Can a generics provider establish non-infringement of a patented method of treating a disease when the label of the drug it is seeking to market closely tracks the steps of that method? Very difficult, if not impossible, as would appear from Vanda Pharma v. West-Ward Pharma (“Vanda”), decided April 2018 by the Federal Circuit. In Vanda, generics provider West-Ward Pharma (“West-Ward”) mounted a strong effort to refute allegation of inducement to infringe Vanda Pharma’s patent on a method of treating schizophrenia, but failed.
Proving inducement to infringe requires showing that the accused infringer possessed “specific intent” to infringe. In pharmaceutical cases, particularly those arising in the Hatch-Waxman framework, specific intent may be supplied by the wording of a drug label. Vanda sheds light on several issues relevant to inferring inducement to infringe based on a drug’s label. For example, can a label’s clear recommendations on ultimate dosage be negated by how a medical provider arrives at the dosage? Or, does finding specific intent require that every practitioner prescribe an infringing dose? Or, can evidence of substantial non-infringing use negate a finding of inducement when the drug’s label instructs performing the patented method?
Induced infringement is defined by 35 U.S.C. § 271(b), which provides that “[w]hoever actively induces infringement of a patent shall be liable as an infringer.” To prove inducement, the defendant must be shown to have possessed specific intent to encourage another’s infringement and not merely that the defendant had knowledge of the acts alleged to constitute inducement. Majority Op. at 18 (internal citation and quotations omitted). Also, for proof of specific intent to depend on the label accompanying the marketing of a drug, “[t]he label must encourage, recommend, or promote infringement.” Id. at 19 (internal citation omitted).
Vanda Pharma (“Vanda”) sells Fanapt® (iloperidone), approved by the FDA for treating schizophrenia. Vanda also owns U.S. Patent 8,586,610 (“the ’610 patent”) which describes treating schizophrenia patients with iloperidone using dosages based on a patient’s cytochrome P450 2D6 (“CYP2D6”) genotype. CYP2D6 encodes an enzyme known to metabolize many drugs, including iloperidone. West-Ward sought to obtain FDA approval for a generic version of Fanapt® and was sued by Vanda for infringement of the ’610 patent in the US district court for the district of Delaware. In response, West-Ward asserted that the ’610 patent was invalid and/or not infringed.
Vanda’s asserted claims, which are directed to a method of treating schizophrenia patients with iloperidone, require first determining whether a schizophrenia patient is a CYP2D6 poor metabolizer (CYP2D6 PM). A CYP2D6 PM is to be administered 12 mg/day or less of iloperidone. A patient who is not a CYP2D6 PM is to be administered amounts greater than 12 mg/day, up to 24 mg/day. The claims further recite that a risk of QTc prolongation for a CYP2D6 PM is lower following administration of 12 mg/day or less iloperidone than it would be if iloperidone were administered in an amount greater than 12 mg/day, up to 24 mg/day. QTc is the time interval between the Q and T waves of heart rhythm, corrected for the patient’s heart rate. QT prolongation can lead to serious cardiac problems.
As expected, West-Ward’s proposed label for use of the generic equivalent to treat schizophrenia is substantially identical to the Fanapt® label. Relevant portions of the proposed label are reproduced below adjacent to a representative claim (claim 1) of the ’610 patent, based on which approval for Fanapt® was obtained.
After a bench trial, the district court found West-Ward to have induced infringement of the ’610 patent. Id. at 6-7. West-Ward appealed.
In one set of arguments, West-Ward contended and that the district court’s finding of inducement was in error because the proposed label lacked express instructions for some of the steps of the claimed method, and because the label did not recommend the claimed dosage.
On the issue of dosage, West-Ward’s position was that the district court had erred in finding the proposed label as recommending oral administration of iloperidone tablets at 12 to 24 mg/day to non-CYP2D6 PMs and 12 mg/day or less to CYP2D6 PMs, as required by the asserted claims. The Federal Circuit disagreed. It pointed out that the proposed label recommends a usual target dose range (12 to 24 mg/day) and a maximum dose (24 mg/day). It then instructs medical providers to reduce the dose for genetic CYP2D6 PMs (a special population) by one-half (see underlined portions of the label), thereby clearly meeting the claims’ requirements. The fact that the label also directs a medical provider to titrate the dosage does not negate its clear recommendations on the ultimate dosage range and maximum amount, the court explained.
West-Ward pointed to another difference between the proposed label and the asserted claims: While the proposed label’s target dose range for non-CYP2D6 PMs (12 to 24 mg/day) includes a dose of 12 mg/day, the independent claims require administering “greater than 12 mg/day, up to 24 mg/day” of iloperidone to these patients. In response, the Federal Circuit observed that it was not necessary that every practitioner prescribe an infringing dose. That the target dose range instructed users to perform the patented method, was sufficient to provide evidence of West-Ward’s affirmative intent to induce infringement, the court noted.
West-Ward further argued that because of the likelihood of a substantial number of non-infringing uses of its generic product, the conclusion that it had induced infringement could not have been correct. For this argument, West-Ward relied on Warner-Lambert v. Apotex 316 F.3d 1348 (Fed. Cir. 2003) (“Warner-Lambert”). While it is true that in Warner-Lambert there was evidence of significant non-infringing use (as high as 89% of the total) and the Federal Circuit had found that there was no infringement under 35 U.S.C. § 271(b), the case was very different.
Importantly, in Warner-Lambert, unlike Vanda, the alleged infringing act was not promoted by the generic product’s label. In Warner-Lambert, generics provider Apotex was seeking FDA approval for an equivalent of Warner-Lambert’s Neurontin® (active ingredient gabapentin) to treat partial seizures, but only after the patent protecting Neurontin® for the same use had expired. Warner-Lambert argued, however, that doctors would prescribe the generic product for all uses that Neurontin® was customarily used for, including treatment of neurodegenerative diseases, which was protected by a different patent owned by Warner-Lambert. And it is the patent on methods for treating neurodegenerative diseases that Warner-Lambert alleged was going to be infringed by Apotex’s generic product. This off-label use, Warner-Lambert asserted, would have been known to Apotex since it was public knowledge. The Federal Circuit responded by observing that mere knowledge of possible infringement by others did not amount to inducement, and that specific intent and action to induce infringement had to be proven. The court explained that if a physician, without inducement by Apotex, prescribed a use of gabapentin in an infringing manner, Apotex’s knowledge of the use would be legally irrelevant. Warner-Lambert at 1364.
Turning back to Vanda, the court clarified that, since West-Ward’s proposed label for the generic product specifically recommends a use protected by a patent, it might be held liable for induced infringement irrespective of substantial non-infringing uses. Majority Op. at 26. In other words, existence of substantial non-infringing use is irrelevant to inducement to infringe under section 271(b). Substantial non-infringing use restriction applies only to contributory infringement under section 271(c).
Approval to market a generic drug requires a showing that the generic product is pharmaceutically equivalent to the brand name drug, i.e., it has the same active ingredient, dosage form, strength, and route of administration under the same conditions of use. As a result, the label accompanying the generic drug must be very similar to that of the brand name drug. Therefore, if either the brand name drug or a method of its use was under patent protection at the time marketing approval was sought, it is fairly certain that the label would make for a very difficult task to establish lack of affirmative intent to induce infringement.