Fingolimod - USA

On Aug. 10, 2020, Delaware Court found multiple sclerosis method of use patent valid & infringed by ANDA filer.

Novartis (Plaintiff) sued many ANDA filers (25 FTF) under Hatch-Waxman Act as Defendants filed ANDAs to market generic version of Gilenya® (0.5 mg capsule) before expiration of US 9,187,405 patent. All of them settled except HEC pharma. US’405 patent claims methods to treat Relapsing-Remitting multiple sclerosis ("RRMS") using  fingolimod at a daily dosage of 0.5 mg, absent an immediately preceding loading dose. Plaintiff asserted that defendant infringed the claims under induced & contributory infringement. Defendant counterclaimed that patent-in-suit is invalid under anticipation & lack of written description support. Delaware court held four-day bench trial from March 2-5, 2020.

Infringement:

1. Induced infringement:

Defendant argued that its label does not instruct physicians to omit a loading dose from the dosing regimen, so it is not practicing one of the elements of the patent claims in suit. Lable does not mention anywhere administration of loading dose. Court, however, said that HEC’s label induces infringement. Nothing in HEC's proposed label says to prescribe anything more or less than 0.5 mg. The label also provides a caution that there is "a greater incidence of adverse reactions without additional benefit" for doses over 0.5 mg. Experts also testified that they have never administered dose greater than 0.5 mg to patients. Court said that the prescribing physician would understand the label to contain the complete dosing information, and the instructions dictate the dose of the drug in question exactly as in the Patent- 0.5 mg daily without a loading dose. If a user follows the instructions, there will be direct infringement. Instructing use that will infringe is an active step that demonstrates a specific intent to infringe.

2. Contributory infringement:

Court said that contributory infringement is found where: ( 1) there is direct infringement; (2) the accused infringer had knowledge of the patent at issue; and (3) the product has no substantial non-infringing uses. HEC is liable for contributory infringement. HEC knew of the '405 Patent and the treatment method it sets forth. Because the only uses for HEC's generic fingolimod product are those identified in the clinical trial section of the proposed label, there is no substantial non-infringing use for which the product is indicated.  If a user follows the instructions on the label, there will be direct infringement.

Invalidity:

1. Anticipation:

HEC argued that the '405 Patent is anticipated by an abstract (Kappos 2006) published in the Journal of Neurology and presented at the European Neurologic Society Meeting in 2006. Kappos 2006 announces an upcoming Phase III trial of 1.25 mg and 0.5 mg doses of fingolimod daily compared to a placebo. Court, however, said that there is insufficient evidence to establish Kappos 2006 as prior art, as it has not been shown to have been available before June 27, 2006 (priority date). A copy of Kappos 2006 with a declaration from an employee from the British Library was offered but not admitted into evidence. The declaration is inadmissible hearsay and, in any event, is internally inconsistent regarding the location and availability of the document. It does not provide any information on the procedures for cataloging, indexing, or shelving of the Kappos 2006. So, it was not publicly available as on priority date.

If Kappos 2006 is considered admissible then also this abstract offers no evidence of effectiveness, which a person of skill would look for as an indication of a treatment purpose. It does not mention a loading dose. Unlike a patent, which is presumed complete, an abstract of an academic paper is not presumed to contain all of the necessary information about the study. Kappos 2006 does not enable the use of 0. 5 mg daily to treat RRMS because it would require undue experimentation.  HEC has failed to prove by clear and convincing evidence that Kappos 2006 anticipates each and every limitation of claims.

2. Lack of written description support:

HEC argued that the ‘405 has no written description support for the negative limitation "absent an immediately preceding loading dose" or for the claimed “0.5mg daily dose”. Court, however, said that examples mentioned in the specification discloses 0.5 mg dose and therefore POSA upon reading the specification would have known that 0.5 mg dose is effective in treating RRMS. With respect to loading dose court said that the absence of an immediately preceding loading dose from the specification, and example, would tell a person of skill that loading doses are excluded from the invention. If a loading dose were directed, the patent would say that a loading dose should be administered initially." But this is not the case here as patent in silent on loading dose. A person of skill in 2006 would not expect a loading dose to be used to treat RRMS with fingolimod. The patent here provides a sufficient written description of the invention such that a person of ordinary skill would know that loading dose is not required in treating RRMS. Thus, the inventors were in possession of the invention.