Data protection and extension of patent rights TRIPS requirements & TRIPS-plus provisions Carlos Correa

 Test data protection

Medicines are subject to two sets of rules: PatentsRegistration requirements The right to exclude But not the right to market or to use Authorization to put a medicine on the market

Test data Safety – Efficacy Preclinical and clinical trials

TRIPS Article 39.3 Members, when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products which utilize new chemical entities, the submission of undisclosed test or other data, the origination of which involves a considerable effort, shall protect such data against unfair commercial use. In addition, Members shall protect such data against disclosure, except where necessary to protect the public, or unless steps are taken to ensure that the data are protected against unfair commercial use.

“Unfair commercial use” -The Drug Regulatory Authority (DRA) may not request the data (approval by reference) -Even if the DRA does use the data, it is not commercial use

Data exclusivity During the data exclusivity period, Authorities cannot use or rely on test data to register generic equivalents

As long as data exclusivity lasts: Generic manufacturers will have to submit their own data to prove safety and efficacy => They will have to repeat the clinical trials and other tests Alternatively, they can only enter the market after expiry of the data exclusivity period

Patent Registration; market entry End patent term Data exclusivity NCE, “standard” situation:

Patent Registration; market entry End patent term Data exclusivity 2. Second indication: Registration 2 nd indication Data exclusivity

Patent Registration; market entry End patent term Data exclusivity 1. NCE, compulsory licensing:

Directive 2004/27/EC  Article 10  1...without prejudice to the law relating to the protection of industrial and commercial property, the applicant shall not be required to provide the results of pre-clinical tests and of clinical trials if he can demonstrate that the medicinal product is a generic of a reference medicinal product which is or has been authorised under Article 6 for not less than eight years in a Member State or in the Community.  A generic medicinal product authorised pursuant to this provision shall not be placed on the market until ten years have elapsed from the initial authorisation of the reference product.

Directive 2004/27/EC  5. In addition to the provisions laid down in paragraph 1, where an application is made for a new indication for a well-established substance, a non-cumulative period of one year of data exclusivity shall be granted, provided that significant pre-clinical or clinical studies were carried out in relation to the new indication.

Directive 2004/27/EC  Article 10a  By way of derogation from Article 8(3)(i), and without prejudice to the law relating to the protection of industrial and commercial property, the applicant shall not be required to provide the results of pre-clinical tests or clinical trials if he can demonstrate that the active substances of the medicinal product have been in well established medicinal use within the Community for at least ten years, with recognised efficacy and an acceptable level of safety in terms of the conditions set out in Annex I. In that event, the test and trial results shall be replaced by appropriate scientific literature.

Data protection: Directive 2004/27/EC: Prevents authorities from assessing applications for generics during 8 years; -Marketing of generics can only be authorized after ten years -One additional year for new indications of known products

Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on products for paediatric use1901/2006 -Paediatric-Use Marketing Authorisation (PUMA): 10 years of market exclusiviity -A medicinal product that has obtained a PUMA can use the existing brand name of the corresponding authorised product

European Parliament and Council Regulation (EC) No 141/2000 of 16 December 1999 on orphan medicinal products141/2000 -Diagnosis, prevention or treatment of a condition affecting fewer than five per ten thousand persons in the Community; -exclusive marketing rights for a ten-year period. Athe request of a Member State, this period can be reduced to six years if that Member State can establish that the conditions justifying the designation as an orphan medicinal product are no longer met or that the price being charged for the medicinal product in question is excessive. -Exclusivity does not prevent the marketing of a second medicinal product if the holder of the marketing authorisation of the original orphan medicinal product has given his consent to the second applicant, or if he is unable to supply sufficient quantities of the medicinal product, or if another medicinal product proves safer, more effective or otherwise clinically superior to the first.

Ukraine: Article 9-Law on Pharmaceutical Products  “If the pharmaceutical product is registered in Ukraine, it is prohibited, for five years after the date of such registration (regardless of the validity of any patent which concerns the medical product), to use the registration information for filing an application for state registration of another pharmaceutical product, except for cases when the right to refer or use such information is received in a due manner”.

Patent term extension

US patent term extension to compensate for delay in approval of medicines (35 USC§156) -Maximum: five years -Total period of effective patent protection may not exceed 14 years (the original patent term, shortened by the regulatory review period, plus the extension)

Council Regulation (EEC) No 1768/92 of 18 June  The product is protected by a basic patent in force;  The product, as a medicinal product, has been granted a marketing authorisation;  The product has not already been the subject of a certificate;  The marketing authorisation is the first authorisation to place the product on the market as a medicinal product;  The certificate applies to the product in the same way as the patent from which it benefits;  The certificate cannot be granted for a period exceeding five years;  The duration of protection afforded by a patent and by the certificate cannot exceed 15 years overall for the holder's first marketing authorisation.

 Impact of TRIPS-plus data exclusivity

Impact of TRIPS-plus on the price of medicines in Costa Rica Number of new products under exclusive rights: from 9% en 2010 to 28% in Annual increase in social security costs: 31%

Colchicine : effects of data exclusivity -Widely available as a generic drug in the USA since the 19th century: second-line treatment for gout -Tests with 185 patients, one week: shortened dosing regime (fewer adverse effects): 3 years of data exclusivity - Familial Mediterranean fever (FMF) (genetic inflammatory Disorder): 7 years of exclusivity under Orphan Drug Act - Lawsuits to remove any other versions of colchicine from the market -Price increase by a factor of more than 50, from $0.09 per pill to $4.85 per pill.