1. BIOLOGICAL AND PHARMACEUTICAL PATENTS IN MEXICO Ing. Eugenio Pérez

2. INDEX Key facts Patent division at IMPI Flow chart of Patent Prosecution Requirements for Patent Protection Plant Varieties Protection and Transgenic Plants Biological and Genetic Material Patenting Patent Protection for Diagnostics Patent Protection for Biological Pharmaceuticals and Pharmaceuticals. Medical use-claims in Mexican Patent Practice. Patent Linkage Biological Pharmaceuticals: Innovators vs Biosimilars

3. KEY FACTS Total population in Mexico is of approximately 113 million people. Mexico is the second largest market of pharmaceuticals in Latin America and the eleventh in the world. Also, it is one of the ten largest drug producers worldwide. This position in the global scenario puts Mexico in a strategic position for the biotech and pharmaceutical industry. The total number of applications filed per year in our country, including all existent patent figures (patents, utility models and industrial designs) is of around 20,000.

4. PATENT APPLICATIONS FILED BEFORE IMPI DURING THE LAST 20 YEARS. http://www.impi.gob.mx/wb/IMPI/impi_en_cifras2

6. PATENT DIVISION AT IMPI IMPI is the Mexican Institute of Industrial Property, which is the official authority in Mexico for the protection of Industrial Property rights. PATENT DIVISION OF IMPI Formal Examination Department Substantive Examination Department Mechanical, Electrical, Utility Models and Industrial Designs Biotechnology, Pharmaceuticals and Chemistry * The approximate number of Patent Examiners at IMPI is of 140.

7. FLOW-CHART OF THE PATENT PROSECUTION 18 months from the Mexican filing date or its recognized priority 1-3 months Filing and Legal date Formal Examination (2 Official Actions maximum) Publication of the patent application Submittance of observations by a third party, if any Substantial Examination (4 Official Actions maximun) Granting of the patent application Patent’s Maintenance (Payment of the Annuities every 5 year, i.e. Quinquenniums) End of the Patent´s life (20 years after the legal date) 6 months

8. REQUIREMENTS FOR PATENT PROTECTION Article 16 of the MIPL- Inventions that are new, the result of an inventive step and susceptible of industrial application within the meaning of this Law shall be patentable, with the exception of: Essentially biological processes for obtaining, reproducing and propagating plants and animals; Biological and genetic material as found in nature; Animal breeds; The human body and the living matter constituting it; Plant varieties.

9. Mexican legislation also contemplates what is not considered an invention: Article 19 of the MIPL: Theoretical or scientific principles; Discoveries of something that already exist in nature, even though it was previously unknown; Schemes, plans, rules and methods for carrying out mental processes, playing games and doing business, and mathematical methods; Computer Programs; Methods of presenting information; Esthetic creations and artistic or literary works; Methods of surgical, therapeutic or diagnostic treatment applicable to the human body and to animals; Juxtaposition of known inventions except where in reality they are so combined or merged that they cannot function separately, or where their characteristic qualities or functions have been so modified as to produce an industrial result or use not obvious to a person skilled in the art.

10. PLANT VARIETIES PROTECTION AND TRANSGENIC PLANTS Patent protection for biological and chemical drugs is permissible in Mexico if and when, the requirements established in Article 16 of our legislation are duly complied. Biological process are not patentable per se, while transgenic plants are patentable if a targeted genetic modification is present. Plant varieties are not protectable as patents but are permissible under the figure Plant Breeders Rights ruled by the Federal Law of Breeder Rights (not administered by IMPI).

11. The process for granting a Plant variety takes about two years.. PROSECUTION FOR OBTAINING A “PLANT BREEDER REGISTRATION ” Filing of a Plant Breeder registration (PBR) application. Formal Examination process: Formal Requirements. The expedition of a filing Certificate is issued by the SNICS. Distinction, Uniformity and Stability Examination (DUS) process takes place when the expedition of the abovementioned certificate takes place. When the DUS examination successfully concludes, then the SNICS grants the Plant Breeder Rights Title.

12. BIOLOGICAL AND GENETIC MATERIAL PATENTING Notwithstanding the patentability exceptions set out in article 16 of MIPL the Biological and Genetic material are considered candidates for patent protection under the following conditions:  They should have been isolated, showing the human intervention for carrying out the invention, i.e. genes may be patented as long as they are not in the human or animal body or as found in nature but rather have been subject to lab work such as, at least, isolation and sequencing and;  Their biological activity, specific and industrial applicability have to be evident. Examples: Isolated cells, microorganisms and molecules such as proteins, antibodies, etc. are considered biological material.

13. PATENT PROTECTION FOR DIAGNOSTICS Products directed to diagnostic applicability and processes for making said products are indeed subject matter susceptible for patent protection. However, it is to note that, as established in Article 19 of the MIPL, subsection VII, methods of diagnosis that are applicable to humans or animals are not considered as inventions therefore, not patentable. Diagnostic methods are patentable as long as they are in vitro. i.e. contacting a compound with a sample from the patient.

14. PATENT PROTECTION FOR BIOLOGICAL PHARMACEUTICALS AND PHARMACEUTICALS Biological Pharmaceuticals are candidates for patent protection, their active substances include biological and/or genetic material patentable under the conditions previously mentioned. The pharmaceuticals and biological pharmaceuticals may have a full coverage protection for product claims drawn to the active substances, pharmaceutical compositions, medicaments and for claims directed to process for making the same. With regard to the medical and therapeutic indication of these types of inventions, article 19 of the MIPL, subsection VII forbids the patenting of methods of surgical, therapeutic or diagnostic treatment applicable to the human body and to animals.

15. In order to provide a wide patent protection for the pharmaceutical and Biological pharmaceutical products in Mexico, the Mexican Institute of Industrial Property (MIIP) allows the medical use claims as follows:  A first medical use claim is permitted as long as the active substance is also claimed in the same patent application. Product “X” for use as medicament. Product “X” for use in the treatment of “Y.” The second medical use drafting under the Mexican practice is the “Swiss- type” format. Use of product “X” for the manufacture of a medicament for the prophylaxis/ treatment of the disease/condition “Y”. MEDICAL USE CLAIMS IN MEXICAN PATENT PRACTICE

16. SECOND MEDICAL USE CLAIMS The second medical “use” claims, adopted in the Mexican practice, avoid statutory rejections under article 19 MIPL subsection VII with regard to methods of treatment applicable to humans or animals during the substantive examination. However, the “use” is not considered as category of invention under article 45 of the MIPL and, the Mexican Institute of Industrial Property (MIIP) still has not set a position about the subject matter that said claims cover for infringement purposes: Are they Products? Are they solely Processes?

17. ARE SECOND MEDICAL USE CLAIMS MOVING FORWARD? The “Swiss-type” format for second medical use claims in Mexico was adopted from the European Patent Office practice. Nowadays said type of claims fell into disuse in the EPO due to modifications in the European Patent Convention where the intended medical and therapeutic use is considered as a technical feature exclusively for pharmaceutical products. This changes in the EPO practice may be mirrored by IMPI in a near future, as recently stated by IMPI´s Patent Director.

18. PATENT LINKAGE The patent – marketing authorization linkage system for pharmaceutical products involves interparty collaboration of IMPI and the Commission for the Protection against Sanitary Risks (COFEPRIS). The linkage system provides that for one side IMPI is required to publish a linkage-gazette listing all valid patents covering allopathic drugs and, on the other side, the COFEPRIS is obliged to observe said gazette to deny marketing authorization for a drug that infringes any of the listed patents. The linkage gazette mainly includes all valid and enforceable patents that claim:  Compounds (active substances) The linkage system in the Article 47 bis of the Rules of MIPL expressly discards from the patent list of the linkage gazette the patents that are directed to production or formulation processes.

19. At the beginning, the linkage gazette only listed those patents comprising a new active substance. On January 13, 2010, the Supreme’s Court decision (circumscribed to judicial and not to administrative authorities), interpreted that pharmaceutical products are not composed solely by their active substance and that ingredients of the composition may provide a therapeutic effect. Notwithstanding the Supreme’s Court decision does not have a direct effect on the administrative authorities practices, the MIIP decided to include in the linkage gazette those patents that claim pharmaceutical formulations (that may involve known active substances). PATENT LINKAGE AND PHARMACEUTICAL FORMULATIONS

20. For the publication of a patent in the linkage gazette, the patentee has to file a request before IMPI mentioning the patent number, the generic name of the active substance, the chemical name of the active substance, the medicament involved and the claims directed to the active substance or pharmaceutical compositions. Recently, and following IMPI´s practice, the interparty enquiry format that COFEPRIS submits before IMPI, with regard to specific patented medicaments has changed, now considering not only the generic, chemical name and chemical formula of the active substance but: Salts. Formulations. Therapeutic indications. Doses. Types of administration. Solvents. Specific characteristics like isomers, polymorphisms. PATENT LINKAGE: IMPI-COFEPRIS INTERPARTY COLLABORATION

21. Even though the Patent-Marketing authorization system has moved forward in favor of patent holders rights, at this point there still exists a gap between Patent protection and the Patent – Marketing authorization linkage system because the linkage system only considers patents involving new compounds and new pharmaceutical compositions. The patents directed to medicaments protected only by second medical use claims are not included in this system as they are interpreted as drawn to known compounds with a different therapeutic indication and do not claim per se a new product. PATENT LINKAGE AND SECOND MEDICAL USES

22. BIOLOGICAL PHARMACEUTICALS: INNOVATORS VS BIOSIMILARS FROM PATENT PROTECTION POINT OF VIEW In regard to Biosimilars (named Biocomparables in Mexico), recently Mexican health law was amended to include them and to differentiate them from generics of small molecules, therefore, the process to obtain an authorization in our country for biosimilars is different from that of chemical synthesis generics, marketing authorization before the Sanitary Registry for biosimilars requires submission of specific clinical trials and if applicable, in-vitro trials to demonstrate the safety, efficacy and quality of the product. The quantity and quality of required trials is determined on case by case basis by the Sanitary Authority.

23. The main distinctions between the biosimilars and generics of small molecules are that the biosimilar and the innovator molecules are not identical mainly due to the production processes (i.e. bacterial vs animal cell systems). Biosimilar applicants have to provide their own data with regard to the integrity of the active substance molecule, the biological activity of the medicament, the safety and eficacy clinical data in patients with the same disease or condition as the innovator. Despite all those conditions, not all the biosimilar medicaments are interchangeable. When a biosimilar medicament shows different and improved activities due to its differences against the innovator, it may be patentable as selection invention. BIOLOGICAL PHARMACEUTICALS: INNOVATORS VS BIOSIMILARS FROM PATENT PROTECTION POINT OF VIEW

24. As a member state of International Treaties such as NAFTA and TRIPS, Mexico is obliged to provide a 5-year exclusivity period for the clinical data package submitted for innovative drugs that obtain a marketing authorization, this exclusivity is independent and unrelated to any patent- derived exclusivity. However, currently Mexican Health law does not contain any provisions in this regard. In spite of the above, in 2012, the Mexican regulatory agency COFEPRIS, issued an internal communication stating that a 5-year exlcusivity period shall be awarded to the data package submitted for any marketing authorization issued on a new molecule and therefore, a third party will not be able to obtain a marketing authorization for the same molecule based on the data provided by the innovator within said period. The circular is limited solely to new molecules and not to new formulations or indications. A further uncertainty exists on whether this practice will be applicable to biologicals or only to chemical synthesis products. PHARMACEUTICAL DATA PACKAGE EXCLUSIVITY (DPE)

25. Thank you ! EUGENIO PEREZ hamburgo 260, col. juárez cp 06600, d.f. méxico phone: 52 (55) 55 33 50 60 ext. 150 fax: 52 (55) 52 08 83 87 52 (55) 52 08 85 07 email: eugenioperez@uhthoff.com.mx