This article was first published in the 2023 Pharmaceutical Patent Review.
Key takeaways
- In Australia, new indications for known pharmaceuticals may be protected by several different patent claim formats, including method of treatment claims, Swiss type claims and EPC 2000 claims.
- Various forms of "skinny labelling" may be adopted by suppliers of generic and biosimilar medicines in an attempt to avoid infringement of second medical use patents when supplying a known pharmaceutical product for an off patent indication in Australia.
- Typically, skinny labelling involves omitting patented indications from the prescribing information (i.e., label) for a generic or biosimilar product, with or without an express statement that the product is not supplied for use in any patented indications. Such measures require regulatory approval. Sponsors of generics and biosimilars may also communicate directly with prescribers and pharmacists regarding the permissible use of their products.
- In a leading Australian case, although such measures were effective to avoid infringement of Swiss type claims, they were not effective to avoid infringement of method of treatment claims because, on the facts of that case, the generic sponsor had "reason to believe" its product would be used for a patented indication despite skinny labelling.
- The more complex regulatory arrangements applicable to biosimilars and other high-cost medicines may provide opportunities for more robust forms of skinny labelling (e.g., omitting patented indications from the scope of regulatory approval and/or reimbursement arrangements), although such measures are yet to be tested before the Australian courts.
Patents for second medical uses
Second medical use patents confer exclusive rights relating to the use of known pharmaceutical substances for new therapeutic indications. An example is provided by the patents granted to Warner-Lambert in several jurisdictions relating to the use of pregabalin (a pharmaceutical previously known and used in the management of seizures) for the treatment of certain types of pain (see Warner-Lambert Company LLC v Apotex Pty Ltd [2014] FCAFC 59 (Pregabalin Case)).
In Australia, several claim formats may be used to protect a new therapeutic indication for a known pharmaceutical substance, including the following:
- Method of treatment claims typically have the form "a method of treating [disease X] comprising administering an effective amount of [substance Y]" or, alternatively, "the use of [substance X] for the treatment of [disease Y]".
- Swiss type claims are purpose-limited process claims typically in the form "the use of [substance X] for the manufacture of a medicament for the treatment of [disease Y]" or "the use of [substance X] in the manufacture of a medicament for the treatment of [disease Y]".
- So-called EPC 2000 claims are purpose-limited product claims typically having the form "[substance X] for use in treating [disease Y]".
While method of treatment claims are prohibited in some jurisdictions, they are generally permissible in Australia: see Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50 (Leflunomide case).
Skinny labelling as a defensive strategy
Skinny labelling refers to certain strategies that a supplier of generic or biosimilar medicines may adopt in an attempt to avoid infringement of a second medical use patent when supplying a medicine for an off patent indication. As discussed below, skinny labelling may take a number of different forms.
Amendments to pharmaceutical labelling
In common with many other jurisdictions, Australia's regulatory regime for therapeutic goods requires the supplier of a prescription medicine to publish a document (generally known as "prescribing information" or a pharmaceutical "label") providing information necessary for the medicine's safe and effective use. Among other things, this prescribing information or label records the therapeutic indications for which use of the product has been granted regulatory approval in Australia.
In its simplest form, skinny labelling involves omitting from prescribing information for a generic or biosimilar product one or more indications that remain patent-protected, retaining only those indications that are off patent. A more elaborate version of skinny labelling involves also including in the generic or biosimilar prescribing information an express statement that the product is not supplied for use in accordance with one or more indications that remain patent-protected (a "disclaimer"). Amendments to prescribing information require the approval of Australia's Therapeutic Goods Administration (TGA). Whether the TGA will approve the inclusion of a disclaimer in generic or biosimilar prescribing information will depend upon the circumstances of each individual case.
In addition to the strategies mentioned above, the supplier of a generic or biosimilar product may communicate with Australian prescribers and pharmacists to inform them that its product should not be prescribed or dispensed for use in one or more patented indications.
Such strategies have been considered in a number of Australian pharmaceutical patent cases:
- In the Leflunomide Case, Australia's High Court ruled that a disclaimer included in the prescribing information for Apotex's generic leflunomide product was effective to avoid infringement of Sanofi's method of treatment claim covering the use of leflunomide for the treatment of psoriasis, enabling Apotex's product to be supplied for the off patent rheumatoid arthritis indication.
- In the Pregabalin Case, a skinny labelling strategy, coupled with undertakings to notify prescribers and pharmacists that Apotex's generic pregabalin products were only supplied for use in the treatment of seizure disorders was ineffective to avoid a preliminary injunction restraining supply of the generic product, in light of evidence that the patented pain indication comprised almost the entirety of the relevant Australian market for pregabalin products.
- In Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116 (Fenofibrate Case), a skinny labelling strategy, coupled with undertakings to notify prescribers and pharmacists that Sun's generic fenofibrate products were only supplied for use in the off patent hypercholesterolaemia indication, was effective to avoid infringement of Swiss type claims relating to the use of fenofibrate in the treatment of diabetic retinopathy, but was not effective to avoid infringement of method of treatment claims covering the latter indication.
The Fenofibrate Case serves to highlight an important distinction between Swiss type claims and method of treatment claims under Australian law, as it currently stands. In that case, Australia's Full Federal Court held that infringement of Swiss type claims is governed, not by the manufacturer's intention, but rather by what the medicament is manufactured "for" as indicated by (for example) the physical characteristics of the medicament as it emerges from the manufacturing process, including its formulation, dosage, packaging and labelling. On the facts of the Fenofibrate case, Sun's skinny labelling strategy was sufficient, in the Full Court's view, to establish that its generic fenofibrate products were not "for" use in the treatment of diabetic retinopathy and thus would not have infringed Mylan's Swiss type claims.
By contrast, the Full Court held that Sun would have infringed Mylan's method of treatment claims for the diabetic retinopathy indication (had they been valid). That is because, having regard to all of the relevant circumstances, Sun had "reason to believe" their generic fenofibrate products would be used for the patented indication, despite skinny labelling.
A similar outcome was reached more recently in Neurim Pharmaceuticals (1991) Ltd v Generic Partners Pty Ltd (No 5) [2024] FCA 360 (Melatonin Case), where a difference in wording between the generic label (treating "poor quality of sleep") versus the originator's patent (treating "non-restorative sleep") was sufficient to avoid infringement of Swiss type claims, but not to avoid infringement of method of treatment claims.
The Fenofibrate and Melatonin Cases highlight the potential benefits of adding method of treatment claims (if not already present) when an international patent application enters the national phase in Australia.
Additional strategies for suppliers of biosimilars and other high-cost medicines
Regulatory marketing approval for small-molecule generic medicines is typically granted on the basis of an appropriate bioequivalence study, without the need for the generic sponsor to provide clinical-trial data demonstrating efficacy. In such cases, regulatory marketing approval granted for the small-molecule generic product typically encompasses all of the indications for which the reference (i.e., branded or originator) pharmaceutical product has been granted marketing approval in Australia.
Australia's process for regulatory approval of biosimilars is different. Commonly, data submitted in support of an application for regulatory approval of a biosimilar includes results of one or more clinical trials, demonstrating efficacy of the biosimilar for at least one therapeutic indication, coupled with material supporting an inference that the biosimilar will also be efficacious in other therapeutic indications for which the reference product is approved in Australia ("extrapolation of indications").
This more complex regulatory pathway may afford the sponsor of a biosimilar additional strategies to limit the indications for which its product is granted marketing approval in Australia to off patent indications.
In most cases, supply of biologicals and other high-cost medicines in Australia is subsidised by the Australian Government under the Pharmaceutical Benefits Scheme (PBS). The indications for which supply of a medicine will be reimbursed under the PBS is determined by the Australian Government, acting on the advice of an expert committee (the Pharmaceutical Benefits Advisory Committee; PBAC).
There may be scope for a sponsor of a biosimilar or other high-cost medicine to limit the PBS listing of its product to exclude patented indications. In particular, PBS-subsidies are ordinarily not available where a product is supplied "off label" (i.e., supplied for a therapeutic indication for which that product has not been granted regulatory marketing approval by the TGA).
Exclusion of patented indications from the scope of regulatory marketing approval and/or PBS-reimbursement for biosimilars and other high-cost medicines has the potential to afford the suppliers of such products with a more robust form of "skinny labelling". However, the availability of such strategies will depend upon the approach adopted by the TGA and PBAC in each individual case. Whether such strategies will be effective to avoid infringement of second medical use claims is yet to be tested before the Australian courts.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.