Considerations from an IP perspective
During the development of a branded product, the aspirations for its use are often large and always hold great potential. Then reality and resources hit, and focus on one, potentially two indications is the outcome. Once proven effective in one indication, leading to a Marketing Authorisation (MA) with a specific label (e.g., paracetamol for the treatment of headache), other marketing authorisations for the same branded product may be obtained later.
The Patent Departments in pharmaceutical companies are always (or should be) part of the whole development process. I.e., from the discovery of the active ingredient to the specific uses of the active ingredient – and even post-launch!
This also means that the patent strategy often involves patent filings related to the composition of matter, manufacture, formulations, methods of treatment, dosage regimens, and specific patient populations. Obviously, not all filed at the same time, with the composition of matter patent expiring first. Furthermore, often one or some of the method of treatment patents (covering the label) expire before others, leaving room – with the expired composition of matter patent – for generic entry for that/those off-patent labelled indications.
When this occurs, the phenomenon ‘Skinny Labelling’ becomes a real option for a generic company to enter the market created by a successful branded drug.
What is Skinny Labelling?
The phenomenon is ‘a thing’ in the US within the pharmaceutical industry. Viewed from a pharmaceutical company’s side, Skinny Labelling may be seen as a “loophole” for generic drug entry. Thus, Skinny Labelling allows a generic drug to be approved for non-patented indication(s) as well as to enter the market before the pharmaceutical company’s patent(s) for other indication(s) expire.
In 1984, the US Congress introduced a law – today known as the Hatch-Waxman Act – which, in essence, was created to establish a regulatory path for generic drug companies to seek US Food and Drug Administration (FDA) approval for generic product before patent(s) covering a branded drug expires as a way to establish a system providing cheaper medications to patients.
As mentioned above, branded drugs are often covered by a set of patents that range from the composition of matter to formulations and indications relevant to the branded drug. From a timeline perspective, these expire at different times due to clinical development and focus within the branded company. Once an MA is obtained for the branded drug, indications may be added to the label upon completion of successful clinical trials and approval by the FDA. Eventually, one or more indications within the approved MA cease to be covered by a patent, leaving room for generic entry for that specific indication (given that any other patents covering the drug, active pharmaceutical ingredient (API), or other broader patents have expired).
The generic drug company can use Skinny Labelling to avoid triggering infringement and, at the same time, potentially enter a market earlier than otherwise impossible due to patent protection.
Recent developments in US Case Law
A recent disruption by the US Court of Appeals for the Federal Circuit decisions changes the assumption of avoiding infringement, i.e., Skinny Labelling for generic companies is no longer without risk.
Until recently, the strategy of a generic company to avoid infringement actions initiated by a pharmaceutical company was not to mention the patented use, thereby decreasing the risk of induced infringement.
Two US Court of Appeals for the Federal Circuit decisions, GlaxoSmithKline v Teva Pharmaceuticals USA Inc and Amarin Pharma Inc v Hikma Pharmaceuticals USA Inc, have attracted some interest in the industry and may be shaking the level of risk for induced infringement.
In the first case, GlaxoSmithKline v Teva Pharmaceuticals USA Inc, Teva’s marketing materials were referencing a still-patented indication – although carved out from their MA. The district court found that there was no induced infringement due to Teva’s skinny label. However, upon appeal, the Federal Circuit reversed the district court’s decision and found that Teva’s marketing material encouraged induced infringement.
In Amarin Pharma Inc v Hikma Pharmaceuticals USA Inc, Amarin sued Hikma for induced infringement as Hikma had launched their generic product listing only one of the two indications approved to Amarin. However, the Hikma label listed side effects of the carve-out indication, and furthermore, Hikma’s marketing materials referenced the patented indication. The district court found that no induced infringement occurred. However, the decision was overturned by the Federal Circuit, which reasoned that the totality of Hikma’s actions could plausibly lead to infringement.
Following the Federal Circuit decision, Hikma has filed a Petition for a Writ of Certiorari with the US Supreme Court, presenting two questions:
- When a generic drug label fully carves out a patented use, are allegations that the generic drugmaker calls its product a “generic version” and cites public information about the branded drug (e.g., sales) enough to plead induced infringement of the patented use?
- Does a complaint state a claim for induced infringement of a patented method if it does not allege any instruction or other statement by the defendant that encourages, or even mentions, the patented use?
Hikma argues in their petition that the court’s ruling “effectively nullified” skinny labelling. The US Supreme Court may be viewed on par with the Enlarged Board of Appeal of the EPO, which is to ‘streamline’ case law and ‘once and for all’ define how to act or not act in relation to Skinny Labelling.
Conclusions
The petition filed by Hikma is still pending. Once the ruling comes out, it will be interesting to see if there will indeed be set pivotal definitions on the boundaries for induced infringement in relation to Skinny Labelling.
Based on the two cases referred to above, it is prudent to involve their in-house counsels throughout the course of clinical development as well as post-launch.
Considerations for pharmaceutical companies
Putting the in-house counsels in charge of ensuring close collaboration with internal stakeholders to monitor generic commercial and regulatory activity. In particular, cooperation with regulatory departments helps in monitoring and analysing generic labels, without promoting any excluded uses. Similarly, establish a process for the commercial teams to monitor and scrutinise any marketing communications issued by a generic competitor. Referring to the branded drug or overall market size, not in relation to the off-patented indication, could be used in infringement actions.
Considerations for generic companies
It would be highly expedient to establish internal policies, e.g., a review of any published material, such as marketing materials, to ensure that functions across commercial, regulatory, and medical affairs are aligned on what can and cannot be communicated about a product. Similar to branded companies, review of any material relating to a composition of matter, use of the same or any other publications, should be done by the in-house counsel. However, keeping track of all this after the product’s launch often becomes more cumbersome.
Overall, creating and executing the right patent strategy requires consistent operating models applicable across the commercial, regulatory, and legal teams, regardless of whether it is a generic or pharmaceutical company.
