Truvada Case Shows Civil Society’s Success With Pre-Grant Opposition

[Note: This story is part of the Supported Series on The Role of Civil Society In TRIPS Flexibilities Implementation, made possible by the Make Medicines Affordable organisation. IP-Watch retains editorial independence over the articles in this series.] 

[This article has been translated into French, Spanish, Portuguese, Russian and Thai, available here.]

The example of Gilead antiretroviral Truvada in Argentina and Brazil shows how civil society efforts to use patent opposition to patents it felt were unjustified were rewarded by patent withdrawal and rejection, even if the situation in Brazil might not be entirely settled.

Patent opposition is one of the flexibilities available under the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). It is also a tool widely used by civil society to challenge patents which they consider unjustified and unlawful. Their analysis of patent applications is recognised as very useful by patent offices, according to several sources.

Truvada is an antiretroviral product from Gilead composed of a combination of emtricitabine and tenofovir disoproxil fumarate (TDF). Gilead has met resistance from civil society groups in some countries when trying to patent the combination drug, and in particular in Argentina and Brazil, where civil society has filed patent oppositions. In Argentina, Gilead withdrew its patent application, while in Brazil, according to sources, the global pharmaceutical company might push its case to courts.

Gilead was asked for comment for this story, but a spokesperson said the company does not comment on the status of its patents and patent applications.

Truvada was also found to be an efficient preventive medicine for people who do not have HIV but are at risk of getting infected. This preventive use of the combination medicine, although recommended by the World Health Organization and UNICEF, beyond IP issues has met resistance in Argentina and Brazil on the account that it might encourage unprotected sex.

Argentina: Civil Society Hails Victory

In November 2016, the Argentina National Institute of Industrial Property requested that Gilead withdraw its patent application for Truvada, according the Fundación Grupo Efecto Positivo (FGEP).

FGEP participated in the case by filing an opposition to the patent application in April 2015, according to the foundation.

Lorena Di Giano, executive director of FGEP, highlighted the important role of civil society in examination of patents. FGEP gets a copy of patent applications that the organisation deems important for health, she told Intellectual Property Watch, and analyses those patent applications against Argentina patentability requirements.

When they find that an application does not meet patentability criteria, in particular novelty, inventive step and industrial application, they submit evidence of those shortcomings to the Argentinean patent office, she said.

In the case of Truvada, by the time FGEP filed a pre-grant patent opposition, a large number of people were receiving Truvada as part of their HIV treatment in Argentina, and the cost of the medicines was representing a substantial burden for the ministry of health. At that time, the cost of the Truvada treatment for the ministry of health was US$2700 per person, per year, which represented US$12million/year in 2015, she explained.

FGEP found that Truvada did not meet the novelty criteria because it is a combination of drugs which had already been patented by Gilead, and in that case is not patentable under the Argentinean legislation, she said.

The work of FGEP contributes to the patent office examination work, according to Di Giano. As explained in a FGEP post [pdf] (in Spanish), the evidence submitted by FGEP were used by the patent office, which included it in its justification for the rejection of Gilead’s patent on Truvada. The office also argued that treatment methods are not considered as an invention in Argentina, the post said.

The patent office asked Gilead to defend its position against the rejection, but Gilead subsequently withdrew its patent application, she said.

The other important aspect of the Truvada case, she said, is that local generics had also filed a patent opposition and were ready to enter the market. As soon as the patent application was withdrawn, they sought to register their products. Local producers entered the market and the price of Truvada dropped significantly, she said. That gave the Argentinean government a cheaper alternative for the medicine, she added.

Argentinean generic producers cannot match the Indian generic prices, she said, but the withdrawal of the patent on Truvada in Argentina allowed generics to enter the market and price competition, reducing prices in a sustainable way. It not only reduced the price for the ministry of health, but also for other procurement agencies in Argentina, she added.

Brazil: Truvada Also Meets Trouble

According to a Make Medicines Affordable (MMA) post, in January 2017, Brazil’s National Institute of Industrial Property (INPI) announced that it had rejected the patent application filed by Gilead Sciences back in January 2004, covering the combination of TDF and emtricitabine.

Sources close to INPI confirmed that the INPI denied the patent request and Gilead appealed. In its first analysis, the appellate commission found no grounds for the appeal, sources said. Gilead then sent a submission which is still under examination, they said. The administrative procedures have not been concluded yet but it is expected that, if INPI confirms the denial, Gilead will go to the courts, sources said.

The rejection of Gilead’s patent application meant that Truvada can be marketed in Brazil at low prices, the MMA said. The Working Group on Intellectual Property (GTPI) coordinated by the Brazilian Interdisciplinary AIDS Association (ABIA) had filed an opposition to the patent application, providing technical, legal and public health arguments.

In particular, the opposition said the patent did not meet the patentability requirements of novelty, inventive activity, and lacked sufficient descriptive clarity and precision. Patents relating to emtricitabine were not filed in Brazil, so emtricitabine was in the Brazilian public domain, the opposition said.

The other drug, TDF, had been previously rejected by the INPI for failing to meet the requirements of patentability, notably, in inventive step.

In August 2016, “Gilead’s patent request was rejected by the National Sanitary Surveillance Agency (Anvisa) that conducts the prior examination of pharmaceutical patents jointly with the patent office, based on arguments presented by GTPI in 2010. However, Gilead went to the courts and successfully reversed the decision, and the application examination went forward,” the MMA post explains.

ABIA/GTPI with the support of MMA sent new technical arguments to the patent office to highlight the lack of an inventive step in the patent application, which served as the basis for the rejection of Gilead’s application, according to the MMA.

ABIA has been struggling with Gilead over patents since 2008, said Pedro Villardi of ABIA. In the case of Truvada, tenofovir was a very old drug and emtricitabine was never patented in Brazil. Putting Truvada in the public domain provides the Brazilian government purchase options, he told Intellectual Property Watch.

Patent Opposition Key, Short Term Issue

According to Prof. Frederick Abbott, Edward Ball Eminent Scholar Professor of International Law at the Florida State University College of Law, patent opposition is very important everywhere, and is an integral part of the patent system.

The difficulty with patent opposition in the short term is that companies may not want to invest in production and distribution until the patent opposition is resolved. So, depending on the complexity of the patent opposition and the time frame, there might not be a near term resolution allowing generic supply to move forward.

Where there is supply capacity, generic entry can promptly follow successful opposition. For something like Hep C treatment, where a successful patent opposition may spill across markets and address a long-term global supply issue, challenging fundamental patents can have substantial long-run benefits.

PrEP Beyond IP Issue, Polemic on Use

Beyond its use to treat HIV patients, Truvada can also be used as a preventive medication. According to Gilead, Truvada became the first antiretroviral product to be approved in the United States for use in combination with safer sex practices to reduce the risk of sexually acquired HIV-1, a strategy called pre-exposure prophylaxis (PrEP).

However, this secondary use of Truvada has received mixed reactions in Brazil and Argentina.

The use of Truvada for PrEP raises questions beyond the IP field, according to Villardi, as the preventive use of the medicine has been seen by some as encouraging unprotected sex. ABIA has started since 2017 a public campaign to raise awareness against high prices, but also against constraints or moral objections to the use of Truvada, and the right to access new prevention tools, he said.

In Argentina, the use of Truvada as PrEP is still under discussion, Di Giano said, and has provoked a lot of debate in the country. The promoters of PrEP are presenting it as a combination prevention measure, but in reality people who use PrEP have a tendency to not use condoms, she said.

The Argentinean Ministry of Health is still analysing the possibility of including Truvada in a public policy, she said. For the moment, FGEP’s position is to promote the use of condoms rather than promoting Truvada as PrEP, she said, adding that the inclusion of Truvada as PrEP would also bring some budget implications if it was included in the Argentinean public health policy.

Being able to acquire or manufacture generic versions of Truvada would help preventive policies such as PrEP recommended by the World Health Organization and UNICEF in their HIV/AIDS treatment guidelines, the MMA post said.

According to the United States Centers for Disease Control and Prevention, “When someone is exposed to HIV through sex or injection drug use, these medicines [PrEP] can work to keep the virus from establishing a permanent infection.”

“When taken consistently, PrEP has been shown to reduce the risk of HIV infection in people who are at high risk by up to 92%. PrEP is much less effective if it is not taken consistently,” it says, adding that “people who use PrEP must commit to taking the drug every day and seeing their health care provider for follow-up every 3 months.”

 

Image Credits: José Luis Schanzenbach