Actavis Group PTC EHF & Anor v Sanofi Pharma Bristol-Myers Squibb SNC

Sanofi was the proprietor of European Patent (UK) No 0 454 511 entitled “N-substituted heterocycle derivatives, their preparation, compositions containing them” (“the Patent”). The Patent had an earliest priority date of 20 March 1990, an application date of 20 March 1991, was granted on 17 June 1998 and expired on 20 March 2011. As described in more detail below, the Patent covered an antihypertensive drug whose international non-proprietary name is irbesartan.

Sanofi obtained Supplementary Protection Certificate GB98/037 for “[irbesartan] optionally in the form of one of its salts” (“the Irbesartan SPC”) based on the Patent and European marketing authorisations EU/1/97/046/001-009 for irbesartan (marketed by Sanofi under the trade mark Aprovel) granted on 27 August 1997. The Irbesartan SPC was applied for on 1 October 1998, granted on 8 February 1999 and expired on 14 August 2012.

Sanofi also obtained Supplementary Protection Certificate GB99/008 for “[irbesartan] optionally in the form of one of its salts and hydrochlorothiazide” (“the Combination SPC”) based on the Patent and European marketing authorisations EU/1/98/086/001-006 for a fixed dose combination of irbesartan and hydrochlorothiazide (marketed by Sanofi under the trade mark CoAprovel) granted on 15 October 1998. The Combination SPC was applied for on 12 March 1999, granted on 21 December 1999 and will expire on 14 October 2013. Sanofi Pharma Bristol-Myers Squibb SNC is the exclusive licensee under the Combination SPC. For present purposes it is not necessary to distinguish between this company and Sanofi, and in the remainder of this judgment I will refer to them collectively as “Sanofi”.

Now that the Patent and the Irbesartan SPC have both expired, the Claimants (collectively “Actavis”) intend to market generic versions of both Aprovel and CoAprovel. It is common ground that the latter will infringe the Combination SPC if the Combination SPC is valid. Actavis contend that it is invalid on the two grounds discussed below. As is so often the case, these contentions raise difficult issues of interpretation of European Parliament and Council Regulation 469/2009/EC of 6 May 2009 concerning the supplementary protection certificate for medicinal products (codified version) (“the Regulation”).

These proceedings were commenced on 26 June 2012 and have been tried on an expedited basis. Thanks to the efficiency of both parties’ counsel, the trial was completed in one day.

It is common ground that, as is normal in patent cases, the Patent must be interpreted in the light of the common general knowledge of the skilled person, or team of skilled persons, to whom it is addressed as at the priority date. It is also common ground that the Patent is addressed to a skilled team comprising a medicinal chemist, a pharmacologist and a clinician. Both parties called an expert witness who is a clinical pharmacologist to educate the court as to the common general knowledge which is relevant for the purposes of the present dispute. Somewhat unusually, the expert witnesses are colleagues in the same institution.

Actavis’ expert was Dr Michael Schachter. Dr Schachter is a Senior Lecturer in clinical pharmacology and therapeutics at the Department of Clinical Pharmacology, Faculty of Medicine, Imperial College, London, which is an internationally recognised centre for hypertension research. He is also a fellow of the Royal College of Physicians and a hypertension specialist consultant at the Peart-Rose Clinic at the International Centre for Circulatory Health at Imperial. The ICCH is a specialist cardiovascular unit which carries out the assessment, investigation and management of patients with hypertension and associated cardiovascular risk factors and is engaged in clinical research including therapeutic trials. Dr Schachter qualified as a doctor at University College London in 1974, having undertaken an intercalated BSc in biochemistry. After his pre-registration year he worked successively at the Royal Marsden Hospital, King’s College Hospital, the Department of Clinical Pharmacology in Oxford and St Mary’s Hospital Medical School before moving to Imperial in 1996. He has published widely, including on hypertension.

Sanofi’s expert was Prof Peter Sever. Prof Sever is Professor of Clinical Pharmacology at Imperial. He is also Honorary Consultant Physician at the Imperial Healthcare NHS Trust; Co-Director of the International Centre for Circulatory Health; Head of the Cardiovascular Disease Prevention Section at the National Heart and Lung Institute; Theme Leader for Cardiovascular Disease Prevention, Biomedical Research Centre, Imperial College Healthcare NHS Trust; and Panel Member of the National Specialty Group for Cardiovascular Medicine, UK Clinical Research Network. He was a Senior Investigator at the National Institute for Health Research in 2009-2012. He graduated from the University of Cambridge in 1965 and completed his medical training at St Mary’s. After various appointments, he became Honorary Consultant Physician and Senior Lecturer at St Mary’s in 1976 and Professor in 1980 (St Mary’s was subsequently incorporated into Imperial). He too has published widely, including on hypertension.

Both experts were very knowledgeable and helpful. Unsurprisingly, there was very little if any difference between them.

In addition, Sanofi called Bénédicte Sergent. She is Sanofi’s Regulatory Affairs Manager. She was a straightforward witness, but through no fault of her own her evidence was of relatively little value. The purpose of her evidence was to explain the procedure by which, and in particular the studies in reliance upon which, Sanofi had obtained the marketing authorisations for Aprovel and CoAprovel. She was not employed by Sanofi at that time, however. Furthermore, as she made clear, her expertise was in regulatory procedure rather than in clinical matters. Thus she was not able to add much to the relevant documents.

The relevant technical background, all of which would have formed part of the common general knowledge of the skilled team, may be summarised as follows.

Hypertension is the technical name for high blood pressure. Hypertension is classified as mild, moderate, severe or very severe depending on how high the blood pressure is compared to normal. A distinction is made between primary (or essential) hypertension, which is predominantly caused by genetic and lifestyle factors, and secondary hypertension, which is due to specific underlying abnormalities. Primary hypertension accounts for about 95% of individuals with raised blood pressure.

In addition to hypertension, the Patent refers to a number of other conditions.

Heart failure. Heart failure results from a divergence between cardiac output and the requirements of the body. This leads to pulmonary oedema (i.e. excess fluid in the lungs), leg or more generalised swelling, shortness of breath and fatigue. The main cause is coronary heart disease (for example, after a heart attack or due to a gradual decrease in the rate at which the heart pumps the blood around the body). Other causes include hypertension, cardiomyopathies (primary and often genetic diseases of the heart muscle) and valvular disease which results in “leaky” valves in the heart.

Venous insufficiency. Venous insufficiency is a term used to describe swelling of the legs usually caused by damage to the veins or to their valves. Venous insufficiency is usually treated with compression stockings and/or surgery.

Glaucoma. Glaucoma is a condition in which loss of vision occurs because of abnormally high pressure in the eye.

Diabetic retinopathy. Diabetic retinopathy results from damage to the blood vessels in the retina in sufferers from diabetes.

Disorders of the central nervous system. These include anxiety, depression, memory deficiencies and Alzheimer’s disease. Such conditions have nothing in common with the conditions discussed above.

There are many important factors that together keep blood pressure at a certain level. A central role in maintaining blood pressure is, however, played by the Renin-Angiotensin System (also known as the Renin-Angiotensin-Aldosterone System) ("the RAS"). In this system, the inactive peptide angiotensinogen is cleaved by renin to form inactive angiotensin I. Angiotensin I is converted to angiotensin II by angiotensin converting enzyme ("ACE"). Angiotensin II is a potent vasoconstrictor and causes an increase in blood pressure.

A number of classes of drugs, including diuretics, ACE inhibitors and angiotensin II receptor blockers have a direct effect on the RAS and thus can be used to control hypertension.

The term “diuretic” is used to describe a broad class of medicinal products with widely differing molecular structures and mechanisms of action which increase the excretion of water and electrolytes (notably sodium ions, but often also potassium ions). Diuretics decrease blood fluid volume, as result of which they were amongst the earliest drugs which were used to treat hypertension in the 1950s. They also appear to affect the RAS. By 1990 they were also used to treat patients with conditions such as congestive heart failure and, in the case of one sub-class, specifically in the treatment of glaucoma. They were not, however, used to treat diabetic retinopathy or disorders of the central nervous system. Diuretics may be divided into the following sub-classes.

Thiazide diuretics. Thiazide diuretics (or benzothiadiazines) are the oldest sub-class of diuretics, having been administered to patients for over 50 years. Thiazides are moderately potent diuretics that act by inhibiting the re-absorption in the kidney of sodium and chloride ions, which produces a corresponding loss of water, reduction in blood volume and cardiac output. They also cause an increase in the excretion of potassium ions. The first effective oral diuretic was chlorothiazide, but many analogues have subsequently been produced. These include hydrochlorothiazide (“HCT”), which was first marketed in 1958. HCT and bendrofluazide (also known as bendroflumethiazide) were both commonly-prescribed thiazide diuretics for patients with hypertension in 1990. Although HCT was one of the most popular diuretics for this purpose, that was not because there was any good clinical data to show that HCT was better than other diuretics. Rather, it appears to have been because HCT was included in official prescribing recommendations and guidelines.

Thiazide-like or thiazide-related diuretics. The compounds in this sub-class are chemically different (albeit related), but pharmacologically similar, to the thiazides. Chlorthalidone was a member of this sub-class which was widely used to treat hypertension in 1990. Metolazone was used to treat heart failure in circumstances where the administration of previous drug combinations proved to be ineffective.

Potassium-sparing diuretics. Potassium-sparing diuretics have a relatively weak diuretic effect and reduce the loss of potassium from the body which is associated with the administration of thiazide diuretics. Well-known examples in 1990 included amiloride, triamterene and spironolactone. Amiloride and triamterene were mainly used in combination with a thiazide, particularly HCT. Spironolactone was used to treat hyperaldosteronism, where there is excessive secretion of the hormone aldosterone leading to hypertension. This is probably the most common cause of secondary hypertension.

Loop diuretics. Loop diuretics are a heterogeneous group of chemicals that share the common property of being potent, relatively short-lived diuretics whose effects are usually complete within four to six hours. These agents act on the ascending loop of Henle in the renal tubule of the kidney. They tend to be administered in the treatment of heart failure as opposed to hypertension. In some circumstances, notably where excess circulating volume is the main factor in maintaining high blood pressure, loop diuretics can be used as antihypertensive agents. Well-known examples of this class in 1990 included furosemide and bumetanide.

Osmotic diuretics. Osmotic diuretics, such as mannitol, were used to reduce or prevent cerebral oedema and to reduce acutely elevated pressure in the eye. They were not regarded as having an antihypertensive effect and were not used in heart failure.

Carbonic anhydrase inhibitors. These agents, such as acetazolamide, inhibit the enzyme carbonic anhydrase and therefore reduce the build up of aqueous humour between the lens and the cornea in the eye. Since this reduces the pressure in the eye, these inhibitors were often prescribed for the treatment of glaucoma in 1990.

By 1990, a number of other classes of antihypertensive drugs had been developed and marketed in addition to diuretics.

Beta-blockers. Beta-adrenergic blocking agents or beta-blockers prevent the action of catecholamines (noradrenaline and adrenaline) at beta-adrenergic receptor sites. The principal effect of beta blockade is to reduce cardiac output. Propanolol was developed in the 1960s and was the first beta-blocker to be widely used in the clinic. Subsequently, products were developed with greater specificity and fewer side effects, amongst other properties, such as atenolol and bisoprolol.

Calcium channel blockers. Calcium channel blockers or calcium antagonists inhibit the movement of calcium ions across ion channels in the cell membranes of the heart and blood vessels. This lowers cardiac output and causes vasodilation respectively, each of which reduces blood pressure. Nifedipine (which is predominantly a vasodilator) and verapamil (which has mixed properties) were well-known examples in 1990.

Alpha-blockers. Alpha-blockers block post-synaptic alpha-adrenoceptors on peripheral sympathetic neurones. This causes vasodilation. A well-known example in 1990 was prazosin.

ACE inhibitors. ACE inhibitors such as captopril or enalapril block the activity of ACE and therefore most of the production of angiotensin II. By 1990, these ACE inhibitors were increasingly being administered to patients with hypertension, either alone or in combination with a diuretic.

Combination therapies. By 1990 it was common to treat hypertension not by a single drug, but by a combination of therapies. This could include two, three or even four drugs, typically of different types. Such combination therapies were frequently more efficacious than treatment with a single antihypertensive drug. Combinations of drugs were administered both separately (but at the same time) and in fixed dose combinations in a single presentation manufactured in advance (e.g. a single tablet or capsule). The advantages of such fixed dose combinations included simplicity and convenience for both carers and patients, improved compliance and lower dispensing costs. The main disadvantage was lack of flexibility. A number of fixed dose combinations of antihypertensive drugs, typically a combination a diuretic and one of the other classes of drugs, had been approved by 1990. These included combinations of HCT and ACE inhibitors.

The use of combination therapies was also well established in other fields. In particular, combinations of drugs were used to treat heart failure. In that case, however, it was usual to administer the drugs separately, rather than in fixed dose combinations, since it was more important to be able to titrate the doses.

There was considerable interest in the 1980s in the development of alternative therapies based on the RAS. This was partly because ACE inhibitors were regarded as effective, but also because it was recognised that ACE inhibitors lost some or most of their efficacy over time (a phenomenon known as “escape”) and caused a dry cough in up to 20% of patients. This led to the development of angiotensin II receptor blockers (“ARBs”). The first ARB to be developed and marketed was losartan. ARBs inhibit the action of angiotensin II on its receptor. Thus they act upon the RAS at a different point to ACE inhibitors. There is no reason why an ARB should be structurally similar to an ACE inhibitor.

Non-steroidal anti-inflammatory drugs (“NSAIDs”). NSAIDs such as ibuprofen are used to treat pain and swelling. They are not used to treat hypertension.

Tranquilizers. Tranquilizers such as barbiturates were used historically to treat hypertension before any truly effective drugs became available, but this had ceased by 1990. They were still used to treat disorders of the central nervous system.

The specification begins by explaining that the compounds according to the invention are ARBs. It then states (page 1 lines 22-27 of the English translation):

“Thus the compounds of the invention are useful in the treatment of cardiovascular complaints such as hypertension and heart failure, as well as in the treatment of complaints of the central nervous system and in the treatment of glaucoma and diabetic retinopathy.”

The specification goes on to say that the invention relates to compounds of a general formula I which is not necessary to set out for present purposes (page 1 line 28 – page 4 line 24) and identifies various preferred compounds (page 4 line 25 – page 5 line 3). It also states that the invention further relates to methods of preparing compounds of formula I (page 5 line 21 – page 7 line 2). It also says that the invention relates to compounds of a general formula II which it is again unnecessary to set out (page 7 line 5 – page 11 line 11). It then describes known methods for preparing compounds of formulas I and II (page 11 line 12 – page 20 line 9).

After describing the manner in which the affinity of the claimed products for angiotensin II receptors was studied (page 20 lines 10-30), but without reporting any experimental results whether in vitro or in vivo, the specification states (page 20 line 32 – page 21 line 3):

“Thus the compounds according to the invention can be used in the treatment of various cardiovascular complaints, especially hypertension, heart failure and venous insufficiency, as well as in the treatment of glaucoma, diabetic retinopathy and various complaints of the central nervous system, for example anxiety, depression, memory deficiencies or Alzheimer's disease.”

The specification goes on to say that that the invention further relates to pharmaceutical compositions containing an effective dose of a compound according to the invention, or a pharmaceutically acceptable salt, and suitable excipients, which are described in general terms (page 21 line 4 – page 23 line 3).

The specification then states (page 23 lines 4-16):

“In addition to the products of formula I above or one of the pharmaceutically acceptable salts, the compositions of the present invention can contain other active principles such as, for example, tranquilizers or other drugs which can be useful in the treatment of the disorders or diseases indicated above.

Thus the present invention relates to pharmaceutical compositions containing several active principles in association, one being a compound according to the invention and it being possible for the other or others to be a beta-blocking compound, a calcium antagonist, a diuretic, a non-steroidal antiinflammatory or a tranquilizer.”

This is the only reference in the specification to the use of a diuretic. It can be seen that the use of diuretics is mentioned in the same breath as beta-blockers and calcium antagonists (which are antihypertensives) and NSAIDs and tranquilizers (which are not). No specific examples are given of any of these. These is nothing to suggest that the combining of the compounds of the invention with these additional active ingredients would be regarded by the skilled reader as anything than a routine step once the compounds of the invention were known. On the contrary, this passage in the specification has every appearance of being a boilerplate passage inserted by the patent attorney who drafted the specification.

The specification describes 29 examples of the invention. None of the examples consists of a pharmaceutical composition containing a compound of the invention together with another active ingredient of the kind referred to the passage at page 23 lines 4-16.

Claim 1 is to a compound of formula I.

Claim 7 is to “A compound according to claim 1, characterized in that it is 2-n-butyl-4-spirocyclopentane-1-((2'-(tetrazol-5-yl)biphenyl-4-yl)methyl)-2-imida-zolin-5-one [i.e. irbesartan] or one of its salts with acids or bases”.

Claims 19 to 23 are as follows:

“19.

A pharmaceutical composition containing a compound according to any one of claims 1 to 7 in association with a beta-blocking compound.

20.

A pharmaceutical composition containing a compound according to any one of claims 1 to 7 in association with a diuretic.

21.

A pharmaceutical composition containing a compound according to any one of claims 1 to 7 in association with a non-steroidal anti-inflammatory.

22.

A pharmaceutical composition containing a compound according to any one of claims 1 to 7 in association with a calcium antagonist.

23.

A pharmaceutical composition containing a compound according to any one of claims 1 to 7 in association with a tranquilizer.”

It should be appreciated that the decision whether to include claims like claims 19-23 at all in a patent of this nature, and if so how to draft such claims, are matters for the choice of the patent proprietor. In practice, the decision will be taken by the patent attorney who drafts the patent application based on legal rather than scientific or technical considerations.

The claims of a patent are to be interpreted in accordance with the principles stated by Lord Hoffmann in Kirin-Amgen Inc v Hoechst Marion Roussel Ltd [2004] UKHL 46, [2005] RPC 9 and summarised by Jacob LJ in Virgin Atlantic Airways Ltd v Premium Aircraft Interiors UK Ltd [2009] EWCA Civ 1062, [2010] RPC 8 at [5].

Claim 20 is to a pharmaceutical composition containing a compound of formula I in association with a diuretic. Thus it is common ground that it is not limited to a combination of irbesartan and HCT. It is also common ground that it is not limited to the use of the claimed pharmaceutical composition for treating any particular condition. Thus it is not limited to compositions suitable for treating hypertension. For example, it would cover a combination of irbesartan and acetazolamide for the treatment of glaucoma. It is also common ground that claim 20 is not limited to fixed dose combinations. Thus, as counsel for Sanofi accepted, it covers a pharmaceutical composition prepared extempore by a pharmacist by combining a compound of formula I with a diuretic in quantities prescribed by a physician.

In my judgment it is clear that the inventive advance (or the technical contribution, to use the language used in the jurisprudence of the Boards of Appeal of the European Patent Office) of the Patent lies in the disclosure of the new compounds of formula I, including irbesartan, as claimed in claims 1-7. It is also clear that, given that invention, claim 20 does not reflect any further inventive advance (or technical contribution). In the jargon of patent lawyers, claim 20 is not independently valid over claims 1-7. On the contrary, it is clear from the evidence of both experts that, given a new ARB such as irbesartan in 1990, it would have been an obvious step for a person skilled in the art to combine it with a diuretic for the treatment of hypertension, including in a fixed dose combination. Furthermore, it is Sanofi’s own case that HCT would have been the most obvious choice for this purpose.

As noted above, Aprovel was authorised by the European Medicines Agency (“EMA”) on 27 August 1997. The Summary of Product Characteristics (“SmPC”) for Aprovel states:

“4.2

Posology and method of administration

Posology

…

In patients insufficiently controlled with 150 mg once daily, the dose of Aprovel [irbesartan] can be increased to 300 mg, or other antihypertensive agents can be added. In particular, the addition of a diuretic such as hydrochlorothiazide has been shown to have an additive effect with Aprovel [irbesartan] (see section 4.5)

…

4.5

Interaction with other medicinal products and other forms of interaction

Diuretics and other antihypertensive agents: other antihypertensive agents may increase the hypotensive effects of irbesartan; however Aprovel [irbesartan] has been safely administered with other antihypertensive agents, such as beta-blockers, long-acting calcium channel blockers, and thiazide diuretics. …

5.1

Pharmacodynamic properties

…

The blood pressure lowering effects of irbesartan and thiazide-type diuretics are additive. In patients not adequately controlled by irbesartan alone, the addition of a low dose of hydrochlorothiazide (12.5 mg) to irbesartan once daily results in a further placebo-adjusted blood pressure reduction at trough of 7-10/3-6 mm Hg (systolic/diastolic).

…”

As this suggests, Sanofi undertook extensive studies on the combination of irbesartan and HCT as part of the work that it did to obtain the marketing authorisation for Aprovel. Further details are contained in the European Public Assessment Report (“EPAR”) for Aprovel. In addition to reporting studies of the pharmacodynamic (page 6) and pharmacokinetic (page 7) aspects of combining irbesartan and HCT, this reports four multicentre, randomised, double-blind, placebo-controlled trials which “indicated that the combination of irbesartan and hydrochlorothiazide led to further reductions of DBP and SBP than when the drugs were given separately” (page 10). It also reports four randomised, double-blind, active-controlled trials of irbesartan compared to atenolol, amlodipine and enalapril, three of which involved additional treatment in combination with HCT (page 10).

As noted above, CoAprovel was authorised by the EMA on 15 October 1998. The EPAR for CoAprovel shows that Sanofi relied upon 18 clinical studies which it had already relied upon when obtaining authorisation for Aprovel, and nine new studies. As the EPAR states at page 9, however:

“Human pharmacology

The pharmacodynamics and pharmacokinetics of both irbesartan and [HCT] are well known. Therefore only a very limited clinical pharmacology program involving 115 subjects in four studies.”

Of those four, two compared the pharmacokinetics of the combination with irbesartan alone and HCT alone and two simply demonstrated bioequivalence of the proposed commercial tablets with the dosage forms used in the earlier clinical studies. In addition, there was a small study to investigate the effect of food on the bioavailability of the commercial tablets. The remaining four studies were further active-controlled studies, which Ms Sergent accepted would not have been essential to obtain regulatory approval.

It is therefore clear that the principal studies which Sanofi relied upon to demonstrate the efficacy and safety of the combination of irbesartan and HCT when seeking the marketing authorisation for CoAprovel had already been undertaken and considered by the EMA when Sanofi obtained the marketing authorisation for Aprovel.

The Regulation enables the proprietor of a patent for a medicinal product to obtain an SPC which extends the duration of the patent with respect to that product so as to compensate the proprietor for the effective loss of patent term caused by the need to obtain a marketing authorisation before the product can be marketed.

The Regulation includes the following recitals:

“[3] 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.

[4] At the moment the period that elapses between the filing of an application for a patent for a new medicinal product and authorisation 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.

[5] This situation leads to a lack of protection which penalises pharmaceutical research.

[6] There exists a risk of research centres situated in the Member States relocating to countries that offer greater protection.

[7] 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.

[8] 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 authorisation has been granted is necessary. A Regulation is therefore the most appropriate legal instrument.”

Articles 1, 3, 4 and 5 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;

…

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 authorisation to place the product on the market as a medicinal product has been granted in accordance with Directive 2001/83/EEC or Directive 2001/82/EEC, as appropriate;

(c)

the product has not already been the subject of a certificate;

(d)

the authorisation referred to in (b) is the first authorisation 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 authorisation to place the corresponding medicinal product on the market and for any use of the product as a medicinal product that has been authorised before the expiry of the certificate.

Article 5

Effects of the certificate

Subject to the provisions of Article 4, the certificate shall confer the same rights as conferred by the basic patent and shall be subject to the same limitations and the same obligations.”

As is common ground, it is well established that the correct approach to the interpretation of the Regulation is that stated by the Court of Justice of the European Union in Case C-482/07 AHP Manufacturing v Bureau voor de Industriele Eigendom [2009] ECR I-7295 at [27]:

“Next, the Court observes that the second sentence of Article 3(2) of Regulation No 1610/96 must be interpreted not solely on the basis of its wording, but also in the light of the overall scheme and objectives of the system of which it is a part (see, by analogy, Case C-292/00 Davidoff [2003] ECR I-389, paragraph 24)”

Actavis’ first contention is that the Combination SPC is invalid because the combination of irbesartan and HCT was not “protected by” the Patent within the meaning of Article 3(a) of the Regulation since it was not specified or identified in the wording of any of the claims of the Patent. Sanofi contend that it is specified or identified in the wording of claim 20 of the Patent.

The issue as to the interpretation of Article 3(a) which this dispute raises was the subject of five references from the courts of this country to the CJEU which the Court ruled upon in its judgments in Case C-322 Medeva BV v Comptroller-General of Patents, Designs and Trade Marks [2011] ECR I-0000 (“Medeva”) and Case C-422/10 Georgetown University v Comptroller-General of Patents, Designs and Trade Marks [2011] ECR I-0000 (“Georgetown”) and its reasoned orders in Case C-518/10 Yeda Research and Development Comptroller-General of Patents, Designs and Trade Marks [2011] ECR I-0000 (“Yeda”), Case C-630/10 University of Queensland v Comptroller-General of Patents, Designs and Trade Marks [2011] ECR I-0000 (“Queensland”) and Case C-6/11 Daiichi Sankyo Co v Comptroller-General of Patents, Designs and Trade Marks [2011] ECR I-0000 (“Daiichi”).

I reviewed the background to Medeva and its progeny, the references and the judgments and reasoned orders in detail in my judgment in Novartis Pharmaceuticals UK Ltd v MedImmune Ltd [2012] EWHC 181 (Pat), [2012] FSR 23 at [14]-[49]. I shall take that exposition as read, and shall not repeat it all here. To recap very briefly, the CJEU ruled in Medeva and Georgetown that Article 3(a) of the Regulation:

“must be interpreted as precluding the competent industrial property office of a Member State from granting a SPC relating to active ingredients which are not specified in the wording of the claims of the basic patent relied on in support of the SPC application.”

In Daiichi and Queensland the CJEU repeated this, except that it used the word “identified” rather than “specified”.

As I commented in Novartis v MedImmune at [42]:

“… the Court did not actually answer question 1 [of the reference in Medeva]. I have to say that, as the national judge who made one of the references before the Court, I am disappointed by this. One of the reasons for the multiplicity of references was the need of the national courts for clear guidance as to the criteria to be applied in deciding whether a product is ‘protected by a basic patent’ within the meaning of Article 3(a). As I shall discuss below, not only has the Court not answered the question referred, but also the guidance it has provided is not sufficiently clear to enable future disputes to be resolved.”

I went on to say at [53]:

“In my view, counsel for MedImmune is also correct to say that the test laid down by the Court of Justice in Medeva and its progeny is unclear save in its rejection of the infringement test in combination cases. In particular, it is unclear precisely what is meant by ‘specified (or identified) in the wording of the claims’. Does this mean that it is sufficient for the product to fall within the scope of the claim on its true construction, or is something more required and if so what? For example, is it sufficient, say, for the claim to incorporate a Markush formula which covers a large number of compounds one of which is the product in respect of which an SPC is sought? Is it sufficient for the product to be defined in functional terms? Even in combination cases, it is not clear to me how the test enunciated by the Court should be applied in a case like Gilead. Regrettably, therefore, it is inevitable that there will have to be further references to the CJEU to obtain clarification of the test.”

Subsequently both the Court of Appeal in Medeva BV v Comptroller-General of Patents [2012] EWCA Civ 523 at [32]-[33] (per Sir Andrew Morritt Ch) and Warren J in Eli Lilly & Co v Human Genome Sciences Inc [2012] EWHC 2290 (Pat) at [63] have agreed that the test laid down by the Court of Justice in Medeva and its progeny is unclear save in its rejection of the infringement test in combination cases and that further references are required to obtain clarification of the test. For different reasons, however, the courts did not consider it appropriate to make a further reference in any of these three cases.

In the present case, Sanofi contends that the combination of irbesartan and HCT is specified/identified in the wording of claim 20 of the Patent since:

I accept points (i) and (ii), but not point (iii). As noted above, ARBs act on the RAS at different points and are structurally different to ACE inhibitors. Whether points (i) and (ii) support the conclusion for which Sanofi contend is another matter.

Counsel for Sanofi submitted that Sanofi’s contention was supported by the judgment of the CJEU in Yeda. I do not agree this for the reasons I gave in Novartis v MedImmune at [58].

As I drew to the parties’ attention at the hearing, although it was not cited by counsel, in Joined Cases 200/044/332/01, 200/081/980/01 and 200/081/996/01 H. Lundbeck A/S v Alfred E. Tiefenbacher GmbH (24 January 2012) the Gerechtshof 's-Gravenhage (Court of Appeal of The Hague) held that a patent claim to a method for preparing escitalopram and the non-toxic acid addition salts thereof specified/identified escitalopram oxalate in accordance with the ruling of the CJEU in Medeva even though the literal wording of the claim did not specify that particular non-toxic addition salt. That case may be distinguished from the present case on two grounds. First, in that case the wording of the claim specified a narrow class of compounds which was structurally defined, whereas here the word “diuretic” embraces a wide variety of different classes of structurally-unrelated compounds. Secondly, in that case the specification of the patent did specifically identify the oxalate, and moreover as a preferred embodiment, whereas here the specification does not mention HCT.

I would comment that the logic of Sanofi’s argument would be essentially the same even if the Patent did not include claim 20 at all. It would still be the case that the skilled reader of the Patent would immediately appreciate from his common general knowledge that irbesartan could be combined with HCT to treat hypertension. Furthermore, the use of such a combination would still infringe the Patent while it was in force.

Actavis contends that the combination of irbesartan and HCT is not specified/identified in the wording of claim 20 of the Patent since:

I accept each of points (i)-(v). Again, whether these points support the conclusion for which Actavis contend is another matter.

In my judgment it is necessary to seek further guidance from the CJEU as to the correct interpretation of Article 3(a) of the Regulation in order to resolve this dispute. To reiterate, the reason why this is necessary is because the Court did not answer question 1 in the previous five references and the rulings it did make do not provide a clear test which can be applied to cases such as the present.

If confirmation were needed that the test is not clear, it is provided by the fact that courts in France, Germany and the Netherlands have already given divergent rulings in parallel cases to the present one. In Case RG 12/55806 Sanofi v Sandoz (10 August 2012) the Tribunal de Grande Instance de Paris (Paris Court of First Instance, Judge Thaunat) refused to grant an interim injunction on the ground that the validity of the French equivalent of the Combination SPC was questionable because claim 20 of the French part of the Patent did not specify/identify HCT as part of the combination. By contrast, in Case 4a O 109/12 Sanofi SA v Actavis Deutschland GmbH & Co KG (15 August 2012) the Düsseldorf Landesgericht (Düsseldorf District Court, Judges Dr Crummeneral, Thomas and Dr von Hartz) granted an interim injunction, holding that there was no serious reason to doubt the validity of the German equivalent of the Combination SPC since the combination of irbesartan and HCT was specified/identified in the wording of claim 20 of the German part of the Patent. Similarly, in Case 425814/KG ZA 12-905 Sanofi SA v Pharmachemie BV (14 September 2012) the Rechtbank ‘S-Gravenhage (District Court of The Hague, Judge Kalden) granted an interim injunction, holding that there was no reasonable likelihood that the Dutch equivalent of the Combination SPC was invalid. Despite noting the second distinction between the present case and Lundbeck v Tiefenbacher, although not the first, the court applied Lundbeck v Tiefbacher and concluded at [4.9]-[4.10] that the combination of irbesartan and HCT was specified/identified in the wording of claim 20.

I shall therefore ask question 1 again (slightly rephrased):

“What are the criteria for deciding whether ‘the product is protected by a basic patent in force’ in Article 3(a) of the Regulation?”

In the hope that it will assist the Court of Justice to provide a clear answer this time, I will offer my own suggested answer to this question. As the Court rightly held in Medeva at [24], the Regulation establishes a uniform system at the European level. It follows that Article 3(a) must be interpreted as involving a question of European, not national, law. As the Court also rightly, albeit implicitly, held in Medeva, it is necessary, but not sufficient, that the marketing of the product by someone other than the proprietor (or a licensee) of the basic patent would infringe the basic patent. As Jacob J explained in Takeda Chemical Industries Ltd’s SPC Application (No 3) [2003] EWHC 649 (Pat), [2004] RPC 3 at [10]-[12] explained, the infringement test proves too much.

What more is required? In my view, the answer is that the product must infringe because it contains an active ingredient, or a combination of active ingredients, which embodies the inventive advance (or technical contribution) of the basic patent. Where the product is a combination of active ingredients, the combination, as distinct from one of them, must embody the inventive advance of the basic patent. Thus in a case such as the present, where the inventive advance of the Patent consists generally of the compounds of formula I, including specifically irbesartan, a medicinal product whose active ingredient is irbesartan is protected by the Patent within the meaning of Article 3(a) because it embodies the inventive advance of the Patent. A medicinal product whose active ingredients are irbesartan and a diuretic such as HCT in combination is not protected by the Patent within the meaning of Article 3(a) because the combination, as distinct from irbesartan, does not embody the inventive advance of the Patent. This is not a question of the wording of the claims of the basic patent, which as discussed above can be manipulated by the patent attorney who drafts it, but of its substance. Thus it would make no difference if claim 20 of the Patent had read “A pharmaceutical composition containing a compound according to any one of claims 1 to 7 in association with HCT”. By contrast, if a later inventor were to obtain a patent for an invention consisting of a combination of irbesartan and substance X which surprisingly had a synergistic effect in treating hypertension, then a medicinal product whose active ingredients were irbesartan and X would be protected by that patent since it would embody the inventive advance of that patent. In my view, this interpretation of Article 3(a) would accord with the object of the Regulation, which is to encourage invention in the field of medicinal products by compensating inventors for the delay in exploiting their inventions due to the need to obtain regulatory approval, and not to confer unjustified monopolies.

For the avoidance of doubt, this interpretation of Article 3(a) would not prevent a patentee from obtaining an SPC in circumstances where the patent protected a single active ingredient A, but the patentee had only obtained a marketing authorisation for that active ingredient in combination with another active ingredient B. In those circumstances, as the Court of Justice held in Medeva, the patentee could obtain an SPC for product A.

Actavis’ second contention is that the Combination SPC is invalid either because the product had already been the subject of an SPC (namely the Irbesartan SPC) contrary to Article 3(c) of the Regulation or because the product had already been the subject of a marketing authorisation (namely the authorisations for Aprovel) contrary to Article 3(d) of the Regulation before the application for the Combination SPC was filed. Sanofi contend that both the Irbesartan SPC and the Aprovel marketing authorisations relate to irbesartan whereas the Combination SPC and the CoAprovel marketing authorisations relate to the combination of irbesartan and HCT, which is a different product, and thus there is no contravention of either Article 3(c) or 3(d).

Again this dispute arises out of the judgment of the CJEU in Medeva, but before considering that it is first necessary to put it in context.

In the Explanatory Memorandum which accompanied its Proposal for the original Regulation (COM(90) 101 final) the Commission of the European Communities stated:

“35.

It occurs very often that one and the same product is successfully granted several authorizations to be placed on the market, namely each time a modification is made affecting the pharmaceutical form, dose, composition, indications, etc. In such a case, only the first authorization for the product to be placed on the market, in the Member State in which the application is presented is taken into account for the purposes of the proposal for a Regulation, in particular for calculating the period of six months which the holder of the basic patent has to submit an application for a certificate. Furthermore, if the first authorization given is also the first authorization to place the product on the market in the Community, it serves as the only reference for all of the Member States for the purpose of calculating the duration of each of the certificates granted in each of the Member States for the same product (see Article B).

36.

Lastly, the product must not have been the subject of a certificate in the Member State concerned. The certificate is designed to encourage research into new medicinal products so that the duration of protection by patent, is sufficient to enable the investments made in the research to be recovered. However, it would not be acceptable in view of the balance required between the interests concerned, for this total duration of protection for one and the same medicinal product to be exceeded. This might nevertheless be the case if one and the same product were able to be the subject of several successive certificates.

This calls for a strict definition of the product within the meaning of Article 2. If a certificate has already been granted for the active ingredient itself, a new certificate may not be granted for one and the same active ingredient whatever minor changes may have been made regarding other features of the medicinal product (use of a different salt, different excipients, different pharmaceutical presentation, etc).

In conclusion, it should be noted that, although one and the same product may be the subject of several patents and several authorizations to be placed on the market in one and the same Member State, the supplementary protection certificate will only be granted for that product on the basis of a single patent and a single authorization to be placed on the market, namely the first chronologically given in the State concerned (the first authorization in the Community being taken only to calculate a uniform duration of different certificates for one and the same product).”

In Case C-181/95 Biogen Inc v SmithKline Biologicals SA [1997] ECR I-357 SKB marketed Energix-B, a vaccine for Hepatitis-B virus, pursuant to licences granted under patents owned by both Biogen and the Institut Pasteur. Biogen applied for an SPC based on its patents after the Institute Pasteur had obtained an SPC based on its patent. In those circumstances the Tribunal de Commerce de Nivelles in Belgium asked whether, where a single medicinal product was covered by several basic patents, the predecessor to the Regulation precluded the grant of an SPC to each holder of a basic patent. The CJEU answered this question in the negative for the following reasons:

“26.

It must be borne in mind in that regard that the third and fourth recitals in the preamble give as a reason for the adoption of the Regulation the insufficient duration of the effective protection under the patent to cover the investment put into the pharmaceutical research. The Regulation thus seeks to make up for that insufficiency by creating a supplementary protection certificate for medicinal products, which may be obtained by the holder of a national or European patent under the same conditions in each Member State.

27.

Article 6 of the Regulation confirms that the certificate is to be granted to the holder of the basic patent or his successor in title. Article 1(c) mentions the basic patents which may be designated for the purpose of the procedure for the grant of a certificate, namely those which protect a product as such, a process to obtain a product or an application of a product. The Regulation thus seeks to confer supplementary protection on the holders of such patents, without instituting any preferential ranking amongst them.

28.

Consequently, where a product is protected by a number of basic patents in force, which may belong to a number of patent holders, each of those patents may be designated for the purpose of the procedure for the grant of a certificate. Under Article 3(c) of the Regulation, however, only one certificate may be granted for each basic patent.”

The CJEU re-iterated this interpretation of the Regulation in AHP, another case in which there were multiple applications by different patentees for SPCs based on the same marketing authorisation for a single product.

These two cases clearly establish that it is possible to obtain one SPC per basic patent per product where there were multiple patents covering one product. Prior to Medeva, it was generally thought that, by parity of reasoning, it was also possible to obtain one SPC per product per basic patent where one patent covered multiple different medicinal products.

It is important to appreciate that Medeva, Georgetown and Queensland were all cases involving vaccines in which the basic patents contained claims in effect either to single antigens or to limited combinations of antigens, but the medicinal products which had received marketing authorisations contained larger combinations of antigens.

In her opinion in Medeva and Georgetown Advocate General Trstenjak reasoned as follows (I quote the admirably succinct summary of Morritt Ch in the subsequent decision of the Court of Appeal):

“18.

The Advocate General … considered at some length (paragraphs 51 to 110) the wider issue of whether and if so how and under what conditions SPCs may be applied for and granted. In that context she concluded (paragraph 70) that, prima facie and in the absence of harmonisation, the definition of 'product' in regulation 1(b) required regard to be had to the subject matter of the patent and not its protective effect. But that interpretation (paragraph 73) would suggest that an SPC could not be granted in relation to a medicinal product containing a number of active ingredients only some of which were the subject matter of the basic patent. She considered (paragraph 79) that such a conclusion would be incompatible with the objectives of the regulation because it would fail to provide sufficient protection to those seeking to develop new active ingredients in medicinal products.

19.

In those circumstances she considered (paragraph 88) that the literal interpretation must be complemented by a teleological one so as to ensure that the protection afforded by SPCs is available to medicinal products in which the combination of active ingredients is only partly the subject matter of a patent. She considered that this would be achieved by construing article 1(b) to include any active ingredient. At the same time, a teleological interpretation must not (paragraph 91) lead to an imbalance of the interests envisaged by the regulation so as to confer too great a benefit on the manufacturer of the medicinal product. In her view the balance was struck by a narrow interpretation of article 3(a) and a broad interpretation of article 3(b).

20.

As to article 3(a), she considered (paragraph 98) that the product under that article must be the same as the product which is the subject matter of the basic patent in order to prevent 'evergreening' …”

It was in this context that the Advocate General said:

“100.

Having particular regard to Article 3(c) of Regulation No 469/2009, according to which only one supplementary protection certificate per product may be granted in the Member State in which the application is submitted, that interpretation of Article 3(a) has the effect, on the other hand, that, for each active ingredient or combination of active ingredients which is the subject-matter of a patent, only one supplementary protection certificate for the extension of that patent’s term of protection may be granted, regardless of the number of combinations of active ingredients in which the patented active ingredient or combination of active ingredients has been used. (33) This makes it impossible for manufacturers of medicinal products to optimise the term of protection under the patent and certificate in relation to an active ingredient by placing the patented active ingredient on the market in a number of combinations of active ingredients as different medicinal products, with a time lag in some cases.

101.

Interpreting Article 3(a) of Regulation No 469/2009 to the effect that the product within the meaning of that provision is the same as the product which forms the subject-matter of the basic patent means that a manufacturer of medicinal products who holds a patent for an active ingredient or combination of active ingredients is free to decide how he will place that patented active ingredient or combination of active ingredients on the market: in one medicinal product with only that active ingredient or that combination of active ingredients, in one medicinal product in combination with other active ingredients, or in a number of medicinal products with differing combinations of active ingredients. For each of those medicinal products, the patented active ingredient or combination of active ingredients must be classified as the product protected by a basic patent in force within the meaning of Article 3(a). Under Article 3(c) of the regulation, however, only one supplementary protection certificate may be applied for in respect of that product, regardless of in how many different combinations of active ingredients the patented active ingredient or combination of active ingredients is placed on the market as a medicinal product.

102.

Having particular regard to the account of the facts in Georgetown University and Others, the special case in which a patent relates to several active ingredients and also to one or more combinations of those active ingredients should not go unmentioned at this point. In such a case, each of those active ingredients and each combination of active ingredients which is used in a medicinal product can be classified as a product within the meaning of Article 1(b) of Regulation No 469/2009. Moreover, the patent belonging to the manufacturer of medicinal products is to be classified as the basic patent within the meaning of Article 1(c) of Regulation No 469/2009 in relation to each of those active ingredients and each combination of active ingredients. Nevertheless, there can be no question of applying for supplementary protection certificates on the basis of that basic patent in relation to each of those active ingredients and combinations of active ingredients used in a medicinal product. That is because, according to the Court’s case-law, only one supplementary protection certificate may be granted for each basic patent. (34)

103.

It follows that the proprietor of a patent relating to a number of active ingredients and also to one or more combinations of those active ingredients must decide in respect of which active ingredient or combination of active ingredients he is going to apply for a supplementary protection certificate on the basis of the basic patent. The grant of a first supplementary protection certificate in respect of one active ingredient or combination of active ingredients in reliance on that patent then precludes the grant of further supplementary protection certificates in reliance on the same basic patent.

104.

On the one hand, that interpretation of Regulation No 469/2009 avoids a situation in which the system of limitation of the duration of protection conferred by a certificate, provided for in the regulation, is undermined by the claims in the patent application being formulated for the purpose of optimising the duration of protection in the sense that they cover both one or more individual active ingredients and a number of combinations of those individual active ingredients. If a supplementary protection certificate could be applied for in respect of each of those active ingredients and each combination of active ingredients, the term of patent and certificate protection in relation to individual active ingredients could subsequently be optimised by placing the individual active ingredients and combinations of those active ingredients on the market in different medicinal products with time lags. (35)

105.

On the other hand, in my view, that interpretation would normally also afford manufacturers of medicinal products the possibility of obtaining appropriate certificate protection by relating their SPC application to the central active ingredient or combination of active ingredients contained in the various medicinal products to be developed.”

Footnotes 33 and 34 cited Biogen and AHP.

Thus the Advocate General’s opinion was that only one SPC could be granted for the active ingredient or combination of active ingredients covered by the basic patent, however many medicinal products, including combinations with other active ingredients, the patented active ingredient or combination of active ingredients might became part of. It would appear that she assumed that, in the vaccine cases under consideration, each of the basic patents disclosed and claimed in essence one invention, even if a patent disclosed and claimed more than one antigen. She does not appear to have considered the case where the patent disclosed and claimed two distinct inventions, each of which was subsequently embodied in different medicinal products.

In its judgment in Medeva the Court of Justice held as follows:

“40.

However, it should be added that, in a situation such as that in the main proceedings, first, only the authorisation in respect of the first medicinal product placed on the European Union market comprising, among its active ingredients, the combination of the two active ingredients identified in the wording of the claims of the patent, namely pertactin and filamentous haemagglutinin, may be regarded as the first MA for that ‘product’ as a medicinal product within the meaning of Article 3(d) of Regulation No 469/2009.

41.

Secondly, where a patent protects a product, in accordance with Article 3(c) of Regulation No 469/2009, only one certificate may be granted for that basic patent (see Biogen, paragraph 28).”

As the Court of Appeal held at [21]:

“The judgment of the Court of Justice makes no reference to the opinion of the Advocate General but is consistent with the observations set out more fully in her Opinion.”

I touched on the question of how [41] of the Court of Justice’s judgment in Medeva should be interpreted in University of Queensland v Comptroller-General of Patents [2012] EWHC 223 (Pat):

“13.

I am aware that some commentators have interpreted this statement literally as meaning that there can only be one SPC per basic patent, whereas other commentators have interpreted it as meaning that there can only be one SPC per product per patent. Counsel for the Comptroller-General informed me that it is the Comptroller-General’s view that the Court of Justice was not intending to change the law as previously stated in Case C-181/95 Biogen Inc v SmithKline Biologicals SA [1997] ECR I-357 at [28], which was generally understood to mean that there can be one SPC per product per patent.

14.

Accordingly, the Comptroller-General accepts that SPCs can be granted in respect of both applications, even though they are based upon the same patent, since they are for different products. In support of this counsel for the Appellants pointed out that the claims of 935 cited above all refer to “HPV-11 or HPV-6 [emphasis added].”

The approach adopted by the Comptroller-General is arguably inconsistent with the opinion of the Advocate General in Medeva, but may perhaps be justified on the basis that the two antigens represented distinct inventions.

It appears, however, that the Dutch Patent Office has adopted the opposite interpretation of Medeva to that adopted by the UK Intellectual Property Office, namely that it prohibits the grant of more than one SPC per patent regardless of the number of products claimed in the basic patent. In Case AWB 10/4769 Georgetown University v Octrooicentrum Nederland (11 July 2012), which is a parallel case to the Georgetown case in this country, the Rechtbank ‘S-Gravenhage (Judge van Walderveen) held that the correct interpretation of Article 3(c) was unclear and decided to refer a question to the CJEU provisionally worded as follows:

“Does [the Regulation], more specifically Article 3(c), in the situation in which multiple products are protected by (the claims) of a basic patent, preclude the proprietor of the basic patent being issued a certificate for each of the products protected?”

A similar judgment was given in a parallel case to the Queensland case. In Sanofi v Pharmachemie the Rechtbank ‘S-Gravenhage acknowledged at [4.23] that the ruling of the CJEU on this question could be relevant to the instant case, but decided not to wait for that ruling due to the urgent nature of the case. The court preferred the interpretation adopted by the UK Intellectual Property Office to that adopted by the Dutch Patent Office.

Against this background, Actavis advance two main, alternative arguments. The first argument is that Article 3(c) should be interpreted in the manner that it appears the Dutch Patent Office is interpreting it, namely there can only be one SPC per basic patent. Here the Patent has already been extended by the Irbesartan SPC, and thus the Combination SPC is invalid. The second argument is that Article 3(c) should be interpreted in the manner which Advocate General Tsrstenjak interpreted it. Actavis contend that, properly understood, that interpretation would mean that it is possible for there to be more than SPC per basic patent, but only where the basic patent discloses and claims more than one inventively distinct product. This is not such a case, and thus the Combination SPC is invalid. In support of these arguments Actavis point out that the grant of the Irbesartan SPC gave Sanofi extended protection not only for irbesartan, but also for the combination of irbesartan and HCT: see Case C-442/11 Novartis AG v Actavis UK Ltd [2012] ECR I-0000. As a third and final alternative, Actavis contend that Article 3(d) of the Regulation should be interpreted so as to achieve the same result.

Sanofi contend Article 3(c) should be interpreted as the UK Intellectual Property Office interprets it. Sanofi say that the key question is what is meant by “product” in Article 3(c) and that it is clear from the existing jurisprudence of the CJEU, including Medeva, that the combination of irbesartan and HCT is a different product to irbesartan. Sanofi contend that Biogen and AHP indicate that there can be one SPC per product per basic patent, and that the CJEU cannot have intended to say anything different in Medeva. Sanofi say that Article 3(d) should be interpreted consistently with this.

I would observe that this problem only arises if Article 3(a) of the Regulation is not correctly interpreted. As Advocate General Tsrstenjak rightly indicated in her opinion in Medeva, the interpretation of Article 3(c) depends on the interpretation of Article 3(a). If Article 3(a) is interpreted in the manner that I have suggested above, then it becomes clear how Article 3(c) should be interpreted. If “the product is protected by a basic patent” within Article 3(a) because the active ingredient (or combination of active ingredients) embodies the inventive advance of the patent, then one SPC may be granted in respect of that product and that patent. If the patent protects two products, because the patent discloses and claims two inventively distinct active ingredients (or combinations of active ingredients), then one SPC may be granted in respect of each product, and hence two SPCs in respect of that patent. Nor is there any problem with Article 3(d) in these circumstances.

As matters stand, however, I agree with the Dutch court that the correct interpretation of Article 3(c) is unclear, and the CJEU should be asked to clarify it. In particular, it cannot safely be assumed that the Court of Justice did not intend to change the law in Medeva merely because it did not say so explicitly: compare the Court’s recent judgment in Case C-130/11 Neurim Pharmaceuticals (1991) Ltd v Comptroller-General of Patents [2012] ECR I-0000 with its earlier judgments in Case C-31/03 Pharmacia Italia SpA [2004] ECR I-10001, Case C-431/04 Massachusetts Institute of Technology [2006] ECR I-4089 and Case C-202/05 Yissum Research and Development Company of the Hebrew University of Jerusalem v Comptroller-General of Patents [2007] ECR I-2839. Accordingly, I shall refer a second question to the Court provisionally worded in the same manner as the question quoted in paragraph 92 above. I do not consider that it is necessary to refer to Article 3(d) in the question, since in my view the issue really concerns Article 3(c).

For the reasons given above, I shall refer the two questions of interpretation of the Regulation discussed above to the CJEU for a preliminary ruling. I will give the parties the opportunity to address me on the precise wording of the questions, and in particular the second question, when this judgment is handed down.