Sergey Nivens /
30 June 2016BiotechnologyElizabeth Ward

Putting the boot into biologic strategies

British comedian Ricky Gervais once famously quipped that “where there is a will, there’s a relative”. The same applies to all lucrative opportunities—if there’s room for debate or litigation then people will fall out over who gets the money, especially if the money involved is substantial.

Generics and biosimilars are high-value properties and provide some spectacular opportunities for full-on fights in the pharma industry. With some blockbuster biological compounds coming off patent over the next few years, the arguments over when and how biosimilar competitors are granted product approvals and at what cost are starting to emerge.

The healthcare industry is facing a real problem in maintaining its profitability and financing its ongoing commitment to invest in future research. Despite increased efficiency in drug approvals and research costs, the cost of getting drugs to market is as high as ever and regulators are often struggling to keep pace with the science and the opportunities presented by new products. In addition, governments and insurers across the world are looking to control costs and open up competition for the benefit of the consumers globally.

Readers will be familiar with generic medicines but not necessarily their biological sisters, known as biosimilars. So-called biological products contain medically active products derived from a biological source, such as insulin and growth hormones. Other examples are biologics that stimulate red blood cell production, tumour necrosis factor inhibitors, which help treat cancer cells, and antibodies that help boost the body’s own immune systems and combat the diseases that attack it.

The original biological product is known as a reference product. Thanks to improved manufacturing techniques and the fact that many reference products are coming off patent in the next few years, these new biosimilar equivalent products are now coming to market and causing a complete storm.

Approval regimes

The EU inaugurated the first regulatory regime to deal with the approval of biosimilars in 2003 and there are currently 19 approved biosimilars in the EU. The US regime lags well behind—there are only two approved biosimilars available to the public there. The EU and US regulators both require strict proof from manufacturers that the activity of any biosimilar product mirrors the efficacy and activity of the original biological reference product. So far, so good. The US and the EU are, however, tackling the battles over biosimilar patent rights in quite different ways.

Patent owners of biological and pharmaceutical products often create ‘patent thickets’ around dosages and secondary medical uses. In practice this gives rights owners extended monopolies in the products. The common thickets are created by patenting everything from manufacturing techniques to dosage regimes. The UK courts haven’t hitherto been too sympathetic to this kind of anti-competitive behaviour and manufacturers of generic medicines have successfully used applications for declarations of non-infringement of a patent to their advantage in the UK. Similar tactics could be used by new manufacturers of biosimilars.

Case study

The latest case in the battle for a declaration of non-infringement in a biosimilar case in the UK is Fujifilm Kyowa Biologics v Abbvie Biotechnology. The defendant, Abbvie, is the owner of a number of patents covering a product known and marketed as Humira (adalimumab). It is a human antibody which binds and neutralises tumour necrosing factor. In 2014 sales worldwide exceeded $12.5 billion. The main use of this antibody is as a combination therapy in cancer treatment but it is also widely used in a number of other indications such as rheumatoid arthritis and Crohn’s disease.

“Manufacturers of generic medicines have successfully used applications for declarations of non-infringement of a patent to their advantage in the UK.”

Abbvie has applied for and been granted a number of patents for secondary medical uses to cover its extended use in these therapeutic areas. These include dosage regimes.

The claimant Fujifilm was set up in 2012 to manufacture and develop biosimilar products, including a biosimilar for Humira. The claimant’s biosimilar is currently in phase III clinical trials. The basic product patent for Humira as a human antibody comes off patent in 2018. Fujifilm has applied to the English High Court for a declaration that some of Abbvie’s dosage patents which are subservient to the main product patent would have been obvious at the filing date.

If it succeeds in this claim, Abbvie will lose the commercial advantage given by such secondary patents, all of which were filed several years after the main product patent. By making an application in this way Fujifilm hopes to clear the way for use of its biosimilar in the lucrative UK and EU markets. If the High Court grants the claimant a declaration of non-infringement on the dosage patents, then once the main patent expires in 2018 Humira’s market share will be drastically affected.

Having said all that, High Court litigation in the EU is currently quite unusual with most manufacturers using European Patent Office (EPO) opposition procedures to delay the grant of European patents for new biosimilars. This is generally less expensive than High Court action. By way of background, the Humira secondary patents which related to dosage regimes for rheumatoid arthritis faced opposition proceedings from around 15 different entities before its grant. From that, one could also deduce that sooner or later several companies would want a slice of this market and that the current case in the High Court was inevitable.

European questions

Opposition proceedings in the EPO have a number of advantages and disadvantages over court action in national states. The two biggest advantages include reduced cost of proceedings and the fact that any decision given by the EPO binds all the member states. The biggest disadvantage is that such proceedings are limited to patents that are at the application stage and that granted patents are the biggest threat to newcomers who wish to enter a market but will potentially face multiple infringement actions in national courts.

In the EU there is not yet a Unified Patent Court (UPC), which would give manufacturers and newcomers the opportunity to validate or challenge the validity of patents covering reference products on an EU-wide basis. The UPC will be a significant force for good when it commences its work, although at the time of writing there are now doubts about it after the UK voters’ decision to leave the EU.

Currently companies have to file their cases in an EU court forum which they believe best suits their cause. With the UK being such a large and influential market, and with its having the third largest share of pharmaceutical research and development in the world, it should be no wonder that the fight arises in the High Court in London.

The killer question is this: is it time for the regulators and indeed patent offices to step in and limit the strategies used by existing biologic manufacturers and allow new suppliers to reach some of the world’s most lucrative healthcare systems? This writer observes that while any such action is to be welcomed from a consumer’s point of view, it is likely to be a strategy that is slow, cumbersome and doomed to fail.

The biggest opportunity for justice for all concerned in the EU will lie in the implementation of the UPC as quickly as possible. As the unitary patent scheme and the UPC are governed by agreements outside the main EU treaties, in theory they should not be affected when the UK leaves the EU. However, now the UK has voted to leave the EU it is possible that it would not be able to join. As London is one of the bases for the UPC’s central division, and as the UK will be a member of the EU for at least the next two years, ratification, clarification and speedy implementation of the court should be welcomed by all.

Elizabeth Ward is a principal at  Virtuoso Legal. She can be contacted at:

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