Mr Justice Birss has continued the recent trend of finding pharmaceutical patents directed to incremental inventions (i.e. to the optimisation of known drugs) invalid for inventive step. In Teva UK Limited & Teva Pharmaceuticals Limited v Leo Pharma A/S & Leo Laboratories Limited, two patents owned by Leo (EP1178808 and EP 2455083) were found to be obvious in view of the common general knowledge in combination with US patent 4,083,974 (Turi).
The case concerns the treatment of psoriasis using an ointment comprising a combination of a corticosteroid (e.g. betamethasone) and a vitamin D analogue (e.g. calcipotriol). Both betamethasone and calcipotriol had been used individually for the treatment of psoriasis before the priority date of the patents and had both been prescribed together for separate administration. However, both of the compounds were known to be stable at a different pH and thus could not simply be combined together in a formulation without one of the components becoming unstable. The invention concerned the development of a combination product using the solvent polyoxyproplene 15 stearyl ether, which was shown to result in a stable product. Teva alleged that the patents were obvious, insufficient and contained added matter. Leo applied to amend the claims and indicated that all the claims were valid. The skilled person for the assessment of inventive step was indicated to be a skilled clinician together with a skilled formulator.
Teva indicated that it was obvious to a skilled clinician to develop a combination product in view of the prescription of the components together but for separate administration. Teva indicated that this would help with patient compliance. Further, Teva argued that a skilled formulator would turn to the Turi document when formulating the combination, which disclosed a topical preparation comprising anti-inflammatory steroids together with the solvent polyoxyproplene 15 stearyl ether. Teva indicated that a skilled formulator would include the solvent in the routine screening which would be carried out for appropriate solvents.
Leo counter argued that a combination would not be made using corticosteroids as there is a prejudice against using such compounds in the art, due to their severe side effects. Further, Leo asserted that there was no suggestion in the art to make a combination product and that this supports an inventive step. Leo additionally argued that a skilled formulator would not use the solvent disclosed in the Turi document in any formulation of the combination. They indicated that there was no stability data in Turi and that the solvent had only been used previously in one approved pharmaceutical product, which would dissuade a skilled formulator from using the solvent as it would need extensive testing before gaining marketing approval. Leo further argued that a skilled formulator would not use the solvent of Turi since it would not be familiar to them.
Although Mr Justice Birss indicated that there were points in favour of both parties, he found Teva’s case more persuasive. He agreed that a skilled clinician would be motivated to make the combination and that although the use of corticosteroids had severe side effects, this was a well-established treatment for psoriasis in the art. Birss indicated that although the combination had not been suggested in the art, this was likely due to the pH incompatibility of the two components. Birss further stated that a skilled formulator would not ignore or dismiss the Turi disclosure but would instead test the solvent. The patents were therefore found to be invalid.
Interestingly, it was indicated in the judgement that although not enough evidence had been submitted in the proceedings to support a selection invention (i.e. regarding the selection of the solvent), the submission of evidence showing the testing of many solvents which did not work and the selection of the present solvent, could be compelling to establish a case for inventive step.