Second medical use patents: why generics are in the dark

Second medical use claims have been around for a number of years, but until the recent decisions in the continuing Warner-Lambert v Sandoz case, there was relatively little guidance on how second medical use claims are interpreted and how infringement could be avoided. There are a number of ways generic companies can avoid infringement of second medical claims.

Pharmaceutical agents are frequently found to be effective at treating more than one disease or disorder. This is of significant benefit as the research and investment required to obtain medical clearance for a compound which has previously passed toxicity testing is less than that required to develop a novel compound. New uses of known products can be protected by patents with so-called second medical use claims.

Warner-Lambert had a patent covering the compound pregabalin, marketed as Lyrica, for its use in treating epilepsy and anxiety disorders. This patent expired and the supplementary protection certificate which extended the life of the patent was allowed to lapse. After the data exclusivity rights expired in July 2014, generic companies have been free to launch a competing product.

However, Warner-Lambert obtained a subsequent patent with second medical use claims directed to the use of pregabalin in treating pain caused by nerve damage and neuropathic pain associated with spinal cord injury. This patent is currently in force in the UK. The issue arises of how generic companies can market a product to treat the original conditions without infringing the claims to the treatment of pain.

Infringement and intention

Second medical use claims were first developed by the Enlarged Board of Appeal at the European Patent Office (EPO) to allow a new use of a pharmaceutical agent to be protected. The claims are written as “the use of pharmaceutical agent in the manufacture of a medicament for treating specific disease”.

Mr Justice Arnold, a UK judge, considered the construction of these claims and determined that for infringement to occur it had to be foreseeable to the manufacturer that the product would be intentionally administered to treat the patented condition. When considering infringement, whose intention is relevant for the “intentional administration”: the manufacturer’s, doctor’s or pharmacist’s?

If the manufacturer’s intention is relevant, one way of avoiding infringement is to use so-called skinny labelling. The patient information leaflet and the labelling on the outside of the packaging clearly state that the medicament is not to be used for treating the protected condition, ie, pain. This provides a clear indication that the manufacturer does not intend the product to be sold for the protected indication. This would appear to be the simplest and easiest way of ensuring that second medical use claims are not infringed.

However, the sale of medicines, in particular prescribed medicines, is not as straightforward as that of other products. A doctor issues a prescription, which is fulfilled by a pharmacist. The labelling of the packaging does little to prevent a doctor from prescribing pregabalin or the pharmacist from dispensing the required product for the protected indication. Prescriptions generally do not provide details of the condition to be treated, so a pharmacist, even if she or he is aware, cannot determine whether the generic form or the branded version of the product should be used.

“A centralised notification system between patent owners, generic companies and the NHS needs to be developed to ensure proper guidance is issued to medical professionals.”

Warner-Lambert made arguments that skinny labelling alone was not sufficient to avoid infringement. Furthermore, evidence was produced in the form of a declaration from pharmacy chains that they would not buy a skinny-labelled product. Therefore, the use of skinny labelling may not provide a commercially acceptable solution.

Doctor’s orders

Arnold considered that the most relevant intention was the doctor’s. Under prescribing rules, if a doctor prescribes a brand name drug such as Lyrica the pharmacist must dispense that product. In contrast, if a prescription refers to the compound name, pregabalin, the pharmacist is free to issue either the branded product or a generic version. It is therefore the doctor who determines which product is sold.

Early in the proceedings Warner-Lambert applied for an injunction to require Sandoz to write to every dispensing pharmacist and doctor within the National Health Service (NHS) informing them to restrict prescriptions for pregabalin for treating pain to the branded form, Lyrica. This was judged to be unnecessary. Therefore, generic companies may not need to go to such lengths in order to avoid infringement.

However, the courts did order NHS England to issue guidance on the prescription of Lyrica for treating pain. Evidence provided at trial of increased prescriptions of the branded product after this guidance was issued and the updating of the prescribing software indicates that this may be an agreeable solution. The change in the prescribing software may be the most important aspect, as this serves as a reminder to physicians to prescribe the correct product.

This approach requires the cooperation of both the patent owner and the generic company with the NHS so that clear guidance can be issued to doctors and prescribing software adapted. Given the currently separate health services for England, Wales, Scotland and Northern Ireland, this may not be a straightforward process.

The Warner-Lambert case also highlights the need for generic companies to act in good faith. Sandoz had previously agreed that it would not launch a full-label pregabalin product onto the market without giving notice. However, Sandoz had sold a consignment of full-label products to LloydsPharmacy after the initial judgment that the patent was invalid. As Warner-Lambert was given leave to appeal, this meant the issue had not been resolved. Although Arnold stated that this action had no effect on his judgment when granting an urgent injunction, such irresponsible behaviour may cause undesirable consequences.

This case deals with second medical use claims in the so called Swiss type format. When re-drafting the European Patent Convention 2000, the legal basis for second medical use claims was introduced into the convention. This allows the ‘new’ style second medical use claims to be employed. These new claims refer to a compound for use in a method of treating a disease. They are compounds claims, as opposed to process claims. Arnold commented that the ruling and guidance provided in this case may not apply to the new style second medical use claims.

While it was intended that both types of second medical use claims should protect the new use of a known product, early case law from the EPO seems to indicate that the scope of protection provided is not identical. Therefore, it will be interesting to see how these claims are interpreted by the courts in the future and whether the foreseeable intention-to-infringe test is maintained or adapted.

A bit of clarity—but not enough

When intending to launch a product covered by a patent a generic company should ‘clear the path’ so that the patent’s validity and any potential infringement issues can be settled before coming on to the market. This can be done by seeking a declaration of non-infringement from either the UK Intellectual Property Office or the courts.

While the Warner-Lambert decisions provide some guidance on how generic companies may avoid infringement of second medical use claims, the actions required are far from clear. The use of skinny labelling may not be commercially possible or completely avoid infringement. A centralised notification system between patent owners, generic companies and the NHS needs to be developed to ensure proper guidance is issued to medical professionals and, perhaps more important, to ensure that the prescribing software is updated.

Given that the relevant intention lies with the prescribing doctor, and so is largely out of the control of the generic company, until such a system exists it may be difficult to prove non-infringement. The courts consider that it is unnecessary to write to every doctor or superintendent pharmacist, but give no guidance on the level of notification that is required. Furthermore, the situation may change when new style second medical use claims are at issue. Therefore, there currently appears to be no fail-safe method of avoiding infringement of second medical use claims. This may, in effect unjustly extend the protection provided by earlier expired patents.

Deborah Hart is a senior associate at  Kilburn & Strode. She can be contacted at: dhart@kilburnstrode.com