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28 April 2016AfricaCharlotte Weekes and Tamsin Cornwell

What the future holds for second medical use patents

Described by legal commentators as “the case of year”, and with numerous interim issues decided, English judge Mr Justice Arnold and the Court of Appeal have already grappled with a number of issues in Warner-Lambert (Pfizer) v Actavis and Mylan & Actavis v Warner-Lambert leading up to the decision of Arnold on September 10, 2015 on infringement and validity respectively.

Arnold found Warner-Lambert’s patent (EP 0 934 061), protecting the use of pregabalin for the treatment of pain, partially invalid for insufficiency and neither directly nor indirectly infringed by Actavis’s skinny label pregabalin product sold for epilepsy and generalised anxiety disorder.

Pfizer’s Lyrica is authorised for use in these conditions and neuropathic pain. Essentially there was held to be no foreseeability on the part of Actavis of the intentional use of Pfizer’s product for pain. Actavis also had taken a number of steps, including writing to Clinical Commissioning Groups and pharmacists, to prevent the use of its product in a potentially infringing manner. Furthermore, the National Health Service (NHS) guidance, which the court had ordered to be issued, would serve to prevent infringement, although Warner-Lambert disagreed.

However, the story is far from over. The validity and infringement issues relating to Warner-Lambert’s second medical use patent for pregabalin are under appeal in the UK. At present, the following questions remain:

1. What steps are adequate/required for a manufacturer of generic pharmaceuticals to take in order to avoid infringement when launching a product with a skinny label?

2. Who decides whether the steps taken are appropriate in the circumstances?

3. If the steps taken are not deemed adequate and it may therefore be considered foreseeable to the manufacturer that a few packs could erroneously be dispensed for the patented indication, what remedy is appropriate for the originator? It cannot be foreseen which pack will be administered for which use.

4. How would damages be calculated? (eg, by a proportion of the sales and determining an appropriate percentage to apply; or by the percentage of the market which is attributable to the patented indication—how accurate can that be and who decides it?; or by a very small percentage being applied to each pack sold because every pack could be dispensed for the patented use?).

5. What must the NHS, other healthcare bodies and healthcare professionals do to ensure there is no use of the skinny label generic product for the patented use (not to avoid infringement themselves but to overcome the broader problem)?

Arnold ended his judgment with an afterword on the “need for a system” to separate the patented market for the substance from the non-patented market by ensuring prescribers write prescriptions for the patented indication by reference to the brand name. He noted that the only body in England appearing to have the necessary power and authority to implement such a system is NHS England. In Wales, Scotland and Northern Ireland the devolved governments have this power and authority.

6. Who will be responsible for enforcing the NHS guidance and policing failures to comply?

7. Can it be appropriate to have penalties against doctors and pharmacists for not following the NHS guidance when these individuals usually fall outside the scope of allegations of infringement by originators?

8. Should regulatory bodies amend their procedures and rules to, eg, become more flexible in allowing amendments to all parts of skinny labels including contraindications where patents for other uses may remain?

“It is unlikely that a harmonised approach in Europe can result unless the regulatory bodies and health authorities collaborate and come up with a workable solution.”

In the context of Swiss form or EPC 2000 second medical use claims, fundamentally a balance needs to be struck between the rights of originators to enforce valid patents; the rights of generic manufacturers to market products for uses which are off patent; and the interests of the public health bodies to ensure patient access to the right medicines in an environment where cost-cutting is essential, without the risk of claims by originators in relation to every skinny label generic launched.

Appeal

The appeal decision in the Warner-Lambert case is expected to give some clarity on the infringement test under sections 60(1)(c) and 60(2) of the Patents Act 1977 for Swiss form claims which are deemed purpose-limited process claims, and potentially on the steps a generic manufacturer must take at launch to avoid infringement.

Further, given the importance of the test to balancing the interests of originators, generic manufacturers, health authorities and the general public, it is likely that some or all of the issues find their way to the UK Supreme Court.

However, infringement of EPC 2000 second medical use claimsconsidered purpose-limited product claims may not be addressed and any such considerations would likely be obiter in any event.

Europe

It is not just the UK that must address these issues—there are multiple disputes between Warner-Lambert and Actavis as well as other generic pharmaceutical companies throughout Europe. Different approaches have already been seen on interim relief and the appropriate test for infringement, as well as different approaches by national regulatory and health authorities where skinny label products are concerned.

It is unlikely that a harmonised approach in Europe can result unless the regulatory bodies and health authorities collaborate and come up with a workable solution. The lack of a harmonised approach creates uncertainty and will require companies to apply new, but no doubt different, approaches to the launch of skinny label products in different countries.

The future?

Before the Warner-Lambert case, companies sold skinny label generic products for off-patent uses and there had been no cases in the UK courts where the issue of potential infringement of a remaining medical use patent was raised. The market size of the patented indication and the value of the market are key factors in the consideration by patentees of the suitability of litigation.

There appears to be an acceptance by patentees that products can be supplied by generic manufacturers for indications that are no longer protected by patents and skinny labels can be used for this purpose. However, it may not be enough for the generic manufacturer to avoid infringement and interim relief proceedings being brought if it simply provides no active encouragement to prescribe or dispense off-label for the patented use.

While some originators may be happy with this, others may consider that additional steps should be taken to reduce the risk of off-label use of the skinny label generic product. However, how burdensome the additional steps required of generic manufacturers will be remains to be concluded.

In the Warner-Lambert v Sandoz case almost two months after Arnold’s judgment, Sandoz argued that it should be permitted to sell full label products because some pharmacies have a policy against stocking skinny label products for regulatory and reputational reasons.

In allowing Warner-Lambert’s application for an interim injunction, Arnold found that “there is no risk of a pharmacy such as Lloyds being in contravention of any regulatory law, rule, principle or guidance if it dispenses a skinny label generic pregabalin product against a prescription for generic pregabalin which does not specify the indication, and it turns out that the patient has been prescribed pregabalin for neuropathic pain (or even other kinds of pain, if the doctor prescribes pregabalin truly off-label)”.

Arnold considered it commendable that Lloyds wanted to adopt this “best practice” and only stock full label products, but he did not consider the reasons to be “soundly based”. If they were, then the fact other pharmacies adopted a different approach was a concern, and may be something which requires guidance from the relevant regulatory bodies. As for reputational consequences, it was a matter for Lloyds to decide what was in its own best interests, but he observed that:

o  Many other pharmacies are stocking and dispensing skinny label pregabalin;

o  The SmPC and PIL for skinny label pregabalin products can and do include the warnings of adverse events when pregabalin is taken for the treatment of neuropathic pain; and

o  Actavis’s skinny label product contains in its PIL the “blue box” wording about prescription of the product for the treatment of conditions not listed in the PIL.

In this case, Arnold noted that if the NHS guidance was proving less effective than anticipated it would be “very disappointing” and thought that it was perhaps due to the novelty of the situation. He reiterated that doctors and pharmacists should not treat his decision in September 2015 as meaning that the NHS guidance may be ignored.

He acknowledged that it may need to be revised if his first instance decision on invalidity and non-infringement stands following the appeal, but the existing guidance should be followed unless and until further guidance is provided once the Court of Appeal gives its decision.

Charlotte Weekes is a partner at  Pinsent Masons. She can be contacted at: charlotte.weekes@pinsentmasons.com

Tamsin Cornwell is an associate at Pinsent Masons. She can be contacted at: Tamsin.cornwell@pinsentmasons.com