The end of a dream: reasoned order puts paid to SPC hopes for adjuvants

Back in March, Mr Justice Arnold referred two short, succinct questions to the Court of Justice of the European Union for a preliminary ruling. Just eight months later we now have, in place of the Advocate General's Opinion and CJEU ruling, what the CJEU calls a "reasoned order". The case in question is Case C-210/13 Glaxosmithline Biologicals SA, Glaxosmithkline Biologicals, Niederlassung der Smithkline Beecham Pharma GmbH & Co. KG v Comptroller-General of Patents, Designs and Trade Marks and the questions referred were these:

Is an adjuvant which has no therapeutic effect on its own, but which enhances the therapeutic effect of an antigen when combined with that antigen in a vaccine, an 'active ingredient' within the meaning of Article 1(b) of Regulation 469/2009/EC ?

2. If the answer to question 1 is no, can the combination of such an adjuvant with an antigen nevertheless be regarded as a 'combination of active ingredients' within the meaning of Article 1(b) of Regulation 469/2009/EC?

The answer given in the reasoned order is as follows:

"Article 1(b) ... must be interpreted as meaning that, just as an adjuvant does not fall within the definition of 'active ingredient' within the meaning of that provision, so a combination of two substances, namely an active ingredient having therapeutic effects on its own, and an adjuvant which, while enhancing those therapeutic effects, has no therapeutic effect on its own, does not fall within the definition of 'combination of active ingredients' within the meaning of that provision".

You can read the reasoned order (which is not currently on the Curia website) here or download it here.

GSK adjuvants reference: still time to comment

The SPC Blog has received the following email from the United Kingdom's Intellectual Property Office this afternoon:

We have received notification of a new case reference to the ECJ.  ...  In GlaxoSmithKline v Comptroller General of Patents [2013] EWHC 619 (Pat) the following questions were referred:

1.            Is an adjuvant which has no therapeutic effect on its own, but which enhances the therapeutic effect of an antigen when combined with that antigen in a vaccine, an 'active ingredient' within the meaning of Article 1(b) of Regulation 469/2009/EC?
 2.            If the answer to question 1 is no, can the combination of such an adjuvant with an antigen nevertheless be regarded as a 'combination of active ingredients' within the meaning of Article 1(b) of Regulation 469/2009/EC?"

 Case summary:

The appellant applied for an SPC relating to the product "an oil in water emulsion comprising squalene, DL-α-tocopherol and polysorbate 80", an adjuvant known as AS03. An additional application was filed for a pandemic influenza vaccine containing the adjuvant AS03.

Question 1 concerns whether or not an adjuvant, such as that common to these applications, can be considered an active ingredient within the meaning of Article 1(b) of the Regulation. Question 2 seeks to determine if the combination of an antigen, such as the influenza vaccine component of the latter application, and the adjuvant may be considered an active ingredient if the adjuvant alone may not.

This case and the questions referred to the court can be viewed on our website at:

http://www.ipo.gov.uk/pro-policy/policy-information/ecj/ecj-2013.htm

If you would like to comment on this case please email policy@ipo.gov.uk by 14 June 2013.

If you'd like to makes comments that will guide the UK government as to whether it should make representations in this reference, you have until Friday to do so.

"Dysfunctional" SPC system needs revision, says judge

Glaxosmithkline Biologicals SA v Comptroller-General of Patents, Designs and Trade Marks [2013] EWHC 619 (Pat), a Patents Court for England and Wales ruling of Mr Justice Arnold, has become the latest SPC case to be the subject of a reference to the Court of Justice of the European Union for a preliminary ruling. 

In short, GSK applied for a supplementary protection certificate for "an oil in water emulsion comprising squalene, DL-α-tocopherol and polysorbate 80", an adjuvant known as AS03 protected by European Patent (UK) No 0 868 918. Later, GSK applied for a supplementary protection certificate for "an adjuvanted influenza vaccine comprising an influenza virus component which is an influenza virus antigen from an influenza virus strain that is associated with a pandemic outbreak or has the potential to be associated with a pandemic outbreak, wherein the adjuvant is an oil in water emulsion comprising squalene, DL-α-tocopherol and polysorbate 80", a vaccine comprising an antigen and AS03 protected by European Patent (UK) No 1 618 889.  In both cases GSK relied upon marketing authorisation EU/1/08/453/001 for a pre-pandemic influenza vaccine against the H5N1 subtype of influenza A virus marketed by GSK under the trade mark Prepandrix. In decision BL O/506/12 the UK IPO decided that neither application was allowable: AS03 was not an "active ingredient" of Prepandrix. GSK appealed to the Patents Court and Arnold J decided to refer the following questions to the Court of Justice:

"1. Is an adjuvant which has no therapeutic effect on its own, but which enhances the therapeutic effect of an antigen when combined with that antigen in a vaccine, an 'active ingredient' within the meaning of Article 1(b) of Regulation 469/2009?

2. If the answer to question 1 is no, can the combination of such an adjuvant with an antigen nevertheless be regarded as a 'combination of active ingredients' within the meaning of Article 1(b) of Regulation 469/2009?"

Andrew Waugh QC (3 New Square) and Emma Fulton (Hogan Lovells International LLP) both emailed to draw the attention of this blogger to the text which we have reproduced in bold type.

84. In case it assists, I shall state my own view on these questions. While I acknowledge the force of counsel for GSK's argument that the primary purpose of the SPC Regulation is to reward innovative research of the kind that led to the development of AS03 and Prepandrix, I find the arguments presented by counsel for the Comptroller more convincing. In particular, I consider that the SPC Regulation was intended to provide a simple and predictable system that could be operated by the competent authorities of the Member States, and in particular the national patent offices, in a uniform manner. To achieve those objectives, it is necessary to have bright-line rules. Article 1(b) is such a rule. In my view the Court of Justice was correct to hold in Pharmacia, MIT and Yissum that it should be strictly interpreted. The result of a strict interpretation is to deny extended protection for what may well be meritorious inventions, but the price of not adopting a strict interpretation is a level of uncertainty and inconsistency which in my opinion is unacceptable. Accordingly, I would answer both questions no.

85. It is worth adding that, as counsel for the Comptroller pointed out, GSK may be able to obtain an SPC for the antigen contained in Prepandrix based on the 889 patent and the marketing authorisation for Prepandrix. Thus refusal of the appeal would not necessarily leave GSK bereft of protection.

86. Finally, I would observe that this is the third time in six months that I have had to refer questions of interpretation of the SPC Regulation to the CJEU. I do so with considerable regret. That this should be necessary demonstrates the dysfunctional state of the SPC system at present. This is primarily due to the poor drafting of the SPC Regulation and to the failure of the European Commission, Council and Parliament to revise it to address the problems which have emerged. Matters have not been assisted, however, by the fact that the Court of Justice's recent case law interpreting the SPC Regulation has not provided the level of clarity and consistency that is required.

This blogger is fully in agreement with the judge's comments.

SPCs on adjuvants??

The SPC blog has found out that a couple of patent offices, Italy and Slovenia, have granted SPCs on vaccine adjuvants (generally vaccine components that modify the immune response to an antigen). We recall from the SPC blog event in January that France had refused such claims, and it wasn't looking too good elsewhere for those seeking this sort of protection.

The medicinal product in question was a combination of antigen + adjuvant, and SPCs were granted to both the adjuvant per se and to the (antigen + adjuvant) as a combination of active substances.

All of this must be considered within the context of the decision in the ECJ Case C-431/04 (MIT) which related to a combination of an active plus a bioerodible matrix that enabled the active to be administered in a therapeutically relevant way. The ECJ decided that:

Article 1(b) of Council Regulation No 1768/92 of 18 June 1992 ...must be interpreted so as not to include in the concept of ‘combination of active ingredients of a medicinal product’ a combination of two substances, only one of which has therapeutic effects of its own for a specific indication.

Does a vaccine adjuvant have a therapeutic effect of its own for a specific indication? A vaccine adjuvant, which itself has some immunological/ physiological effect on a host, might at least be considered to be more of an active substance than a matrix to allow slow release.

Let's throw into the mix (not literally) that some adjuvants for vaccines are being considered as monotherapies in their own right, such as CpG for cancer ...

Moreover, it's an interesting one for patent attorneys and their regulatory teams. Do you argue that an adjuvant is an active, which may be necessary if trying to obtain an SPC on a combination of an old active with new adjuvant, for example. Or do you argue that the adjuvant is a mere excipient to assist in the regulatory process?

If anyone has any other SPC related information on SPCs granted or refused on adjuvants, please do share them with us.