On April 13, 2018, the United States Court of Appeals for the Federal Circuit issued a decision in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals Int’l Ltd  upholding the validity of U.S. Patent 8,586,610 (“the ’610 patent”), which claims a method of personalized treatment for schizophrenia. The Federal Circuit further affirmed the district court’s finding of infringement and awarding of injunctive relief that will exclude a generic version of Fanapt® in various strengths for treating schizophrenia from the market until the ’610 patent expires. [1]

The case arose from a Hatch-Waxman case involving the Abbreviated New Drug Application (“ANDA”) No. 20-5480 filed by West-Ward Pharmaceuticals International Limited, West-Ward Pharmaceuticals Corp. (“West-Ward”). West-Ward sought approval to commercialize a generic version of Fanapt® in various strengths for treating schizophrenia. Fanapt®, with iloperidone as the active ingredient, is an atypical antipsychotic owned by Vanda Pharmaceuticals Inc. (“Vanda”) for treating schizophrenic patients.

At the time of the ANDA filing, U.S. Reissue Patent 39,198 (“the ’198 patent”) was the only patent listed in FDA’s Orange Book for Fanapt®. Vanda filed a lawsuit in 2013 in the U.S. District Court for the District of Delaware (“the District Court”) alleging that West-Ward infringed the ’198 patent, which expired on November 15, 2016. The ’610 patent issued on November 19, 2013, will expire on November 2, 2027, and was listed in the Orange Book for Fanapt® after West-Ward filed its ANDA No. 20-5480. In 2014, Vanda sued West-Ward for infringement of the ’610 patent. West-Ward further amended its ANDA No. 20-5480 to contain a Paragraph IV certification that the’610 patent is invalid and/or not infringed.  

The ’610 patent relates to a use of an existing compound iloperidone. In particular, the ’610 patent relates to methods for the identification of genetic polymorphisms that may be associated with a risk for QT prolongation after treatment with iloperidone and methods of administering iloperidone to patients with such genetic polymorphisms. [2] Representative Claim 1 of the ’610 patent reads as follows:

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 iloperidone, 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.

West-Ward challenged the validity of the ’610 patent on multiple grounds, including ineligibility of subject matter under §101. The Supreme Court has established a two-step framework (“the Mayo test”) for determining patent subject matter eligibility under 35 U.S.C. § 101: the first step is to determine whether a claim at issue is directed to a patent-ineligible concept, such as a law of nature, a natural phenomenon, or an abstract idea; the second step is “a search for an ‘inventive concept,’— i.e., an element or combination of elements that is ‘sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the [ineligible concept] itself.’” [3] According to the Federal Circuit, if the claims are not directed to a patent ineligible concept at step one, step two does not need to be addressed. [4] West-Ward argued that the claims of the ’610 patent are directed to a natural relationship between iloperidone, CYP2D6 metabolism, and QT prolongation, and add nothing inventive to those natural laws and phenomena. The Federal Circuit rejected West-Ward’s arguments, finding that the asserted claims are not directed to patent-ineligible subject matter at step one.  

In analyzing patent eligibility, the Federal Circuit emphasized that “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.’” [5] According to the Federal Circuit, the claims in the ’610 patent are different from the claims in Mayo, which were directed to a diagnostic method based on the relationships between the concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm. Although the representative claim in Mayo recited administering a thiopurine drug to a patient, the representative claim as a whole was not directed to the application of a drug to treat a particular disease. The representative claim in Mayo did not go beyond recognizing a need to increase or decrease a dose. [6] In contrast, the ’610 patent claims are directed to a method of using iloperidone to treat a particular disease; i.e. schizophrenia. The ’610 patent claims recite a method of treating patients based on a relationship that makes iloperidone safer by lowering the risk of QTc prolongation. What is claimed is not the natural relationship between CYP2D6 metabolizer genotype and the risk of QTc prolongation, but an application of the natural relationship. [7] The Federal Circuit concluded that the claims in the ’610 patent “are directed to a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.” [8]

The Federal Circuit further affirmed the district court’s holding that the asserted claims were not invalid under § 112 for lack of written description.

Aside from upholding the eligibility of the claims in the ’610 patent and the validity of the ’610 patent, the Federal Circuit further upheld the District Court’s finding of infringement and awarding of injunctive relief. According to the Federal Circuit, “amendments to an ANDA, including a Paragraph IV certification for a later-issued patent, can constitute an act of infringement under §271(e)(2)(A).” [9] In addition, the Federal Circuit indicated the District Court made factual findings that the proposed label for the proposed ANDA product “recommends” that physicians perform the claimed steps, and thus West-Ward is liable for induced infringement of the asserted claims. [10] The Federal Circuit further affirmed the District Court’s grant of injunctive relief that resets the effective date of an approval of ANDA No. 20-5480 not earlier than the expiration of the ’610 patent, which is November 2, 2027. [11]

In summary, a personalized medical treatment for schizophrenia was found patent eligible at the Federal Circuit. The Federal Circuit further sustained the District Court’s finding of infringement by filing an ANDA application and affirmed the district court’s grant of injunctive relief. The Federal Circuit’s decision encourages the development of the tailored use of drugs to individual patients based on their predicted response or risk.  

[1] Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals Int’l Ltd., 2018 WL 1770273 (Fed. Cir. Apr. 13, 2018).
[2] See the ’610 patent, Abstract.
[3] See Opinion, at 27 (citing Alice Corp. Pty. v. CLS Bank Int’l, 134 S. Ct. 2347, 2355 (2014) (citations omitted) (alteration in original) (quoting Mayo, 566 U.S. at 72–73, 75–79)).
[4] See Opinion, at 28.
[5] See Opinion, at 28. (reciting Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1050 (Fed. Cir. 2016)).
[6] See Opinion, at 29-40.
[7] See Opinion, at 30.
[8] See Opinion, at 32.
[9] See Opinion, at 14.
[10] See Opinion, at 21-22.
[11] See Opinion, at 38.

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