Applying Presumption of Patent Infingement Against Biosimilars

Before filing lawsuits to assert patent rights against generics or biosimilars, the patent holder essentially operates in the dark. This is because, particularly in cases where the summary of product characteristics (“SmPC”) of the biosimilar/generic drug has not yet been published, or when it is not clear from the limited information in the SmPC whether the patent has been infringed, the relevant sections of the biosimilar/generic product's dossier must be examined to assess whether the patent has been infringed, which can only be done through a court order. The most important factor in persuading the court that such an examination is necessary and reasonable is the strong likelihood of patent infringement, in other words, the presumption of patent infringement.

According to the relevant provisions of the licensing regulation governing abbridged marketing authorisation (“MA”) applications, it is possible for a generic product to obtain an abbridged MA by referencing the dossier of an original product whose data exclusivity period has expired and by claiming and proving that it is fundamentally similar to the reference product. Essentially, the presumption of infringement mentioned above arises precisely from this condition. In cases where the formulation, manufacturing process, indication, and similar characteristics of the original product are protected by patent(s), a generic product that claims and proves to be fundamentally similar to the original product in all these respects is also considered highly likely to infringe these patent(s). Based on this assumption, courts are inclined to examine and evaluate the relevant parts of the generic product's dossier through an expert panel to determine whether the patent holder's rights are potentially being infringed.

Given that the basis of the presumption of infringement, which is accepted in the context of generic products, lies in the fundamental similarity between the generic product and the original product, the question arises whether such a presumption of infringement can be applied to biosimilar products, and if so, on what grounds.

Indeed, the market for biosimilar products is rapidly growing in Turkey, as it is worldwide, and the risk of patent infringement on biological products is increasing.

The regulations regarding the MA procedures of biosimilar products in Turkiye are set out in the Guideline on Biosimilar Medicinal Products (“the Guideline”) issued by the Turkish Medicines and Medical Devices Agency (“TİTCK”) of the Ministry of Health.

It would not be incorrect to say that the Guideline in question is a reflection of the "EU Guideline on Similar Biological Medicinal Products" and essentially contains very similar provisions.

In the Guideline, a biosimilar medicinal product is defined as "a human medicinal product that shows a high level of similarity to a licensed biological reference medicinal product."  It is evident that the regulator has raised the bar for biosimilar products compared to generic products, requiring a high level of similarity rather than just fundamental similarity. Additionally, the Guideline mandates that the active substance of a biosimilar medicinal product must be highly similar to the active substance of the biological reference medicinal product on a molecular and biological basis. In terms of dosage and route of administration, the Guideline requires that the biosimilar product must have the same dosage and route of administration as the biological reference medicinal product. Moreover, the pharmaceutical form, formulation, excipients, or presentation of the pharmaceutical form of the biosimilar medicinal product is expected, in principle, to be the same as that of the biological reference medicinal product. However, if this expectation is not met and there are some differences, the biosimilar medicinal product is expected to justify these differences with additional data, considering that variations in these areas may pose potential safety risks.

When all considered together, if the innovative elements related to the active substance, dosage, route of administration, pharmaceutical form, formulation, and presentation of the pharmaceutical form etc. of the biological reference medicinal product are protected by patents, it can be argued that a biosimilar product that claims and proves to be highly similar to the biological reference medicinal product for the purpose of obtaining a marketing authorisation, is highly likely to infringe these patents. In other words, there exists a presumption of patent infringement.

There is no doubt that some defense strategies commonly used in patent disputes between generic and original products will also be employed by biosimilar medicinal product manufacturers. The most commonly used and well-known of these strategies is the carve-out of patented features, such as posology, dosage regimen and indications, from the SmPC of the biosimilar medicinal product.

Indeed, according to the official website of the European Medicines Agency (EMA), for marketing authorization applications for biosimilar drugs, information directly related to the patented indication can be deleted from sections 4.1. therapeutic indications, 4.2. posology and method administration and 5.1. pharmacodynamic properties of the SmPC.

Although the Guideline or the Turkish Medicines and Medical Devices Agency (“Agency”) has not addressed this issue with as explicit as that of the European Medicines Agency, it is known that, according to established practice over many years, generic products obtained MA through abbridged MA application are permitted to omit information related to patented indications, dosage regimens, pharmaceutical forms, and similar aspects of the original product from the SmPC. It is clear that Agency’s practice will also apply to biosimilar products.

However, another important point to note for the Turkish market is that, according to the perspective of the courts, the carve-out of patented indications, dosage regimens, and similar information from the SmPC document alone does not eliminate the possibility of patent infringement or the presumption of patent infringement.

Just as the patent holder of the original product,  the patent holder of the biological reference medicinal product can also present evidence demonstrating that the biosimilar product inevitably uses patented features, even if these features are carved-out from the SmPC, and demonstrate the presumption of infringement and prevent the biosimilar product from the market.

Although there have been no cases in Turkiye yet where patents for biological reference medicinal products have been enforced through the courts to remove biosimilar products from the market, it is clear that with the expiration of protection periods for relevant patents and considering the billion-dollar market share of biological/biosimilar products, patent disputes between biological reference products and biosimilars are likely to begin soon and will be quite intense. However, the advantage will depend not only on the “creative” solutions of the parties but also on what the regulatory authorities expect regarding safety and efficacy criteria, and, of course, the perspectives of the courts.