The European Court of Justice [1] rendered a decision [2] that states drug companies can’t receive patent extensions covering the combination of two substances when only one is an active ingredient and the other controls the release of the first.
Drug companies often try to extend patent protection and, under EU rules, drug makers can apply for a “Supplementary Protection Certificate [3].” The certificate, granted for a maximum of five years, acts as a patent term extension for time lost from when a company first applies for a drug patent to its authorization, which can be as long as 15 years. The SPC is not an automatic right and has to be applied for in each individual state. The SPC covers a combination of what was claimed in the patent in relation to the marketed drug and what is covered by the marketing authorization.
MIT holds a European patent covering the drug Gliadel 7.7 mg Implant [4], which is the combination of polifeprosan, a polymeric, biodegradable excipient, and carmustine, an active ingredient already used in intravenous chemotherapy with inert excipients and drug additives for the treatment of brain tumors. Gliadel comes in the form of a device which is implanted into the cranium for the treatment of recurrent brain tumors. The mechanism of its action consists in the carmustine, a highly cytotoxic active ingredient, being released slowly and gradually by the polifeprosan, which acts as a bioerodible matrix.
MIT requested a supplementary protection certificate for carmustine in combination with polifeprosan. The German Patent Office rejected the rejected that application for an SPC on the ground that polifeprosan could not be considered to be an active ingredient within the meaning of Article 1(b) and Article 3 of Regulation No 1768/92.
MIT claimed that polifeprosan is an essential component of Gliadel since it enables carmustine to be administered in a therapeutically relevant way for the treatment of malignant brain tumors, thereby contributing to the efficacy of the medicinal product. It is consequently not a mere excipient or an ancillary component.
The Court looked at the following questions:
1. Does the concept of “combination of active ingredients of a medicinal product” within the meaning of Article 1(b) of Regulation [No 1768/92] mean that the components of the combination must all be active ingredients with a therapeutic effect?
2. Is there a “combination of active ingredients of a medicinal product” also where a combination of substances comprises two components of which one component is a known substance with a therapeutic effect for a specific indication and the other component renders possible a pharmaceutical form of the medicinal product that brings about a changed efficacy of the medicinal product for this indication (in vivo implantation with controlled release of the active ingredient to avoid toxic effects)?
As set out in Article 1(b) of Regulation No 1768/92, ‘product’ means the active ingredient or combination of active ingredients of a medicinal product. However, it does not define the concept of ‘active ingredient’. The court stated that the expression ‘active ingredient’ is generally accepted in pharmacology not to include substances forming part of a medicinal product which do not have an effect of their own on the human or animal body.
In a lengthy opinion, the court concluded that a substance which does not have any therapeutic effect of its own and which is used to obtain a certain pharmaceutical form of the medicinal product is not covered by the concept of active ingredient, which in turn is used to define the term product. Therefore, the combination of such a substance with another substance which does have therapeutic effects of its own cannot give rise to a combination of active ingredients within the meaning of Article 1(b) of Regulation No 1768/92.
The fact that the substance without any therapeutic effect of its own renders possible a pharmaceutical form of the medicinal product necessary for the therapeutic efficacy of the substance which does have therapeutic effects doesn’t change the results.