It is possible to obtain a patent from the European Patent Office (EPO) based on a new medical use of a known drug. The claim can be directed to using the drug to treat a different disease, or using the drug in a new method of treatment, such as a new route of administration or a new dosage. The EPO has wellestablished requirements for the patentability of these so-called “second medical use” claims, but it does not consider issues of patent infringement. Infringement in Europe is currently assessed on a country-bycountry basis by individual national courts.

Although these second medical use claims have been available in Europe since the 1980s, until recently it has been unclear how the manufacture and sale of a drug for a patented use can be distinguished in practice from the manufacture and sale of the same drug for a non-patented use. The English Court of Appeal has now clarified how infringement of such second medical use claims should be assessed in the United Kingdom1 . 

The Pregabalin Case in the United Kingdom

As discussed in our earlier article,2 Warner-Lambert has been involved in litigation across Europe relating to a second medical use patent granted by the EPO, directed to the use of pregabalin in the manufacture of a medicament for treating pain.

Pregabalin is approved for use in the United Kingdom in the treatment of general anxiety disorder (GAD), epilepsy, and neuropathic pain. Actavis was sued for infringement by Warner-Lambert after it applied for approval to sell pregabalin in the UK under a "skinny label" that referred only to the treatment of GAD and epilepsy, not covered by Warner-Lambert's patent. Warner-Lambert argued that the Actavis product would inevitably be used by physicians and prescribed by pharmacists for the treatment of pain, even though that treatment was not specifically mentioned on the product packaging.

The Court of Appeal concluded that Warner-Lambert's patent was invalid, and so there was no requirement to consider infringement. However, it took the opportunity to clarify the test that should be applied when considering infringement in this situation. The Court acknowledged that it is not straightforward to find a suitable balance between the needs of the parties: "The law is struggling on the one hand to give the patentee a proper reward for his contribution to the art by elucidating the new use for the drug, whilst at the same time not excluding the competing manufacturer from making and marketing the drug for its known purpose."

A key issue was whether a second medical use claim will only be infringed when it can be shown that the manufacturer specifically intends for its product to be used to treat the patented indication. The Court reviewed decisions from a number of other European courts that considered this issue, but found a variety of different approaches. In some cases, only the uses stated on the product packaging were taken into account, others looked at whether there was some element of encouragement by the manufacturer, and others considered whether steps had been taken by the manufacturer to prevent use for the patented indication.

The Court of Appeal concluded that one needs to consider what the manufacturer knows or can reasonably foresee as the consequences of its actions in order to determine whether the manufacturer intended its product for the patented use. It may be possible to find such an intention when the product is formulated specifically for the infringing use, or is indicated for that use in the packaging or labelling. However, the Court concluded that the absence of the patented use from the drug label cannot be enough to conclude that there was no intention to use the drug for the patented use. A negative intention can only be concluded where the manufacturer has taken all reasonable steps within its power to prevent the patented use from occurring.

The Court concluded that the question to be considered was whether Actavis knew, or could foresee, that at least some of the prescriptions written generically for pregabalin to treat pain would be fulfilled with its drug. The Court recognised an obligation on a manufacturer to take active steps if it is to enter a market where it stands to benefit from the patentee's patented invention. In order to avoid infringement, the manufacturer must show that it has taken all reasonable steps in its power to prevent its drug from being used in accordance with the patent.

What Must Be Done To Avoid Infringing Uses?

The approach proposed by the UK Court is consistent with the findings in related French proceedings,3 which assessed what another manufacturer, Sandoz, had done to prevent use of its pregabalin product for the patented indication in France. Sandoz had sent an information email to doctors and pharmacists prior to launch, stating that its product was not indicated for neuropathic pain. Sandoz had also agreed to send more explicit messages to physicians and pharmacists to describe how to prescribe or dispense its drug, in order to avoid infringement. Although Sandoz had a larger share of the market than was represented by non-pain use, the French court concluded that Sandoz had done enough to avoid direct infringement of Warner-Lambert's patent.

It is not clear from the UK decision what steps a manufacturer might need to take in the UK to establish that it did not intend for its product to be used for a patented indication. There is clearly a burden on the manufacturer to try to limit the use of its product to the non-patented uses. However, the Court's test does suggest that factors that are outside the control of the manufacturer, such as those based on the structure and processes of the healthcare system, will not be held against it.

In view of the flexibility that is afforded to individual doctors and pharmacists in the UK, it is unlikely that the efforts required by this test will be able to completely prevent the off-label use of generic products for patented uses. In some cases, patentees may need to consider taking further action themselves to enforce the prescription of only their approved drug for the patented use. For example, Pfizer has successfully obtained an injunction in the UK against NHS England (which oversees the operations of the English National Health Service), requiring them to instruct doctors to prescribe pregabalin only by the Pfizer brand name Lyrica when it is for use in treating pain4.

Despite the inability to completely prevent physicians and pharmacists from prescribing a generic drug for a patented indication, it is clear from this decision that a second medical use patent can be valuable. It can impose a burden on other manufacturers to try to prevent their products being used in accordance with the patent. A patent filing strategy involving follow-up patent applications directed to specific uses of a drug can therefore limit, or at least disrupt, the market for third party products, even after the basic patent protection for the product itself has expired.