“Generic drug manufacturers accused of infringement should fully appreciate the subjective nature of a § 101 defense when evaluating their litigation risk.”
The Federal Circuit’s decision in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, No. 2016-2707, addresses the complicated topic of patent eligibility in the pharmaceutical space. The case confirms that amending an Abbreviated New Drug Application (ANDA) to address a patent issued after the original ANDA’s filing can infringe the later-issued patent. The decision also upheld the district court’s decision finding Vanda’s personalized medical treatment claims patent eligible under § 101.
Much of the decision compares Vanda’s claims to those found ineligible for patent protection in the U.S. Supreme Court’s decision in Mayo Collaborative Services v. Prometheus Laboratories, 132 S. Ct. 1289 (2012). While the ultimate patentability conclusions are opposite, the claims in Vanda and Mayo are very similar, highlighting the thin—and often unpredictable—line that divides eligible and ineligible subject matter. Generic drug manufacturers must account for this unpredictability in gauging their litigation risks.
Vanda owns a New Drug Application (NDA) for FANPAT (iloperidone), an antipsychotic drug used to treat schizophrenia. Id. at 4. Upon filing the NDA, Vanda listed U.S. Reissue Patent No. 39,198 in the Food and Drug Administration’s Orange Book for iloperidone. Id. at 2. In 2013, West-Ward filed its ANDA seeking approval to manufacture and sell a generic version of iloperidone. Id. at 5. While West-Ward’s ANDA was pending, the Patent Office issued U.S. Patent No. 8,586,610. Soon thereafter, Vanda listed the ‘610 Patent in the Orange Book. Id. at 6. West-Ward amended its ANDA to include a certification that the ‘610 patent was invalid or not infringed. Id.
The ‘610 patent discloses a method of treating schizophrenia patients with iloperidone, including analyzing the patient’s genotype and determining the proper iloperidone dosage based on that genotype. Id. at 3. The human body metabolizes iloperidone with an enzyme encoded by the CYP2D6 gene. Id. Some individuals have low CYP2D6 activity, and therefore poorly metabolize drugs like iloperidone. Id. These poor metabolizers are at a higher risk for an abnormal heartbeat when treated with iloperidone. Id. The ‘610 patent teaches that poor metabolizers, who can be identified by a genetic test, should be treated with a lower dose of iloperidone to reduce that risk. Id.
Vanda sued West-Ward for infringement of the ‘610 patent in the District of Delaware. Id. West-Ward raised several defenses at trial, including (1) that amending its ANDA could not constitute an act of infringement because the ‘610 patent issued after the original ANDA filing date and (2) that the ‘610 patent was invalid under § 101 as directed to patent-ineligible subject matter. Id. at 12, 26. After a bench trial, Judge Sleet found that West-Ward’s proposed generic drug-induced infringement and that the ’610 patent was not invalid. Id. at 6-7. West-Ward appealed.
The Hatch-Waxman Act states that “it shall be an act of infringement to submit an application” seeking to manufacture, use, or sell “a drug. . . the use of which is claimed in a patent.” Id. at 13-14 (quoting 35 U.S.C. § 271(e)(2)). This allows brand-name and generic drug manufacturers to litigate issues of infringement and invalidity before a generic version of the drug is actually sold or marketed. Id. at 14. ANDA applicants who want to market their generic drug prior to patent expiration can certify that the patents listed in the Orange Book for the relevant drug are either invalid or would not be infringed by the proposed generic drug. Id. at 5. These certifications are referred to as “Paragraph IV certifications.” Id. West-Ward alleged that filing an amended ANDA with an updated Paragraph IV certification did not constitute an act of infringement when the updated certification addressed a patent that was not listed in the Orange Book when the ANDA was originally filed. In other words, does amending a Paragraph IV certification to address a subsequent patent constitute “submit[ting] an application” under § 271(e)(2)?
The Federal Circuit found that it does. First, the ’610 patent was a patent “for a drug. . . the use of which is claimed in a patent” under 35 U.S.C. § 271(e)(2)(A) regardless of whether it issued before or after West-Ward’s initial Paragraph IV certification. Id. at 14. Second, the proper infringement analysis must consider the amended ANDA, including the amended Paragraph IV certification. Id. (citing Ferring B.V. v. Watson Labs., Inc.-Fla., 764 F.3d 1382, 1390 (Fed. Cir. 2014) and Bristol-Myers Squibb Co. v. Royce Labs., Inc., 69 F.3d 1130, 1135 (Fed. Cir. 1995)).
Third, the FDA regulatory framework “expressly contemplates certifications for patents that issue after the ANDA is filed.” Id. at 16. NDA applicants have a continuing obligation to update patent information even for patents that issue after the FDA approves the drug. Id. Furthermore, ANDA applicants have a corresponding duty to update Paragraph IV certifications, even as to subsequently issued patents, until the ANDA is approved. Id.
Finally, legislative history further supports a finding that amendments to Paragraph IV certifications addressing subsequent patents can infringe. Id. Under certain circumstances, the FDA’s approval of an ANDA will be stayed for thirty months if the drug manufacturer brings suit for patent infringement. Id. at 17. Earlier versions of the statute permitted a stay if suit was brought within 45 days of a Paragraph IV certification, including amended certifications. Id. This allowed for multiple 30 month stays if patents issued after the ANDA filing date. Id. In 2003, Congress amended the provision to provide a stay only for Paragraph IV certifications made in response to patents existing when original ANDA was filed. Id. In light of this, the Federal Circuit concluded that an amended Paragraph IV certification addressing a subsequent patent could be an infringing act.
After affirming that West-Ward’s ANDA induced infringement of the ‘610 patent, the court addressed whether the infringed claims were even patent-eligible. West-Ward argued that the claims were ineligible under § 101 because they were directed to a natural relationship between iloperidone, CYP2D6 metabolism, and the abnormal heartbeat iloperidone can induce. Id. at 26.
Determining subject-matter eligibility requires a two-step process. Id. at 27. First, the court must determine whether the claims of the ‘610 patent are directed to a patent-ineligible concept, in this case, a law of nature. Id. If the claims are directed to an ineligible concept, then the court must determine whether the claims reflect an “inventive concept.” Id. Here, the majority did not reach the second step of the inquiry, finding that the claims were not even directed at ineligible subject matter. Id. at 28.
Much of the court’s opinion compares the ‘610 patent’s claims with those the Supreme Court found ineligible in Mayo Collaborative Services v. Prometheus Laboratories. In Mayo, the representative claim recited “a method for optimizing treatment of a . . . disorder” comprising the steps of (1) administering a particular drug, (2) determining the level of that drug in the patient’s blood, and (3) adjusting the patient’s dose upward if the drug appears below a certain threshold and adjusting the dose downward if the drug appears above a certain threshold. The ‘610 patent recites a method of “treating a patient” with a drug, comprising the steps of (1) determining how a patient will metabolize the drug using a genetic test, and (2) administering one of two dosages depending on the results of that genetic test. Representative claims of the ’610 patent and the patent at issue in Mayo are presented below:
Both claims correlate an individual’s ability to metabolize the drug with the proper dosage for that individual. But, according to the majority opinion, the claims in Mayo merely recited that natural relationship, while the ‘610 patent “claims an application of that relationship.” Id. at 30. The court found that the ‘610 patent’s recitation of specific dosages, and the specification’s explanation of the significance of those specific dosages, distinguished this case from Mayo. Id. The court also seemed persuaded by the representative claims’ respective preambles. Vanda’s claimed, “a method for treating a patient” while Mayo’s claimed “a method for optimizing therapeutic efficacy for treatment” of a particular disorder. Id. at 29.
While the subject matter-eligibility inquiry inherently requires some line-drawing, the court relied on a very thin line to distinguish Vanda’s claims from Mayo’s ineligible ones. Chief Judge Prost dissented from the majority opinion, stating that she would have held the ‘610 patent claims were directed to a law of nature and therefore ineligible. Id., dissent at 2. In her opinion, claims that merely apply a law of nature are not patent-eligible either. Id.
This decision highlights the difficulty courts have had in applying the Supreme Court’s subject-matter eligibility, including from Mayo and Alice Corp. v. CLS Bank. Generic drug manufacturers accused of infringement should fully appreciate the subjective nature of a § 101 defense when evaluating their litigation risk.