I-Mak Blog

Gilead denied patent for hepatitis C drug sofosbuvir in India

14 January 2015

The Indian Patent Controller has today rejected one of Gilead’s key patent applications which covered the drug sofosbuvir, used to treat hepatitis C (HCV). The oral drug, which first received regulatory approval in the US in November 2013, and has been priced by Gilead at US$84,000 for a treatment course, or $1,000 per pill in the US, has caused a worldwide debate on the pricing of patented medicines. A study from Liverpool University showed that sofosbuvir could be produced for as little as $101 for a three-month treatment course.


Challenges to some of the most important patent applications on sofosbuvir (a ‘patent opposition’ - a form of citizen review allowed in many countries) were filed in India by the Initiative for Medicines, Access & Knowledge (I-MAK) and the Delhi Network of Positive People (DNP+) in November 2013 and March 2014.


Gilead has signed voluntary licence agreements with multiple generic producers in India, but these agreements impose many restrictions, including which countries can access the drugs produced under these licences, as well as invasive restrictions on medical providers and patients with respect to distribution and use of the drug. With the patent being denied, other companies that have not signed the licence are now free to produce. Entry by additional generic manufacturers should increase the open competition needed to bring prices down dramatically, especially in those countries that have been excluded from the voluntary licence agreement, and thereby increase access to the medicine. Countries where the drug is unaffordable, and which were excluded from the licences, should make every effort to import more affordable generic versions from other producers who did not sign a licence in India.


MSF is in the process of expanding treatment for people with hepatitis C in nine countries, and has been negotiating access to this medicine, which is expected to become the backbone of any HCV regimen in the coming years.


Below are responses to the news by Doctors Without Borders/ Médecins Sans Frontières (MSF), the Initiative for Medicines, Access &Knowledge (I-MAK.org), the Delhi Network of Positive People (DNP+), and Dr. Andrew Hill, Researcher at Liverpool University


“Sofosbuvir has proved to be a billion-dollar blockbuster drug and we hope today’s decision opens the floodgates for more open competition that could rapidly lower the price. This drug makes hepatitis C treatment more effective and easier for patients and doctors, so broad access to affordable versions will allow treatment to be scaled up dramatically.  Gilead’s drug access programme for developing countries is already showing its limitations, with the company planning to impose conditions for the supply and distribution of the drug to patients and treatment providers in developing countries, in order to protect the company’s ability to charge unaffordable prices in wealthy countries. Getting sofosbuvir out of the stronghold of Gilead’s monopoly will be crucial to expanding treatment for people with hepatitis C globally.


“India’s status as the ‘pharmacy of the developing world’ is once again in the spotlight and this is a good opportunity for generic producers in India to swiftly ramp up production to levels needed to treat the 185 million people infected with hepatitis C worldwide.” 

Dr. Manica Balasegaram, Executive Director, MSF Access Campaign


“The move to reject Gilead’s patent application really opens up the playing field, so we hope to now see many other generic companies starting to produce more affordable versions of this drug.  The bottom line here is that India’s patent law doesn’t give monopolies for old science, for compounds that are already in the public domain. Gilead’s strategy of charging as much as US$84,000 per treatment for a drug that is predicted to be simple and cheap to produce, and is now un-patentable in India, has been exposed for what it is – seeking to squeeze as much profit out of the sick as possible.”

Tahir Amin, lawyer and Director of the Initiative for Medicines, Access &Knowledge (I-MAK.org)


“This is a happy day for the millions of people who urgently need hepatitis C treatment across the globe. People with hepatitis C everywhere should be able to have access to this treatment, but millions of our friends in middle-income countries have been left out in the cold by Gilead. This decision provides hope that people in countries that have been excluded from Gilead’s licensing deals will be able to access low-cost generic versions of sofosbuvir.”

Vikas Ahuja, Delhi Network of Positive People (DNP+)


“We know from various manufacturers in India that they could produce this drug in the future for as little as $101 for the full three month treatment course.  That’s roughly $1 per pill, which is a big improvement over the $1,000 per pill Gilead is charging in some countries. At the current prices, sofosbuvir is unaffordable for widespread use in most countries of the world.”

 Dr. Andrew Hill, Senior Research Fellow, Department of Pharmacology and Therapeutics,

Liverpool University




I-MAK Files Patent Challenge on Hepatitis C drug Sofosbuvir in India

Hepatitis C (HCV) drugs represent the difference between life & death for people around the world today. The World Health Organization that estimates 185 million people live with this disease, and 90% of those live in low- and middle-income countries. Over four times the number of people live with HCV than with HIV.

On Thursday, 21 November 2013 I-MAK filed an opposition at the Kolkata Patent Office against Gilead/Pharmasset's application for Sofosbuvir (Applicaiton No. 3658/KOLNP/2009), a nucleotide prodrug.

The notice of opposition and accompanying documents can be found here.

Our press statement issued with MSF is below:

New Delhi/New York, 22 November 2013—Médecins Sans Frontières (MSF) supports the ‘patent opposition’ just filed at India’s Patent Office by the Initiative for Medicines, Access & Knowledge (I-MAK), which aims to prevent US pharmaceutical company Gilead/Pharmasset from gaining a patent in India on sofosbuvir, a drug for hepatitis C that is coming to market soon with an anticipated exorbitant price.

Gilead is expected to charge around $80,000 for one treatment course of sofosbuvir in the US. Even if offered at a fraction of this price in developing countries, this drug will be priced out of reach. The patent opposition—a form of citizen review allowed in many countries—offers technical grounds to show a drug does not merit patenting under India's Patents Act. This opposition was filed to ensure that affordable generic versions of sofosbuvir can be produced to help the millions of people infected with chronic hepatitis C in developing countries access the drug. 

“Old science, existing compound,” said Tahir Amin, lawyer and director of I-MAK.org. “India’s patent law doesn’t give monopolies for old science or for compounds that are already in the public domain. We believe this patent on sofosbuvir does not deserve to be granted in India and have the legal grounds to prove it.”

Sofosbuvir is the first of several oral hepatitis C drugs expected to come to market in the coming year. It cures hepatitis C in a much shorter time period than today’s available treatment, and for some forms of hepatitis C, eliminates the need to use the injectable drug pegylated interferon, which can be difficult to administer and causes many serious side effects. Gilead is anticipated to receive marketing approval for sofosbuvir in the US on 8 December.

MSF has started providing hepatitis C treatment for a small number of people co-infected with HIV in its clinic in Mumbai, but cost (as high as $5,000 per patient) and complexity of today’s available treatment means that patient numbers remain extremely low despite considerable needs.

“In our projects, we need access to medicines like sofosbuvir that are easier for patients to take so we can expand treatment to more people. If the drug is unaffordable, the majority of the most vulnerable groups will remain untreated,” said Dr. Simon Janes, medical coordinator with MSF in India. “We know from our experience providing HIV treatment over more than a decade in dozens of developing countries that treatment needs to be simple and affordable—preferably less than $500 to start with. An unaffordable price for this drug will have a chilling effect on funders and governments who need to start financing and providing treatment.”

The World Health Organization estimates there are 184 million people infected with hepatitis C worldwide, with the disease causing half a million deaths each year. The vast majority of these people live in developing countries where—with the exception of Brazil and Egypt—there is no provision for universal access to hepatitis C treatment in public healthcare programmes.

“The world is waking up to a new crisis with hepatitis C,” said Olga Stefanishina of the Ukrainian Community Advisory Board. “More and more people are being diagnosed with chronic hepatitis C but are left to die because there’s no affordable treatment. With this patent opposition in India, we are starting the fight for better treatment that people can afford and governments can provide. We have no time to wait for charity or country-by-country negotiations—low cost generic drugs must be made available to all high-burden countries without discrimination.”

India has been called the ‘pharmacy of the developing world,’ because it produces many affordable generic versions of drugs patented elsewhere. More than 80% of the HIV medicines used in developing countries come from India, which is able to produce these medicines because its patent law sets the bar high for which medicines do and do not merit patenting, allowing generic manufacturers to compete for the market and drive prices down.

“The hepatitis C drugs coming out of the drug pipeline, including sofosbuvir, are compounds that are relatively simple and cheap to make,” said Dr. Andrew Hill, a pharmacologist at Liverpool University who has published a study showing that sofosbuvir could be produced for as little as US $62-$134 for a 12-week treatment course. “The profit projections for the oral hepatitis C drugs are staggering, and stand in no relation to what it costs to make these drugs.”


Voluntary License Scorecard

In the last year, a number of public health organizations -- including the HIV Medicines Alliance, UNAIDS, Clinton Health Access Initiative, UNITAID and the Medicines Patent Pool -- have taken steps to enter the voluntary licensing space. In our latest report, "Voluntary Licensing: Optimizing Global Efforts and Measuring Impact", we comment on the efforts taken by these global health institutions and offer suggestions to ensure that licenses are pursued in a strategic, access-maximizing manner. We note that the stakes are particularly high when it comes to creating normative standards, as pharmaceutical companies are unlikely to agree to terms more generous than those endorsed by these agencies, which are seen as representing the entire HIV community.

In examining our collective commitment to universal access, we note that accepting access to affordable ARVs for some while endorsing the exclusion of others is an abdication of our collective responsibility to the global patient community. We acknowledge that concessions may be necessary to move a specific negotiation forward; however, to endorse a framework of exclusion is a breach of our community's mandate to promote universal access.

In our report, we highlight that existing originator access programs already cover on average 75% (and at best, 90%) of people needing antiretroviral therapy. We argue that the true value-add of global health institutions is to close this gap, and to advocate for coverage of the middle-income countries that are being systematically left behind, particularly for second-line ARVs which are often priced out of reach. These countries account for one fourth of total patients needing ART, or roughly 3.5 million people. The HIV epidemic in these countries is often concentrated in vulnerable communities plagued by stigma and discrimination and ignored by governments.

It is these communities that struggle the most to access treatment and need the intervention of public health institutions to make access a reality.

For this reason we propose recommendations for the Medicines Patent Pool, who aims to act as the lead negotiator for all future ARV licenses.  We also offer a new measurement tool applicable to all public health organizations working in the licensing arena, which can assess licenses facilitated or endorsed by these institutions. This "Voluntary License Scorecard" offers a set of indicators for both structuring license terms and standards and monitoring their impact on an ongoing basis. The indicators are categorized as follows:

- Global Patient Coverage (measured as compared to the status quo, and as compared to the goal of 100% universal access)
- Financial Impact (including tracking actual purchase volumes and prices on an ongoing basis)
- Market Impact (assesses the extent to which the licenses foster a healthy and competitive marketplace)
- TRIPS flexibilities (the impact of the license on the use of safeguards in national law, examination, opposition, compulsory licensing)

The Voluntary License Scorecard is available within our 4 page report here.


Update on I-MAK's patent observations against Abbott Laboratories in Europe 

In 2011, the European Patent Office (EPO) proceeded to grant the patent on heat-stable lopinavir/ritonavir despite the evidence we submitted at the pre-grant observation stage. The granted patent EP1663183 B1 (Application No. 04816820.7) covers ritonavir and/or lopinavir, a water-soluble polymer, and a surfactant. The polymer has a glass transition temperature of at least 50 degrees and the surfactant can have an HLB value from 4-10.

Subsequently, five companies -- Teva, Mylan Generics UK, Roche, Hetero and Janssen (J&J) -- have filed post-grant oppositions at the EPO against granted patent EP1663183 B1 .  The post grant oppositions filed by these companies raise several of the issues and evidence raised in our pre-grant observations, but which the EPO did not require Abbott to address before finally granting the patent. We hope the post-grant opposition process addresses the issues that were not dealt with during examination.

Copies of the post grant oppositions are available here. The cases are pending and it will take at least another year before a final determination is given by the EPO.

However, from the parent Application No. 04816820.7, Abbott has three further divisional applications pending:

EP divisional Application No. 10181250.1: covers essentially the same product as the granted parent patent.  I-MAK's observation against this application was aimed at Abbott's claim that the addition of a surfactant with a hydrophilic lipophilic balance (HLB) of 4-10 was inventive. We argued that the inclusion of the surfactant with an HLB of 4-10 would have been obvious to a person skilled in the art in light of Abbott's prior patents, as well as publications in the field documenting the advantages of using surfactants in solid dispersion formulations. We also highlighted for the Examiner that this is a case of double patenting: the parent patent also covers what is claimed in the divisional application.

A copy of our observation and supporting evidence is available here.

EP divisional application 10181268.3: claims a method of
preparing a solid dosage form which comprises preparing a homogeneous melt of ritonavir and/or lopinavir, at least one surfactant and at least one water-soluble polymer having a glass transition temperature of at least 50 degrees Celsius, and allowing the melt to solidify to obtain a solid dispersion product.

I-MAK's observation and evidence, a copy of which is available here, focused on three key issues arising from the examination history of the application to date:

1) The fact that the divisional claims were actually product-by-process claims and should be examined as such. Under the European Patent Convention, product-by-process claims should be treated as product claims, and the burden is on the applicant to demonstrate that the claimed invention is new and inventive, and results in another product over that already covered in the prior art.

2) If the claims were to be treated as method claims, the application should be rejected for lack of inventive step, since the use of melt extrusion technologies and methods as applied to poorly soluble compounds such as ritonavir and lopinavir were well-documented in the field prior to the application being filed and would have made their use obvious.

3) That Abbott has failed to address the technical problem it claims to have solved, namely that the claimed invention provides for a solvent-free method of making the solid dosage form of this product, since solvents have a number of disadvantages. Despite the Examiner agreeing with Abbott having solved the technical problem, our observation shows the patent specification as filed contradicts these findings as it specifically includes the use of a solvent process. Indeed, nowhere in the claims as filed in the divisional application are solvents expressly excluded from use in the claimed invention. Moreover the evidence submitted with our observation shows that known melt extrusion technologies already solved the problem of not needing to use solvents.

This issue was also raised in our final observation to the parent application 04816820.7 after Abbott reformulated the problem during examination in order to overcome objections to the patent. Unfortunately, the EPO failed to ask Abbott to address these issues before granting the patent. We hope the EPO takes notice of these issues this time around.    

EP divisional application 10181264
: cover substantially similar claims to the parent application. The case is still being prosecuted and the Examiner appears unconvinced thus far about the patentability of this application. I-MAK is monitoring the examination of the application.

It should be noted that Abbott’s strategy of filing multiple divisional patent applications does not fall squarely within the classic defintion of life cycle management, or “evergreening”. The divisional patents, if granted, would expire at the same time as the parent patent. Instead, Abbott’s strategy of using divisional applications appears to be aimed at ensuring the broadest scope of protection given the various amendments to the claims it had to make as a result of our observations during the examination of the parent application.  Abbott is also likely concerned that since the post grant oppositions have been filed against the granted parent patent, obtaining granted patents for the divisionals may further delay any potential generic entry in Europe as post-grant oppositions at the EPO can take up to 2-3 years. To that end, these divisonals form part of the patent strategies companies use to increase transaction costs for generic entrants who might be seeking to challenge patents.

These cases at the EPO could have serious implications for low- and middle-income countries (LMICs) since patent examiners in LMICs (e.g. Viet Nam) often rely on EPO examinations in their own examination process.

More updates to follow.


Granted Pharmaceutical Patents in Egypt

As part of ongoing efforts to make patent information for medicines more transparent, we have completed a preliminary review of pharmaceutical patents granted in Egypt between 1 January 2005 - 31 December 2010. The full report and analysis can be downloaded here.

The report is only a preliminary assessment as the full text of the granted Egyptian patents were not available to us at this time. As such the analysis was based on corresponding U.S., European and/or international patent (PCT) documents and whether they related to patents listed for marketed products on the U.S FDA Orange Book. However, with this initial information to hand, it is hoped that it will enable users to focus efforts and resources on obtaining the complete patent documents for those patents that may be of interest.

The projected was carried out in collaboration with Dina Iskander of the Egyptian Initiative for personal Rights, as part of her research on the impact of TRIPS on pharmaceutical patenting in Egypt.