The marriage between molecular biology and in silico technologies has driven medical innovation at an unprecedented rate in recent years.

Notably, artificial intelligence is assisting the discovery and development of treatments for complex diseases. AI-based research requires the interrogation of vast datasets to identify biological features (or 'biomarkers') that suggest certain drugs can be used for particular indications and/or subsets of patients within a particular disease group, and working out what those drugs are. This form of medicine is often referred to as personalised or targeted medicine, because it can reach smaller groups of people with rarer conditions than has previously been the case.

For research and development companies working in this area, however, a dilemma arises: as drugs target smaller populations of people, how can sufficient returns be obtained to make the investment worthwhile? It's a challenge illustrated clearly by a recent development in the supplementary protection certificate (SPC) regime, which I'll explore here. 

The original design of the SPC system

The SPC system provides up to five years additional exclusivity protection for a medicinal product, on top of the period of the underlying patent, when the term of that patent has been eroded while waiting for a marketing authorisation for the product. This secures adequate exclusivity protection for the investment made in such products as against such delays.

The SPC system works well for medicinal products consisting of novel active ingredients. This was fine for the medicines sector when the original SPC legislation was introduced in 1993, but it wasn't designed to adapt to many of the developments of modern drug discovery. Nowhere is this clearer than the debacle over the protection of second medical uses of active ingredients. 

The Neurim ruling

Before its July 2012 ruling in Neurim Pharmaceuticals (1991) Ltd v Comptroller-General of Patents the approach taken to SPCs by the CJEU was that once an SPC is granted for a product containing an active ingredient based on its marketing authorisation, it's not possible to obtain a further SPC for a product containing the same active ingredient for a second or subsequent medical use. 

In Neurim, however, the CJEU cast doubt on this "strict approach" when it decided that melatonin for the treatment of insomnia in humans could be subject to an SPC on the basis of a marketing authorisation granted for this use. This was despite the fact that melatonin for regulating the seasonal breeding of sheep had already been the subject of an earlier marketing authorisation. 

The CJEU reasoned that SPC protection for a "different application" of a known active ingredient is permissible. It did so by adopting a "teleological' approach" to the meaning of a product: the court should apply the purpose of the SPC legislation to provide sufficient protection for the investment made in the research and development of medicinal products. 
If the teleological approach were to determine SPC protection, this surprising decision seemed to open up the possibility of obtaining SPCs for other purpose limited products, such as personalised medicines targeted at sub-populations.

Eight years moved on, however, and such thoughts turned to nothing.

The U-turn on second indications in Santen

In Santen v Director of the French Patent Office (INPI), the Court of Appeal of Paris referred two questions to the CJEU, asking what "different application" in the Neurim decision meant. 

Santen had sought an SPC for its Ikervis treatment, an eye drop emulsion containing the active ingredient ciclosporin for the treatment of severe keratitis in adult patients with dry eye disease. The application was based on a patent and a central marketing authorisation for Ikervis.

Ciclosporin had not previously been authorised for this indication, but it had been the subject of an earlier marketing authorisation in the form of a product called Sandimmun. Sandimmun indications include the treatment of an eye inflammation condition called endogenous uveitis. 

The SPC application was rejected by the director of the French Patent Office on the basis that the marketing authorisation for Ikervis would not be the first to place the product on the market as a medicinal product.

The CJEU held that an SPC cannot be based on a marketing authorisation where it covers a new therapeutic application of an active ingredient (or of a combination of active ingredients) and that active ingredient or combination has already been the subject of an earlier marketing authorisation for a different therapeutic application.

The CJEU in Santen has unequivocally rejected the ruling in Neurim and as a result SPCs will not be permitted for second medical uses when the active ingredient has already been the subject of an earlier marketing authorisation.

What now?

Neurim appeared a puzzling decision at the time, because it was not supported by the design of the legislation or the previous case law. Manufacturers nonetheless made investment decisions on the basis of it, and generic companies modified their launch plans.

The CJEU has now reversed direction on the issue, effectively invalidating the whole class of second medical use SPCs. In the process, any prospect of obtaining SPCs on medicines re-purposed for use in sub-populations has disappeared.

If SPCs are to cover second medical use products, or products re-purposed for treating sub-populations, then amendment of the legislation will be needed.

Find out more

If you'd like to discuss any of the issues raised in this article, please contact a member of our Life Sciences and Healthcare team.  

Paul England is the co-author (with Simon Cohen) of A User's Guide to Intellectual Property in the Life Sciences, coming soon from Bloomsbury Professional.