Teva brought revocation proceedings based on anticipation and obviousness against AstraZeneca’s (AZ) Patent for the treatment of asthma in the High Court. AstraZeneca later brought infringement proceedings against Teva. The joined hearing took place in June 2014.
Mr Justice Sales decided that AZ’s patent which protects their medicine “Symbicort”, a combination of formoterol and budesonide for the treatment of an acute condition of asthma, was invalid on the grounds of obviousness. AZ’s application to amend the claims was rejected on the basis that it would impermissibly add matter ie new information which was not disclosed in AZ’s original patent application.
Asthma is a respiratory disorder characterised by the narrowing and inflammation of the airways of the lung. During an asthma attack, a patient may use a bronchodilator which will give immediate relief. However it is also important to control long-term inflammation by use of a maintenance treatment. A typical treatment at the priority date, June 1998, of AZ’s Patent was the use of a short acting beta agonist (SABA) for relief; and an inhaled corticosteroid (ICS) on its own or in conjunction with a long acting beta agonist (LABA) for maintenance treatment.
Formoterol is a LABA, but unlike other LABAs it has a rapid onset of action. Due to its long-lasting effect it is useful as part of the maintenance treatment. Since it has rapid onset of action, it could potentially also be used as relief treatment. Budesonide is an ICS.
EP (UK) 1,085,877 is for the use of a composition comprising formoterol and budesonide in a single inhaler which can be used for both maintenance and for relief of an acute condition of asthma.
Teva relied on a 1993 patent as prior art on the basis of which it challenged both the novelty and the inventiveness of the AZ Patent. The invention in the 1993 prior art document was for the use of formoterol and budesonide in combination for simultaneous, sequential or separate administration for the treatment of respiratory disorders such as asthma.
The person skilled in the art (PSIA) and the common general knowledge (CGK)
In assessing inventiveness, the court must consider not only the teaching contained in any prior art, but also the CGK which a skilled person brings to bear upon the reading of that art. This raises the question of who such a person is, and what might constitute the CGK?
AZ’s Patent was addressed to a clinician with a specialist interest in the management and treatment of asthma. Sales J held that it was common ground that leading text books and guidelines on the care of asthma were included in such a person’s CGK. He classified “primary articles” of CGK to include standard reference works, guidelines on asthma, clinical trials and prominent journal articles. AZ relied on the fact that the UK and US guidelines, which dated from 1993-1997, recommended only SABAs for relief, and that the US guidelines had a warning that LABAs (such as formoterol) should not be used for relief. Sales J did not consider the guidelines to be a definitive statement of CGK since they were aimed at a range of practitioners in asthma including those such as GPs with less specialist knowledge in respiratory medicine. He also noted that there were no full safety trials carried out on the use of LABAs (such as formoterol) for relief treatment nor were there any granted marketing authorisations for use of LABAs for relief. Therefore, it would not have been correct for the guidelines to suggest off label use. He also held that in June 1998 the PSIA would have had a better understanding of different treatments for asthma and that since formoterol had a rapid onset, the PSIA would have appreciated that this could be used as a relief drug.
Sales J referred to previous authorities that indicated that CGK includes not just information directly in the mind of the notional skilled person, but such information as he would be able to locate by reference to well-known textbooks. He stated that “this guidance needs to be adapted and kept appropriately up to date for the procedures for dissemination of scientific knowledge in the age of the internet and digital databases of journal articles.” So “if there is a sufficient basis, that in the background CGK relating to a particular issue to make it obvious to the unimaginative and uninventive skilled person that there is likely to be – not merely a speculative possibility that there may be – relevant published material bearing directly on that issue which would be identified by such a search, the relevant CGK will include material that would readily be identified by such a search.” It is interesting to note that Sales J acknowledges the possibility that search results from digital databases and even the internet may form part of the CGK.
Sales J then went on to discuss “secondary articles” such as relevant leading articles considered as CGK and relied on by Teva. He held that the references in these articles to the possible use of formoterol for relief were so extensive that it would have been obvious to the PSIA that formoterol could have been used as a relief drug, and that since formoterol is a LABA, that it could be used alongside an ICS for maintenance treatment.
Sales J considered articles relied on by both parties as “tertiary articles”. These articles were published after the priority date and therefore did not form part of the CGK in June 1998, but were indicative of what the PSIA would have thought in light of the available literature in June 1998. He stressed the importance of exercising caution in assessing such submissions and held that in this case, they were not of great assistance in relation to assessing the CGK at the date of the prior art publication, nor at the priority date of the Patent.
Prior art must be construed at the date of its publication, whereas for the question of obviousness, the prior art document must be considered in light of the CGK at the priority date of the Patent in suit (in this case 1998). In fact Sales J found that nothing had changed in relation to the CGK between 1993 and June 1998, the period in issue, for the purposes of interpreting at 1998, the 1993 prior art document. The reader brings the 1998 CGK to bear on understanding of the document of the 1993 prior art. Sales J noted that the prior art document taken on its own did not show that the idea of using formoterol and budesonide for both maintenance and relief was obvious in June 1998. However, by reference to the 1993 priority document read in light of the CGK in 1998, it was held that the AZ Patent was obvious and therefore invalid. Sales J considered the four stage approach to assess obviousness as set out in Pozzoli Spa v BDMO SA and the guidance provided in MedImmune v Novartis. He concluded that in June 1998, the PSIA would have regarded it obvious to combine the dose of formoterol and budesonide for both maintenance and relief therapy with a fair expectation of succeeding in securing effective treatment of asthma, particularly as the fast onset of formoterol was well known in 1998.
He stressed that AZ’s Patent had not made any attempts to explain why the use of formoterol and an ICS in combination for both maintenance and relief would be safe, that AZ had not carried out any phase 3 trials to establish the safety of the treatment since they did not wish to incur the costs of carrying out trials to establish safety before securing a monopoly. Implicitly, these factors suggested that AZ were aware that there was no issue to be overcome in those respects, and in doing so they could be taken to be accepting the obviousness of their solution.