Special Report: A Look Behind Hepatitis C Patent Challenges Worldwide

A case at the High Court in India set for 15 December could decide whether a patent on some of the most important drugs to fight hepatitis C should be removed. It is one of many attempts to challenge patents on hepatitis C drugs in various countries around the world and serves as an opportunity to learn more about the group leading the legal case.

The organisation responsible for bringing the dispute is Initiative for Medicines, Access & Knowledge (I-MAK), a US non-profit organisation with a history of fighting HIV patents. It has asserted that the patent does not meet the legal standards for novelty, obviousness, inventiveness, among other grounds in India. The case focuses on sofosbuvir, made by US company Gilead. Sofosbuvir is included in several drugs made by Gilead, including Sovaldi, Harvoni and Epclusa.

The most widely used, Sovaldi, received marketing approval from the US Food and Drug Administration (FDA) in 2013 and the European Commission in 2014. It also has been approved for use in around 79 countries including Australia, India, Indonesia, the Philippines, New Zealand, Canada and Switzerland.

These drugs are important because they have revolutionised hepatitis C treatment by providing a rapid cure with few or no side effects. Previous drugs did not cure but managed the condition, sometimes with horrible side effects. Gilead has said they are an extraordinary innovation.

Even before they were formally launched, Tahir Amin, co-founder and co-executive director at I-MAK, said he and others realised the environment for hepatitis C treatment was about to change, and expected high prices.

“We had a big discussion about what should be our strategy, realising that a significant number of people have hepatitis C. And as organisations who work on access to medicines realised we were facing another problem like we did with HIV,” he said. “When these new drugs came to the market they were going to be priced really high. It turns out they were.”

Organisations who work on access to medicines realised we were facing another problem like we did with HIV. When these new drugs came to the market they were going to be priced really high. It turns out they were. – I-MAK’s Tahir Amin

When Sovaldi was launched, for example, it cost around $84,000 for a three-month course according to Médecins Sans Frontières (MSF). I-MAK met MSF and Treatment Action Group, and put together a strategy. As result, I-MAK became the first organisation to file an opposition to the patent in India, as far back as 2013.

Of course, many things have changed since then. Prices have dropped in many countries, for example. MSF said Gilead and Bristol-Myers Squibb (BMS) charged – through their access programs – a price of $1,400 to $1,800 per 12-week treatment in 2015. Gilead has offered voluntary licences to Indian manufacturers, who can now produce the drugs for as little as $74. It has stated that high-quality, low-cost generic versions of its chronic hepatitis C medicines can reach 101 developing countries via such licenses. Last week, MSF said it had secured deals to get sofosbuvir and daclatasvir at $120.

The problem is, say the organisations, is that the prices are not this low everywhere. In countries where a common combination is used – of sofosbuvir and daclatasvir, made by Bristol-Myers Squibb, can be as much as $77,000 in the UK and $96,404 the US, according to Andrew Hill, a pharmacologist at the University of Liverpool. In contrast, lower prices are most often available from generic companies.

Curiously, despite the low prices in India, I-MAK says it is still pursuing patent actions here.

The focus of the High Court hearing, for example, is a patent on the base compound, or active ingredient within sofosbuvir, that was originally granted by the Indian patent office in 2016.

The application for a patent on this compound was first rejected by the Indian patent office in January 2015, following a pre-grant opposition filed by I-MAK and other organisations, including the Delhi Network of Positive People (DNP+) shortly after the drug was introduced. Gilead sought recourse in the High Court, on the basis that the patent office had not followed correct procedure and won, said Amin. The case was subsequently sent back to the patent office and in May 2016, it reheard the case and subsequently granted a patent.

I-MAK says it reacted immediately to this loss. It filed a writ at the Delhi High Court to get the decision reversed on the basis that procedure had not been followed either. The arguments were accepted as grounds for a new hearing, and that was due last week. The hearing has now been postponed until December, however.

The organisation is trying to argue that the patent should never have been awarded in the first place on the basis of literature it has collected.

“As lawyers we have to do look at it from what patent law does. On those legal principles – the law of obviousness or the inventive step, or novelty – we think these patents don’t pass muster,” he said. “Patent offices around the world have limited capacity to make these examinations. They have so many applications to deal with and go into details.”

So, for example, I-MAK will argue that years before Gilead filed its patents on the base compound, nucleosides like sofosbuvir already existed within other antiviral treatments. Sofosbuvir is only slightly different from these other nucleosides. “We have literature on these nucleosides whether they were for cancer or HCV,” he said.

The lawyers and their partners are targeting other kinds of patents too. Take the prodrug, a compound that helps humans metabolize the inactive base compound once it enters the body. They argue that the prodrug has accompanied nucleoside treatments for decades. And, since sofosbuvir is a nucleoside, using this type of prodrug was an obvious choice to activate the basic molecule. That’s why I-MAK and others have launched a pre-grant opposition to the granting of a patent on that prodrug at the Indian patent office. A decision is yet to be made. Patents on the crystalline forms of compound are also under fire.

Gilead said it had no comment to make on these arguments.

As a result, it has launched patent oppositions to base compounds, the prodrug and crystalline forms throughout the world. China rejected a patent application on the prodrug in 2015 – although that is now under appeal by Gilead. The application on the base compound has also been opposed too. Late last month, it challenged six different patents on the base compound in the US (IPW, IP and Health, 25 October 2017).

Other organisations have filed similar oppositions – sometimes supported by I-MAK and sometimes independently: the Working Group on Intellectual Property (GTPI) – a collective of civil society organisations coordinated by the Brazilian Interdisciplinary Aids Association (ABIA) and Fundación Grupo Efecto Positivo (FGEP) and Doctors of the World are examples in Brazil, Argentina and Europe.

The challenges are not just focused on Gilead’s compounds either. In February, I-MAK, DNP+ and supported by MSF filed two patent challenges on BMS’s daclatasvir. These also are currently under examination at the Indian patent office.

Some cases are pending, and some have been rejected – and are under appeal as is the case in Brazil. The intent, says Amin, is that if the patent is rejected in several countries – even in countries like India where the prices are already low – there might be a knock-on effect around the world and more scrutiny by patent examiners.

What’s interesting, said Amin, is that the situation is almost a rerun of what happened when it challenged the patents on Gilead’s lifesaving HIV drug tenofovir a decade ago.

Then, countries such as Malaysia, started asking for compulsory licences and manufacturers began to offer different countries voluntary licences too, he said. This allows generic companies to produce HIV drugs at low prices but limits where they can be sold, as part of the licence.

In August, IP-Watch and Global Health Policy News reported that Gilead announced that it had offered four middle-income countries (Malaysia, Thailand, Belarus, Ukraine) a sofosbuvir voluntary licence. And Malaysia decided to issue CL instead (IPW, IP and Health, 24 August 2017).

The problem with voluntary licences, said Amin, is that they generally deter generics companies from disputing patent applications. That has certainly happened in India, he argues, and it is also why I-MAK is continuing its cases. Gilead said it had no wish to comment on voluntary licences.

Whether the Indian court will accept or revoke the base compound patent is unclear. But, says I-MAK, it has also submitted a post-grant opposition to the patent. That way, if the Indian court throws out this particular case in December, it can fall back on this second attempt to get rid of the patent in India.

“We’ve done that because we feel that the patents are undeserved, said Amin. “We see a fundamental problem with a patent rewarding exclusivity.”