The main purpose of the Mexican Linkage System is to improve communication between the Mexican Patent & Trademark Office (IMPI) and the Mexican Federal Commission for the Protection against Sanitary Risk (COFEPRIS), in order to prevent issuance of marketing authorizations for generic versions of patented pharmaceutical drugs.
Under the Linkage System, the IMPI issues a Special Edition of the Official Gazette known as the "Gazette for Medicaments" (GM), similar to the Orange Book published by the Food and Drug Administration (FDA) of the US government. The statutory bases for the Linkage System are set forth in the Health Supplies Regulation (HSR), Article 167bis and in the Industrial Property Law Regulations (IPLR), Article 47bis, both enacted on September 19, 2003. Further, IMPI issued a guideline for the publication of the GM and the legal framework is completed by a decision of the Supreme Court on eligibility of formulation patents.
The GM is published every six months (in February and August) and contains a list of granted patents in-force organized by active principle. Each gazette replaces entirely the former issue in full.
Unlike FDA’s Orange Book, patent listings are not owned by a specific company and they are not related to a specific approved pharmaceutical product, but to the non-proprietary name (INN) of the active principle. Hence, more than one patent could be listed for the same active principle regardless of how many products are actually registered before COFEPRIS. Additionally, a patent could be listed more than once to the extent that is covers more than one active principle.
From the regulatory perspective the Linkage System is very relevant. Since its enactment, along with the dossier that is filed before COFEPRIS for obtaining a marketing authorization of a pharmaceutical product, it is mandatory to file an statement under oath (patents compliance declaration) that patents are not infringed by the product. This statement may contain a declaration that the applicant of the marketing authorization is the patent assignee or the authorized licensee of record in Mexico of the corresponding patent. When there are not patents in-force covering the product which marketing authorization is sought, the patents compliance declaration may state that there are not any patents covering the product known to the applicant of the marketing authorization.
The statutes are silent regarding the procedure for listing a granted patent in the GM. However, in the practice there are two known ways of listing a patent. One is a formal petition filed before IMPI and the other is a bona-fide proceeding available only for companies having a membership to the National Chamber of Pharmaceutical Industry (CANIFARMA), which is described in the IMPI guidelines for publication of the GM. These proceedings are not mutually exclusive.
The formal petition requires submitting a request for inclusion in the GM before the IMPI. In such request, it is necessary to prove that the patent is related to a product considered an “allopathic medicament”; the correspondence between the INN and the active principle of the claimed product; the identification of the active principle in the patent; and the claim covering the product. Additionally, the request must include specific bibliographic information about the patent and information about licensees (if any). Nevertheless, it is important to consider that the information that is ultimately published in the GM is decided solely by IMPI.
On the other hand, the bona-fide proceeding comprises submitting a request for inclusion through CANIFARMA. CANIFARMA groups almost every pharmaceutical company and has two main groups representing either predominantly innovator or predominantly generic companies. These groups are in turn grouped in different associations, mainly AMIIF (Mexican Association of Pharmaceutical Research Industries) and ANAFAM (National Association of Drug Manufacturers). The submission must be made by the patent owner along with a copy of the patent title and granted claims. The submissions are collected by CANIFARMA, who integrates and shares the full list for consultation, particularly with both groups. CANIFARMA submits to the IMPI those patents that have no objection to be published at the chamber level. Typically, only second medical use patents are currently opposed to by this procedure.
There is not a statutory period of time for filing a request, so generally it could be filed at any time after the granting of a patent and once an INN has been assigned to the drug. Usually those requests made at least one month in advance of the publication that will follow are included if the requirements are met.
It is possible to file an appeal before the Federal District Court (FDC) if the IMPI denies the inclusion of a patent in the GM either tacitly by not publishing or expressly through a formal rejection issued by IMPI in response to the request of the patent owner. The FDC’s decision, in turn, can be appealed in a final stage before a Federal Circuit Court (FCC) by the affected party (applicant or by the IMPI).
Regarding eligible patents for the GM, only process patents are expressly excluded. Nevertheless, in the beginnings of the implementation of the system the IMPI erroneously decided that only active principle patents were suitable for inclusion because the IPLR refers to a patents list by active principle. In consequence, several appeals were submitted for inclusion of patents referring to formulations, compositions and second uses. As a result, a decision by the Supreme Court was issued in February 2010, establishing a criterion whereby formulation/compositions patents became expressly eligible for listing in the GM. From July 2012, IMPI started listing formulation patents in the GM without litigation. Second medical use patents are still rejected for publication by IMPI as the decision by the Supreme Court was silent with regard to this kind of patent. IMPI has lost most of such cases and more than 40 second use patents have been successfully listed so far by judicial order.
More than 1000 granted patents have been listed in the GM, based on a review of all publications of the GM, from the first to the last. Around 23% have expired, so nowadays there are about 770 patents in force listed in the GM. Of these, around 43.5% are active principle patents, 35.6% are combinations of active principles patents, 17.3% are formulation patents and 3.6% are second use patents. Around 12% are biotechnology drug patents.
Regarding some practical effects of the linkage system, it is worth mention that the guideline issued by the IMPI for publication of patents in the GM includes a process for intergovernmental consultation upon the patents compliance declaration is received by COFEPRIS. If a relevant patent is identified by COFEPRIS, through IMPI or the GM, COFEPRIS should not grant a marketing authorization to an unauthorized third party.
The implementation of the Linkage System has changed the practices of the regulatory groups of all pharmaceutical companies, including patent holders. This is because a relevant patent must be licensed or assigned to the actual holder of the marketing authorization in order to be able to file the patents compliance declaration before COFEPRIS. Furthermore, under the patent law (IPL), in order to have effects before third parties, such as COFEPRIS or the general public, any license or assignment must be registered before IMPI. At the beginning, COFEPRIS accepted copies of the license agreements along with the patents compliance declaration but then upon consultation with IMPI, COFEPRIS started to require the register of the agreement at the IMPI. This practice has complicated the launch of products in Mexico, because generally this requirement is not part of the register process of a drug from the regulatory perspective in other countries and these documents do not exist very often, particularly when the commercialization of the product in Mexico will be made through a subsidiary or a local distributor.
It is important to mention that a patent that it is not listed is equally enforceable through a normal infringement procedure, but it will not be considered in the consultations of COFEPRIS with IMPI and a sanitary register of an infringing product could be granted.
Regrettably, despite the fact that the Mexican linkage system has indeed given some degree of legal certainty for both generic drugs manufacturers and drug patent holders, there is still significant uncertainty. For example, the linkage system is only applicable to allopathic drugs, but it is not available for medical devices or veterinary medicines, despite of the fact that the rationale behind patent enforcement during registration of a product before is equally applicable to these products.
Also, the publication of the scope of patents listed in the GM needs improvement as currently there are some patents listed that cover multiple compounds due to judicial decisions issued at the beginning of the system, but are published just once as “several active principles”, without expressly identifying the INN of the active principles. With regard to biotechnology drugs, the role of process patents will increasingly have to be discussed given the stringent regulatory requirements for approval of this kind of drug, and the high impact of processes in the quality of the end product.
Likewise, there is no obligation for patent holders to list in the GM all relevant patents related to a pharmaceutical product. Therefore, generic drug manufacturers face great uncertainty when assessing patent coverage around a pharmaceutical product. This situation gets worst because second use patents are not clearly eligible for publication under the current interpretation of the statutory provisions, which in turn was caused paradoxically by the pressure of the same generic companies to exclude them when the system was enacted.
In this sense, policy makers qualifying linkage systems as undesirable in view of the promotion of public health do not understand that the role of linkage systems is not enforcing patents per se or making harder the availability of generic drugs, since the enforceability of a patent does not depend on such patent being listed or not. Linkage systems simply provide information to all stakeholders of the pharmaceutical industry.
The Mexican linkage system is now more than 10 years old and it must evolve towards a scheme providing higher legal certainty to all interested parties, promoting fair market competition and allowing the government to take measures for maximizing the positive impact of health care innovation in the benefit of society at large.