Sofosbuvir - a $2.54bn infringement in the US, but not in Europe

It is a common misconception among inexperienced (typically would-be) patentees that getting a patent for their invention will give them the right to commercialise it. As I have had to explain quite often to new clients, there is a big difference between these two things. A patent only gives you the right to stop others from doing what the claims cover, while being free to put your invention into practice is dependent on not being found to infringe anyone else's patent.

A good recent example of this difference is the verdict from the case of Idenix Pharmaceuticals LLC v Gilead Sciences Inc, as reported here and many places elsewhere. Gilead were found to have infringed US 7,608,597, and have been ordered to pay $2.54 billion in damages. Gilead have their own patent on the infringing drug, known as Sovaldi and Harvoni and with the generic name sofosbuvir, which I have written about here and here in relation to the European patent. Gilead do, of course, have a corresponding US patent for the drug, but this did not help them in their case against Idenix.

What is also interesting about this case though is the contrast that it shows between what can be achieved in the US and what can be done with the same starting material in Europe. Claim 1 of the US patent is very brief, and reads as follows:

1. A method for the treatment of a hepatitis C virus infection, comprising administering an effective amount of a purine or pyrimidine 𝛽-D-2'-methyl-ribofuranosyl nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.

Claim 1 of the only corresponding granted European patent EP2319856B1, however, is very very long indeed, much too long to be reproduced in full here. It starts off in a similar vein, defining a pharmaceutical composition for use in a method for the treatment or prophylaxis of a Hepatitis C virus infection in a host, but then goes on for a further two pages with various structural features and alternatives. What was possible in the US therefore seems to be impossible in Europe in this case. Not only would sofosbuvir alone not be an infringement of the European patent (I am fairly sure about this, but happy to be proven wrong), but also European courts do not go for such huge damages as are found in the US (although the headline $2.5 billion figure is very likely to be whittled down on appeal).

Another interesting feature of this long-running story is that an infringement action has already been tried by Idenix against Gilead in Europe, but this ran aground when Mr Justice Arnold at the England & Wales High Court found that Idenix's patent EP1523489B1 was invalid (see the IPKat post here), and this was upheld on appeal. So, at the moment at least, it looks like Gilead have done very well in Europe to keep their patent on sofosbuvir and also avoid it infringing anyone else's, but the story is very different in the US. This seems to be largely down to more thorough examination in Europe, both at the EPO and the courts (although this does not always apply: see my recent post here), compared with the generally far more lenient USPTO and more patent friendly court system in the US.

Sofosbuvir EP opposition - an update

As I reported in February last year, Gilead's European patent EP2203462B1 to sofosbuvir (Sovaldi) was opposed by various organisations, the first of which was Médecins du Monde (MdM). Their main reason for opposing the patent seemed to be that Gilead was charging a high price for the drug, which is effective for treating Hepatitis C. The opposition has recently concluded, following oral proceedings earlier this month. A press release issued on October 5th indicated that MdM's opposition was partially successful, and that "the quality of the patent was weak". Details of how exactly the patent fared as a result of the opposition were, however, missing, except for a mention that "the patent extended beyond the content of the patent application as filed" (suggesting an Article 123(2) issue). Another report from IP Watch did not provide much in the way of further illumination, and as yet there has been no word from Gilead or the EPO on the outcome.

The decision and minutes of the oral proceedings have not yet appeared on the EP register for the case, and are unlikely to do so for some time. It can, however, be inferred from what has already been said, and in particular a document that has appeared on the register, what actually happened.

In their preliminary opinion, issued on January 28, 2016, the opposition division indicated that claim 1, corresponding to the racemate (shown here), had been specifically disclosed in the application as filed. Claims 2 and 3, however, which were directed to the enantiomers (or diastereomers - see the comment below), did not appear to be disclosed. Whether the disclosure was sufficient to disclose the enantiomers was something that was due to be discussed at the oral proceedings.

Gilead filed a large number of auxiliary requests, the first of which had a set of claims that had been amended to define the enantiomers instead in terms of the slow and fast eluting isomers obtainable by a specific method that was disclosed in the application. The clue that this succeeded at oral proceedings is this document, issued shorty after the proceedings, that contains amendments made to the summary of the invention, and indicating that this corresponds to the first auxiliary request. This shows that claims 2 and 3 have been removed from the application, clearly indicating that claim 1 survived, but that the specific claims to the enantiomers did not.

As a result, the patent seems to me to have survived pretty well, and not really limited in any substantial way. It will, of course, be irritating to Gilead that the specific claims to the enantiomers have gone, but the patent as amended would still protect the drug. Reports (such as this one, for example) that suggest generics may be able to enter the market sooner than expected, therefore seem to be a bit wide of the mark.

UPDATE 3/11/16: The grounds for the decision have now appeared on the EP register. As expected, claim 1 to the racemate stands, and the claims to the enantiomers/diastereomers have gone.

Sofosbuvir revisited - a chemical puzzle

I last wrote about the blockbuster drug sofosbuvir in February 2015, around the time when a few oppositions were being filed against Gilead's European patent for the drug. The oppositions are currently going through the usual procedures at the EPO, and oral proceedings have been scheduled for 4-5 October 2016. From a quick look at the preliminary opinion of the opposition division, it looks like the patent will be upheld. With ten opponents and a huge amount of material on record, however, it still looks like a Herculean task for the patentee.

Chemical structure of sofosbivir (Wikipedia).

In the meantime, however, I noticed a recent article about a claim being made in the US that a patent owned by the University of Minnesota is infringed by the drug. The article does not mention the patent by number, but after doing a bit of simple searching I think it could be US6475985, titled "Nucleosides with antiviral and anticancer activity", which was granted to the University in 2002 (and was, incidentally, not cited as prior art in the EP oppositions), considerably before the earliest priority date for the sofusbuvir patent in 2007. Claim 1 of this patent reads as follows:

There are other independent claims that are directed to a chemical compound, rather than to a therepeutic method, but claim 1 does seem to have at least the use of sofosbuvir within its scope. It is, however, a bit of a complicated puzzle to figure out whether it does. Can anyone confirm this?

Sofosbuvir

It is well known that while a drug is protected by a patent, its price will be higher than it would otherwise be. This is, of course, the reason for having a patent. Sometimes this price can be very high indeed, for example where a patented drug is very much more effective than anything else currently available, for which people will be prepared to pay a lot more. In a free market, the price of any patented drug would be determined simply by how much the patent holder could get away with charging. The optimum price for the patent holder will be the one that maximises profits, which will of course not necessarily be the maximum price they can get away with. The market in drugs, however, doesn't always work like that, and in some cases the market is, for various reasons, not free at all. Whereas in the US, pharmaceutical companies can charge pretty much whatever they like and see what the market can bear, in Europe the situation is much more complicated. In the UK, the NHS will strike a deal with pharmaceutical companies to get the best price they can, and there is an incentive for the patent holder not to charge too much because otherwise the patented drug will not be considered cost effective by NICE and will therefore not be generally prescribed.

It is obvious that there are many factors in play when a patent holder decides what to charge for their drug in each country they wish to sell it in. In some countries it might not be possible to even get a patent for the drug. A decision will then need to be made on whether to market the drug in that country at all, if the price that can be charged is not worth it. In other countries where a patent is possible, a patent holder may need to charge the same price throughout an entire region, in order to prevent parallel importation from becoming a drain on profits. This is the case in Europe, where different deals may be struck in different EU countries, resulting in different prices being charged. Sometimes the price being demanded is so high that complaints start to be raised.

A recent complaint about high pricing relates to the price Gilead are currently charging for their patented drug Sofusbuvir (trade name: Sovaldi or Virunon), a new drug for treating hepatitis C virus (HCV) infections. In the UK, a price of £35,000 for a typical 12 week treatment course has been quoted (see the Wikipedia link above). NICE have as yet not issued any guidance as to whether Sofusbuvir should be funded on the NHS, although a decision is expected this month (see here).

In France, the issue has been raised by the charity Médecins du Monde, which describes itself as "an international humanitarian organisation providing medical care to vulnerable populations affected by war, natural disasters, disease, famine, poverty or exclusion". It has recently, however, apparently extended its remit to cover objecting when high prices are charged for patented drugs. A press release of theirs, issued on 10 February, states:

Today, Doctors of the World - Médecins du Monde (MDM) has filed a European patent challenge against the Hepatitis C virus (HCV) drug, sofosbuvir. In recent months, Médecins du Monde and its partners have raised the alarm around the problems caused by the cost of new treatments against hepatitis C and of sofosbuvir in particular. The U.S.-based pharmaceutical company Gilead holds a monopoly for sofosbuvir and is marketing a 12-week course treatment at extremely high prices – 41 000 euros in France and 44 000 euros in the United Kingdom – thereby hindering access to the drug for People Living with HCV.

A patent challenge is a legal procedure by which the validity of a patent is questioned. While using sofosbuvir to treat hepatitis C represents an important step forward, the molecule itself is not sufficiently innovative to warrant a patent. If successful, it can encourage competition from generic versions of sofosbuvir, which can drive price reductions closer to the cost of production. According to experts, this cost for sofosbuvir may be as low as $101 USD for a 12-week course.

Since Gilead is prioritizing its private rights over human rights, imposing unconscionable prices for healthcare systems, Doctors of the World – MDM has decided to challenge Gilead. This is the first time in Europe that a medical non-governmental organisation (NGO) uses this procedure to improve patient access to drugs. MDM believes that the price of sofosbuvir is unjust in part because public funds were used to research and develop the drug.

“We are defending universal access to healthcare: the struggle against health inequality involves safeguarding a healthcare system based on solidarity,” explains Dr Jean-François Corty, MdM’s French Programmes Director.“Even in a ‘rich’ country like France, with an annual medicines budget of 27 billion euros, it is difficult to meet this cost. We are seeing an arbitrary rationing approach that excludes patients from care, and this is unacceptable.”

According to the World Health Organisation (WHO), an estimated 130 to 150 million individuals are living with chronic hepatitis C. Within the European Union, it is estimated that between 7.3 and 8.8 million people are living with the virus. In France, 230, 000 people are reportedly chronic carriers of hepatitis C.

“Patent challenges have already been used by civil society in India, Brazil, the United States and around the world to remove weak or unmerited patents for drugs and to make low-cost generic versions available,” explains Olivier Maguet,MdM board member delegate for hepatitis C. “This has led to a substantial reduction in the cost of treatments, enabling access to drugs of patients who would otherwise be deprived of life-saving medicines.” Doctors of the World - Médecins du Monde is taking up the fight to promote universal access to treatment against HCV in Europe and the rest of the world. MdM is also launching a public debate in France on the drug pricing mechanism and its impact on the healthcare system.

MdM do not actually indicate what patent is being opposed, but a copy of the opposition itself is linked to on this page, and states that the patent is EP2203462 (EP register here), which was granted on 21 May 2014. The deadline for filing oppositions does not end until 21 February 2015, so there is a chance that others may join in over the next few days, possibly making MdM's politically motivated contribution irrelevant. Given the very high value of the patent in question (which appears to be of the order of billions of whatever currency unit you favour), I think there is a very high probability of this happening. I suspect this one will run for a very long time, regardless of MdM's opposition.

UPDATE 20/2/15: As expected, more oppositions have been filed. Two further notices of opposition were filed yesterday: one by Dr. Holm Herbert Fleischer, a German doctor, and another by Ellis IP Limited (presumably acting as a straw man on behalf of an unidentified opponent). There seems to be a consistent theme among the three oppositions so far filed that there is an issue regarding the patent claiming the two stereoisomers of sofosbuvir, and in particular whether this is directly and unambiguously derivable from the application as filed (Article 123(2) EPC), whether the application discloses the invention sufficiently (Article 83 EPC) and whether the claimed invention has a valid right to priority (Article 87 EPC).

UPDATE 24/2/15: Four further oppositions have now been filed, making a grand total of seven now that the opposition deadline has passed. These extra four have been filed in the names of Actavis Group PTC ehf, STADA Arzneimittel AG, ZBM Patents and IPS. the latter two being apparently further strawmen oppositions. The six other oppositions, which were presumably made for sound commercial reasons rather than being politically motivated, make the MdM opposition seem a bit of a wasted effort.

UPDATE 5/3/15: The EP register now indicates a total of ten opponents, another three apparently getting in at the last minute. These are:

1. MEDECINS DU MONDE
2. Fleischer, Holm Herbert
3. ELLIS IP LTD
4. Pharmaceutical Works POLPHARMA
5. Generics [UK] Ltd (trading as Mylan)
6. Teva Pharmaceutical Industries Ltd
7. Intellectual Property Services (IPS)
8. STADA Arzneimittel AG
9. ZBM Patents - Zea, Barlocci & Markvardsen
10. Actavis Group PTC ehf

It looks like Gilead's representative (Sheila Wallace of Marks & Clerk) will be kept quite busy for some time.

In a related matter, a commenter has kindly pointed me to this article in the Grauniad. According to the author, who was lucky enough to have been successfully treated with sofusbuvir, socialism would be the answer to the problem of big pharma charging high prices for new drugs. He neglects, however, to explain how this would help in discovering these new drugs in the first place.