Losartan SPC extension under Paediatric Regulation

01 November 2009

Eleanor Root, Mary Smilie

This article was first published in the August edition of the World Intellectual Property Review.

The UK Court of Appeal rejects a narrow construction of the requirements to obtain paediatric extensions to Supplementary Protection Certificates, bringing the UK into line with other Member States.


On 19 August 2009, just days before the SPC for losartan (an anti-hypertensive) expired, the UK Court of Appeal  overturned the decision of the High Court (which followed that of the UK Intellectual Property Office) and agreed that the SPC should be extended for 6 months under the Paediatric Regulation.  This brought the UK in line with the approach adopted elsewhere in Europe where SPC extensions were granted during the course of the summer.  The case turned on the interpretation of the meaning of “irregularities”and the ability to correct such irregularities; this was finally given a wide interpretation, largely into line with the reasoning of the Dutch Patent Office, the guiding principle being the purpose of the Paediatric Regulation – namely to reward those who carry out investigations into the potential benefits or risks of treating children (0-18 years) with any given product and disseminating that information on a Community wide basis.

With the publication of the Judgment on 17 September 2009, it is apparent that there is scope for further clarification on the Paediatric Regulation before the transition period finishes on points that the Court of Appeal did not consider it could give further guidance. These include whether an expired SPC can be extended, and what constitutes unreasonable behaviour by the applicant when it comes to the determination of time limits for an applicant to supplement its application with missing material.


Originators of medicinal products can in effect extend their period of patent protection, providing certain conditions are met, by the Supplementary Protection Certificate (“SPC”) scheme which was introduced by Regulation EEC/1768/92 and now replaced by a codified version EC/469/2009 (the “SPC Regulation”).  This is to make up for the time taken to develop a medicinal product and obtain regulatory approval which in effect eats into the patent term.  One of the features of the SPC is that, like the patent on which it is based, it is national; an SPC has to be applied for in each Member State where it is wanted.

As an incentive to encourage the research into the use of medicinal products in children, provision has been made for a possible 6 month extension to an SPC by the Paediatric Regulation EC/1901/2006 (“Paediatric Regulation”).

Losartan is one of the first drugs for which a Paediatric Extension has been sought (under the transitional provisions) and therefore the first real test of the interpretation of the Paediatric Regulation.  In this case the different Member States, at least initially, have not all interpreted the requirements in the same way. 

The UK Court of Appeal considered that this type of case would be suitable for a referral to the European Court of Justice, but in reality it would not often be feasible bearing in mind the time-scales involved.  Accordingly, the national courts must of necessity decide and so in this case the Court of Appeal was prepared to give guidance as far as it considered it legitimate on administering the Paediatric Regulation.


E I Du Pont Nemours & Co (“Du Pont”) originally applied for a patent for losartan on 9 July 1987, which expired on 9 July 2007. The Marketing Authorisation (“MA”) for Cozaar, the branded product containing losartan sold by Du Pont’s licensee Merck was granted in Denmark on 26 September 1994.  Therefore just over seven years of marketing had been lost by the time Cozaar was authorised and was put on the EU market.  Du Pont applied in 13 Member States for an SPC, which was granted in all cases and these were due to expire on 1 September 2009.  

During the five year transitional period for the Paediatric Regulation, the applicant has to file the application for the 6 month SPC extension at least six months before the SPC expires.  This transitional arrangement is in place until 26 January 2011 after which the general provision is that the application for a paediatric SPC extension should be filed not later than two years before SPC expiry.  Accordingly, the problems experienced by Du Pont are therefore only likely to be seen during the transitional period, as there is currently a period of “catch-up” for existing products where it takes time to do the clinical studies, and obtain the necessary Regulatory approvals.

In this case, Du Pont had the deadline of 1 March 2009.  They filed their application on 18 February 2009 in 13 Member States, including the UK.  The application filed with the UK Intellectual Property Office (“UK IPO”) and corresponding offices of the relevant Member States was deficient in that it did not contain an MA including a statement referred to in Article 28(3) and the product was not authorised in all Member States as required by Article 36(3). 
There is much cross-referring in the SPC and Paediatric Regulations which makes life difficult for the reader but the pertinent parts for this case are set out below.

Article 8 of the SPC Regulation sets out the required content of the application for an SPC and Article 8(1)(d) deals with the issue of an extension to the SPC.

Article 8 of the SPC Regulation

Content of the application for a certificate

1. The application for a certificate shall contain:

(d) where the application for a certificate includes a request for an extension of the duration:
(i) a copy of the statement indicating compliance with an agreed completed paediatric investigation plan as referred to in Article 36(1) of [the Paediatric Regulation];
(ii) where necessary, in addition to the copy of the authorisation to place the product on the market as referred to in point (b), proof of possession of authorisations to place the product on the market of all other Member States, as referred to in Article 36(3) of [the Paediatric Regulation].

As can be seen, this cross refers to Article 36 of the Paediatric Regulation.

Article 36 of the Paediatric Regulation

1. Where an application under Article 7 or 8 includes the results of all studies conducted in compliance with an agreed paediatric investigation plan, the holder of the patent or supplementary protection certificate shall be entitled to a six-month extension of the period referred to in Articles 13(1) and 13(2) of Regulation (EEC) No. 1768/92 .

The first subparagraph shall also apply where completion of the agreed paediatric investigation plan fails to lead to the authorisation of a paediatric indication, but the results of the studies conducted are reflected in the summary of product characteristics and, if appropriate, in the package leaflet of the medicinal product concerned.

2. The inclusion in a marketing authorisation of the statement referred to in Article 28(3) shall be used for the purposes of applying paragraph 1 of this Article.

3. Where the procedures laid down in Directive 2001/83/EC have been used, the six-month extension of the period referred to in paragraph 1 shall be granted only if the product is authorised in all Member States. 

The reference to the procedures laid down in Directive 2001/83 refers to the Directive which deals with the Marketing Authorisation system and in particular regulates the Mutual Recognition Procedure which is relevant in this case.

To follow the cross-referencing, see the relevant sections of Articles 7, 8 and 28 of the Paediatric Regulation.

Article 7 of the Paediatric Regulation

1.  An application for marketing authorisation under Article 6 of Directive 2001/83/EC in respect of a medicinal product for human use which is not authorised in the Community at the time of entry into force of this Regulation shall be regarded as valid only if it includes, in addition to the particulars and documents referred to in Article 8(3) of Directive 2001/83/EC, one of the following:

(a) the results of all studies performed and details of all information collected in compliance with an agreed paediatric investigation plan;
(b) a decision of the Agency granting a product-specific waiver;
(c) a decision of the Agency granting a class waiver pursuant to Article 11;
(d) a decision of the Agency granting a deferral.

For the purposes of point (a), the decision of the Agency agreeing the paediatric investigation plan concerned shall also be included in the application.

2. The documents submitted pursuant to paragraph 1 shall, cumulatively, cover all subsets of the paediatric population

Article 8 of the Paediatric Regulation [required from 26 January 2009]

In the case of authorised medicinal products which are protected either by a supplementary protection certificate under Regulation (EEC) No 1768/92, or by a patent which qualifies for the granting of the supplementary protection certificate, Article 7 of this Regulation shall apply to applications for authorisation of new indications, including paediatric indications, new pharmaceutical forms and new routes of administration.

For the purposes of the first subparagraph, the documents referred to in Article 7(1) shall cover both the existing and the new indications, pharmaceutical forms and routes of administration.

Article 28 of the Paediatric Regulation

1. …
Where authorisation is granted, the results of all those studies shall be included in the summary of product characteristics and, if appropriate, in the package leaflet of the medicinal product, provided that the competent authority deems the information to be of use to patients, whether or not all the paediatric indications concerned were approved by the competent authority.

3. If the application complies with all the measures contained in the agreed completed paediatric investigation plan and if the summary of product characteristics reflects the results of studies conducted in compliance with that agreed paediatric investigation plan, the competent authority shall include within the marketing authorisation a statement indicating compliance of the application with the agreed completed paediatric investigation plan.  …

What came to be the key article for interpretation in this case was Article 10 of the SPC Regulation.

Article 10 of the SPC Regulation

3. Where the application for a certificate does not meet the conditions laid down in Article 8, the authority referred to in Article 9(1) shall ask the applicant to rectify the irregularity, or to settle the fee, within a stated time.
4. If the irregularity is not rectified or the fee is not settled under paragraph 3 within the stated time, the authority shall reject the application.

6. Paragraphs 1 to 4 shall apply mutatis mutandis to the application for an extension of the duration.

Returning to the facts of this case, the reason that Du Pont’s application was deficient was because the varied MA containing the statement of compliance under Article 28(3) was only issued by the reference member state (the Dutch regulatory authority, the Medicines Evaluation Board (the “MEB”)) in April 2009.
Furthermore, despite the obligations for submission and processing of variations under the Mutual Recognition Procedure only 25 of the 26 Member States had issued their varied MAs by 6 July 2009. 

Only on the 9 August 2009 did  the last Member State grant the necessary variation to the relevant MA requiring the inclusion of the statement of compliance required by Article 28(3).

UK Case

At first instance , the UK IPO hearing officer refused the application for the extension, as there were three requirements which had to be met:

(i) All measures in the agreed Paediatric Investigation Plan (the “PIP”) had to be complied with;
(ii) The relevant results of paediatric studies had to be included in the authorised product information (Summary of Product Characteristics and Package Leaflet); and
(iii) The medicinal product the subject of the PIP had to be authorised in all Member States.

This decision was appealed by Du Pont to the High Court on 22 May 2009, where the decision to reject the application was upheld .  The High Court considered whether the missing information could be submitted after the deadline set out in Article 10 of the SPC Regulation (set out above).

On this, Du Pont argued that a deficiency in their application was a deficiency within Article 10(3) and it should be given time to put it right.  The UK IPO submitted that Article 10(3) was to correct formalities in any application which may need correction, but was not concerned with substantive deficiencies.

The Judge found little guidance in the authorities as to what amounts to an irregularity within Article 10(3) save an observation from Advocate General Fennelly in Biogen  that the provision “provides for a degree of flexibility on the part of the competent national industrial property office, to ensure that applications are not needlessly obstructed by procedural difficulties”.

It was held by the High Court that the failures and deficiencies could not be described as deficiencies within Article 10, because by the time the application deadline of 1 March had passed, Du Pont could not satisfy the relevant criteria. 
The Court of Appeal agreed with the UK IPO and the High Court that the objectives of the Paediatric Regulation are to be achieved by the three substantive requirements as set out above.  Furthermore, the meaning of “authorisations to place the product on the Market of all the Member States” must “give way to the entire purpose of the Paediatric Regulation and the clear intention that you are not to get your reward unless products carrying the information generated by carrying out the agreed PIP are authorised EU wide”, in other words, there is no sense in saying that an MA which does not include the information is enough to get the reward.

However, the decision of the High Court was overturned on the basis of the interpretation of Article 10 of the SPC Regulation.  

Jacob LJ found that the UK IPO Hearing Officer’s decision “took a faintly absurd position”.  It accepted that Article 10(3) of the SPC Regulation was mandatory in nature and required it to state a time for Du Pont to cure the irregularity (it set a deadline of 6 July 2009).  However, at the same time it held that the irregularity could not be cured in any event.  Therefore the date set was pointless.

Jacob LJ found no reason to give “irregularity” such a restrictive meaning, and “every reason to give it a wide enough meaning to encompass cases such as the present where the defect is cured after the date of application”.  In Du Pont’s case, unless it had behaved unreasonably, where the necessary Article 28(3) statement and updated MAs from all Member States had not come into existence by either the date of application or the last possible date for an application, time should be extended so that it obtains the reward before the basic SPC expired. 

The decision was given at the oral hearing (held on 19 August 2009) so that the UK IPO could extend the SPC before it expired.   In the Judgment handed down on 17 September 2009 Jacob LJ stated that the reasons for the decision were largely the same as that of the Dutch Patent office.

Stanley Burnton and Ward LJJs agreed, with further discussion regarding the meaning of “irregularity”, and with the additional suggestion that “an irregularity is a failure of the application to contain the requisite documents”.

Situation in other Member States

It appears that the various Member States took different approaches in coming to the conclusion that the SPC extension could be granted and they did so over different time periods.  Of note, is that the Dutch Patent Office granted the SPC extension on 2 June 2009, in full knowledge of the ruling given at the time by the UK High Court, which had upheld the UK IPO decision not to grant the six month extension.  The Dutch Patent Office reportedly had two pieces of evidence from the MEB, a compliance statement dated 16 April 2009 and an end-of-procedure notification, which were not submitted to the UK High Court. The Dutch IPO considered that the documents from MEB could be added to the application post-filing to rectify it and stated its disagreement with the UK High Court on this point.

Further, as regards Italy, it is interesting in that it was not the Italian PTO which issued the official communication about the grant of the paediatric extension for losartan, but instead the Italian Regulatory Authority, AIFA.  The communication said that AIFA had accepted the variation to the MA to add the paediatric information, and also that the patent owner or SPC owner has the right to the 6 month SPC extension period. 


The Court of Appeal Judgment brings the UK into line with the rest of Europe, in clarifying the interpretation of the requirements to obtain a SPC extension of 6 months under the Paediatric Regulation.  The scenario and corresponding issues arising may well be limited to the transitional period, where in some respects applicants are under time pressure as their existing SPCs are coming up to expiry, and time is lost, as it is eaten up obtaining the relevant regulatory approvals.   

In an ideal world, the Court of Appeal would have liked to make a reference to the ECJ, but with only days to the expiry of the SPC it realised the practical necessity for it to make a decision.  It is a decision based on the purpose of the Paediatric Regulation which is to encourage specific research into medicines suitability (or unsuitability) for children and dissemination of the resulting knowledge.  It would be against that purpose where an applicant who has done everything it can to fulfil the requirements to obtain the reward under the Paediatric Regulation is denied that reward because of the relevant regulatory authorities not fulfilling their obligations in respect of deadlines under the regulatory procedures. 

The UK IPO asked for future guidance on how late an applicant could be in supplementing its application with missing materials.  The guidance given was that “in setting the Article 10(3) period the Comptroller can and should take into account all relevant factors.  These will include the reasons for the failure to include all the Article 8(1) materials in the application, the extent to which the applicant is guilty of unreasonable conduct or delay, and how close to the date of expiry of the SPC full compliance with Article 8(1) is expected”.  The guiding principle is the purpose of the Paediatric Regulation.

As this Judgment was made “just in time” the question of whether a SPC can be extended once it has expired remains unanswered.  Jacob LJ stated that it is not clear whether an SPC can be extended after it has expired. 

Seemingly it would be difficult to do so in a practical sense, because once the SPC does expire, generic companies would be in a position to launch their product (quite lawfully), and logistically it would be difficult for them to withdraw that product from the market, should a SPC extension be granted after that time.  It would also be seemingly unfair, in adding some uncertainty as to whether or not it was safe to launch the product.  If a future court should find that it is possible, then the practical solution to the problem of generic product having come on the market, might lay in a compulsory licence, with some royalty payable by the generic companies to the rights holder for the six month period.