 Well, I have been asked to talk about non-patent exclusivities and I should be focusing mainly on two non-patent exclusivities, data exclusivity and market exclusivity. But I was asked also to talk briefly about supplementary protection certificates which are not in fact really a non-patent exclusivity because they are keyed to a basic patent. But I won't say too much about them because another aspect of the focus of my talk is the degree to which regulatory exclusivities can be used to incentivise new uses. Rather than the development of new molecules and for reasons I'll very briefly go through supplementary protection certificates are not really a terribly viable way of incentivising new uses. There's a lot of text on this slide to which I will not particularly speak but essentially supplementary protection certificates which Catherine briefly referred to requires a basic patent. So it's going to be subject to all the vagaries of the validity of the basic patent and if you've got a basic patent for a use you're subject to the problems which Catherine outlined in particular. What is more with supplementary protection certificates, the legislative framework was designed really to incentivise new molecules rather than new uses of old molecules. And you see this in articles three of the regulation down there. You can't get a new SPC, you can't get an SPC if the product has already had an SPC for which it needs to have had a marketing authorization and the authorization must be to be in the first to place the product on the market anywhere. So it's not good for new uses for already authorised products. I mean in the context of Tadda Laffill it might be okay because the product had not previously been authorised for any other indication. So there again it would only be, it wouldn't be the SPC framework which was problematic, it would be the underlying patent framework which was problematic. But even where you do have use patents there have been attempts to get around the SPC framework which is key to incentivising new chemical entities rather than new uses of the already authorised chemical entities. I've set out on this slide the case law in relation to that. First one, the Pharmacia case shows how on a purely sort of literal reading of the SPC regulation how limiting that is a marketing authorization as a veterinary medicinal product precludid getting an SPC in relation to a marketing authorization for a human medicinal product. There was then the case, a couple more cases, Massachusetts Institute of Case, a very hard case, a very good demonstration of how inadequate the SPC system is actually in providing incentives. There was a drug which was toxic, an anti cancer drug which was toxic until a way of providing a delivery mechanism in it using a sort of glorified sponge in the brain was developed. And no SPC could be secured for that because this highly toxic drug which became much less toxic in this delivery mechanism was not actually, it wasn't a new marketing authorization. There had been previous marketing authorisations in other indications in which that toxicity could be dealt with. Neurim was a very special case we keep on going back to which did actually suggest you could actually, even within the framework of the SPC system, get an SPC for a new use previously marketed for a product which had previously had a marketing authorization. That is being challenged, it's being cut back in the Abraxis case. The Advocate General suggested that Neurim was wrong. The Court of Justice didn't on the fact that that case had to actually engage with that because it was a new formulation case, not a new use case. In the Santin case again the Advocate General has suggested that Neurim was wrong. It looks as if on the fact of this particular case there are some new formulation aspects to it that there are new indication aspects to it as well. It looks as if the Court of Justice may not be able to duck that but I think Sir Richard Arnold has lots of experience in the Court of Justice ducking questions on SPCs to which they have been put so we should just have to see. But that's essentially all I was going to say about SPCs. I don't hold out much hope for SPCs as a way of protect incentivising new uses. Firstly because they're key to a basic patent which is subject to the vagaries of patent law and secondly because the SPC system is not designed itself to incentivise new uses. Now here are two regulatory exclusivities. First one data exclusivity otherwise called regulatory data protection. Now this protects the regulatory data you file clinical trial results that are filed in order to secure a marketing authorization. And so it's only protecting that data so it doesn't actually preclude a second applicant doing its own clinical trials for the same indication or for other indication in relation to the same product. Now that's very rare. Obviously there is no real incentive to just do this again. There are also ethical issues about repeating the same trials which have already been undertaken in the past and which you know pretty much the outcomes in relation to. But that's not to say it hasn't been done and there is certainly a case in Europe where generic company got a particular indication in relation to a cancer drug during the protected term of exclusivity in relation to during the data protection period for the product. We'll look at this in more detail. A couple of headline points to emphasise now. Regulatory data protection is mandated by TRIPS and with a lot more specificity by the various trade agreements you have being entered into bilateral trade agreements or multilateral trade agreements being entered into throughout the world. Because what is said in TRIPS as we shall see is a little bit vague. It sort of has its origins back in attempts in days gone by to protect clinical trials data under trade secrets law. And indeed, even though you'll find the mandate to protect regulatory data in article 39 of TRIPS where you also find the mandate to protect trade secrets, I think it's important to see it as a very different sort of protection these days to trade secrets law. My reason for that is not only it has a separate legal basis under a separate paragraph of article 39 TRIPS but also there is this trend in recent years to much greater clinical trial transparency so you can actually get an awful lot of data in relation to the clinical trials which have been undertaken. As a result of freedom of information applications whether under the EU framework or in the US. And indeed now in Europe there's a particular portal which they're setting up to actually file clinical trial results with regulatory authorities will very much be designed to facilitate that. So I think it's important to decouple regulatory data protection or data exclusivity from trade secrets law and indeed there is soft law in the EU which does decouple the two. It says you cannot use clinical data which has been disclosed for reasons of transparency to found your application for a marketing authorization. I think on an international basis there's potentially more of a problem in theory one could in certain other countries which I would suggest not actually implementing article 39 TRIPS properly. You can actually use or there's nothing in particular to stop you using clinical trial data secured under freedom of information in the European framework but using that outside Europe. So I'll be talking more about regulatory data protection in practice in both Europe and a little bit in the United States. Secondly there's market exclusivity which is a distinction here and we have this only for often medicinal products in Europe. It doesn't matter if the second applicant has undertaken its own clinical trials on the product. If you're talking about a marketing authorization which overlaps with that of the first applicant you still don't get your marketing authorization for the period of exclusivity. You have an absolute market exclusivity. The first person to secure a marketing authorization for an often indication that's an indication for a very small patient population. The first person to secure that marketing authorization has exclusivity for the particular period of time which the legislation provides and so you'll see from that point of view that is not challenged by greater clinical trial transparency. It's irrelevant that you can get the clinical trial data from the first applicant in terms of the second applicant securing a marketing authorization. So the exclusivity is absolute. That under data exclusivity is in practice pretty absolute in Europe as we shall see but there are sort of gaps in it and particularly on an international basis. Here is article 393 of Trips to which I referred. Now what you'll immediately see when you look at that particularly because it's been underlined is that it is keyed to all the principle of data exclusivity. It applies only in those cases where you're talking about a marketing authorization for a new chemical entity and thus on the face of this this is of little or no use in relation to protecting new indications. Moreover it's only mandated in respect of pharmaceuticals and agrochemicals and in fact in Europe data exclusivity has been extended into other areas such as new chemicals generally under the reach legislation. Biocidal products that will be sort of bit like agrochemicals but for non-agricot for uses and even things like health claims on food. They each have their own different regulatory exclusivity framework but each intended to incentivise people to each of them require each of these regulatory frameworks require applicants for marketing authorisations or for these health claims to put in data which supports those marketing authorisations or those health claims and so what you're doing in these is protecting that data. So let's look in more detail at the system in Europe. So this is the what is called the 8 plus 2 plus 1 system and it's a system we have had in place in Europe since 2005 for human medicinal products. There was a system in place before that a sort of six year in some countries or 10 years in other countries or 10 years essentialised marketing authorisations. Before that I was involved in a lot of litigation in the court of justice under that previous system and it's quite interesting that the one of the major shortcomings of the previous system in that it did not show itself capable of providing an incentive for securing new indications was one which was actually addressed in the legislation which established this new system which we've had since 2005. So here as I say it protects against the generic of a reference medicinal product for this 8 plus 2 years so the generic applicant cannot rely on the clinical data of the first applicant until 8 years has passed when it can file its marketing authorisation seeking to rely on that. Then it can't actually get a marketing authorisation until the further 2 years has passed after that 8 years. So effectively the first person who first secures a marketing authorisation gets a 10 year period of exclusivity. And for example ICOS in relation to the Tavilafel case will have secured irrespective of any pattern protection a 10 year period of marketing exclusivity from the first marketing authorisation in Europe. So where do new indications come into this? Well if you as the first applicant secure a new indication providing significant clinical benefit during the first age years you get an extra year extending your 10 years to 1 to 11 years across the board. You will now ask who assesses what is a significant clinical benefit. That is done within the committee on human medicinal products within the EMA and they make an assessment of that. And they are essentially medically qualified practitioners and there have been cases where their assessments have been problematic or there have been cases where their assessments have been challenged within the sort of framework provided for by this. But that is the only protection you get within that system for new indications and they have to be new indications with a significant clinical benefit. It is also worth flagging up that if you have got two sort of separate applicants both working on the same molecule they can both get sort of exclusivities under this in relation to their own indications on which they are working. The only problem, the only time you can't get an applicant you can't get a protection for a new indication is if the same applicant or related applicants are developing a new indication. And we'll see a few references to that in the case law when we come to that. But before I come to that for completeness there are another couple of regulatory exclusivities in the legislation. This first one here a new indication of a well established substance non cumulative period of one year of data exclusivity for new indications. Nobody knows what that means. That was introduced by the politicians at the last stage of the legislation. I don't believe it has ever been used in practice and so we will talk no further about it. Change of legal status. That is when you get when you support the classification of a change from for example prescription only medicine to pharmacy only medicine or general sales medicine. And there are also provisions for pediatric use marketing authorisations where there is no other pediatric incentive. Normally the pediatric incentive is keyed to the SPC's six month period of extension to an SPC. It is also keyed to orphan indications as well when you go to two year extension in those limited cases. Now here very briefly are a number of cases in relation to regulatory data protection and data exclusivity for human medicinal products. We've had determinations of its importance to actually establish that something is a new active substance so that it gets the eight plus two and the potential plus one protection. That was not the case in Sepricor which was the enantiomer of a previously authorised racemate that was held by the regulatory authority not to be a new active substance that was challenged in that case. It failed for procedural reasons. Techfiddler on albagio if you dig into the assessment reports very interesting cases they're both multiple sclerosis drugs. Very interesting cases where there were questions as to whether or not these were new chemical entities was one a metaboliser previously authorised substance. In the other case there have been some previously authorised mixture of substances one of which was an estra of this or one of which was a free acid of this. And they were quite interesting. It's quite interesting to analyse the assessment reports from how they came to the conclusion that these are new active substances. But when we look at new indications how to assess this significant clinical benefit how do the medics go about that. There have not been very many of these. I've not got a complete listing of them. It's not terribly transparent in the EMA system. Torysol yn byw'r zaitiga are both positive assessment reports. I'll talk a little bit more about zaitiga. There are some negative assessment reports there. One particular case to flag up and to emphasise the point I made that even if a company develops a new indication it doesn't get any further and it's completely indication out of left field. It doesn't get any new protection for that beyond possibly the plus one across the board in relation to the marketing authorisation. And that is demonstrated by the Novartis cases although I think I thought those might have gone to the Court of Justice. Those are the general court references anyway. But I was going to give you a case study of zaitiga which is quite an interesting one particularly because it was a drug which was developed in the UK. A major advance in the treatment of prostate cancer. But the new chemical entity itself was developed back in 1992. Institute of Cancer Research funded by Cancer Research UK under its then name. And so back in 1992 developed that new chemical entity Patent Filed. Patent then licensed out via NRDC or now BTG. And then licensee I think was Beringa Ringelheim Lodge Company. Eventually withdrew. There were problems about the sort of nothing particularly wrong with the drug but the mechanism of action was questioned. And then the people at ICR pushed back on that. Eventually undertook some phase one trials and the patent was licensed out again. And then Johan de Bono at ICR actually published a rationale for further studies to try and overcome some of these prejudices and undertook. Got some funding from a US startup to undertake some phase one to clinical trials. Those showed promise a used patent was filed and eventually marketing authorisations were granted in 2011. That is nearly 20 years after in development of the new chemical entity patent itself. Showing you once again these patents not terribly, not necessarily that much use in incentivising this sort of activity. Especially as we will see that in 2016 the Europe the EP use patent was revoked by the EPO opposition division. We cannot just blame the English courts for revoking use patents. That's far from over there. And indeed this wasn't a vagary in this case of the European patent office and indeed the appeal was subsequently withdrawn. Because in the States the use patent was revoked by the patent trial and appeal board. And the CAFC, the appeal body there upheld that last year. So the NCE patents expired. Use patent has been blown out of the water in both major jurisdictions. So where's data exclusivity come into this? Well data exclusivity in the United States expired in 2018 and there are indeed generics on the product on the market in 1918. Data exclusivity in the European Union does not in fact expire till 2022 because there's an 11 year period of protection for this because it got a major significant marketing or an extension of marketing authorization offering significant clinical benefit. So that is a case study of not so much of protecting new uses but of demonstrating how effective data exclusivity can be particularly as we have it in Europe in comparison with patent protection. Veterinary medicinal products I've got relatively little time but we'll not say much about this except to say that before 2005 it was the same system as we had for human medicinal products. They've tweaked it in 2005 to incentivize new products for bees and fish and indeed to get product to extend the use of an already authorised product into new food producing species. And the reference to MRL data that's maximum residue limits because when you've got seeking marketing authorisations in relation to food producing species you have also to go into the sort of pesticide residues which are allowed in those food producing animals. Now there's no sign of any change to the regulatory data protection regime for human medicinal products but we have as a result of the new veterinary medicinal products regulation last year. A new system for data protection in Europe for veterinary medicinal products which is even more tailored to provide incentives for what's regarded as being desirable aims. New antimicrobial products for certain species. Bees, bees the sort of the most favoured animal of all. You can get up to 18 years regulatory data protection if you do something good for bees. And the sort of standard for other species going back down to 14 plus potential of four extra years where you extend with an extra year for each new species and so on and so forth. I won't go into the detail but I make the point that you can really and here's another bit of it in relation to new maximum residue level data and indeed this antimicrobial antiparasitic tailoring. You can tailor regulatory exclusivities in a way which is not open to you with patents. So not only are you not subject to the vagaries of patent law and to the fact that patents had to be applied for too early but also you're not subject to the rigidity of patent law. Often medicinal product exclusivity. Now this is gives you as I said a sort of absolute market exclusivity irrespective of whether a second applicant undertakes their own trials. And in Europe it's for 10 years plus you can get an extension of two in relation to pediatric studies. It can be cut back to six years where you make too much money. There are exceptions for inadequate supply or for similar products which provide a technical advance. So the exclusivity again the nature of the exclusivity it does incentivize technical development. There have been a couple of cases in relation to that but I haven't got the time to go through those in detail. What I will make the point about because it's always nice to have some chemistry in these slides is I emphasize at the top it's against the same medicinal product or in Europe and it's a big difference from the United States a similar medicinal product for the same indication. So what do I mean by similar? Again this is assessed it's not assessed by patent judges it's assessed by scientists by medics. And those two cancer treatments leukemia treatments were regarded as being similar under the often medicinal products regime. You'll see they've got the same basically the same left hand side. But there are differences there and I'd be interesting for the patent lawyers amongst you to speculate on you know whether even with our sort of brand new equivalents etc etc in the UK those will be regarded as equivalent under that sort of framework or even if having filed path application justifying yourself on the basis of one of those you will be allowed a breath of claim which actually encompassed the others. I don't know but this is what is being achieved or what can be achieved in the context of regulatory frameworks. And why is this a good thing? Why is it a good thing to disincentivise similar products? Because why should you be incentivising new chemical entities which are merely me twos which don't actually provide any significant therapeutic benefit? You shouldn't necessarily I mean you know and anyway if people want to do that they've got a patent system allows them to do that. But why should you be incentivising that sort of activity with the regulatory system? In the United States I don't have time to go through this in detail but the periods are actually rather shorter even though the headline period for new chemical entity exclusivity in the States is five years it is in practice because there's a patent linkage there seven and a half years. And they have their own orphan drug exclusivity shorter term but significantly different from that in Europe. It's only key to the same drug for the same indication not similar same or similar drugs for a new indication. They also have exclusivities for animal drugs. So conclusions SPC's not really a basis for incentivising new indications. Regular data protection and data exclusivity not much of a protection for not much of an incentive for new indications unless it does provide a significant therapeutic benefit. And then you get your extra year across the board not just in relation to that indication. But it is as in the case of Zaitiga a valuable incentive to seek the first marketing authorization for a product which has weak old or non-existent patent protection. And you can tweak it as you've seen in the case of Ethereum medicinal products often medicinal products marketing exclusivity because by their very nature often indications are indications is key to indications. It protects new indications irrespective of how old the product is. And it also protects again in Europe at least against similar products and against me to work. So between them those two regulatory frameworks I suggest offer the way forward to some of the questions which have been posed in this session. Thank you very much.