Second medical use patents

Second medical use patents are those directed to the protection of the use of a known drug, which is already known to be useful in the treatment of a first medical condition, in the treatment of a further medical condition for which it was not previously known to be effective. Such patents are common, including in Australia where their validity was notably recently confirmed in the High Court of Australia (Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd & Ors [2013] HCA 50 ‘the Leflunomide case’).

Second medical use patents can, however, present particular legal difficulties when a generics company applies for regulatory approval to sell the drug for treatment of the first medical condition, which we will assume is by this time ‘off patent’, but there is a perceived significant risk that the drug will be prescribed by pharmacists for treatment of the second, patented, medical condition. In such a scenario, the generics company’s supply of the drug will not be a direct infringement of the method of treatment claims of the second medical use patent. Therefore, to prevent that supply, the patentee must rely upon the contributory infringement provisions of the Australian Patents Act (Section 117).

In the scenario described, where the generics company’s only stated intention and instruction to medical practitioners relates to supply of the drug for treatment of the first, off patent, condition then the most likely leg of s117 which the patentee will rely upon is s117(2)(b) which has effect when the use of a product, which has been supplied by a supplier, infringes a patent and the product is not a ‘staple commercial product’ andthe supplier had ‘reason to believe’ that the person would put the product to the infringing use.

Skinny-labelling

In an attempt to reduce the risk that they will be found to have the requisite reason to believe that the supplied drug would be put to the infringing medical treatment the generics company may employ a ‘skinny-labelling’ strategy. This practice involves deliberately carving out the infringing medical treatment from the drugs product information document (PID) which may occur by effectively stating in the PID that the drug being supplied is indicated for the off patent treatment but is not indicated for the treatment covered by the second medical use patent.

The Leflunomide case

These issues were considered in the Leflunomide decision where the High Court resolved, based on the facts presented, that it had not been shown that the generics supplier (Apotex) possessed the requisite reason to believe the drug would be put to the medical use claimed in the Sanofi patent and thereby avoided a finding of contributory infringement. In the Leflunomide case Apotex had proposed to supply Leflunomide for the treatment of psoriatic arthritis and rheumatoid arthritis and had carved out, on their PID, the treatment of psoriasis not associated with symptoms of arthritis. The relevant Sanofi patent was directed to a method of treating or preventing psoriasis. This finding by the High Court, even in light of evidence presented that psoriasis is a diagnostic criterion of psoriatic arthritis and that the vast majority of patients with psoriatic arthritis will have or will develop psoriasis and in the face of a contrary finding by the Full Court of the Federal Court of Australia (FCAFC), provided the generics community with a sense of optimism that the practice of skinny-labelling could be an effective shield to allegations of contributory infringement.

The Lyrica case

This optimism has been somewhat tempered by the recent decision of the FCAFC in Warner-Lambert Company LLC v Apotex Pty Ltd [2014] FCAFC 59 (‘the Lyrica case’). The facts of the Lyrica case, in brief, are that Warner-Lambert (Warner-Lambert and the related entities involved in the case are referred to here as Pfizer) is the patentee for a patent relating to the treatment of pain including but not limited to neuropathic pain (the pain patent) using pregabalin (sold by Pfizer under the name Lyrica) and is also a co-owner on a patent relating to the use of pregabalin to treat seizures (the seizure patent). Apotex had initially obtained the necessary registrations for their generic version of pregabalin for both neuropathic pain and seizure indications and initiated revocation proceedings for both the pain patent and the seizure patent. A confidential agreement was reached between the parties in relation to the seizure indication and so Apotex limited their revocation attempt to the pain patent and amended the registrations for their generic pregabalin to be confined to the seizure indication.

Apotex did not oppose a Pfizer injunction application for their proposed supply for the neuropathic pain indication and had provided an undertaking that they would not supply their generic pregabalin to the sizeable hospital market until a final determination was made on infringement. Apotex also proposed to provide certain materials around their generic pregabalin registered for the seizure indication to affirm its limitation to that indication including: (i) a pro forma letter to medical practitioners; (ii) a pro forma letter to pharmacists; and (iii) a general circular. The purpose of this material was stated by Apotex to be to direct the various parties involved in the prescribing and supply chain that Apotex’s generic pregabalin was indicated only for treatment of seizures and was not indicated for treatment of neuropathic pain.

Pfizer applied for injunctive relief to restrain Apotex’s supply of generic pregabalin, relying on s117(2)(b) to allege likely infringement of the pain patent. The underlying argument was that Apotex’s generic pregabalin would ultimately be prescribed or provided by pharmacists to patients for the treatment of neuropathic pain, thereby infringing the pain patent, and that Apotex would have reason to believe that this would be the case. It was not in dispute that pregabalin was not a staple commercial product.

A range of evidence was presented by Pfizer including, relevantly, that: (i) the market for the seizure indication in Australia was so small as to be practically negligible; and (ii) that the prescribing practices of medical practitioners are such that they often do not note the indication for which the drug is prescribed but rather just identify the drug itself.  That results in pharmacists having no knowledge of the actual indication and therefore typically offering any lower cost generic drug to the patient,  even if the generic drug is not registered for treatment of the patient’s condition (an off-label generic substitution).

The FCAFC favoured Pfizer’s evidence and so granted the injunction appeal to restrain Apotex from supplying all of their generic pregabalin products. It is important to note that, given the nature of the hearing which was addressing the interlocutory appeal, the court simply observed that whether or not Apotex had the requisite reason to believe to support an actual finding of contributory infringement under s117(2)(b) is something that could not be resolved before the full trial. The decision was simply that Pfizer had made out a prima facie case (they had shown they had a sufficient likelihood of success at trial) and, on the balance of convenience, it was desirable to maintain the status quo until trial and so grant the injunction.

What might this mean for generics companies?

This decision is a warning to generics companies and others that the practice of skinny-labelling, and even the issuance of marketing material to medical practitioners and pharmacists reinforcing that a drug is only indicated for an off patent treatment, may not be sufficient to ward off a finding of contributory infringement under s117(2)(b).  The risk of contributory infringement is even greater if there is evidence that the drug supplied is likely to be issued to patients for the patented treatment. Evidence showing the size of the off patent market and addressing the prescribing habits of medical practitioners and related supply by pharmacists will likely be of relevance.

What might this mean for patentees?

For patentees there will be a level of relief that the decision handed down by the High Court in the Leflunomide case has not opened the flood gates to allow third parties to supply generic versions of drugs which they believe will be used in the treatment of conditions covered by their second medical use patents. The on going value of second medical use patents to an originator company in protecting their innovations is therefore affirmed.

Conclusion

From a practical perspective the Leflunomide case was never likely to signal a carte blanche ability for generics companies to supply a drug, for an off patent indication, which still has a patented indication when there is a significant likelihood that it will be prescribed or supplied by pharmacists for that patented use. Likewise, this recent decision by the FCAFC does not mean that skinny-labelling is an entirely futile exercise. Rather, the decisions indicate that a finding of contributory infringement, based on the general scenario set out earlier in this article, will very much depend on the particular facts of the case and supporting evidence presented.

What can be confidently stated is that, given the Leflunomide case involved the High Court overturning the findings of the FCAFC and the Lyrica case involved the FCAFC overturning a decision of a single judge of the Federal Court, contributory infringement continues to be a challenging area of law for the courts.