Many hold the view that Gilead’s revolutionary treatment against hepatitis C (sofosbuvir) marked the beginning of a shift in position toward the high prices of medicines, as high-income countries were also faced with an untenable burden to their health systems. In a number of lower and middle-income countries civil society organised itself to increase access to sofosbuvir for millions in need.
According to a post by the International Treatment Preparedness Coalition (ITPC), in 2015 in Morocco, some 625,000 people were infected with chronic hepatitis C virus, provoking a liver condition leading in a significant number of cases to cirrhosis or liver cancer.
Gilead’s new treatment, commercialised under the name of Sovaldi, was first approved in the United States in December 2013, at a cost of US$84,000 for a 12-week treatment.
In 2014, Gilead announced generic licensing agreements to increase access to hepatitis C treatments in 91 developing countries. The agreement was with seven India-based generic pharmaceutical manufacturers. The deal, however, excluded some middle-income countries, with high prevalence of chronic hepatitis C, such as Egypt and Morocco.
Morocco started local production of sofosbuvir without the consent of Gilead, since, as underlined in the ITPC post, the multinational pharmaceutical company did not have any “blocking” patent in Morocco on the molecule.
According to Othoman Mellouk of ITPC, the Indian generic pharmaceutical industry has shifted interest in recent years, gotten too large, started playing the game of the pharmaceutical industry, and started taking voluntary licences. Interestingly, he said, there is an emergence of new generic producers in Iran, Morocco, and Egypt. He voiced concerns over alleged efforts by Gilead to call into question the quality of these new generics.
A push by civil society led Gilead in 2017 to extend its sofosbuvir voluntary licence agreement to Ukraine, Malaysia, Thailand, and Belarus, according to civil society sources.
However, in September 2017, Malaysia announced the approval of a government use licence, also known as a compulsory licence, for sofosbuvir. According to a post by hep Coalition, some 500,000 people are infected with hepatitis C in Malaysia. Malaysia is the first country in the world to have taken such a step for sofosbuvir (IPW, Health & IP, 15 September 2017).
According to an article posted to Intellectual Property Watch (IPW, Inside Views, 24 August 2017) by Fifa Rahman, postgraduate researcher in Intellectual Property Law, International Trade, and Access to Medicines at the University of Leeds, the Malaysia Ministry of Health started price negotiations with Gilead in 2016, but “the news emerged around this time that Gilead was unwilling to go below [US]$12,000 for a complete course of 12-week treatment,” she said, a price unaffordable for most Malaysian household.
A post by Make Medicines Affordable (MMA) underlined the advocacy efforts of the Positive Malaysian Treatment Access & Advocacy Group to push for the compulsory licence. In 2003, Malaysia was the first country to issue a compulsory licence on an HIV drug, it said.
Global Civil Society Effort Yields Results in Access
Priti Krishtel, co-founder and co-executive director of the Initiative for Medicines, Access & Knowledge (I-MAK), told Intellectual Property Watch that even back in 2011, before new direct-acting antivirals (such as sofosbuvir) came to market, many civil society organisations were talking about how to make sure that when those new drugs were finally approved by drug regulatory authorities, they reach people needing them.
I-MAK really stepped in to work on a global patent strategy to make sure that the drugs would reach patients, she said. At that time there was no global coordinated patent strategy. Some countries had taken on patent cases by civil society, such as in Thailand and India, “so we knew it was possible,” she explained.
“But we did not do anything of this scale before as a movement,” Krishtel said. Between 2011 and 2014, in countries such as Malaysia, Ukraine, Brazil, Argentina, India, Thailand, Vietnam, China, Russia, Morocco, and Egypt, civil society got together and started to wonder about “what if we started to target unmerited patents in these countries and if we also joined forces so it is a coordinated effort.”
The Open Society Foundation supported many of these groups at the time, and Médecins Sans Frontières (MSF, Doctors Without Borders) was a very supportive partner, as well as the Treatment Action Group, she said. I-MAK was coordinating this hepatitis C effort, and in each country groups were carrying forward the advocacy strategy, she said.
“What we have seen over the last five years has really been amazing,” Krishtel said, as I-MAK filed the first patent opposition on sofosbuvir in 2013, and then proceeded to file more cases, not only on sofosbuvir but also on other direct acting antivirals (sofosbuvir drug category).
Over the last five years there has been an unprecedented number of patent challenges across the global South, and “it has been really exciting to see the results, although we are not done as we need a few more years to understand the full impact of the action we are taking,” she said.
Countries are rejecting sofosbuvir patents, such as China, Argentina, and Ukraine, so “we are in a really good position,” she said, adding that an important point is that companies are coming to the negotiating table in some countries, like in China and Brazil, and prices have come down.
Sergey Kondratyuk of the All-Ukrainian Network of People Living with HIV/AIDS mentioned to Intellectual Property Watch that despite the rejection of its patent on sofosbuvir, and a voluntary licence agreement, Gilead continues to file patent applications related to sofosbuvir in Ukraine.
According to Krishtel, this patenting strategy is happening in every country. Companies use different types of patenting strategies, and one of the main battles I-MAK is fighting is against follow-on patenting, or secondary patenting, also known as evergreening, she said. Even if one patent is rejected on a product, there are other patents that need to be challenged on the same product. The civil society movement is not going after one patent, but after multiple patents in each country, she detailed.
Other patenting strategy includes divisional patenting and continuation patenting, she said.
Divisional, Continuation Patenting, Keeps Application Alive
Tahir Amin, co-executive director of I-MAK, explained that continuation patent applications in the United States refer to practice whereby if a patent application is rejected by the patent office, the applicant can file it again. The applicant keeps the same initial filing priority date, but he/she can reapply so as to have different types of protection from that first application, he told Intellectual Property Watch. Companies use this to keep pending applications in the system in order to adjust the invention according to how the field is developing, so they can tweak the claim, he said.
The availability of this strategy in the United States opens the door to any patent eventually getting granted, he said, adding that to his knowledge, only the US allows continuation applications.
Most countries allow divisional applications, according to Amin, which usually comes about when an application is filed which does not concern one invention only. The IP office will then ask that the application be divided according to the number of inventions the applicant is applying for.
Companies might then try to file a divisional application from the parent application, while the parent application is still pending, which allows them to “have another go” with the new patent application. This happens a lot in Europe and in India, he said. Since it keeps the patent application “alive,” it creates legal uncertainty, in particular for generic competitors, he said.
Continuation and divisional applications give “applicants more than one bite of the cherry,” said Amin. Both continuation and divisional applications need to be filed before the parent application is granted.
Beyond Patent Opposition, Monitoring IP Offices, Next Steps
Over the last five years, “we have been using a number of strategies and tactics” for sofosbuvir, Krishtel said. Beyond patent opposition, the civil society coalition has also engaged in IP offices’ monitoring, transparency, and accountability work, and has been deeply engaged with them, through meetings and strategic dialogues, for example.
They are also engaging with health ministries.
“We are in close dialogue with ministries of health to ensure that they are aware of those patenting tactics, and they are watching out for the rising costs of medicines,” she said.
Sofosbuvir legal and advocacy strategies are happening in over 50 countries, she added.
Talking about the next steps for the advocacy movement, Krishtel said, “What we don’t want is complacency,” which would lead to a situation where every time there is a problem for treatment access, there is reliance on the civil society for solutions.
“We would really like to see is some of these solutions embedded within governments and government offices,” she said. “For example, we have to act collectively on patents that we see are not good and are not in compliance with the law.”
“It is a big fight for us, and one that we think is worth it…. [B]ut the world we want to see is one where these patents are not granted to begin with,” she said, calling for stronger standards for patents, and better quality of patents.
US Trial and Appeal Board Decline Review Gilead Patent
In November, I-MAK filed the first-ever set of US patent challenges against sofosbuvir with the US Patent Trial and Appeal Board. I-MAK challenged six patents, arguing that the sofosbuvir’s patents do not meet patentability criteria such as novelty and non-obviousness (IPW, IP & Health, 25 October 2017).
According to a 4 May I-MAK press release, the US Patent and Trademark office (USPTO) Patent Trial and Appeal Board (PTAB) declined to institute a review on one of Gilead’s [sofosbuvir] “prodrug” patents. The PTAB cited “the timing of Gilead’s initial applications was before certain evidence that had been submitted by I-MAK,” the release said.
Sofosbuvir’s prodrug is “a compound which helps humans metabolize an inactive drug base compound once it enters the body,” according to the release. “Because sofosbuvir is a nucleoside, and the prodrug in sofosbuvir has accompanied nucleoside treatments for decades, I-MAK argued that the use of the prodrug was an obvious choice, rather than a ‘novel and non-obvious’ one.”
“Gilead’s three main prodrug patents on Sovaldi extend its monopoly on the drug by four years, to 2029,” according to the release. “Eight additional patent challenges to other Gilead patents, including on the Sovaldi base compound and crystalline structures, remain before the PTAB with decisions expected in the coming weeks.”