As summer vacations end, school for kids and big kids starts up, and we return to the reality that is September, we present a little big kid patent school and some good news for holders of pharmaceutical method patents – in the form of the Federal Circuit’s Vanda decision. Vanda gives patentees some strength in resisting a challenge to patentable subject matter under 35 USC §101 and also some confidence in asserting infringement against a deep-pocket infringer.
Vanda Pharmaceuticals v. West-Ward Pharmaceuticals International, Ltd., 887 F.3d 1117, 126 U.S.P.Q.2d 1266 (Fed. Cir. 2018)
Vanda’s patent relates to a method of treating schizophrenia patients with iloperidone wherein the dosage range is based on the patient’s genotype.
Claim 1 of the patent:
A method for treating a patient with iloperidone, wherein the patient is suffering from schizophrenia, the method comprising the steps of:
determining whether the patient is a CYP2D6 poor metabolizer by: obtaining or having obtained a biological sample from the patient;
performing or having performed a genotyping assay on the biological sample to determine if the patient has a CYP2D6 poor metabolizer genotype; and if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 12 mg/day or less, and if the patient does not have a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day,
wherein a risk of QTc prolongation for a patient having a CYP2D6 poor metabolizer genotype is lower following the internal administration of 12 mg/day or less than it would be if the iloperidone were administered in an amount of greater than 12 mg/day, up to 24 mg/day.
In short, the claims of the patent at issue required treatment of schizophrenia with iloperidone to be performed with different dosing ranges depending on whether the patient was a poor metabolizer of CPY2D6. Because the claims at issue related to a method of treatment, for West-Ward to be liable for infringement, West-Ward must induce the physicians to practice the method.
Akamai Techn. Inc. v. Limelight Networks (797 F.3d 1020, 116 U.S.P.Q.2d 1344 (Fed. Cir. 2015, en banc) confirmed that an act of direct infringement must be proven before there can be a finding of indirect infringement and that direct infringement requires all the steps of the claimed method to be performed by, or attributable to, a single entity. In the real world, at least the steps of “assaying” and “administering” are seldom performed by a single actor, and if they are, that actor is most likely to be a doctor. That was the case here, where the plaintiff put forth evidence below of direct infringement in the form of physician testimony and corroborating patient records showing that a doctor had performed or caused to be performed, all of the active steps. These steps included obtaining a biological sample, performing the claimed genotyping steps, and administering an adjusted dose of iloperidone to a patient based on genotype in accordance with Vanda Pharma’s claim.
(As a side note, the two substeps of the determining step could have been written as a single step: “performing or having performed a genotyping assay on the a biological sample obtained from the patient to determine if the patient has a CYP2D6 poor metabolizer genotype” to avoid even a potential assertion that a third party obtained the sample, and thus that there was no direct infringement by a single entity.)
Doctors are seldom the target of enforcement actions, for a variety of practical reasons. First and foremost, 35 U.S.C. § 287(c) bars a medical procedure patent owner from enforcing that patent by obtaining an injunction, monetary damages, and attorney fees, against a medical practitioner and a related health care entity based on the medical practitioner’s performance of a medical activity. Moreover, even for patents on devices such as a diagnostic kit, patentees would prefer to sue the manufacturer of such an infringing diagnostic kit or the laboratory performing the tests – not only because one suit in one jurisdiction (or at least a few suits in a limited number of jurisdictions) would stop the infringement instead of pursuing doctors in multiple actions, but because in terms of damages the award would cover all or most infringing items, not just those few used by an individual physician . As a result, in addition to proof of direct infringement, a theory of indirect infringement is necessary to get at the target defendant, typically the entity performing the “assaying” step of the claimed method or the entity marketing the assay test kit.
Vanda confirms that the drug label can support inducement of method of treatment claims, especially those involving multiple discreet steps in addition to simply administering a therapeutic agent. Under US law, where the proposed label instructs users to perform the patented method, the label itself may provide evidence of affirmative intent to encourage direct infringement. (In the Hatch-Waxman context, where a generic drug has yet to enter the market, the content of the label is often the evidence for proof of intent.)
The defendant West-Ward argued that there was insufficient proof for a finding that the proposed label would encourage or recommend a direct infringer, such as a doctor, to perform all of the claimed method steps. In support of this position, the defendant pointed out that the label does not direct the performance of a genotyping test to determine whether or not a patient is a CYP2D6 poor metabolizer, and that other types of assays are available to determine metabolizer status (such as enzyme assays). Indeed, on this point the label states only that: “[poor metabolizers] of CYP2D6 have higher exposure to iloperidone compared with [extensive metabolizers] and [poor metabolizers] should have their dose reduced by one half. Laboratory tests are available to identify CYP2D6 [poor metabolizers].”
Nevertheless, the court agreed with Vanda that this language was sufficient to support the finding below that the label recommends practitioners perform or have performed a genotyping assay. The court took note of the finding below, based on expert testimony for both parties, that the “laboratory tests” referred to in the label are “genotyping tests.” In addition, the court rejected the defendant’s argument that the existence of substantial non-infringing uses precluded a finding of specific intent as a matter of law. Unlike contributory infringement, inducement under Section 271(b) does not include any language regarding non-infringing substitutes. Thus, a finding of induced infringement can still occur even if the actions of some, but not all physicians, are infringing. The defendant also argued that there was no inducement because there is no label instruction satisfying the claim element of “obtaining a biological sample.” But the court rejected this argument and agreed with the finding below that the label implicitly recommends obtaining a biological sample, since a sample is required in order to perform the genotyping test.
According to the Federal Circuit, a “proposed label [that] ‘recommends’ that physicians perform the claimed steps” was sufficient to establish specific intent and support liability for induced infringement. Vanda, 887 F.3d at 1130-33.
Focusing on these specific findings, and noting that regardless of any substantial non-infringing uses, the Federal Circuit upheld the District Court’s finding that the label supported liability for induced infringement.
In a second positive development, the Vanda court confirmed that the diagnostic method claim satisfied the patentable subject matter requirement of 35 USC §101.
Vanda’s asserted claims were directed to a “method of treating” a patient suffering from schizophrenia with a drug called iloperidone. Iloperidone is metabolized by the liver cytochrome P450 enzyme, CYP2D6, and high levels of iloperidone or its metabolites were known to cause a serious side effect in the form of a heart arrhythmia, QT prolongation, which is referred to as QTc when corrected for the patient’s heart rate.
According to the specification of the ‘610 Patent, the inventors discovered “an association between genetic polymorphisms in the CYP2D6 locus, corresponding increases in the concentrations of iloperidone or its metabolites, and the effect of such increases in concentrations on corrected QT (QTc) duration relative to baseline.” The asserted claims recite active steps relating to determining whether a patient is a CYP2D6 poor metabolizer and administering an appropriate dose based on metabolizer status. In brief, the active steps recited in the claim are “determining” whether the patient is a poor metabolizer by “obtaining” a biological sample and “performing” a genotyping assay followed by “administering” to the patient a specific dose of “12 mg/day or less” for poor metabolizers or “an amount that is greater than 12 mg/day, up to 24 mg/day” for a patient that lacks a CYP2D6 poor metabolizer genotype.
The Federal Circuit recalled the Supreme Court’s two step inquiry for determining subject matter eligibility, commonly referred to as “the Mayo/Alice inquiry ( Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 132 S. Ct. 1289,182 L. Ed. 2d 321, 101 U.S.P.Q.2d 1961, 80 U.S.L.W. 4225 (2012) / Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 110 USPQ2d 1976 (2014)).” Under Step 1, the question is whether the claimed subject matter is “directed to” a judicial exception, such as a law of nature, a natural product, or an abstract idea. If it is not, then the inquiry ends there and the claim is deemed patent eligible. However, if the claim is found to be “directed to” a judicial exception, then the inquiry proceeds to Step 2, in which the claim is examined to determine whether or not it adds “significantly more” to the judicial exception, or is merely an attempt to claim the law of nature, natural product, or abstract idea itself. In the vast majority of diagnostic method cases finding claims lacking in patentable subject matter under §101, the courts have found that the subject matter was directed to an exception, typically a law of nature (e.g., the “natural” correlation between CYP2D6 and metabolization of iloperidone) and the case has focused on the “significantly more” aspect – which has proved hard to satisfy.
Here, surprisingly to the contrary, the majority of the Federal Circuit found the claims to be eligible under Step 1. Quoting Mayo and the Federal Circuit decision in CellzDirect, (Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042 , 1050 (Fed. Cir. 2016)) the majority notes the following:
“[T]oo broad an interpretation of ineligible subject matter could eviscerate patent law because all inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas. Accordingly, at step one, it is not enough to merely identify a patent-ineligible concept underlying the claim; we must determine whether that patent-ineligible concept is what the claim is ‘directed to.’”
Here, claims directed to treating a specific disease (schizophrenia) with a specific drug (iloperidone) in a specific patient population (CYP2D6 poor metabolizers, or not) in a specific way (by administering a defined dose to each patient population) to achieve a specific result (lower risk of a serious side effect) were patent eligible at Step 1 of the Mayo/Alice inquiry.
However, as a point of caution, the claims at issue in Vanda were similar enough to those found ineligible in Mayo to warrant significant attention in both the majority opinion and by the dissent. The majority characterized Vanda’s claims as “a novel method of treating a disease” and therefore patent eligible and distinguishable from the claims found ineligible in Mayo which were “directed to a diagnostic method” based on “entirely natural processes.” In dissent, Judge Prost contends that “[t]he majority fails to reconcile [the] substantive similarity between our case and Mayo.” Judge Prost would have found the claims ineligible as directed to a natural law, stating that he would find the asserted patent claims to be directed to a law of nature, and argued that there was “no inventive concept in the claims once the natural law at issue is properly understood in view of Mayo.” In Judge Prost’s view, the natural law is the fact that a reduction of iloperidone dosage in poor metabolizers may reduce QTc prolongation,” and argued that “[t]he recitation of specific dosages adds no more than a conventional application of that natural law.”
West-Ward’s motion for rehearing en banc was denied by the Federal Circuit in August. Thus, for the moment, Vanda provides a ray of hope for diagnostic method claims of similar nature, where assaying of a specific factor provides information which is then used to adjust treatment – for not only are such claims directed to patentable subject matter under this decision, but are infringed by a viable target defendant enabling enforcement in a reasonable manner.