Docket No. 2016-2707, -2708
PROST, LOURIE, HUGHES
April 13, 2018
Brief summary: DC finding of infringement of later-issued OB patent by amended ANDA, and that method of treatment claims are patentable under § 101 affirmed.
Summary: WW appealed DC holding after a bench trial that the asserted claims of Vanda’s Orange Book-listed US 8,586,610 relating to treatment of schizophrenia with iloperidone (Fanapt® (NDA 22-192)) “wherein the dosage range is based on the patient’s” cytochrome P450 2D6 (CYP2D6) genotype infringed and not invalid under § 101, § 103, or § 112 for lack of written description. Vanda is the exclusive licensee of Aventisub’s Reissue 39,198 (also OB-listed; expired in 2016) about which the parties stipulated that claim 3 was infringed and not obvious; this decision was not appealed (see FN3). Representative ‘610 claim 1 requires “determining whether the patient is a CYP2D6 poor metabolizer” by a CYP2D6 “genotyping assay”, who the ‘610 patent explains could lead to cardiac problems, and if so administering the lower of two claimed dose ranges. The FC opinion explains that the FDA approved iloperidone based, at least in part, on the invention disclosed in the ‘610 patent”. At the time WW filed its ANDA (including a label “substantially identical in all material respects to the Fanapt® label” including that the dose “should be reduced by one-half for poor metabolizers of CYP2D6”), “the ‘610 patent had not yet issued and only the ‘198 patent was listed in the” OB and a first suit based on the ‘198 patent began. After the ‘610 patent issued, Vanda filed suit regarding the same and WW amended its ANDA to include a paragraph IV statement as to the ‘610 patent. The DC found that WW’s “proposed products induce infringement” of the ‘610 claims “but do not contributorily infringe them”, and that WW’s “submission of a paragraph IV certification…is an act of infringement”. On invalidity, the DC concluded “that ‘the asserted claims depend upon laws of nature’” but “that while it may have been conventional to investigate for side effects,” WW “has not proven by clear and convincing evidence that the precise test and the discovered results were routine or conventional.” The DC found Vanda was not entitled to § 271(e)(4)(A) relief (effective date of FDA approval not earlier than expiration of the infringed patent) regarding the ‘610 patent because it issued after the ANDA was filed, but that “injunctive relief was appropriate…pursuant to its ‘general equitable power’”, and enjoined WW from manufacturing, using, offering to sell, or selling its ANDA product (which the FC panel found was proper). The DC did find that WW’s filing of its amended ANDA was an act of infringement of the ‘610 patent.
The FC panel first determined that the DC had jurisdiction over the case under § 271(e)(2) (“Vanda alleged that [WW] infringed…under § 271(e)(2)(A) by filing the ANDA…Nothing more was required to establish the [DC’s] subject matter jurisdiction….”) The FC also found that WW’s “arguments relating to whether there was a qualifying act of infringement raise potential merits problems, not jurisdictional issues” (Caraco II, US 2012), and that “an actual controversy has existed between the parties from the time when the suit was commenced” (Teva, FC 2007; Arizonans, US 1997).
WW argued “that there can be no infringement under § 271(e)(2) because the ANDA was filed befor the ‘610 patent issued” (WW’s ANDA was amended to include the ‘610 patent after it issued). The FC panel concluded, however, that the DC “properly conducted its infringement analysis for the ‘610 patent” because “‘application’ in § 271(e)(2) includes amendments to the ANDA” (Gross, US 2009; Ferring, FC 2014 (“The infringement analysis under § 271(e)(2)(A) ‘require[s] consideration of the amended ANDA.’”); Bristol-Myers, FC 1995)).
WW also argued the DC erred in finding induced infringement under § 271(b) “because Vanda failed to prove the requisite direct infringement and specific intent to induce infringement” (Limelight, US 2014 (“direct infringement is a necessary predicate”); DSU Med., FC 2006 (“must [establish] specific intent to encourage another’s infringment”); AstraZeneca I, FC 1998 (“[c]ircumstantial evidence can support a finding of specific intent…Where ‘the proposed label instructs users to perform the patented method…the proposed label may provide evidence of [the ANDA’s applicant’s] affirmative intent to induce infringement.”); Takeda, FC 2015 (“[t]he label must encourage, recommend, or promote infringement”); Sanofi, FC 2017)). But the FC panel “agree[d] with Vanda that a patentee does not need to prove an actual past instance of direct infringement by a physician to establish infringement under 35 U.S.C. § 271(e)(2)(A)” (Bristol-Myers, FC 1995; Warner-Lambert, FC 2003; Glaxo, FC 1997). “Accordingly,” the FC panel wrote, “Vanda can satisfy its burden…by showing that if the proposed ANDA product were marketed, it would infringe the ‘610 patent” (Ferring, FC 2014 (“the ANDA itself dominates the analysis”)). The FC panel also agreed with Vanda that the DC did not err in its infringement analysis because WW’s proposed label “recommends that practitioners perform or have performed” the genotyping assay and dose reduction of the ‘610 claims. The FC panel also explained that “[i]n the context of [the] off-label use case where there [are] ‘substantial noninfrining uses,’ [it] decline[s] to ‘infer’ intent to induce infringement” (Warner-Lambert, FC 2003).
Regarding patentability under § 101, the FC panel explained that “[t]his case…is not Mayo” as “the claims in Mayo were not directed to a novel method of treating a disease”. Here, even though “[t]he inventors recognized the relationships between iloperidone” and “CYP2D6 metabolism”, “the ‘610 patent claims are directed to a method of using iloperidone to treat schizophrenia” (“an application of that relationship…‘a new way of using an existing drug’ that is safer” (Mayo, US 2012)). In addition, “unlike the claim in Mayo” which “did not do beyond recognizing (i.e., ‘indicates’) a need to increase or decrease a dose”, “to the extent that preemption is a concern, the ‘610 patent claims do not ‘tie up the doctor’s subsequent treatment decision’” (CellzDirect, FC 2016). Judge Prost dissented on this point.
The FC panel also found the DC did not err in finding the ‘610 patent contains adequate written description since, e.g., “the reported results ‘show that patients can be more safely treated…if the dose…is adjusted based on the CYP2S6 genotype of each patient” and “provides a specific example” (Scriptpro, FC 2014 (“[t]he disclosure of a dose outside of the claimed range does not compel a finding that the asserted claims lack” WD)).