Understanding Brazil’s Service Guideline #37 for the Examination of Patent Applications Claiming Pharmaceutical Products and Processes

On September 25, 2017, the Director of the National Sanitary Surveillance Agency (ANVISA) issued internal guidelines (Orientação de Serviço #37/2017) regarding the procedures to be used by the agency when examining patent applications claiming pharmaceutical products and processes in light of public health (in accordance with Article 229-C of Patent Statute #9,279/96, Resolution RDC #168, of 2017, the Joint Ordinance ANVISA/INPI #001, of 2017, and Ordinance GM/MS #736, of 2014).  According to these guidelines, ANVISA will follow the following procedures when reviewing applications claiming pharmaceutical products and processes.

  1. Upon receipt of a patent application from the Brazilian Patent Office (Instituto National da Propriedade Industrial (INPI)), ANVISA will assess the subject matter of the application to verify compliance with the provisions of Article 229-C of IP Law #9,279/96. Article 229-C provides that pharmaceutical patent applications shall receive a prior approval by ANVISA (often referred to as “prior approval” or “prior consent”). Specifically, Article 229-C provides that: “The grant of patents for pharmaceutical products and processes shall depend upon the prior approval from the National Sanitary Vigilance Agency.” 
  1. Once it is determined that prior approval or prior consent by ANVISA is required, an application is assessed with respect to its (1) health risk; and (2) interest under the drug or pharmaceutical assistance policies within the Brazilian Unified Health System (SUS). 
  1. The health risk of the application is assessed by determining whether the pharmaceutical product or process claimed comprises or results in substances included in List E (which is a list of prohibited plants which may give rise to narcotic and/or psychotropic substances) or List F (a list of substances banned in Brazil) based on Ordinance SVS/MS #344, of 12 May 1998, which relates to plants and substances (including salts and isomers thereof) that are prohibited for use in the country. Applications which do not claim a pharmaceutical product or process that comprise or result in substances included in Lists E or F are not considered to present a health risk.  If the application is considered to present a health risk, ANVISA will deny prior consent or prior approval and return the application to INPI, which will dismiss the application. 
  1. After determination of the absence of health risk, the application is reviewed to determine whether or not the pharmaceutical product or process is of interest to the drug or pharmaceutical assistance policies under SUS. An application is determined to be of interest to the drug policy or pharmaceutical assistance policy under SUS when:
    • The subject matter is related to one of therapeutic applications defined by Ordinance MS/GM #736, of 2014 as listed in Annex I (provided below); or
    • It is related to a product incorporated into SUS (except for drugs that are part of the Basic Component of Pharmaceutical Assistance (CBAF), which is guided by the National List of Essential Medicines (RENAME) in force); or
    • It is related to a product of potential interest to the SUS according to Annex II (provided below).

If the application is of no interest to the healthcare policy, ANVISA will grant prior consent or prior approval and send the application back to INPI for further processing.  However, if an application is determined to be of interest to the drug or pharmaceutical policies under SUS, ANVISA will send the application back to INPI for further processing along with a report providing an analysis of the patentability requirements to be used by INPI during examination.

An important take away is that according to the service guidelines, ANVISA is able to provide an opinion addressing the patentability requirements of applications claiming pharmaceutical products or processes.  Regrettably, this is a continued attempt by ANVISA to try and  work around case law that has clearly established that the agency is not allowed to evaluate the patentability requirements of such applications under Article 229-C.

Annex I 

Viral Diseases (antiviral and antiretroviral diseases)

Neglected diseases:

Dengue

Chagas Disease

Schistosomiasis

Rocky Mountain spotted fever

Filariosis

Leprosy

Leishmaniasis

Malaria

Systemic mycoses

Tuberculosis

Neurodegenerative diseases

Alzheimer’s

Parkinson’s

Immunosuppressants

Rheumatoid arthritis

Transplant rejection

Mental diseases (antipsychotics/anticonvulsants)

Epilepsy

Psychosis / Schizophrenia

Neoplasias / Cancer (Oncology products)

Products obtained by biological routes

Provided that the therapeutic application is included in ordinance GM/MS 736/14

Vaccines and sera

Vaccines of the National Immunization Program

BCG vaccine

Hepatitis B vaccine

Diphtheria, tetanus, pertussis, hepatitis B and Haemophilus Influenza B vaccine

Diphtheria, tetanus and pertussis vaccine

Polio vaccine (VIP / VOP)

Pneumococcal vaccine (Pneumo 10, PN 23)

Human rotavirus vaccine

Meningococcal C vaccine

Yellow Fever vaccine

Hepatitis A vaccine

Measles, mumps and rubella vaccine

Measles, mumps, rubella, and varicella vaccine

Diphtheria and tetanus vaccine

HPV vaccine

Influenza vaccine

Rabies vaccine

Vaccines for sexually transmitted diseases

Vaccines for neglected diseases

Vaccines for cancer

Hemoderivatives

Plasma concentration of factor VIII

Von Willebrand factor

Prothrombin complex (partially activated or human)

Recombinant activated factor VII concentrate

Plasma and recombinant factor concentrate

Plasma concentration of factor IX

Factor XIII concentrate

Excluded:  Fibrinogen, Tranexamic Acid and Desmopressin Acetate

Annex II

            Roadmap to identify patent applications of potential interest for SUS

  1. The patent application, to be identified as of potential interest to SUS, in addition to complying with Article 6 herein, should also comply with at least one of the following criteria:
    • Be related to a product registered with a sanitary authority of any country or region;
    • Be related to a substance under an active phase II clinical trial or higher, in any country or region, for a therapeutic application of interest to SUS;
    • Be related to high-cost drug that is part of the Specialized Component of Pharmaceutical Assistance (CEAF);
    • Be related to the drug provided in Partnership for Productive Development (PDP) or equivalent;
    • Be related to a request for priority examination made by the Ministry to Health to the INPI;
    • Has been filed with INPI less than six years ago.
  2. The patent application included in item A above may be exempted from a patentability examination for the purposes of supportive data if the application satisfies any of the below:
    • The product has its incorporation into SUS denied by the National Commission for the Incorporation of Technologies (CONITEC); or
    • The product is excluded from SUS; or
    • The invention is unlikely to be incorporated into SUS after conducting a prospective analysis.

Please continue to watch the BRIC Wall Blog for further updates on ANVISA and prior approval or consent in Brazil.

This post was written by Lisa Mueller and Roberto Rodrigues of Licks Attorneys.

 

AstraZeneca’s Crestor® Patent is Invalidated by the Brazilian Federal Courts

On June 5, 2015, the 13th Federal District Court of Rio de Janeiro invalidated Astrazeneca’s patent BR PI0003364-2 covering Crestor® (rosuvastatin). The Judge, the Honorable Marcia Nunes Barros, agreed with the arguments submitted by the Brazilian Patent Office and National Sanitary Vigilance Agency (ANVISA) that the patent was obvious over the prior art. The Honorable Barros is the same Judge that recently issued a decision holding that ANVISA was allowed to examine patentability requirements during prior approval/consent analysis under Article 229-C of the Patent Statute.

According to the decision, the use of the tribasic calcium phosphate to stabilize statins was expressly recommended in the prior art document PT 547 000E. Even though the use of the term “potentially” in the prior art did not denote certainty regarding stabilization, according to the Court, this meant that tribasic calcium phosphate was “probably useful for stabilizing statins”.

Additionally, although the prior art document recited a pH value of at least 8, preferably 9, for the stabilization of statins, the Court held that this pH value related to the stabilization of fluvastatin and not rosuvastatin. The Court referred to the Handbook of Pharmaceutical Excipients, which stated that tribasic calcium phosphate had a pH value of 6.8 at 20% solubility.

The Court held that a person of ordinary skill in the art (POSITA) would have known from PT 547 000E that tribasic calcium phosphate could be used to stabilize statins. Therefore, because the pH of a stabilizing agent varies based on concentration, a POSITA would have been motivated to investigate using tribasic calcium phosphate to stabilize a statin (in other words, it was “obvious to try”). The Court found this to be true because the pH value of 8 recited in PT 547 000E referred to the stabilization of a different statin (fluvastatin) and not rosuvastatin. Other prior art, such as WO 97/23200, described using a pH value of between 7.0 to 8.0 to stabilize the HMG-CoA inhibitor, E)-3,5-dihydroxy-7-[4′-4″-fluorophenyl-2′-cyclopropyl-quinolin-3′-yl]-6-heptenoic acid.

Therefore, according to the Court, a PHOSITA at the time of the invention would have understood that different statins required different pH values for stabilization. Even though tribasic calcium phosphate only had a pH value of 6.8 based on its solubility data, the Court held that a PHOSITA would have been motivated to test tribasic calcium phosphate as a stabilizing agent for rosuvastatin.

Interestingly, despite the fact that the court-appointed expert issued a report concluding that the patent was valid, the Judge mentioned international standards for assessing inventive step, including the U.S. Supreme Court’s decision in KSR Int’l Co. v. Teleflex, Inc., in concluding that the technical solution presented in the patent was obvious to try and that there was a reasonable expectation of success.

This post was written by Lisa Mueller and Roberto Rodrigues and Luiza Cotia of Licks Attorneys.

13th Federal District Court of Rio de Janeiro Holds that ANVISA Can Examine Patentability Requirements of Patent Applications Claiming Pharmaceutical Inventions

One of the most contentious issues in the Brazilian pharmaceutical landscape is role of National Sanitary Vigilance Agency (ANVISA) during the prior approval/consent analysis of patent applications claiming pharmaceutical inventions. Article 229-C of Brazil’s Patent Statute (Statute) provides that ANVISA shall have the right to provide approval of patent applications claiming pharmaceutical inventions (often referred to as “prior approval” or “prior consent”). Specifically, Article 229-C provides that: “The grant of patents for pharmaceutical products and processes shall depend upon the prior approval from the National Sanitary Vigilance Agency.”

During the past few years, the courts in Brazil have issued decisions holding that Article 229-C did not grant ANVISA the power to examine patent applications for compliance with the patentability requirements under the Statute. Moreover, these cases held that ANVISA was solely limited to determining whether or not a patent application was against public health according to Article 18, I of the Statute and nothing more.

The most favorable decisions for patent owners were issued by District Courts sitting in Brasilia. Specifically, several Courts issued preliminary injunctions ordering ANVISA to grant prior approval of patent applications claiming pharmaceutical inventions holding that the examination of patentability requirements by ANVISA was illegal (for example, in May 2015, the 15th Federal District Court granted a preliminary injunction requested by Novartis on a writ of mandamus filed against ANVISA).

However, on June 11, 2015, the Honorable Marcia Nunes de Barros of the 13th Federal District Court sitting in Rio de Janeiro denied a preliminary injunction and held that ANVISA was permitted to examine a patent application claiming pharmaceutical inventions for compliance with the patentability requirements. The case was filed by Abbvie, Inc. and related to two patent applications involving Kaletra® (lopinavir/ritonavir).

In a 30-page decision, the Judge described the importance of Article 229-C and ANVISA’s ability to examination patent applications for compliance with the patentability requirements under the Statute in order to avoid the patenting of inventions to merely “incremental innovations”. Specifically, the Judge stated that: “…taking into consideration the systematic element, it seems clear, as already exposed, that the goal of the rule that included ANVISA in the proceeding of deciding about pharmaceutical patents, was clearly to include a vision over public health during examination, in a way to avoid the granting of undue patents, with highlights to the incremental ones”.

Unfortunately, but not surprisingly, this unfavorable decision will be used by ANVISA with respect to currently pending and future filed patent applications. However, it is too soon to assess how this decision will impact the current framework relating to Article 229-C and ANVISA with respect to patent prosecution. This decision should be carefully analyzed and rebutted by patent owners in order to avoid what could be a potential game changer in the pharmaceutical sector that might negatively impact innovator companies in Brazil.

Patent owners should keep in mind that the Federal Courts sitting in Brasilia have traditionally been more inclined to hold that ANVISA cannot examine patent applications for compliance with patentability requirements. Hopefully, this decision will not impact Judges sitting in Brasilia.

This post was written by Lisa Mueller and Roberto Rodrigues of Licks Attorneys.

Recent Brazilian Jurisprudence Concerning the Scope of ANVISA’s Prior Consent

Article 229 of the Brazilian Industrial Property Law #9.279/96 was amended with the publication of Brazilian Law 10.196 on February 14, 2001, to add Section 229-C which provides that “The grant of patents for pharmaceutical products and processes shall depend upon the prior consent from the National Sanitary Vigilance Agency.” Thus, as a result of the addition of this provision, any patent application related to a pharmaceutical product or process became subject to the “prior consent” of the National Sanitary Vigilance Agency (ANVISA), whose mandate is to protect the public by preventing “the production and commercialization of products and services that are potentially harmful to human health.” Therefore, in effect, Section 229-C provides for a two-tier examination process for pharmaceutical products and processes in Brazil.

In view of the inherent conflict between ANVISA and the Brazilian Patent Office {the National Institute of Industrial Property (INPI)} regarding the review of the patentability requirements (namely, novelty, inventive step, enablement of the claims, clarity, etc.) of patent applications directed to pharmaceutical products and processes, an administrative proceeding was conducted before the Attorney General’s Office (AGU) on July 22, 2008. The result of the proceeding was the issuance of Opinion No. 210/PGF/AE/2009 on October 16, 2009 (Federal Opinion), which was subsequently approved by the Attorney General. The Federal Opinion held that ANVISA’s statutory duty to review pharmaceutical patent applications for prior consent should be limited to the examination of issues closely related to its institutional purposes, namely, issues related to public health. Unhappy with the Federal Opinion, ANVISA filed a request for reconsideration with the AGU. On July 1, 2011, the AGU issued Opinion No. 337/PGF/EA/2010 (Second Opinion), which was subsequently approved by the Attorney General, reaffirming the conclusions stated in the Federal Opinion. Specifically, the Second Opinion ratified that ANVISA was required to limit its examination of patent applications only to issues of public health for purposes of granting or denying prior consent.

On August 19, 2013, a civil pro-ANVISA action was brought by a Federal Public Prosecutor in Brazil seeking to:

(1) declare null and void the Federal Opinion;

(2) declare and recognize the legal authority of ANVISA to analyze the patentability requirements for pharmaceutical product and process patent applications; and

(3) declare the full applicability of the provisions of Article 229-C concerning ANVISA’s granting of prior consent.

A preliminary injunction request was also sought to immediately declare null and void the Federal Opinion until a decision on the merits was issued. The trial judge denied this request and an appeal was made to the Federal Circuit. The Circuit court decided not to rule on this appeal until a final decision on the merits was issued by the lower court.

A decision by the trial judge was issued on September 12, 2013, summarily dismissing the claims of the Federal Public Prosecutor. Essentially, the judge held that it did not make sense to assign to ANVISA, the institutional purpose of which is to protect the health of the population, the additional role of reviewing the patentability requirements of pharmaceutical product and process applications for which INPI was charged with the same responsibility. The judge concluded that a fair interpretation of the law was to avoid this sort of “double” patentability analysis.

It is expected that ANVISA will appeal the trial judge’s decision to the Federal Court of Appeals. Please watch the BRIC Wall for future updates on any such appeal.

This post was written by Lisa Mueller and Gustavo de Freitas Morais of Danneman Siemsen.