Is pharmaceutical research and development work obvious?

A recent line of cases presents a difficulty for the pharmaceutical industry, with patents being ruled invalid on the basis of obviousness where industry-standard research processes are followed. 

The latest case (Teva v  Bayer) saw the High Court declaring invalid a patent for the salt form of Bayer’s cancer drug sorafenib, marketed under the brand name NEXAVAR. NEXAVAR is approved in the US and EU for treatment of various cancers such as those affecting the kidney, liver and thyroid. 

Israeli generics producer, Teva, challenged the patent in multiple jurisdictions, including the UK. Teva argued that the patent was invalid on the grounds of obviousness. A patent can be revoked due to obviousness if the claimed invention would have been obvious to a person or team suitably skilled in the relevant art, equipped with information which formed part of the state of the art when the patent was filed.  

In this case, the relevant skilled person was a “skilled team” of drug developers, including a “skilled formulator”. Note the extensive range of skills and expertise that are assumed to be present before the obviousness analysis begins. 

The court identified a 2001 journal article as the closest prior art. This article, including among the list of authors one from Bayer, discussed sorafenib and its utility in cancer therapy. It disclosed the preliminary results of a Phase I clinical trial for sorafenib, in which the authors reported findings from a clinical trial of oral sorafenib. The journal article included references to the relevant dose and chemical structure, but did not disclose the salt form of sorafenib. 

The judge in the UK case said that the key question was, based on the journal article as a starting point, “what would the Skilled Team do next?” His conclusions were as follows:

• The journal article provided the skilled team with “a strong (but not irresistible) motivation to investigate [sorafenib] with a view to identifying a formulated drug”.
• The skilled team would first have followed up the relevant references in the journal article, which would have given them the chemical formula for sorafenib and the relevant dose range.
• They would then have had to characterise the free base form of sorafenib. In the course of this process they would discover that the free base of sorafenib was insoluble and unsuitable for oral administration. However, the clinical trial results published in the journal article would have reassured them that a sufficiently soluble formulation of sorafenib was achievable, because such a formulation would have been used in the clinical trial. So the skilled team would have been motivated to carry out a salt screen with the aim of identifying a soluble salt form of sorafenib.
• Would the skilled team have included tosylate in the screen? They “would have said to themselves ‘we cannot make any firm theoretical predictions, so let’s get on and make a selection of salts and test them’”. Most research teams would have selected tosylate salt for inclusion in the screen, and that this inclusion would have been “the result of standard and routine considerations”. The screen would then have identified tosylate as the appropriate form to develop sorafenib as a drug.  

Following this reasoning, Bayer’s patent was found to be invalid. This paves the way for Teva to launch a generic version of the product.  
 
The decision is in line with the Supreme Court’s ruling in Actavis v ICOS (discussed here). That case concerned a patent claiming low dose levels of erectile dysfunction treatment tadalafil. The patent was obvious, the court concluded, because standard dose-ranging studies would have led the skilled team to the claimed invention.

As demonstrated by these cases, the complexities of the pharmaceutical research and development process do not prevent a patent from being found invalid for obviousness in the UK, if each individual step needed to reach the claimed invention would, in the court's analysis, have been obvious to the relevant skilled team. All of that investment and ingenuity is taken as read, it seems. 

It remains to be seen whether Bayer (which also lost a challenge by Teva against a patent concerning the same invention in Germany) will appeal the decision.