The opposition division decided that European patent 2 627 318 as amended in accordance with auxiliary request 2 met the requirements of the EPC. The patent proprietor and the opponent filed appeals.
Claim 1 as granted related to:
"A composition comprising
(a) a pharmaceutically active protein, peptide or mixture thereof,
(b) a mixture of a hydrophilic polymer and a non-ionic detergent, wherein the non-ionic detergent is present in said composition in an amount of between 0.2 and 0.01 mg/g, and the weight ratio of hydrophilic polymer to non-ionic detergent is from 18:1 to 22:1 (wt-%), and
(c) a mixture of a polyalcohol and a sugar, wherein the weight ratio of polyalcohol to sugar is from 2:1 to 5:1 (wt-%),
wherein the composition is free of animal or human serum albumin, gelatine, amino acids selected from histidine, lysine and methionine, and/or immunoglobulins."
Claim 2 as granted defined:
"A composition comprising
(i) a pharmaceutically active protein, peptide or mixture thereof,
(ii) a mixture of a hydrophilic polymer and a non-ionic detergent, wherein the non-ionic detergent is present in said composition in an amount of between 0.2 and 0.01 mg/g, and the weight ratio of hydrophilic polymer to non-ionic detergent is from 2:1 to 30:1 (wt-%), and
(iii) a sugar, wherein no polyalcohol is present and the composition is free of animal or human serum albumin, gelatine, amino acids selected from histidine, lysine and methionine, and/or immunoglobulins, and wherein the composition is not a composition comprising <= 1.6 ng neurotoxic component of Botulinum toxin, 1.0 mg of hyaluronic acid, 10.0 mg of sucrose and 0.2 mg of polysorbate 80."
With the statement of grounds of appeal, the appellant-opponent filed documents D9 and D10.
The appellant-opponent justified the filing of the new facts, arguments and documents in view of the conclusion in the decision under appeal that the appellant-opponent had not discharged the burden of proof on insufficiency.
The appellant-opponent's objection do not address the considerations which led to the decision under appeal, but rather change the dimension of the objection to the extent that it confronts the appellant-patent proprietor and the Board with a fresh case. The Board does therefore not admit these new facts, arguments and evidence into the appeal proceedings under Articles 12(2), 12(4) and 12(6) RPBA 2020.
The Board concludes that the patent as granted fulfills the requirement of sufficient disclosure.
The compositions of claims 1 and 2 as granted comprise in addition to the pharmaceutically active protein or peptide a mixture of a hydrophilic polymer and a non-ionic detergent as well as a sugar. Due to the defined weight ratios of the hydrophilic polymer in relation to the detergent, the claims also require specific concentration ranges for the hydrophilic polymer. Claim 1 as granted further defines the presence of a polyalcohol in a defined weight ratio to the sugar, whereas claim 2 as granted excludes the presence of a polyalcohol.
The compositions from documents D5 and D1 differ from the compositions defined in the claims as granted in the substantially higher content of the non-ionic detergent and the hydrophile polymer and their ratio or the drastically higher content of the ionic detergent in the absence of a hydrophile polymer.
The patent reports in its experimental section that compositions in accordance with claims 1 and 2 which are lyophilized show stability over 12 months storage.
The appellant-opponent argued that the patent only demonstrated stability for lyophilized compositions not covered by the claims and that the stability profiles of proteins depend on the nature of the protein and the excipients. In its view it was therefore not credible that a stabilizing effect is achieved over the whole scope of the claim.
The Board considers that the patent substantiates in the experimental section that exemplified compositions covered by the claims allow for the preparation of stable lyophilised Botulinum toxin formulations.
In the absence of substantiated arguments from the appellant-opponent to the contrary, this effect may be considered representative for the whole scope of the claims.
Information contained in D1, D4, D5 and D6 does not affect the teaching in the patent regarding the stabilizing effect of the compositions as defined in the claims as granted, which are concerned with particular new combinations of the defined excipients.
The Board therefore considers that the problem to be solved may be formulated as the provision of an alternative composition for stabilizing a pharmaceutically active protein or peptide.
For the assessment of inventive step of claims 1 and 2 as granted it is therefore decisive whether or not the skilled person would have expected that the protein stabilisation in the compositions as described in documents D5, D2 or D1 would be retained in compositions as defined in claims 1 and 2 as granted.
The Board observes that it is evident from document D5 that protein compositions such as Botulinum toxin are highly sensitive and that the stability of such compositions depends on a variety of factors. In view of this sensitivity it would not have been obvious to the skilled person that the compositions with the reduced detergent concentration and the changed content of hydrophile polymer as defined in the claims of the patent represent a solution to the problem of providing an alternative composition for stabilizing a pharmaceutically active protein or peptide.
Accordingly, the Board concludes that the patent as granted fulfills the requirement of inventive step.
The patent is maintained as granted.