Isobel Finnie, partner at European intellectual property firm Haseltine Lake, alongside associate Catherine Williamson, discuss the growing patent battle between pharmaceutical branded drugs and their cheaper, generic counterparts.
Patent
Across European countries, healthcare costs are a topic of significant debate and in the UK NHS funding is a perpetually thorny issue. At a patient level, we aren’t usually too concerned if our doctor prescribes us a patented pharmaceutical or a generic version of a drug, as long as it works to help us feel better. But it’s a different story for the healthcare and pharmaceutical industries - and we need the patent system to both reward and incentivise innovation through securing a period of protected market exclusivity, which means we can continue to get new and improved drugs, whilst also encouraging competition to keep costs affordable for health services.
The complexity of this balancing act has been highlighted by the issue of “second medical use patents.” This type of patent provides protection for the use of a drug to treat a particular disease (second medical use) where the drug was already known to treat another disease (first medical use). This type of new technology is particularly advantageous since the safety of the drug in subjects is already known and it is therefore quicker and easier to get regulatory approval for the new use. Re-purposing known drugs gets effective treatments to patients more rapidly than developing completely new drugs, and for a fraction of the cost. A series of recent UK court decisions has provided some interesting discussion and guidance on both the scope of protection afforded by these patents and how they may be enforced in the UK and the rest of Europe.
These cases involved Warner-Lambert (a subsidiary of Pfizer) and Actavis. Warner-Lambert are the owners of two patents relating to the drug pregabalin. The first patent relates to pregabalin per se, whereas the second patent is a second medical use patent relating to the use of pregabalin for treating pain.
Warner-Lambert has authorisation to market pregabalin, which they sell under the trade mark Lyrica, for epilepsy, generalised anxiety disorder (GAD) and neuropathic pain. Upon expiry of the first patent, Actavis began preparations to launch a generic version of pregabalin under the trade mark Lecaent. Since the second patent (relating to the use of pregabalin for treating pain) was still in force, Actavis opted to launch Lecaent with a “skinny label”, meaning that the patented use to treat pain was not included in the “Summary of Product Characteristics” that must be included with the drug.
However, Warner-Lambert were concerned that Actavis’ product Lecaent would still be provided to patients to treat pain, despite the fact that the use of pregabalin to treat pain was protected by their patent and authorisation had not been given to market Lecaent for the treatment of pain. In the UK, approximately 90% or more of prescriptions for pregabalin are written generically (i.e. specifying pregabalin rather than Lyrica or Lecaent). This is encouraged by the prescribing software used by GPs. In addition, only about 5% of GPs specify the use of the drug on their prescriptions. Where a prescription is written generically, the pharmacist would be free to dispense either Lyrica or Lecaent. It would therefore be very difficult to ensure that only Warner-Lambert’s product is given to patients for the treatment of pain.
The courts have considered whether Actavis infringe Warner-Lambert’s second medical use patent by marketing their generic drug Lecaent, and the lengths to which Actavis should go to ensure that their product is not dispensed for the patented use.
The Court of Appeal has provided guidance on the interpretation of second medical use patents. The patent in question in the present case specifically relates “use of pregabalin or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain”. The Court of Appeal indicated that the use of the word “for” in the phrase “for treating pain” requires that the manufacturer knows or can reasonably foresee the ultimate intentional use for pain, and does not require that the manufacturer has that specific intention or desire himself.
This guidance was followed by the judge in the High Court decision announced in September last year. The judge considered that there may be intentional administration of Lecaent for pain if a pharmacist dispenses Lecaent and he or she knows that pregabalin has been prescribed for pain. However, the judge took into consideration the steps taken by Actavis to prevent Lecaent from being provided to patients for the treatment of pain and concluded that it was not foreseeable to Actavis that Lecaent would be intentionally administered for the treatment of pain except in a small number of exceptional cases, which the judge considered to be too small to merit consideration. The steps taken by Actavis included notifying pharmacists specifically that Lecaent was not licensed for the treatment of neuropathic pain.
Despite this, the judge commented that, “I remain more convinced than ever that the best solution to the problem of protecting the monopoly conferred by a second medical use patent while allowing lawful generic competition for non-patented indications of the substance in question is to separate the patented market for the substance from the non-patented market by ensuring that prescribers write prescriptions for the patented indication by reference to the patentee’s brand name and write prescriptions for non-patented indications by reference to the generic name of the substance.”
This is in-line with an order the judge made prior to the full trial, requiring the National Health Service to publish guidance that pregabalin should be prescribed for the treatment of neuropathic pain by the brand name Lyrica. This guidance should be adhered to by doctors so far as is reasonably possible. However, the effectiveness of guidelines in preventing a generic drug from being dispensed for a patented use will rely on a suitable system being put into place by the relevant government authorities. The judge commented that patentees and generic companies should cooperate with the relevant government authorities as far as possible to assist in putting such a system into place. It is noted that in relation to the present case, software providers assisted in setting up such a system by adding an alert to prompt prescribers to prescribe Lyrica for pain.
It is also interesting to note that, prior to the full trial, the judge refused a request for the court to issue an order against Actavis specifying, amongst other things, that each pack of Lecaent should include a removable notification stating that “This product is not authorised for the treatment of pain and must not be dispensed for such purposes”, and that any agreements between Actavis and a pharmacy to supply Lecaent should include the condition that the pharmacy shall use reasonable endeavours not to supply or dispense Lecaent for the treatment of pain. The judge stated that granting the request would create a greater risk of injustice than refusing it, in particular since such order would delay Actavis’ entry into the market and may also deter pharmacists from stocking Lecaent. This decision enabled Lecaent to be marketed for non-patented uses such as epilepsy and GAD without delay and without further disadvantaging the sale of Lyrica for the treatment of pain.
Since the High Court decision in September 2015, a further decision was issued by the Court of Appeal on 13 October 2016. A final decision on whether Actavis infringe Warner-Lambert’s second medical use patent by marketing their generic drug Lecaent was not made. However, the judges disagreed with the High Court judge’s decision that both Actavis and the prescribing pharmacist must know that Lecaent is being dispensed for the treatment of pain. The Court of Appeal judges commented obiter dictum that the issue to decide was whether Actavis knew or could foresee that at least some of the prescriptions written generically for pregabalin to treat pain would in fact be fulfilled with Lecaent. The Court of Appeal judges further commented that if the test of knowledge was satisfied, it should have been considered whether Actavis had taken all reasonable steps in their power to prevent Lecaent from being used to treat pain.
Exactly how a system enabling generic companies to market products for non-patented uses without inadvertently infringing second medical use patents would work remains to be seen. However, it is encouraging that these issues are now being considered as the development of new uses for known drugs is growing. We await further guidance with interest.