Yissum Research and Development Company of the Hebrew University of Jerusalem v Comptroller-General of Patents

Judgment

RICHARD ARNOLD Q.C. :

1. This is an appeal by Yissum Research and Development Company of the Hebrew University of Jerusalem (“Yissum”) from a decision of Mr R.J. Walker on behalf of the Comptroller-General of Patents dated 29 July 2004 (BL O/222/04). By his decision the hearing officer essentially refused Yissum’s request for the grant of a Supplementary Protection Certificate in respect of its European Patent (UK) No. 0129003B2 entitled “Cosmetic and dermatological compositions containing 1-alpha-hydroxycholecalciferol” (“the Basic Patent”) pursuant to Council Regulation 1768/92/EEC of 18 June 1992 (“the Regulation”), although he left the door ajar to a possible amendment of the application.

The Regulation

2. Recitals 1 to 9 of the Regulation state:

“1. Whereas pharmaceutical research plays a decisive role in the continuing improvement in public health;

2. Whereas medicinal products, especially those that are the result of long, costly research will not continue to be developed in the Community and in Europe unless they are covered by favourable rules that provide for sufficient protection to encourage such research;

3. Whereas at the moment the period that elapses between the filing of an application for a patent for a new medicinal product and authorization to place the medicinal product on the market makes the period of effective protection under the patent insufficient to cover the investment put into the research;

4. Whereas this situation leads to a lack of protection which penalizes pharmaceutical research;

5. Whereas the current situation is creating the risk of research centres situated in the Member States relocating to countries that already offer greater protection;

6. Whereas a uniform solution at Community level should be provided for, thereby preventing the heterogeneous development of national laws leading to further disparities which would be likely to create obstacles to the free movement of medicinal products within the Community and thus directly affect the establishment and the functioning of the internal market;

7. Whereas, therefore, the creation of a supplementary protection certificate granted, under the same conditions, by each of the Member States at the request of the holder of a national or European patent relating to a medicinal product for which marketing authorization has been granted is necessary; whereas a Regulation is therefore the most appropriate legal instrument;

8. Whereas the duration of the protection granted by the certificate should be such as to provide adequate effective protection; whereas, for this purpose, the holder of both a patent and a certificate should be able to enjoy an overall maximum of fifteen years of exclusivity from the time the medicinal product in question first obtains authorization to be placed on the market in the Community;

9. Whereas all the interests at stake, including those of public health, in a sector as complex and sensitive as the pharmaceutical sector must nevertheless be taken into account, whereas, for this purpose, the certificate cannot be granted for a period exceeding five years; whereas the protection granted should furthermore be strictly confined to the product which obtained authorization to be placed on the market as a medicinal product.”

3. Articles 1 to 4 of the Regulation provide:

“ARTICLE 1

Definitions

For the purpose of this Regulation:

(a) ‘medicinal product’ means any substance or combination of substances presented for treating or preventing disease in human beings or animals and any substance or combination of substances which may be administered to human beings or animals with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in humans or in animals;

(b) ‘product’ means the active ingredient or combination of active ingredients of a medicinal product;

(c) ‘basic patent’ means a patent which protects a product as defined in (b) as such, a process to obtain a product or an application of a product, and which is designated by its holder for the purpose of the procedure for grant of a certificate;

(d) ‘certificate’ means the supplementary protection certificate.

ARTICLE 2

Scope

Any product protected by a patent in the territory of a Member State and subject, prior to being placed on the market as a medicinal product, to an administrative authorization procedure as laid down in Council Directive 65/65/EEC or Directive 81/851/EEC may, under the terms and conditions provided for in this Regulation, be the subject of a certificate.

ARTICLE 3

Conditions for obtaining a certificate

A certificate shall be granted if, in the Member State in which the application referred to in Article 7 is submitted and at the date of that application -

(a) the product is protected by a basic patent in force;

(b) a valid authorization to place the product on the market as a medicinal product has been granted in accordance with Directive 65/65/EEC or Directive 81/851/EEC, as appropriate. For the purpose of Article 19(1), an authorization to place the product on the market granted in accordance with the national legislation of Austria, Finland or Sweden is treated as an authorization granted in accordance with Directive 65/65/EEC or Directive 81/851/EEC, as appropriate;

(c) the product has not already been the subject of a certificate;

(d) the authorization referred to in (b) is the first authorization to place the product on the market as a medicinal product.

ARTICLE 4

Subject-matter of protection

Within the limits of the protection conferred by the basic patent, the protection

conferred by a certificate shall extend only to the product covered by the authorization to place the corresponding medicinal product on the market and for any use of the product as a medicinal product that has been authorized before the expiry of the certificate.”

The application

4. The Basic Patent was granted on 19 July 1989. It states at page 2 lines 37-43 of the specification that the inventors have unexpectedly discovered that particular cholecalciferol derivatives are highly effective in the treatment of certain skin orders. It acknowledges that compositions containing hydroxyl derivatives of cholecalciferol are described in the literature, but states that none of these publications discloses topical application for the treatment of skin disorders of a composition wherein 1-alpha-hydroxycholecalciferol or 1-alpha-25-dihydroxycholecalciferol is present in the composition at a concentration from 0.001 to 1.0 µg per gram of the composition.

5. Claims 1 and 25 of the Basic Patent are as follows:

“1. A composition for use in topical treatment of skin disorders consisting of dermatitis, eczema, psoriasis, lack of adequate skin firmness, dermal hydration and sebum secretion, which comprises between 0.001µg and 1.0 µg per gram of the composition of a compound of the formula

wherein R is H or OH, and a suitable carrier to manufacture a cream, an ointment or a lotion.

25. The use of 1-alpha-hydroxycholecalciferol or 1-alpha, 25-dihydroxycholecalciferol for the manufacture of a composition for the topical treatment of skin disorders selected from dermatitis, eczema, psoriasis, lack of adequate skin firmness, dermal hydration or sebum secretion.”

When R is OH in the formula represented in claim 1, the compound is 1-alpha, 25-dihydroxycholecalciferol, commonly known as calcitriol.

6. The application for the SPC was filed on 11 June 2002. The application identified the product to be protected as “calcitriol (chemical name: 1-alpha, 25-dihydroxycholecalciferol)”. The application also stated that the first authorisation to place this product on the market in the UK was PL 10590/0047 (“the UK Marketing Authorisation”), which was granted to Galderma (UK) Ltd on 12 December 2001. The UK Marketing Authorisation, a copy of which was supplied with the application, identifies the authorised product as “Silkis ointment” (“Silkis” is a registered trade mark). It states that the product comprises calcitriol, as active, with liquid paraffin, white soft paraffin and alpha-tocopherol as excipients. It also states that the product is authorised for “topical treatment of mild to moderately severe plaque psoriasis (psoriasis vulgaris) with up to 35% of body surface area involvement”.

7. The examiner dealing with the application wrote to the applicant on 1 July 2002 to draw attention to other medicinal products having calcitriol as the sole active ingredient which had been granted marketing authorisations in the United Kingdom before the authorisation for Silkis ointment. The examiner concluded from this that the application did not comply with Article 3(d) of the Regulation. He identified the previously authorised medicinal products as “Calcijex” (registered trade mark) and “Rocaltrol” (registered trade mark). Calcijex is a sterile, isotonic, clear, aqueous solution containing calcitriol for intravenous injection and is used for the management of hypocalcaemia in patients undergoing dialysis for chronic renal failure. Rocaltrol comprises soft gelatine capsules, containing calcitriol and various inactive ingredients, and it is intended for oral administration to patients with chronic renal failure or post-menopausal osteoporosis.

8. Yissum’s patent attorneys responded on the 24 December 2002 with a request to amend the application to identify the product to be protected as “combination of calcitriol (chemical name: 1-alpha, 25-dihydroxycholecalciferol) with an ointment base” in order to distinguish the product of the application from Calcijex and Rocaltrol. This amendment did not satisfy the examiner and in a further letter dated 5 February 2003 he maintained his objection under Article 3(d) of the Regulation. On 18 July 2003 Yissum’s attorneys wrote to the examiner with a detailed rebuttal of the examiner’s position and requested a hearing if the examiner was still minded to reject the application. The examiner was not persuaded by the arguments put to him and so the matter came before the hearing officer for a hearing.

9. At that hearing Yissum’s primary case was based upon identifying the product to be protected as calcitriol, just as it had done in the application as originally filed. Yissum also advanced an alternative case based upon identifying the product to be protected as a combination of calcitriol and an ointment base, as it had sought by the amendment to the application. In his decision the hearing officer rejected both cases.

The hearing officer’s decision

10. The hearing officer began his assessment by considering the purpose of the Regulation. He noted that, as stated by Jacob J in Takeda Chemical Industries Ltd’s SPC Applications (No. 3) [2004] RPC 3 at [2], the purpose of the Regulation was:

“to give patentees ‘adequate effective protection’ in cases where their patent for a medicinal product would provide inadequate remuneration because of delays in marketing authorisation.”

The hearing officer concluded that this purpose extended to new medicinal products where the innovation resided in a new therapeutic application or use of known compounds. He considered that this conclusion was justified by the terms of the Recitals, in particular Recitals 2, 3, 8 and 9, and supported by paragraphs 12 and 29 of the Commission’s Explanatory Memorandum on its proposal for a Regulation published in April 1990. These state (emphasis added):

“12. However, the proposal is not confined to new products only. A new process for obtaining the product or a new application of the product may also be protected by a certificate. All research, whatever the strategy or final result, must be given sufficient protection.

29. The purpose of the expression ‘product protected by a patent’ is to specify what types of invention may serve as a basis for a certificate. The proposal does not provide for any exclusions. In other words, all pharmaceutical research, provided that it leads to a new invention that can be patented, whether it concerns a new product, a new process for obtaining a new or known product, a new application of a new or known product or a new combination of substances containing a new or known product, must be encouraged, without any discrimination, and must be able to be given a supplementary certificate of protection provided that all of the conditions governing the application of the proposal for a Regulation are fulfilled.”

Nevertheless, he observed that the grant of a supplementary protection certificate depends on all of the conditions for supplementary protection being fulfilled.

11. The hearing officer next considered the definition of “product” in Article 1(b) of the Regulation. In this connection he cited certain observations of Jacob J in Draco AB’s SPC Application [1996] RPC 417. At page 438, lines 30 to 35 Jacob J stated:

“It will be noted that the two recitals use both the phrase medicinal product and product. Without more there could be ambiguity. This is because authorisations typically are not for active ingredients as such. They are much more tightly drawn, generally to dosage and formulation or presentation. That has to be so because the actual performance of an active ingredient depends on these matters in addition to the active ingredient itself.”

Jacob J went on to note that the authors of the Regulation had thought about the difference between the active ingredient and the actual formulation, and in so doing had defined “medicinal product” and “product” in Article 1. He then stated at page 439, lines 1 to 5:

“I have no doubt, nor do I think anyone else would have any doubt, that recitals 8 and 9 must be read as using these definitions. So strictly confined to the product which obtained authorization means: strictly confined to the active ingredient of that which is presented for treatment.”

12. The hearing officer then considered Yissum’s primary case as presented before him. This case proceeded on the basis that the product to be protected was “calcitriol”. In essence Yissum argued that references in the Regulation to “a medicinal product” should be interpreted as meaning “a relevant medicinal product”, so that the UK Marketing Authorisation would constitute the first authorization to market the relevant medicinal product, namely Silkis. Since this case is no longer pursued, it is unnecessary for me to set out his reasoning for rejecting this case at length. I note, however, that amongst the hearing officer’s reasons were that the terms “product” and “medicinal product” had to bear the same meanings throughout the Regulation, and in particular had to have the same meaning in Article 4 as in Article 3. The hearing officer concluded that, if the product to be protected was defined as “calcitriol”, the application failed to meet the condition laid down in Article 3(d) of the Regulation.

13. The hearing officer then considered Yissum’s alternative case, based on identifying the product to be protected as “calcitriol in combination with an ointment base”. The hearing officer began by recalling Jacob J’s observation in Draco that “strictly confined to the product which obtained authorization means: strictly confined to the active ingredient of that which is presented for treatment”. On this basis he expressed the view that, if the objective was to define the product as that which was covered by the UK Marketing Authorisation, this definition was an unacceptable generalisation. As I understand it, this is because the product specified in the Marketing Authorisation is an ointment comprising three particular excipients, not any ointment containing calcitriol.

14. The hearing officer proceeded to consider whether the ointment base, or more particularly the ingredients of the ointment base in Silkis, were an “active ingredient or combination of active ingredients of a medicinal product” within Article 1(b) of the Regulation. For the purpose of determining what were the active ingredients of Silkis, he held that the UK Marketing Authorisation was the starting point, but that the terms of the UK Marketing Authorisation should not be regarded conclusive. Nevertheless, he found nothing to contradict the statement in the UK Marketing Authorisation that the active ingredient was calcitriol. In particular he was not persuaded by evidence from Isabelle Preuilh, a Project Manager in the Pharmaceutical Development Department at Galderma R&D, that “the ointment base is a necessary ingredient of Silkis ointment (without which the calcitriol would not be sufficiently effective in treating psoriasis)” that the ingredients of the ointment base were active ingredients of Silkis. Nor was he persuaded to take a different view by the decision of the Court of Justice of the European Communities in Case C-392/97 Farmitalia Carlo Erba srl’s SPC Application [1999] I-5553 that, where the marketing authorisation refers to an active ingredient in the form of a salt, the certificate was capable of covering the active ingredient as such also its various derivatives such as salts and esters, insofar as they are covered by the basic patent. Accordingly, he concluded that the ingredients of the ointment base were not active ingredients but excipients, and that calcitriol was the sole pharmacologically active ingredient of Silkis. He therefore rejected Yissum’s contention that Silkis contained a combination of active ingredients which included the ingredients of the ointment base.

The appeal

15. On the appeal Yissum did not advance the primary case which it had advanced before the hearing officer, but instead a new primary case based upon identifying the product to be protected as “calcitriol for the topical treatment of psoriasis”. It maintained the same alternative case based upon identifying the product to be protected as “a combination of calcitriol and an ointment base”.

16. During the course of the hearing of the appeal, it emerged that Silkis ointment does not fall within Claim 1 of the Basic Patent since the concentration of calcitriol is 3 µg per gram of ointment. While this can be discerned from a comparison of the UK Marketing Authorisation with Claim 1, I believe that the hearing officer was not made aware of this.

17. In support of its new primary case, Yissum argued essentially as follows:

(a) the purpose of the Regulation was to encourage research into new medicinal products by compensating for the loss of effective patent protection during the period taken to obtain marketing authorisation;

(b) the Regulation applied to all types of innovation without discrimination, including innovation consisting of finding new medical applications of known products;

(c) the definition of “product” in Article 1(b) of the Regulation was to be interpreted teleologically having regard to the purpose of the Regulation and the fact that it applied to all types of innovation;

(d) the SPC system lay at the interface between the patent system and the marketing authorisation system;

(e) the “active ingredient” for the purposes of the Regulation was not necessarily the active ingredient specified in a marketing authorisation;

(f) in the context of the Regulation, the expression “active ingredient” must relate to the product protected by the basic patent, and in the case of an invention relating to the application or use of a compound it had to incorporate that application or use;

(g) accordingly, “product” in Article 1(b) should be interpreted as meaning the active ingredient or combination of active ingredients the subject of the innovation of the basic patent, which in the case of a Swiss form patent claim must incorporate the use, provided that this was within the scope of the marketing authorisation;

(h) on that basis, the product was calcitriol for the topical treatment of psoriasis because that was what was protected by Claim 25 of the Basic Patent and within the scope of the UK Marketing Authorisation;

(i) the first marketing authorisation for that product was the UK Marketing Authorisation for Silkis and therefore the application complied with Article 3(d) of the Regulation.

18. In support of its alternative case, Yissum argued essentially as follows:

(a) if (contrary to its primary case) the product could not be defined by reference to the use, it was still necessary to identify the product firstly by reference to the basic patent and secondly by reference to the marketing authorisation;

(b) the Basic Patent indicates at page 3 lines 20-34 that dermatological compositions containing calcitriol should be formulated in a form suitable for topical application such as an ointment, cream, lotion or spray, while the UK Marketing Authorisation is limited to an ointment;

(c) calcitriol plus an ointment base was properly to be regarded as a combination of active ingredients since it was not necessary for each component of a combination to have separate activity if the combination as a whole was active and the ointment base for necessary for effective application of calcitriol to skin disorders;

(d) on this basis, the product was the combination of calcitriol with an ointment base;

(e) the first marketing authorisation for that product was the UK Marketing Authorisation for Silkis and therefore the application complied with Article 3(d) of the Regulation.

19. The Comptroller argued essentially as follows:

(a) although one of the purposes of the Regulation was to reward innovation, another was to provide certainty for third parties;

(b) the Regulation did not discriminate against second medical use patents, since an SPC could be granted where the basic patent was a second medical use patent provided that the “product” had not already been the subject of a marketing authorisation;

(c) in order to identify the “product” it was necessary to apply the definitions in Article 1 of the Regulation to the basic patent and the marketing authorisation and then to make a finding as to what the product was;

(d) identification of the “product” was not a matter for the choice of the applicant during the application procedure;

(e) Jacob J had been right to say in Draco that protection was strictly confined to the active ingredient of that which was used for treatment and covered by the basic patent and the marketing authorisation;

(f) “active ingredient” was an expression whose meaning was clear and well-understood: it referred to the pharmacologically active substance and not to either the particular therapeutic use of that substance or any excipients contained in the formulation;

(g) this interpretation was supported by the reasoning of the Court of Justice in Case C-31/03 Pharmacia Italia SpA’s Application (19 October 2004) at paragraphs 19-20, where the Court of Justice held that the intended use of the medicinal product was not decisive and that there was no distinction between use of a medicinal product for human use and use of it for veterinary purposes;

(h) in the present case the product was calcitriol since that was the active ingredient identified in the UK Marketing Authorisation and covered by the Basic Patent, and although the wording of the marketing authorisation was not necessarily conclusive (since it might contain an error) there was no evidence here to lead to a contrary conclusion;

(i) Yissum’s primary case was wrong because the therapeutic use was not part of the definition of “product”, and such an approach would cause a number of problems with interpretation and application of other provisions of the Regulation, such as Article 4;

(j) moreover, the identification of the use as “topical treatment of psoriasis” was an arbitrary one which was supported neither by Claim 25 of the Basic Patent (which refers to “topical treatment of skin disorders selected from dermatitis, eczema, psoriasis, lack of adequate skin firmness, dermal hydration or sebum secretion”) nor by the terms of the UK Marketing Authorisation (which refers to “topical treatment of mild to moderately severe plaque psoriasis (psoriasis vulgaris) with up to 35% of body surface area involvement”);

(k) Yissum’s alternative case was wrong because the definition of “product” in Article 1(b) was restricted to active ingredients and did not include excipients and because the ingredients of the ointment base were clearly excipients;

(l) moreover, the identification of the combination as “calcitriol with an ointment base” was an arbitrary one which was neither supported by the Basic Patent (Claim 25 of which refers to “a composition for topical treatment” and the specification of which refers to creams, sprays and lotions as well as ointments) nor by the terms of the UK Marketing Authorisation (which identifies the specific excipients contained in the ointment);

(m) on either case, Yissum’s approach amounted to re-writing the Regulation rather than merely interpreting the existing regulation as the Court of Justice had done in Farmitalia and it created undue uncertainty for third parties;

(n) given that the product was calcitriol, the application did not comply with Article 3(d) of the Regulation.

The MIT reference

20. Shortly before the hearing of the appeal, the parties became aware of a recent reference from the Bundesgerichtshof to the Court of Justice, Case 431/04 Massachusetts Institute of Technology’s Application. In this case the Bundesgerichtshof has referred the following questions on the interpretation of Article 1(b) of the Regulation to the Court of Justice for a preliminary ruling:

“1. Does the term ‘combination of active ingredients of a medicinal product’ with the meaning of Article 1(b) of the Regulation mean that the components of the combination must all be active ingredients with a therapeutic effect?

2. Is there a ‘combination of active ingredients of a medicinal product’ also where a combination of substances comprising two components of which one component is a known substance with a therapeutic effect for a specific indication and the other component renders possible a pharmaceutical form of the medicinal product that brings about a changed efficacy of the medicinal product for this indication (in-vivo implantation with controlled release of the active ingredient to avoid toxic effects)?”

The second component referred to in the second question is a particular polymer, namely a high molecular weight polyanhydride prepared by polycondensation of dicarboxylic acids with a weight average molecular weight of greater than 20,000, which is used to form the matrix of a slow-release implant.

21. In its grounds for making the reference, the Bundesgerichtshof observes that the terms “active ingredient” and “combination of active ingredients” are to be given an autonomous interpretation in European law, citing Case C-449/03 Rockfon A/S v Specialarbejderforbundet i Danmark [1995] ECR I-4291, paragraph 28 et seq, but that these terms are not defined in the Regulation. It also points out that Article 4a(2) of Council Directive 65/65/EEC differentiates between active ingredients and excipients, as does Article 11(2) of Parliament and Council Directive 2001/83/EC. It goes on to state that it considers that there are two possible interpretations of Article 1(b) and sets out various arguments in support of each interpretation. The first interpretation is that the definition of “product” in Article 1(b) only covers “active ingredients” having a therapeutic effect as opposed to “excipients”. The second interpretation is that the expression “combination of active ingredients” extends beyond combinations of ingredients each of which has its own therapeutic effect to a combination of components in which one component obtains its therapeutic efficacy from its combination with one or more other components without which its specific therapeutic effect cannot be achieved.

Reference to the Court of Justice

22. Both parties submitted that, with regard to Yissum’s primary case, their respective interpretations of the Regulation were acte claire, but that if I did not accept their interpretation, I should refer the question of interpretation to the Court of Justice. With regard to Yissum’s alternative case, Yissum submitted that the position was acte claire but that I should not refer the matter even if I disagreed, while the Comptroller submitted that the position was not acte claire and should be referred having regard to the MIT reference.

23. The meaning of the term acte claire was explained by the Court of Justice in Case 283/81 CILFIT Srl v Ministry of Health [1982] ECR 3415. In essence, I must not only be sure what the answer to the question of interpretation is, but sure that other courts in the Community and the Court of Justice would take the same view.

24. Since this is not a court of last resort, I am not obliged to make a reference even if I consider that the interpretation of the Regulation is not acte claire, but have a discretion to exercise as to whether or not to make a reference. If it had not been for the MIT reference, I would not have referred the case to the Court of Justice but would have come to a decision myself. Given the existence of the MIT reference, however, I have concluded that I should exercise my discretion to refer.

25. The first question asked by the Bundesgerichtshof is directly on point so far as Yissum’s alternative case is concerned. The Bundesgerichthof’s grounds for making the reference demonstrate that the interpretation of Article 1(b) of the Regulation is not acte claire at least to that extent. In those circumstances, I consider that I should refer similar questions to the Court of Justice with respect to Yissum’s alternative case. That will have a number of advantages: it will avoid the risk of my making a wrong decision which subsequently has to be reversed by the Court of Appeal or House of Lords once the judgment of the Court of Justice in MIT is known; it will enable the parties before me to present their arguments on the question of interpretation to the Court of Justice; it will enable the Court of Justice to consider the question of interpretation in the context of a different factual situation which may assist it in giving full consideration to the problem; and it will avoid the risk that the answer given by the Court of Justice in MIT does not render the answer to the present issue acte claire and the consequent need for a reference at a later stage of these proceedings.

26. So far as Yissum’s primary case is concerned, this raises a different question of interpretation of Article 1(b). Nevertheless, it is one that is related to the questions referred in MIT. I consider that the answer to it is not acte claire despite the Court of Justice’s observations in Pharmacia Italia since that was not a second medical use case, but a case where the animal and human uses were the same. Given that I am referring the question of interpretation raised by the alternative case to the Court of Justice, it makes sense to refer the question of interpretation raised by the primary case as well.

27. I will hear Counsel as to the precise form of the questions to be asked.