The recent Commercial Court case of Glaxo Group Limited v Patents Act (2009), is the only Irish decision in recent times to deal with the revocation of a patent on the grounds of lack of inventive step. In this revocation application, taken by Ivax International BV (“IVAX”), Mr Justice Charleton considered the concept of obviousness and held that Glaxo’s asthma inhaler medicine SERETIDE, which consists of a mixture of two products, must be revoked for want of inventive step. This article reviews the position in Ireland concerning the revocation of pharmaceutical patents on the basis of obviousness in light of the recent Glaxo case.
Sections 57 and 58 of the Patents Act 1992 (as amended) (the “Act”) provide the Irish statutory basis for the revocation of patents and is reflective of Article 138 of the European Patent Convention. Of principle concern to the Glaxo case was Section 58(a) of the Act, which provides that a patent may be revoked where “the subject-matter of the patent is not patentable under this Act”. Under Irish law, an invention must involve an inventive step before it can be patented and this is the case where, having regard to the state of the art, the invention is not obvious to a person skilled in the art.
The Glaxo case
The patent at issue in the Glaxo case was for putting two existing medicaments that make up SERETIDE, salmeterol and fluticasone propionate into a simple preparation. Glaxo also had two patents for each of the individual medicaments that made up SERETIDE. In the proceedings, Ivax had argued that the combining of these two medications into one product for use by asthma sufferers was obvious and therefore the invention lacked inventive step.
Mr Justice Charleton noted the previous UK decision of Pumfrey J. in Cipla Limited v Glaxo Group Limited (2004), in which the corresponding UK patent for SERETIDE was revoked in that case. However, Charleton MJ noted that substantially different facts were argued and new witnesses called in the Irish litigation and these differences were based upon a prejudice in the state of the art concerning the mutual chemical reactivity of the two compounds. As such matters were not argued in the UK litigation it therefore warranted a full review of the evidence in the Irish proceedings and “with an open mind”.
Regarding, the concept of obviousness, Mr Justice Charleton stated that “an obvious step is the antithesis of an inventive step” and that the burden of proving that the combination of molecules in SERETIDE was obvious rested with the party attacking the patent, i.e. Ivax.
Mr Justice Charleton noted the difference in approach between the test adopted by the European Patent Office on the one part, i.e. (i) determine the closest prior art, (ii) establish the technical problem to be solved and (iii) based on (i) and (ii) consider whether or not the claimed invention would have been obvious to the skilled person, and the four step test adopted by the English courts on the other, which was restated by Jacob LJ in Pozzoli SPA v BDMO SA (2007) as follows:
- identify the notional “person skilled in the art” and the relevant common general knowledge of that person;
- identify (or if necessary construe) the inventive concept of the claim in question;
- identify what, if any, differences exist between the cited prior art and the inventive concept of the claim; and
- do these differences, when viewed without any knowledge of the alleged invention as claimed, constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention.
Charleton MJ stated a preference for the European test but applied the English test to the patent in question, as this test had been agreed between the parties for the purposes of the proceedings, having considered that “neither test changes the result by its application”.
The judge, disregarding the benefit of hindsight and whether a particular research avenue may seem sensible as having any bearing on the test of obvious, considered that the task before him was to assess:
“whether it would have been obvious to a person skilled in the art, and therefore having common general knowledge, to take the new long acting â-agonist salmeterol, an anologue of salbutamol, perhaps in a physiologically acceptable salt form, and to combine it with the new steroid fluticasone propionate in a pharmaceutical preparation.”
Against this issue, Mr Justice Charleton considered that Glaxo’s previous combination for asthma, VENTIDE, which combined a shorter acting but quicker relief â-agonist (salbutamol) and a less effective steroid (beclomethasone dipropionate), was an important factor on whether the combination of the two constituent products of SERETIDE was an obvious step. In his analysis, Mr Justice Charleton also approved the up-to-date analysis of “obvious to try” by Lord Walker in the House of Lords decision in Connor Medsystems v Angiotech Pharmaceuticals (2008).
The judge noted that much of the evidence presented at trial dealt with the issue of whether the common general knowledge of the person skilled in the art would include prejudices such that a person skilled in the art would reject the combination in SERETIDE at discussion stage or even out of hand on the relevant priority date, namely 8 September 1989. If such a prejudice existed in the state of the art then the judge considered that even trying the combination of the constituent products of SERETIDE would be considered inventive and not obvious.
At the trial of the action, Glaxo submitted that the prejudice in the common general knowledge was that the person skilled in the art would: (i) have expected the two components to exhibit chemical reactivity and instability and (ii) possess no clinical motivation to create the combined preparation in view of serious concerns about the regular use of â-agonists in asthma therapy, in combination or otherwise. An initial claim of prejudice relating to the synergistic activity of the two products was not subsequently pursued by Glaxo at trial.
Charleton MJ held that any decision as to obviousness would depend on the analysis of the evidence by the person skilled in the art. In the judge’s view such a notional person in almost all pharmaceutical cases would be a team. Whilst not identifying all of the members of the team in this instance, the judge was prepared to accept that the team would be led, if not heavily influenced, by a medicinal chemist. A formulation chemist was also referred to in the judgment as forming part of the team. The judge concluded that the objective test to be determined by the team is based on the state of the art globally and that it is not simply a question of what a skilled and highly committed asthma specialist would have found in Ireland as of the priority date. For that reason, the evidence given at the trial concerning clinical practice in Ireland at the relevant priority date was considered to be of very limited benefit.
- Risk of reactivity
Regarding the first prejudice, concerning the risk of reactivity, Mr Justice Charleton formulated the relevant questions to decide as follows:
“Was the chemistry involved in the two compounds of fluticasone propionate and salmeterol, or a physiologically acceptable salt, preparation in the human body like salmeterol xinafloate, such that at the state of knowledge in 1989 the team considering developing a combination product would have rejected an attempt to combine these?”
“Would the skilled team proceed to testing in order to determine stability notwithstanding these issues?”
In answering these questions, the judge deemed it appropriate to look at the nature and cost of relevant testing as a starting point, as this would be in the knowledge of the team considering the reactivity of the products. Regarding the constituent products, salmeterol and fluticasone propionate, the judge considered it fair for the team to infer the inherent stability of these products over a relevant shelf life since each of these compounds had been patented previously as individual compounds.
Charleton MJ considered that the team leader, a medicinal chemist, would have considered steric hindrance (the influence of the spatial configuration of reacting substances upon the rate, nature and extent of reaction) as part of the common general knowledge and that this would provide a “real incentive” for the team to be optimistic that any theoretical problems of reactivity could be overcome. The judge also considered that the team would be influenced by what had been achieved by Glaxo in the prior combination in VENTIDE. As a result, the judge rejected any prejudice of reactivity arising as at the priority date as it did not follow that a reaction between the degradation products of salmeterol xinafoate (which was a stable drug with regulatory approval) and fluticasone propionate would occur.
- Regular â-agonist therapy
In respect of the regular use of â-agonist therapy in the treatment of asthma, Charleton MJ noted that whilst the evidence presented at the trial of the action suggested that the tide of regular use was turning against it, this change in attitude occurred in the early nineties and therefore after the priority date (1989). In addition. the judge noted that a textbook from 1988 with its chapter on asthma written by one of Glaxo’s witnesses, Dr Costello, had recommended the regular use of â-agonist therapy at the more extreme end of the illness. As a result, the judge also rejected any prejudice related to the regular use of â-agonist therapy.
Revocation for lack of inventive step
As a result of excluding the above prejudices to the common general knowledge, Mr Justice Charleton could not accept that the team would not have had any motivation to create a combined preparation of salmeterol and fluticasone propionate. This was based in part on two prior art papers by a Dr Barnes and a Dr Ruffin respectively in 1988 detailing possible treatment compounds for asthma which would influence the team towards considering such treatments. Further, it was held that the combination in SERETIDE was not inventive as it was already obvious from Glaxo’s pre-existing combination product, VENTIDE. Combination therapy for the treatment of asthma was therefore held by Charleton MJ to be an application of prior art and the patent was revoked accordingly.
The decision is understood to be under appeal to the Supreme Court.