by Dennis Crouch
Vanda is an important patent eligibility case drawing a fine line between the the eligible personalized medicine treatment claims and the ineligible methods of Mayo and Ariosa.
In a split decision, the Federal Circuit has affirmed the validity/infringement of Vanda’s U.S. Patent No. 8,586,610 covering a schizophrenia treatment using iloperidone. The claims require personalized dosage — depending upon the patient’s metabolization rate of iloperidone (“CYP2D6 activity”).
West-Ward filed an Abbreviated New Drug Application (ANDA) that substantially copied Vanda’s FANPAT application — Vanda then sued for infringement.
ANDA-Filing infringement is an oddity – filing of an FDA application to make a generic version of a patented drug is the act of infringement.
It shall be an act of infringement to submit— (A) an application … for a drug claimed in a patent or the use of which is claimed in a patent.
35 U.S.C. 271(e)(2). Infringement was straightforward here because the proposed package label recommends personalized dosage based upon the aforementioned metabolic activity (and thus would induce infringement).
Eligible Subject Matter: The primary dispute is whether the claims survive the Mayo and Ariosa — i.e,. are they eligible or are they instead directed to an unpatentable law of nature.
The claims at issue in Vanda were roughly parallel to those found unpatentable in Mayo v. Prometheus. In Mayo, representative claim 1 of the challenged Patent No. 6,355,623 was directed to treatment method that involved (a) administering a drug (6-thioguanine); and then (b) determining blood level of the drug. A low blood level (less than about 230 pmol per 8×108 red blood cells) indicates a lack of effectiveness and a need for a higher subsequent dose while a high blood level (greater than about 400 pmol per 8×108 red blood cells) indicates potential for toxicity and that the next dose should be reduced.
In finding the claim invalid, the Supreme Court unanimously held that the correlation between blood level, efficacy and toxicity was an unpatentable law of nature and that the administration and determination steps were already well known in the art and thus insufficient to transform the claim to a patent eligible invention.
In Vanda, representative claim 1 is directed to a method of treating a patient suffering from schizophrenia by (a) determining whether the patient is genetically a poor metabolizer of the drug (CYP2D6 genotype) then (b) administering iloperidone to the patient (12-24 mg per day if good metabolizer; <12 mg per day if poor metabolizer) in order to reduce the risk of “QTc prolongation” for poor metabolizers.
First the dissent — Chief Judge Prost identified the similarity here and explained her position that “the asserted patent claims [are] directed to a law of nature.” At its crux, the invention began with the discovery of the health problems created by treating folks with lower CYP2D6 activity and recognition that a lower dose would be appropriate.
Importance of the preamble: The majority (Judges Lourie and Hughes) took the other side – and argued that the claiming differences were important between Mayo and Vanda. Importantly, for them, the preamble in Mayo directed the claims toward “a method of optimizing therapeutic efficacy” while the Vanda claims are directed to “a method for treating a patient.”
This case, however, is not Mayo. First, the claims in Mayo were not directed to a novel method of treating a disease. Instead, the claims were directed to a diagnostic method based on the “relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm.” Id. This “relation is a consequence of the ways in which thiopurine compounds are metabolized by the body—entirely natural processes. And so a patent that simply describes that relation sets forth a natural law.”
Although the representative claim in Mayo recited administering a thiopurine drug to a patient, the claim as a whole was not directed to the application of a drug to treat a particular disease. See id. at 74, 87. Importantly, the Supreme Court explained that the administering step was akin to a limitation that tells engineers to apply a known natural relationship or to apply an abstract idea with computers. See id. at 78 (comparing the claim in Mayo to “Einstein telling linear accelerator operators about his basic law and then trusting them to use it
where relevant”). To further underscore the distinction between method of treatment claims and those in Mayo, the Supreme Court noted that “[u]nlike, say, a typical patent on a new drug or a new way of using an existing drug, the patent claims do not confine their reach to particular applications of those laws.” Id. at 87.
In this case, the ’610 patent claims are directed to a method of using iloperidone to treat schizophrenia. The inventors recognized the relationships between iloperidone, CYP2D6 metabolism, and QTc prolongation, but that is not what they claimed. They claimed an application of that relationship. Unlike the claim at issue in Mayo, the claims here require a treating doctor to administer iloperidone in the amount of either (1) 12 mg/day or less or (2) between 12 mg/day to 24 mg/day, depending on the result of a genotyping assay. The specification further highlights the significance of the specific dosages by explaining how certain ranges of administered iloperidone correlate with the risk of QTc prolongation. See, e.g., ’610 patent at col. 4 ll. 1–15. Thus, the ’610 patent claims are “a new way of using an existing drug” that is safer for patients because it reduces the risk of QTc prolongation. Mayo, 566 U.S. at 87
Very important case here. Although I believe that the invention should be patent eligible, the majority’s approach appears to latch onto simple patent drafting tricks as the basis for distinguishing Mayo — an approach directly rejected by the Supreme Court in Mayo.
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; and 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.
A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:
(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and
(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder,
wherein the level of 6-thioguanine less than about 230 pmol per 8×108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and wherein the level of 6-thioguanine greater than about 400 pmol per 8×108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.