Atripla was granted a marketing authorisation on 13 December 2007. The rationale for the product was described by the European Medicines Agency as follows: “The rationale for the fixed combination of efavirenz, emtricitabine and tenofovir DF is to simplify HIV-treatment regimens and to improve adherence to therapy by providing combination antiretroviral therapy for administration as a single, once-daily tablet. The individual active substances are already approved to be used together in combination therapy of HIV-1 infected patients.” The SPC Regulation The SPC Regulation enables the proprietor of a patent for a medicinal product to obtain an SPC extends the duration of the patent with respect to that product so as to compensate the proprietor for the effective loss of patent term caused by the need to obtain a marketing authorisation before the product can be marketed. The SPC Regulation includes the following recitals: “[3] Medicinal products, especially that are the result of long, costly research will not continue to be developed in the Community and in Europe unless they are covered by favourable rules that provide for sufficient protection to encourage such research. [4] At the moment the period that elapses between the filing of an application for a patent for a new medicinal product and authorisation to place the medicinal product on the market makes the period of effective protection under the patent insufficient to cover the investment put into the research. [5] This situation leads to a lack of protection which penalises pharmaceutical research. [6] There exists a risk of research centres situated in the Member States relocating to countries that offer greater protection. [7] A uniform solution at Community should be provided for, thereby preventing the heterogeneous development of national laws leading to further disparities which would be likely to create obstacles to the free movement of medicinal products within the Community and thus directly affect the establishment and the functioning of the internal market. [8] Therefore, the creation of a supplementary protection certificate granted, under the same conditions, by each of the Member States at the request of the holder of a national or European patent relating to a medicinal product for which marketing authorisation has been granted is necessary. A Regulation is therefore the most appropriate legal instrument.” Articles 1, 3, 4 and 5 of the SPC Regulation provide, so far as relevant: trial
“Article 1 Definitions For the purpose of this Regulation: (a) ‘medicinal product’ means any substance or combination of substances presented for treating or preventing disease in human beings or animals and any substance or combination of substances which may be administered to human beings or animals with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in humans or in animals; (b) ‘product’ means the active ingredient or combination of active ingredients of a medicinal product; (c) ‘basic patent’ means a patent which protects a product as defined in (b) as such, a process to obtain a product or an application of a product, and which is designated by its holder for the purpose of the procedure for grant of a certificate; … Article 3 Conditions for obtaining a certificate A certificate shall be granted if, in the Member State in which the application referred to in Article 7 is submitted and at the date of that application - (a) the product is protected by a basic patent in force; … (c) the product has not already been the subject of a certificate; … Article 4 Subject-matter of protection Within the limits of the protection conferred by the basic patent, the protection conferred by a certificate shall extend only to the product covered by the authorisation to place the corresponding medicinal product on the market and for any use of the product as a medicinal product that has been authorised before the expiry of the certificate.
Administration. As noted above, it was known that resistance had developed very quickly to all the NNRTIs which were under investigation. At that time, the skilled person would have been aware of three strategies to overcome the problem of HIV resistance: increase the dose of the failing drug, which can work in certain circumstances, but often has limited success due to toxicity concerns at higher doses; find a new drug with a different resistance profile; or combine two or more drugs, if possible with complementary resistance profiles. Combination therapy In August 1992, because monotherapy for HIV was failing as a result of resistance, combination therapy was also being considered. When two or more agents are given in combination there can be one of four interactions: indifferent – the result is equal to the result of the most effective drug by itself; antagonistic – the result is significantly worse than the indifferent response; additive – the result is to the combined action of each drug used separately; or synergistic – the result is significantly better than the additive response. The theory behind combination therapy for HIV was that, by targeting the replication pathway of HIV at two different steps or using drugs that had different mechanisms of action on the same enzyme, the chances of inhibiting replication are increased, and hence the chances of developing resistance are reduced. Combination therapy was also thought to have a number of other potential advantages, including the potential to allow lower doses and thus reduce toxicity and increase patient compliance. The idea of combination therapy was accepted as a basis for further investigation in August 1992, and interest in combinations of HIV drugs was growing. The motivation to combine different drugs was described by Prof Seley-Radtke in her first report in the following terms: “In 1992, researchers and clinicians were desperate to find improved treatments for HIV was essentially still a death sentence at that time. Those working in the field were trying everything in an effort to find something that worked.” The Patent The Patent was applied for on 3 August 1993 with an earliest claimed priority date of 7 August 1992. It is entitled “Benzoxazinones as inhibitors of HIV reverse transcriptase”. It was granted on 2 November 2000 and expired on 2 August 2013.