Patent protection of the newly discovered indications as well as the dosages, dosage routes and dosage regimen of the new forms of use, constitute an important part of managing intellectual property rights pertaining to pharmaceuticals. In the pharmaceutical area, a different field of use of a known molecule can be subject to a patent. If such a use is a secondary or further use, this type of patents is called “second medical use” patents. In consideration with the basic principles of patent laws, a second medical use should be meeting the criteria of novelty and inventive step in order to be lawfully granted patent protoction. The novelty herein is arising out of the novel curative use of an already known substance. In other words, the substance in question is already known but the curative use for a particular illness is not yet known.
Since there was no explicit provision under EPC 1973 regarding the second medical use, patentability of such use was controversial in some countries until EPC 2000 amendment. Yet, with the decision G5/83 of the EPO Enlarged Board of Appeal, patentability of the second medical uses was accepted on the condition that they are presented in a special type of claim called as “Swiss type claim”. In order to overcome the inconsistencies between the decisions taken by different countries, Article 54/5 which explicitly permits patentability of the second medical use was incorporated into EPC 2000 which endedthe discussions in this regard.
As a result, pharmaceutical companies have their second medical use patents for certain indications of drugs, patent terms of which have been expired, which may further delay the generic pharmaceuticals’ entry into the market. However, the additional protection conferred by these second medical use patents became sometimes practically inapplicable. This problem that the pharmaceutical companies face with has been the controversial issue in the pharmaceutical sector for the recent years and has been the subject of numerous lawsuits. In order to understand the problem, it is beneficial to review the lawsuit filed in England by Warner-Lambert against Actavis which is a commonly known dispute in this matter. However before getting into details of this case, it is important to mention the procedure between marketing authorization of pharmaceutical products and their access to the end-users, and the role of the healthcare authorities during this process. This is because, in practice, reasons for not being able to benefit from the protection of the second medical use patents are based on the deficiencies in the regulations.
As is known, in most of the countries including Turkey, it is necessary to obtain a marketing authorization (MA) from the healthcare authorities for a particular pharmaceutical in order to sell these products and the sale of these pharmaceuticals is only possible after completion of certain requirements, which are changing from country to country, such as pricing and sales permit. Generic pharmaceutical companies can make abridged applications for their generic products which are mainly similar to a previously licensed original product by referring to the dossier of such original product upon expiry of the data exclusivety term, if any, which is provided to the original product and which again, changes from country to country. MA applications can be made for one or more indications. In this way, the generic pharmaceutical companies can limit their MA applications for specific indications and remove the indications which are still under protection of second medical use patents from the summary of product characteristics (SmPC) and Product Information Leaflet (PIL) of the products by a method called “carve-out”. The labels in which the carve-out method is applied reflect a more limited scope in terms of approved indications as opposed to the original products and, thus, are considered as “skinny labels”.
Generic pharmaceutical companies which apply this method are in the position of declaring an intention not to use those pharmaceuticals for the indications which are under continuing protection of the second medical use patents, and therefore they refrain themselves from probable direct infringement lawsuits which can be filed against them. However, carving out the patented indications from the generic pharmaceutical does not always mean that such pharmaceutical would not, in practice, be used for those indications.
In a scenario where a physician in fact prescribes a pharmaceutical product to a patient for the use of such product in relation to a patented indication but the prescription only specifies the name of the original pharmaceutical product without any notes on the targetted indication, and the pharmacy has the authority to substitute the original product with a generic, the pharmacy may give a generic product to the patient in lieu of the original. As a result, the generic pharmaceutical would be used for the patented indication. In fact, pharmacies cannot know the exact indications for which the pharmaceutical is prescribed in a system where the indications are not noted in the prescription and the original product, which is actually patented for the indication that it is prescribed for, may be substituted with a generic product by the pharmacist. When it is taken into consideration that the generic pharmaceuticals costs less as compared to the originals, subsitution of an original product with a generic pharmaceutical by the pharmacist is a very common situation which is even supported by the healthcare authorities in order to decrease the healthcare expenditures. Therefore, in these cases, the problem which can be considered as an infringement of second medical use patents arises. Because, although the generic pharmaceutical company carves the patented indications from the label and limits the intended use of such pharmaceutical for certain indications; in practice, such pharmaceutical may still continue to be used for the patented indications, with or without the manufacturer’s intention which appears to be an important element to be take into account during infringement analizes within this skinnly-label-consept.
As mentioned above, the commonly known case relevant to this subject is the lawsuit filed in England by Warner-Lambert against Actavis. Warner-Lambert, one of the group companies of Pfizer INC, was the owner of the second medical use patent for the active ingredient “pregabalin” for the treatment of neuropathic pain. Warner-Lambert marketed its pharmaceutical named “Lyrica” with the active ingredient “pregabalin”, for the treatment of epilepsy, anxiety disorder and neuropathic pain. Thereafter, Actavis, made an MA application for a generic pharmaceutical named “Lecaent” including “pregabalin” as the active ingredient by limiting the use of the applied pharmaceutical with only the indications not protected by the aforementioned patent. In other words, the approved indications of the generic pharmaceutical of Actavis did not include the patented indication which belongs to Warner-Lambert and thus, the generic pharmaceutical named “Lecaent” has been placed on the market with a “skinny label”.
However, as indicated above, even when a generic pharmaceutical has been marketed with a “skinny label”, it may still be possible to use this pharmaceutical for the patented indications in practice because of regulatory systems. Besides, in England, where the incident that is the subject matter of the Warner-Lambert/Actavis lawsuit occurred, some prescription writing methods triggered such consequence. Therefore, Warner-Lambert filed a patent infringement lawsuit with a request for interim relief against Actavis. The court of first instance first determined, while setting forth the merits of the case in its decision, that the patent had been written in the form of a “Swiss type claim”, in other words in the form of “use of pregabalin for manufacturing of a pharmaceutical for the treatment of neuropathic pain”. Afterwards, the court declared that in order to determine whether Actavis infringed the patent or not, it was necessary to find an answer to this question: “Has the “Lecaent” as a pharmaceutical, preparation of which includes pregabalin, been manufactured with the intention of treating neuropathic pain?”.
In order to answer this question, the court set forth that it was required to discuss who may be associated with the intention herein and what should be the nature of this intention. The court was of the opinion that the physician and the pharmacy could not been associated with the infringement claims since they were not manufacturing this pharmaceutical. As per the court, the party who will be associated with the infringement should be the manufacturer of the pharmaceutical due to the claim type of the patent which was subject to this lawsuit and in the case at hand, the manufacturer was Actavis. However, the court decided that Actavis had no intention of infringement since it did not intend to use this pharmaceutical named “Lecaent” for the treatment of “neuropathic pain” while marketing the same. Because, Actavis made an MA application by excluding the patented indication and also by exhibiting a proactive approach as it sent warnings to the pharmacies and related institutions for not to prescribe and sell the relevant pharmaceutical for the treatment of the patented “neuropathic pain” indication. As a result, the court ruled that Warner-Lambert had no sufficient claim which should be heard. The court also stated that even if there was a sufficient claim to be heard, it still would have refused Warner-Lambert’s claim since the results of issuing this ruling was more likely to cause irreparable prejudice to Actavis than the results of not issuing it might have caused against Warner-Lambert.
On the other hand, the lawsuit filed by Pfizer against Actavis in Germany on the basis of the same grounds was concluded in favour of Pfizer and an interim injunction was granted against Actavis. In relation to the lawsuit filed in Spain, the court refused the infringement claim but at the same time it was possible to achieve some regulatory measures to be taken before Spanish healthcare authorities for preventing the possible infringing situation. As these examples reveal, the question of whether the products marketed with “skinny label” cause patent infringement or not is interpreted controversially in different countries.
If the foregoing discussions on the applicability of the second medical use patents in practice are examined in relation to Turkey, we should first mention the Ministry of Health’s circular setting forth that if an approved pharmaceutical product includes the same active ingredient in the same pharmaceutical form and dosage with a pharmaceutical product SmPC and PIL of which have been published, then the SmPC and PIL of the new product should be prepared identical with the previous product’s published SmPC and PIL. Yet, patented indications and non-pharmaceutical information (shelf life, formulation, storage temperature etc.) are exempted from this requirement. Accordingly, generic pharmaceutical companies have the opportunity to remove a patented indication from their MA applications for their pharmaceuticals to be made before the Ministry of Health in Turkey by the carve-out method to avoid infringing patented indications. Therefore, by taking into consideration the prescription methods of pharmaceuticals and regulatory system in Turkey, we shall evaluate the problem of whether a generic pharmaceutical marketed with a “skinny label” would cause an infringement to the second medical use patents or not in accordance with the local legislation.
At this point, we should briefly explain the regulatory system in Turkey. Some physicians in Turkey only write the name of a pharmaceutical product without stating the prescribed indication on the prescription. In the past, there have been frequent cases where some physicians tried to prevent the pharmacists from offering generic pharmaceuticals to the patients instead of original pharmaceuticals specifically prescribed by the physician. However, Ministry of Health once again issed the circular that substitution of an original pharmaceutical with generics by a pharmacist is scientifically and legally correct and ordered the physicians to cease their’ practices for preventing the substitution. Therefore, it shall be noted that the substitution of pharmaceuticals is legally possible and supported by the health authorites in Turkey. Moreover, the electronic MEDULA system which is established for use of healthcare stakeholders including pharmacies by the reimbursement authority, Social Security Institution, technically allows the aforesaid substitution. Public healthcare institutions and the private healthcare institutions contracted with the Social Security Institution use e-prescription system which must contain indications. Pharmacist shoud be aware of indications of products and should not substitute the original product with the generic products with skinly label for patented indications. For the substitution between some special products which are subject to different reimbursement rules per the Regulation, the MEDULA system requires an exact “indication conformity” in addition to an explicit reference to the indication in the prescription. For these types of products, use of one for the other with skinny label is not technically possible within the system. Because the pharmacist must match the indications for conformity in the system, otherwise its reimbursement is deined by the Social Security Institution. However, if prescriptions do not refer to indications, generic products which are not approved for a patented indication may be given by the pharmacists to the patients whom were actually prescribed for an original product.
In Turkey, In view of the foregoing, it is controversial whether above mentioned senerios may constitute infringement to the second medical use patents under the current legislation. It is argued among the authors that a generic pharmaceutical manufacturer declares an intention to manufacture its pharmaceutical product only for the unpatented indications by carving out the patented indications from the label. In order to determine whether or not there is any infringement, one should evaluate if activities of the generic pharmaceutical company despite the limited indications are encouraging and inciting for the use of such pharmaceutical for the carved-out indications.
The Patent Decree Law sets forth special provisions for the persons who do not directly infringe but contribute to and participate in the performance of the acts conducting patent infringement. Accordingly, the right holder of a patent is entitled to prevent third parties from handing over to persons who are unauthorized to use the patented invention, the elements or means which are related to an essential part of the invention that is the subject matter of the patent and rendering possible implementation of the patented invention. Herein, use of a feature of the invention which is essential and enables implementation of the invention in a manner serving to infringement of the patent is in question. If this feature is inevitably used in an infringing manner, the possibility of the “patent infringement with contribution” increases. However, if this essential feature is a commonly available product in the market which can be widely used outside the scope of the patent infringement, it is explained that additional indicators, in other words “the acts inciting the patent infringement”, shall be required. For example, when it is known that a pharmaceutical product subject to an indication patent is indicated for various other illnesses and if there is no manipulation or incitement for the use of the main feature of the pharmaceutical for the patented indication, the possibility of patent infringement decreases. If there is manipulation or incitement, the possibility of patent infringement increases.
Is it possible to associate the physicians and the pharmacists to the infringing act in the event that they prescribe or sell the generic pharmaceutical for the patented indication? Primarily, it shall be noted that in accordance with Article 136/1(b) and 136/1(e) of the Patent Decree Law No. 551, it is possible to associate the acts of physicians and the pharmacists with infringement in certain situations.For a product with a “skinny label”, it is necessary to evaluate on a case by case basis the situations where the liability of the physician and the pharmacist may occur by considering whether or not the carved-out indications are stated in the prescription by the phisican; whether or not those skinny labed products are defined in the MEDULA system as the generic of the original product; whether or not it is a special product where the “indication conformity” is required in the reimbursement rules; whether or not e-precription is used and the circumstances in which the pharmacies do not pay attention to the indications. Still, due to pharmaceuticals industry culture in Turkey, even when this liability is determined, it is not widely applicable practice for the pharmaceutical companies to sue physicians and pharmacies.
Deficiencies, resulting from the regulations which cause the direct or indirect infringement of the rights of the pharmaceutical companies arising out of the second medical use patents, should be eliminated by the healthcare authorities and the pharmaceutical companies shall have to take necessary measures to that end. As a matter of fact, in England, Germany, Spain where the Warner-Lambert dispute was faced, some measures in healthcare regulations were taken for preventing these kinds of infringements. We believe there are also several regulatory measures that the pharmaceutical companies can take for preventing the infringement when the healthcare system in Turkey is taken into consideration.
