the label as evidence of infringement, wherein under FDA regulations Teva's label comprising instruction for administration of the drug would be identical to Eli Lilly's label.  Based on this determination, the District Court found defendants had induced infringement, and this appeal followed.

The Federal Circuit affirmed, in an opinion by Chief Judge Prost joined by Judges Newman and Dyk.  The opinion recognized the Supreme Court's overriding teaching that induced infringement requires a finding that literal infringement had occurred.  Moreover, inducement also requires an intent to induce, which requires that the alleged infringer "knew or should have known" that her actions would induce infringement.  In order for more than one actor to practice the steps of a claimed method and for literal infringement to lie, the Supreme Court-approved standard is that either one of the actors works at the "direction or control" of the other actor, or the actors form a joint enterprise.  With regard to the question of "direction or control," the panel set forth the revised Akamai standard operationalized as a two-prong test.  The first prong of that test is whether one actor "'conditions participation in an activity or receipt of a benefit' upon anothers' performance of one or more steps of a patented method," and the second prong is whether that actor "'establishes the manner or timing of that performance,'" citing the Court's Akamai decision following remand from the Supreme Court (italics in opinion).  The District Court held that the first prong was satisfied because folate administration was a precondition for the physician administering B12 and the drug, and that the second prong was satisfied because the physician prescribed the dose and administration schedule to the patient.

With regard to the District Court's decision on the first prong, the Federal Circuit held that this determination was supported by the evidence of record.  Contrary to Teva's argument that reduction of toxicity was not conditioned by a patient taking folate, the opinion states that what was conditioned was whether the physician administered the drug to the patient (i.e., a physician would only administer the drug if a patient had taken the prescribed amount of folate at the proper schedule):

What is relevant is whether the physician sufficiently directs or controls the acts of the patients in such a manner as to condition participation in an activity or receipt of a benefit—in this case, treatment with pemetrexed in the manner that reduces toxicities—upon the performance of a step of the patented method and establishes the manner and timing of the performance [italics in opinion].

The panel also noted that the District Court's conclusions on this point were supported by the Physician Prescribing Information and Patient Information comprising the FDA-approved label as well as expert testimony (wherein both parties' experts agreed on the importance of folate pre-administration).  Finally on this point, the panel stated that such "conditioning" did not require that a legal obligation be imposed on one of the parties or that the step comprise an "unavoidable technological prerequisite to participation."

With regard to the second prong, the District Court and the panel relied upon the product label.  This information comports with the dosage amounts and frequencies encompassed by the asserted claims.  Expert testimony supported the finding that it was the physician who prescribed folate (in administered amount and frequency) to the patient.

Taken as a whole, the panel found no reversible error in the District Court's factual determinations.

The panel then turned to whether Eli Lilly had established that defendants exhibited the requisite intent to induce infringement, which required evidence of specific intention and acts and not mere knowledge of the patent in suit.  The District Court once more relied on the generic product label (identical to Eli Lilly's label).  The District Court and the Federal Circuit rejected Teva's argument that the label was not sufficient to provide specific evidence of inducement, because it purportedly did not show how physicians (the direct infringer) do act rather than as they may act.  The panel's reaction to that argument was that "[t]he question is not just whether [those] instructions describ[e] the infringing mode, . . . but whether the instructions teach an infringing use such that we are willing to infer from those instructions an affirmative intent to infringe the patent," citing Takeda Pharm. USA, Inc. v. West-Ward Pharm. Corp. and that "it is irrelevant that some users may ignore the warnings in the proposed label," citing AstraZeneca LP v. Apotex, Inc.  Also relevant to the panel's decision was that the label (in both the Physician Prescribing Information and Patient Information) emphasized how important folate administration was for reducing toxicity associated with administration of the drug.  This portion of the opinion concludes "[i]n sum, evidence that the product labeling that Defendants seek would inevitably lead some physicians to infringe establishes the requisite intent for inducement."

With regard to the invalidity issues, the opinion first considered Teva's indefiniteness contentions.  The factual basis for these were that the term "vitamin B12" was indefinite, because there were various species of the vitamin (claimed as vitamin B12, hydroxycobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo-10-cobalamin perchlorate, azidocobalamin, cobalamin, cyanocobalamin, or chlorocobalamin); the District Court found that the term meant cyanocobalamin based on expert testimony.  The panel noted that it does not defer to this expert testimony because satisfaction of the statute is a question of law.  But the opinion does note that the question of how the skilled worker would understand the term is a question of fact reviewable for clear error, and found no such error in the District Court's finding (a definition that was supported even by defendant's expert).  Upon consideration of how the term was used in the claims, and despite some apparent inconsistency in claim language, the Federal Circuit agreed that the skilled worker would have understood the meaning of the term.

With regarding to obviousness, the panel referenced the District Court's "thorough opinion" that the prior art did not motivate the skilled worker to practice the claimed method, and specifically that the skilled artisan would not have been motivated to "(1) use folic acid pretreatment with pemetrexed; (2) use vitamin B12 pretreatment with pemetrexed; or (3) use the claimed doses and schedules of folic acid and vitamin B12 pretreatments with pemetrexed."  The focus of these determinations was that the art did not show any correlation between pemetrexed toxicity and vitamin B12 deficiency (although there was evidence of a correlation with folate deficiency).  Expert testimony from both sides established that there was no recognition in the art that vitamin B12 deficiencies were associated with cancer treatment with antifolate compounds.  Nor was there evidence from the art that B12 would have been routinely administered (or that its administration schedules would have been routine) in cancer treatment.  The panel made similar determinations in affirming the District Court's finding that the claims of the '209 patent were not invalid under the obviousness-type double patenting doctrine.

Eli Lilly benefited in this case by having prevailed at the District Court, in large part due to the burden of finding clear error to overcome the District Court's decision.  But the opinion does set forth an affirmation of the Court's two-prong test for finding that more than one actor can perform the steps in a claimed method sufficient to satisfy the unitary standard for finding literal infringement.

Eli Lilly & Co. v. Teva Parenteral Medicines, Inc. (Fed. Cir. 2017)
Panel:  Chief Judge Prost and Circuit Judges Newman and Dyk
Opinion by Chief Judge Prost

Comments

[Atari Man]

Excellent result - and quite surprising coming from Judges Prost and Dyk.

[EG]

Hey Atari Man,

Not as surprising as you might think as Prost authored the 10-0 en banc decision (Dyk joined that decision) in the Limelight remand from SCOTUS on 271(a) applying to multi-actor (joint) infringement. I've got to hand it to the Federal Circuit on this particular question-they've essentially dared SCOTUS to overturn their Limelight remand ruling, and so far, Our Judicial Mount Olympus continues to "blink."