Melatonin – UK

 

On Dec. 04, 2020, UK High Court found second medical use patent valid & infringed by Mylan.

Neurim holds EP 1,441,702 patent, which is related to use of melatonin in improving the restorative quality of sleep, in a patient suffering from primary insomnia.  Mylan/Generics UK plans to bring generic version of drug in the market. The issues before court concerned the invalidity of patent as Mylan admitted infringement if patent is found valid. Mylan asserted that claims of patent are invalid under lack of novelty, lack of inventive step & insufficiency. Claims 1 and 4 were of relevance here:

1.       Use of a prolonged release formulation comprising melatonin in unit dosage form comprising 2 mg of melatonin, in the manufacture of a medicament for improving the restorative quality of sleep in a patient aged 55 years or older suffering from primary insomnia characterized by non-restorative sleep, wherein the medicament comprises also at least one pharmaceutically acceptable diluent, preservative, antioxidant, solubilizer, emulsifiers, adjuvant or carrier.

4.         A medicament for use in improving the restorative quality of sleep in a patient aged 55 year or older suffering from primary insomnia characterized by non-restorative sleep, which comprises a prolonged release formulation comprising melatonin in unit dosage form, comprising 2 mg of melatonin, and at least one pharmaceutically acceptable diluent, preservative, antioxidant, solubilizer, emulsifiers, adjuvant or carrier.

Mylan cited various prior arts among which “Haimov 1995” was closest one. It disclosed effects of melatonin replacement therapy on melatonin-deficient elderly insomniacs by administering 2 mg sustained-release melatonin. With respect to novelty, Court held that Haimov in no way anticipates the patent because study was directed to a completely different matter. The focus was on “melatonin-deficient” individuals, because the aim of the study was to see if the curing of such a deficiency would improve sleep. There was certainly no focus on restorative sleep or quality of sleep in the technical sense as claimed in patent. Court thus concluded that Skilled Person would have learned nothing about the effect of melatonin on Primary Insomnia characterized by non-restorative sleep from Haimov. 

With respect to inventive step, Mylan combined this reference with another references such as “MELATONEX label and Zisapel”. MELATONEX is a dietary supplement containing melatonin which is sold in USA without prescription. MELATONEX supplementation can help to restore the melatonin for a restful, natural sleep. Zisapel is a review of the literature in the area of melatonin treatment. It neither reported any original research nor did it give any meta-analysis of the data reviewed. Court said that Zisapel goes nowhere close to exploring any relationship between non-restorative sleep in Primary Insomniacs and melatonin. There is nothing to render the invention in the patent obvious to the Skilled Person.

With respect to insufficiency also, Court did not convince with Mylan’s argument.  Mylan contended that there was no data in the patent which evidenced the claimed effect, namely an improvement in the restorative quality of sleep in a patient suffering from Primary Insomnia characterized by non-restorative sleep.  Court focused on Examples 2 and 3 and considered whether they render the patent plausible. Court said that these examples disclose reasonably large clinical study in patients who were Primary Insomniacs at least some of whose sleep was characterized by its non-restorative quality. These studies were conducted on established lines and resulted in a statistically significant outcome in that it enabled the conclusion that melatonin enhanced the restorative value of sleep. Thus Court rejected the contention that the patent is invalid by reason of insufficiency.