The European Patent Office’s (EPO) Board of Appeal recently considered whether a new mode of administration for a patented drug can be considered an inventive feature in second medical use claims. Its decision highlights the importance that clear and unexpected technical effects have in meeting the requirements for inventive step, and the caution needed when considering modes of administration as subject to new patent applications.
The case: Amgen and apremilast
Marketed as Otezla® by biotechnology company Amgen (Europe) GmbH, the compound apremilast uses therapeutic agents known as PDE4 inhibitors to treat inflammatory diseases such as psoriasis and psoriatic arthritis.
Historically, apremilast has presented difficulties when administered orally, including inducing vomiting. When taken in this way, the PDE4 inhibitors within apremilast would also often lack specificity for the PDE4 receptors within the body, sometimes even cross-reacting as PDE3 inhibitors, which can affect the regulation of heart muscle.
In an effort to solve these problems, Amgen considered avoiding these challenges using an orally administered ‘stereomerically pure’ form of apremilast.
Following this research, Amgen applied to seek protection as a second medical use for apremilast when administered orally. To support this, it claimed that the drug’s capability to be administered orally counted as an inventive step, a claim that was challenged by multiple parties.
What does the EPO say about medical use patents?
Under Article 53 of the European Patent Convention (EPC), it is not possible to grant a patent for “methods of treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.”
Nevertheless, it is possible to protect the use of products – particularly substances or compositions – in methods of treatment or surgery if that use demonstrates what is known as an ‘inventive step’. Essentially, this means that it may be possible to secure patents protecting the different ways in which a product is used or employed, provided these are not obvious.
Under Article 54(4) of the EPC, a known product can be protected in a ‘first medical use format’ if it is found to have a use in a medical treatment context for the first time.
Furthermore, under Article 54(5), a substance or composition that has already been used in a method of treatment can be protected in a ‘second medical use format’ for use in a further, distinct method of treatment. This may involve a new disease, but it could also extend to new modes of administration (e.g. subcutaneous, oral), a new dosage regimen, or the treatment of specific patient subgroups.
Furthermore, they also need to demonstrate ‘inventive step’, the definition of which has not always been clear where the second medical use format is concerned.
Whilst first medical use claims provide a broad protection, subsequent patent applications concerning the same product, but a non-obvious use, need to be more specific.
Amgen’s application: novelty and effect
Amgen’s argument boiled down to two key points: the oral administration of apremilast was a new mode of administration and therefore novel; and the benefits of administering the ‘stereomerically pure’ apremilast orally constituted an unexpected effect. Put together, both would qualify the compound for protection under the ‘second medical use format’.
Point one – The mode of administration
The EPO’s Board of Appeal first reviewed the EPO Guidelines for Examination, which suggested that a claim for second medical use format protection lacks novelty over previous disclosures of a compound’s medical use if it only cites the mode of administration as a new feature, and not a specific therapeutic effect.
The Appeal Board, however, rejected this, instead considering the interpretation of medical use in G2/08. According to this, where a medicament is known to treat a specific illness under Article 54(4), further medical use of the substance – such as a different mode of administration – could be considered a characterising feature.
As such the mode of administration (such as the oral administration claimed by Amgen) could be considered novel in the second medical use format.
Point two – The unexpected effects
According to Amgen, the unexpected effects materialised through the various advantages the ‘stereomerically pure’ apremilast had when taken orally compared to previous compounds.
These were not enough, however. According to the Appeal Board, this was because there was already a strong motivation in the market to stereomerically develop apremilast, and its use orally was an obvious route. Other suitable forms of administration were limited, making the case a “one way street”, according to the Board.
As such, although the Board decided that mode of administration could be considered novel, it revoked Amgen’s patent because the mode of administration was, in this case, too obvious, despite its unexpected advantages.
What lessons can we learn from Amgen’s case?
Whilst this decision contradicts the EPO Guidelines on modes of administration as an inventive feature in second medical use claims, it does highlight the need to show clear and unexpected technical effects from a claimed mode of administration in an application.
Furthermore, particular caution should be taken when trying to claim a particular administration route as an inventive feature, not least because it represents a finite number of possible alternatives that would be obvious to try, unless there is compelling reasons against its use by such a mode.
Second medical use may be available as a form of protection, but it is incumbent upon the patentee to ensure every effort has been made to demonstrate both novelty and inventiveness. Just because something has overcome the novelty hurdle, does not mean it will do the same for the inventive one.
This article was co-written by Anya Mottram.