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nicola dagg, Allen & Overy LLP
Patent cliffs remain one of the biggest issues facing the 54(5) expressly allowed patent protection for second medical pharmaceutical industry. In 2012 and 2013 a number uses, and that new dosage regimes per se, were patentable as a of high-value branded drugs have lost or will lose their “new use”, as long as this use satisfied the requirement of novelty patent protection (for example Sanofi and Bristol-Myers’ “Plavix”, Novartis’ “Diovan”, Eli Lilly’s “Cymbalta”, Novartis’ The very recent case of Hospira v Novartis in the UK “Reclast” and Merck’s “Propacae”). The resultant erosion illustrates that intrinsically “open-ended” dosage regime claims of earnings is vast. In the light of this, originators’ ability to (in this case the claimed second medical use was the method of extend the patent life of their medicines through securing administering zoledronic acid, a bisphosphonate, intravenously at good secondary patents (composition patents, patents for new intervals of at least six months for the treatment of osteoporisis) polymorphs/formulations, synthesis patents and patents for new remain vulnerable to invalidity attacks for insufficiency. In this case Arnold J found that the claims, which he concluded extended to any dose and dosage interval that worked, had a broad scope placing an undue burden on “a skilled team to carry out a substantial programme of clinical trials to find out what doses and dosing intervals are efficacious, and then claim the results”. They were “But do these second-use patents
accordingly invalid for insufficiency (but not for obviousness). really afford the or ig inator the
But do these second-use patents really afford the originator the effective protection that it seeks against effective protection that it seeks
aggressive generic entry? Arguably they do not for two reasons. First, European regulatory legislation is drafted to against agg ressive gener ic entr y?”
facilitate access to generic drugs in the EU, and second, there is current uncertainty around how an originator establishes a case for infringement of a second medical use patent. What is happening in practice? As soon as the originator’s first-use patent expires, generics can enter “Second Medical Use” patents (new therapeutic uses for the market with their competing products to the patented first known active ingredients) are an important component of the use. However in so doing they may still face the originator’s potential second-line patent protection. In the UK, patentability second-use patent wall. European regulatory law affords generics of a second medical use was confirmed by the Court of Appeal (having already obtained a marketing authorisation for their decision in Actavis v Merck. The Court held that second medical generic drug by an “abridged procedure” by reference to the use claims were allowable even where the novelty resided solely originator’s drug) the option of adopting “skinny” labelling. That in a new dosage regime or other form of administration of a is, they are entitled to “carve out” of the Summary of Product known substance. The Court of Appeal noted that “Research Characteristics and patient information leaflet, any references into new and better dosage regimes is clearly desirable, and that to indications or dosage forms, which are protected by patents there is simply no policy reason why, if a novel non-obvious in force. The permission for a carve out must be obtained at regime is invented, there should not be an appropriate patent national level in recognition of the fact that the second use reward”. Second medical use patents are now expressly permitted patent may not be valid in all the member states. Furthermore by section 4A (4) of the Patents Act 1977, provided the claim is when a carve out is requested, the individual member state in the form “substance x for use in the treatment of disease y”, decides if a statement to explain why certain therapeutic following the Enlarged Board of Appeal of the European Patent indications or dosage forms are missing from the package leaflet Office’s G2/08 Kos decision. The latter confirmed that EPC art should be included. If such a statement is included it should use Editorial policy and sElEction critEria: nominEEs havE bEEn sElEctEd basEd upon comprEhEnsivE, indEpEndEnt survEy work with both gEnEral counsEl and patEnt lawyErs in privatE practicE worldwidE. only spEcialists who havE mEt indEpEndEnt intErnational rEsEarch critEria arE listEd 14 • Articles
the internAtionAl who’s who of pAtent lAwyers
the “blue box concept”: “(Active substance) which is contained & Nephew the Court of Appeal reaffirmed this, and observed in (product) (may also be/is also) authorised to treat other that there was no requirement that the users at the end of the conditions which are not mentioned in this leaflet. Ask your supply chain need to have an already formed intention (in doctor or pharmacist if you have further questions”. relation to the patented use), but that an “inherently probable” These carve outs ignore market realities. In the UK where 86 view is sufficient. These requirements must be proved on the per cent of physicians’ prescriptions are by reference to a drug’s usual standard of probabilities, and “it is likely to be the case active ingredient name, the dispensing pharmacist, not being where the supplier proposes or recommends or even indicates aware of the indication for which the product is prescribed, can the possibility of such use in his promotional material” that there supply the active ingredient without regard for whether it is the innovator product or generic product for any ongoing second On the basis of these judgments, will the originator be able to argue that the generic “knows” or that “it is obvious in the circumstances”, that when it puts its products on the market with a skinny label that at least some of this product will used for the patented second medical use indication? The “it has been suggested that judges will scope of section 60(2) of the Patents Act 1977 in
the highly regulated pharmaceutical field is (as yet) have to be flexible with regards to the unclear; highly fact dependent; and the evidential
requirements for the originator can be difficult scope of injunctions”
to meet. For example one may have to look to the plausibility of quantities sold by the generic in the light of the market demand for the first use indication. One would also have to look very carefully at all the circumstances surrounding the promotion, sale and marketing of the generic drug. Maybe the current European approved wording medical use patent. Under these circumstances it is almost for the “skinny label” (“may also be/is also, authorised to treat inevitable that significant amounts of the generic drug will be other conditions which are not mentioned in this leaflet”) dispensed for the patented second medical use. could be enough to indicate the generic supplier’s proposed or Currently originators cannot rely on the use of patent litigation in these circumstances to stop generic product being Even if the originator can prove infringement of its second dispensed for the second medical use. This is because it is medical use patent, it may face the additional challenge of unlikely that the UK courts will find this generic substitution obtaining an injunction to prevent this use. The difficulty lies to be a direct infringement of their patent rights under section in the fact that only that proportion of the marketed generic 60(1) Patents Act 1977 - the generic’s “skinny” label denying drug that is being used for the second medical use is infringing. the originator the possibility of showing that the drug is In these circumstances the originator’s liability in a cross manufactured or sold for the patented second medical use (Court undertaking in damages to cover the permissible use of the of Appeal in Actavis v Merck). This interpretation is supported generic drug will be significant. For these reasons it has been by the Dusseldorf court’s 2004 judgment in Ribavirin, where suggested that judges will have to be flexible with regards to the the court stated that the defendant’s leaflet did not set out the scope of injunctions (namely, that they grant an injunction only patient group named in the patent, and hence the product was in respect of the infringing use). One possibility is to suspend not “manifestly prepared” for the use specified in the patent. the injunction pending the ascertainment of the infringing use, However two 2010 judgments of the English Court of provided that the generic pays a royalty to compensate the patent Appeal, concerning liability for indirect patent infringement owner for infringing use (but is this not effectively compulsory under section 60(2) of the Patents Act 1977 (by supplying any licensing?). It is interesting to note that in France where the of the means relating to an essential element of the invention) generic has clearly carved out certain indications it is virtually could improve the ligation prospects of originators holding impossible in practice to obtain an injunction on the basis of an second medical use patents. In Grimme Maschinenfabrik v Scott originator’s dosage regime patent (judgment of the Paris court of it was held that the knowledge and intention requirements of first instance, Actavis v Merck (2010), currently under appeal).
the provision were satisfied if, at the time of supply or offer of One solution for originators is to work to reform the current supply, “the supplier knows, or it is obvious in the circumstances, European regulatory labelling system so as to inform health-care that ultimate users will intend to put the invention into effect”. providers, pharmacists, and the public that a generic drug with In other words if it was reasonably foreseeable that the generic the skinny label is only authorised for use in relation to the uses drug would be dispensed for the patented second medical use this would suffice to show indirect infringement. In KCI v Smith Editorial policy and sElEction critEria: nominEEs havE bEEn sElEctEd basEd upon comprEhEnsivE, indEpEndEnt survEy work with both gEnEral counsEl and patEnt lawyErs in privatE practicE worldwidE. only spEcialists who havE mEt indEpEndEnt intErnational rEsEarch critEria arE listEd

Source: http://www.allenovery.com/SiteCollectionDocuments/secondmedicaluse.pdf