Substitutability Key Factor in Obviousness Analysis
In 2017 NZIPOPAT 23 Merial Inc v Alleva Animal Health Limited the Assistant Commissioner declined to make a finding of obviousness even though the prior art primarily only differed in not mentioning the specific salt of levamisole used and despite allowing salts of levamisole to be used...
Allevia opposed Merial’s 1953 Act patent application for injectable parasiticidal formulations of levamisole and macrocyclic lactones, wherein the levamisole is levamisole phosphate. Allevia’s strongest ground of opposition was that Merial’s proposed invention is obvious with respect to a foreign specification published in 2002. That earlier specification claimed an injectable veterinary compound formulation containing levamisole or salts thereof and macrolide vermifuge, and the specification includes preferred formulations and examples that use levamisole hydrochloride – but not levamisole phosphate.
Amongst other things, the Assistant Commissioner held that the following were part of the common general knowledge at the priority date:
Levamisole is typically used in a salt form since the salts tend to dissolve better in water than the base.
The two most well-known levamisole salts are levamisole hydrochloride and levamisole phosphate.
While levamisole is usually present as the hydrochloride salt, levamisole phosphate is known to be less irritating than levamisole hydrochloride.
Levamisole phosphate is the preferred levamisole salt for use in preparing injectable formulations, as the hydrochloride salt of levamisole causes tissue irritation at the site of injection.
Injectable formulations have formulating challenges and constraints (i.e. achieving shelf stable dissolved or suspended combination formulations).
Alleva argued that the skilled person would understand the prior art’s use of the term ‘salts’ to include both levamisole hydrochloride and levamisole phosphate, particularly so given that they are the two main salts of levamisole used in veterinary medicine. Merial argued that there is no motivation to substitute levamisole phosphate and that any such substitution could lead to stability, efficacy and tolerability issues.
While both specifications have overlapping ranges of levamisole concentrations, the preferred formulations and examples involving levamisole or levamisole hydrochloride in the prior art specification were lower and outside the levamisole concentration range of the opposed application. Alleva downplayed the difference, considering Merial’s higher range to be likely due to the need to accommodate the required doses of both active ingredients while maintaining a practical injection volume.
However, the Assistant Commissioner held that the differences between the specifications constitute steps which would not be obvious to a normally skilled but unimaginative addressee. In particular, the substitution of levamisole phosphate may not be a straightforward choice because the substitution could affect the overall stability and other properties of the composition. The Assistant Commissioner found support for this conclusion in a third party’s patent specification covering similar subject matter which noted the difficulty in achieving an acceptable formulation even for highly experienced formulation chemists.