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Neutral Citation Number: [2013] EWHC 619 (Pat)
Case No: CH/2013/0043
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT
Rolls Building
Fetter Lane, London, EC4A 1NL
Date: 21 March 2013
Before :
THE HON MR JUSTICE ARNOLD
--------------------Between :
GLAXOSMITHKLINE BIOLOGICALS SA
- and COMPTROLLER-GENERAL OF PATENTS,
DESIGNS AND TRADE MARKS
Appellant
Respondent
----------------------------------------Daniel Alexander QC (instructed by Simmons and Simmons) for the Appellant
Charlotte May (instructed by the Treasury Solicitor) for the Respondent
Hearing date: 8 March 2013
---------------------
Approved Judgment
I direct that pursuant to CPR PD 39A para 6.1 no official shorthand note shall be taken of this
Judgment and that copies of this version as handed down may be treated as authentic.
.............................
THE HON MR JUSTICE ARNOLD
THE HON MR JUSTICE ARNOLD
Approved Judgment
GSK v Comptroller
MR JUSTICE ARNOLD :
Contents
Topic
Paragraphs
Introduction
The SPC Regulation
Technical background
Immunity
Vaccination
Influenza vaccines
Vaccine antigens
Adjuvants
AS03
Prepandrix
Earlier case law
Pharmacia
MIT
Yissum
Neurim
Bayer CropScience
The issue in the present case
Conclusion
1-4
5-6
7-32
8-15
16-18
19-23
24-26
27-32
33-36
37
38-56
39-41
42-47
48-51
52-56
57-66
67-81
82-86
Introduction
1.
On 10 October 2008 the Appellant (“GSK”) filed application SPC/GB08/046 for a
supplementary protection certificate for “an oil in water emulsion comprising
squalene, DL-α-tocopherol and polysorbate 80”, an adjuvant known as AS03 which is
protected by European Patent (UK) No 0 868 918.
2.
On 18 August 2011 GSK filed application SPC/GB11/043 for a supplementary
protection certificate for “an adjuvanted influenza vaccine comprising an influenza
virus component which is an influenza virus antigen from an influenza virus strain
that is associated with a pandemic outbreak or has the potential to be associated with a
pandemic outbreak, wherein the adjuvant is an oil in water emulsion comprising
squalene, DL-α-tocopherol and polysorbate 80”, a vaccine comprising an antigen and
AS03 which is protected by European Patent (UK) No 1 618 889.
3.
In both applications GSK relied upon marketing authorisation EU/1/08/453/001 for a
pre-pandemic influenza vaccine against the H5N1 subtype of influenza A virus
marketed by GSK under the trade mark Prepandrix.
4.
By a decision dated 19 December 2012 (BL O/506/12), Dr C.L. Davies, the Deputy
Director of the UK Intellectual Property Office, acting on behalf of the Comptroller,
decided that neither application was allowable as it stood since AS03 was not an
“active ingredient” of Prepandrix, although she was prepared to give GSK an
opportunity to amend the applications. GSK has appealed against this decision. It is
common ground that the resolution of the appeal depends on an issue of interpretation
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GSK v Comptroller
of Article 1(b) of European Parliament and Council Regulation 469/2009/EC of 6
May 2009 concerning the supplementary protection certificate for medicinal products
(codified version) (“the SPC Regulation”) upon which a preliminary ruling from the
Court of Justice of the European Union is required.
The SPC Regulation
5.
6.
The SPC 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.
(9)
The duration of the protection granted by the certificate should be such as to
provide adequate effective protection. For this purpose, the holder of both a
patent and a certificate should be able to enjoy an overall maximum of 15
years of exclusivity from the time the medicinal product in question first
obtains authorisation to be placed on the market in the Community.
(10)
All the interests at stake, including those of public health, in a sector as
complex and sensitive as the pharmaceutical sector should nevertheless be
taken into account. For this purpose, the certificate cannot be granted for a
period exceeding five years. The protection granted should furthermore be
strictly confined to the product which obtained authorisation to be placed on
the market as a medicinal product.”
Articles 1, 2 and 3 of the SPC Regulation provide:
GSK v Comptroller
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“Article 1
Definitions
For the purposes of this Regulation, the following definitions shall apply:
(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 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 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 authorisation procedure as laid down in
Directive 2001/83/EC of the European Parliament and of the Council
of 6 November 2001 on the Community code relating to medicinal
products for human use or Directive 2001/82/EC of the European
Parliament and of the Council of 6 November 2001 on the Community
code relating to veterinary medicinal products 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 authorisation to place the product on the market as a
medicinal product has been granted in accordance with
Directive 2001/83/EC or Directive 2001/82/EC, as appropriate;
THE HON MR JUSTICE ARNOLD
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GSK v Comptroller
(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.”
Technical background
7.
The following account is based upon evidence given by Professor Geert Leroux-Roels
in an expert report submitted by GSK prior to the hearing before the Deputy Director
and upon scientific literature which he exhibited to that report. Professor LerouxRoels is an experienced and distinguished scientist in the field of immunology.
Having held a number of positions at Ghent University between 1983 and 1995, he
has been Director of CEVAC – The Centre for Vaccinology – Ghent University
Hospital since 1995. He is an author of over 250 publications in the field. His
evidence was not tested in cross-examination, but there is no reason to think that it is
not technically accurate. Any inaccuracies in the following summary will be
attributable to me.
Immunity
8.
Immunity is the general term used to describe the body’s ability to resist infection by
a particular pathogen (a microorganism that typically causes a disease upon infection
or in the context of failing immunity). There are, broadly speaking, two main types of
immunity: innate immunity and adaptive immunity.
9.
Innate immunity describes the various resistance mechanisms that are first
encountered by a pathogen upon infection. These are general and non-specific
responses which are present in all individuals at all times and are not affected (nor
enhanced) by repeated exposure to a particular pathogen. Aspects of the innate
immune response include, for example, anatomical barriers to infection, the
“complement system” (the coating of a pathogen by proteins which facilitates its
removal by phagocytes, which engulf the coated pathogen) and the responses that are
triggered by recognition of a pathogen-associated molecular pattern (PAMP). PAMPs
are molecules that are specifically associated with groups of pathogens. They are
recognised by receptors, such as Toll-like receptors (TLRs), expressed extra- or
intracellularly in antigen-presenting cells (APCs) of the innate immune system. APCs
are cells (such as dendritic cells, monocytes and macrophages) that display foreign
antigen complexes with major histocompatibility complex (MHC) on their surface.
Recognition of PAMPs by TLRs triggers signals, including the secretion of cytokines,
which help initiate immune responses.
10.
Adaptive immunity occurs after the innate response and describes the response of
antigen-specific lymphocytes to a particular antigen, including the development of
immunological memory. Unlike innate immunity, adaptive immunity can be boosted
by repeated exposure to a particular antigen. It involves both humoral responses and
cellular responses.
11.
The adaptive immune system comprises B and T cells. B and T cells are antigenspecific lymphocytes which are named according to their sites of development in the
Bone marrow and Thymus respectively.
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GSK v Comptroller
12.
B cells recognise antigens via B cell receptors or BCRs, and respond by proliferating
and producing and secreting antibodies. B cells are divided into two main classes:
conventional B cells (which have highly diverse antigen receptors and are generated
in bone-marrow) and B-1 cells (which have less diverse antigen receptors and are
self-renewing in peritoneal and pleural cavities).
13.
T cells have highly variable receptors (T cell receptors or TCRs), which recognise
complexes consisting of antigens bound to MHC molecules, for example on the
surface of APCs of the innate immune system. Facilitator (CD4+) or “helper” T cells
(e.g. Th1, Th2 and Tfh cells) primarily act by secreting cytokines which stimulate
other parts of the immune system, such as macrophages to clear the pathogen.
Adaptive effector (CD8+) or “killer” T cells secrete cytokines and cytotoxic factors to
kill cells infected with pathogens.
14.
Both B and T cells have so-called “memory” cells, which mediate immunological
memory and are more sensitive and therefore respond more rapidly upon re-exposure
to a particular antigen.
15.
Adaptive immunity is an important aspect of vaccination as it is responsible for longterm immunity to particular pathogens. Over the last two decades an increased
understanding of both innate and adaptive immunity and how they interact has led to
significant advances in both vaccinology and adjuvant technology.
Vaccination
16.
Vaccination has been one of the most important contributions to public health in the
past century. Its immediate aim is the protection of an individual by the generation of
a long lasting (ideally permanent) and protective immunity. Its ultimate aim is the
eradication of particular diseases. Eradication (or near eradication) has been achieved
for several human diseases, most famously for smallpox. Examples of well known
diseases for which there are vaccines include rabies, diphtheria, pertussis (whooping
cough), tetanus, polio, measles, mumps and rubella.
17.
Vaccines are designed to produce an immune response which, when established as
part of an individual’s adaptive immunity, recognises a particular pathogen (or parts
thereof) and protects that individual against future infection by that pathogen.
Accordingly, vaccination involves striking a balance between inducing a protective
immune response whilst at the same time ensuring that no disease or other adverse
side effects occur as a result of vaccination.
18.
Generally speaking, vaccines contain three main components:
i)
An antigen, a term which is derived from “antibody-generator”.
ii)
An adjuvant, which is usually co-administered with the antigen to stimulate
and/or modulate the immune response to the antigen.
iii)
An excipient, which primarily relates to the formulation of the antigen and
adjuvant in a particular solvent, but which can also convey other properties
such as stability and preservation.
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GSK v Comptroller
Influenza vaccines
19.
In classical vaccination the antigen tends to be well established and characterised and
remains unchanged, for example the diphtheria and tetanus toxoid vaccines, which
have been in use for over 40 years. Such vaccinations take place at predictable time
points, for example, during infant years, adolescence or prior to travel, and therefore
supply of these vaccines can be managed to meet what is a predictable demand.
20.
By contrast to the well-established and stable nature of the antigens mentioned above,
certain viruses, for example influenza, are prone to variation. In the case of the
influenza virus, mutations in the original virus strain can result in the appearance of a
variant strain. Different influenza virus strains are named according to their type (e.g.
influenza A or B), the species from which the virus was isolated (omitted if human),
location of isolate, the number of the isolate, year of isolation, and, in the case of
influenza A viruses, the haemagglutinin (H1 to H16)) and neuraminidase (N1 to N9)
subtypes. For example the 220th isolate of an H5N1 subtype influenza A virus in
Hong Kong in 1997 is designated: influenza A/chicken/Hong Kong/220/1997
(H5N1). A “clade” (or subclade) describes a group (or subgroup) of related viruses
descendent from a common ancestor.
21.
In the case of diseases like influenza, vaccines can be developed in the pre-pandemic
phase in order to “prime” the population for an eventual pandemic outbreak. Priming
not only achieves initial immune protection, but can also result in a better response to
subsequent booster vaccinations.
22.
In the case of influenza, the virus in the eventual pandemic outbreak may be a variant
of the virus originally identified in the pre-pandemic phase because of the highly
variable nature of the influenza virus. Therefore, ideally, an influenza vaccine
developed in the pre-pandemic phase should be able to induce the broadest protection
possible. Cross-reactivity (an adaptive immune response that is able to recognise not
only the vaccine antigen, but also related variants of the antigen) is therefore a
valuable property of such a vaccine.
23.
If a pandemic outbreak occurs, typically large amounts of vaccine product must be
readily available within a short period of time to satisfy the global demand. This can
be achieved by a vaccine that induces the necessary immune protection with the
lowest amount of vaccine possible. So-called “antigen sparing” is therefore another
important factor in the context of pandemic vaccines.
Vaccine antigens
24.
Vaccine antigens are selected so that when an immune response is produced against
the antigen, it will protect the individual against future infection by particular
pathogens.
25.
Many vaccines contain whole pathogens (e.g. viruses or bacteria), which is feasible
when suitable versions can be administered to induce the necessary immune response
without leading to disease or side effects. The administration of the whole pathogen
tends to be more immunogenic and stimulates both innate and adaptive immune
responses. This has the advantages of eliciting stronger and potentially broader
immune responses and can produce longer lasting protection. However, whole
THE HON MR JUSTICE ARNOLD
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GSK v Comptroller
pathogen vaccines have the disadvantages that they can have poor safety profiles and
produce adverse side effects.
26.
Where whole pathogen vaccines are not feasible, other approaches are needed and
vaccines may comprise inactive split parts or sub-units of pathogens or recombinantly
derived antigens. In recent decades there have been significant advances in peptide
(and carbohydrate) engineering and recombinant technology that have enabled the
large-scale manufacture of highly specific, safe, tolerable and highly purified
antigens. However, one of the main challenges to modern vaccines that comprise such
antigens is that the antigens may not be sufficiently immunogenic or potent and may
induce only a weak immune response.
Adjuvants
27.
The concept that the immune response to antigens can be improved by the addition of
certain compounds into the vaccine formulation was demonstrated approximately 100
years ago when aluminium salts were first used in vaccine formulations. Such
compounds are referred to as “adjuvants” (derived from the Latin word “adjuvare”
which means “to help or aid”).
28.
The last few decades have seen extensive research and development in the field of
adjuvants. There has been a surge in adjuvant technology which has been assisted by
a greater understanding of innate and adaptive immunity and their close interaction at
the molecular level in the response to a pathogen.
29.
It is important to be clear as to exactly what an adjuvant does and what it does not do.
It is something which aids the process of generating an antigen-specific antibody
response, but it does not generate antibodies itself. The main way in which an
adjuvant works is to amplify the immune response.
30.
What an adjuvant does is to provide a quantitative change in the immune response
which in turn leads to a qualitative change in the immune response. The first thing the
adjuvant can do is to stimulate cytokine production, a general immune response that is
not specific to any antigen. The second thing the adjuvant can do is to stimulate the
antigen presentation of APCs. This leads to stimulation of the adaptive immune
response, which leads to a greater generation of antigen-specific antibodies.
31.
These quantitative effects are of value in themselves since they enable antigensparing. In addition, however, they lead to a qualitative effect which is greater crossreactivity. When the body is exposed to an antigen, it normally produces what is
described as a polyclonal response. That is to say, it does not just generate one
antibody to the antigen, rather it generates a group of different antibodies which will
be specific to different parts (epitopes) of the antigen. Within that polyclonal group, a
small proportion will bind not only to that antigen, but also to related antigens. That is
referred to as cross-reactivity. Because adjuvants cause more antibodies to be
produced, this can result in increased cross-reactivity.
32.
Developing a new adjuvant involves considerable research and development. An
adjuvant must interact with the immune system to elicit an improved response to the
antigen, but equally it must be safe.
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GSK v Comptroller
AS03
33.
AS03 has the following main components:
i)
polysorbate 80 (polyoxy-ethylene sorbitan-20 monooleate) - a surfactant;
ii)
DL-α-tocopherol – a vitamin E analogue; and
iii)
squalene – an essential intermediate in the biosynthesis of cholesterol, steroid
hormones and vitamin D.
34.
AS03 is an oil-in-water (o/w) emulsion adjuvant system, distinguished from other o/w
emulsions by the presence of α-tocopherol. By comparing AS03 with an adjuvant
formulation in which α-tocopherol was replaced by an equal volume of squalene, αtocopherol has been shown to significantly and positively influence the kinetics and
the magnitude of the cytokine responses in vitro and in vivo, the antigen loading in
monocytes, the granulocyte recruitment to the draining lymph nodes, and the
magnitude of the antibody response to the model antigen HBsAg. Thus AS03 is
superior to previous o/w emulsion adjuvants.
35.
There is good evidence that the presence of AS03 in a pre-pandemic influenza
vaccine, namely Prepandrix, has three benefits:
36.
i)
increased immunogenicity, including a high antibody response;
ii)
antigen-sparing; and
iii)
cross-reactivity.
These benefits are not expected to be specific to the use of AS03 in a pre-pandemic
influenza vaccine, but they are of particular advantage in that context.
Prepandrix
37.
This vaccine comprises an antigen known as A/Indonesia/05/2005 (H5N1) like strain
used (PR8-IBCDC-RG2) together with AS03. Studies have demonstrated that the
presence of the AS03 is an important factor in ensuring that the vaccine satisfies the
criteria for licensing by the United States Food and Drug Administration and the
European Medicines Authority.
Earlier case law
38.
The issue arising on this appeal involves consideration of a number of decisions of the
CJEU, which I shall take in chronological order.
Pharmacia
39.
In Case C-31/03 Pharmacia Italia SpA [2004] ECR I-10001 an SPC application had
been made in Germany for the active ingredient cabergoline, which was protected by
a basic patent filed in 1981. The application was based on a marketing authorisation
for cabergoline granted for the human medicinal product Dostinex in Germany in
June 1994. By virtue of the transitional provision contained in Article 19(1) of
THE HON MR JUSTICE ARNOLD
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GSK v Comptroller
Regulation 1768/92/EEC (the predecessor of the SPC Regulation), an SPC could only
be granted for a product if, on the date the Regulation entered into force, it was
protected by a basic patent and “the first authorization to place it on the market as a
medicinal product in the Community was obtained after” 1 January 1988. The first
authorisation for Dostinex in the Community had been granted in the Netherlands in
October 1992, but there had been an earlier authorisation for cabergoline as the active
ingredient of a veterinary medicinal product called Galastop granted in Italy in
January 1987. In these circumstances the Bundesgerichtshof (Federal Court of
Justice) referred the following question to the Court of Justice:
“Is the grant of a supplementary protection certificate in a
Member State of the Community on the basis of a medicinal
product for human beings authorised in that Member State
precluded by an authorisation to place the same product on the
market as a veterinary medicinal product granted in another
Member State of the Community before the date specified in
Article 19(1) of the Protection Certificate Regulation, or is the
sole determining factor the date on which the product was
authorised in the Community as a medicinal product for human
beings?”
40.
The applicant argued that it was the date of first authorisation to place the product on
the market for human use which was relevant, whereas the Commission and the
United Kingdom contended that the relevant date was that of the first authorisation to
place the product on the market for either human or veterinary use. Advocate General
Jacobs advised the Court of Justice to adopt the latter interpretation. In his Opinion he
considered Article 3(d) as well as Article 19(1), saying (footnote omitted):
“48.
Finally the applicant invokes the scheme of the Regulation and
in particular the effect of Articles 3(c) and (d).
49.
In my view however the scheme of the Regulation also
supports the view that the system of supplementary protection
certificates which it establishes does not distinguish between
medicinal products for, on the one hand, human use and, on the
other hand, veterinary use, whether generally or for the specific
purpose of Article 19.
50.
In particular, the interpretation which I am suggesting appears
consistent with Article 3(c) and (d). Article 3(c) includes as a
condition for obtaining a certificate that the product has not
already been the subject of a certificate and thus precludes the
grant of more than one certificate for a product in a Member
State even if it has been authorised as a medicinal product
more than once. Article 3(d) includes a further condition that
the marketing authorisation covering the product in respect of
which a certificate is sought is the first authorisation to place
that product on the market as a medicinal product and thus
precludes the grant of a certificate on the basis of a second
marketing authorisation even if an application for a certificate
has not been made on the basis of the first marketing
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GSK v Comptroller
authorisation. Those provisions highlight the significance for
the system put in place by the Regulation of the notion of one
certificate per product without distinction depending on the
number of authorisations. Although the authorisation referred
to in Article 3(b) and (d) is the first authorisation in the
Member State in which the application for the certificate is
made whereas that at issue in Article 19 and the question
referred is the first Community authorisation, to my mind the
principle underlying Article 3 equally suggests that no
distinction should be drawn for the purpose of Article 19
depending on whether the relevant authorisation was for
human or veterinary use.”
41.
In its judgment the Court of Justice followed the Advocate General’s advice, holding:
“20.
It follows, first, that the decisive factor for the grant of the
certificate is not the intended use of the medicinal product and,
second, that the purpose of the protection conferred by the
certificate relates to any use of the product as a medicinal
product without any distinction between use of the product as a
medicinal product for human use and as a veterinary medicinal
product.
21.
Whilst noting that the term ‘first marketing authorisation in the
Community’ must be interpreted in the same way in each of the
provisions of the regulation in which it is used, it should be
pointed out that, according to the sixth recital in its preamble,
that regulation seeks to provide a uniform solution at
Community level to the problem of inadequate patent
protection, 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. However, an interpretation
such as that proposed by Pharmacia would prevent the
realisation of that objective. Under Pharmacia’s interpretation,
the duration of the protection conferred by the certificate,
calculated in accordance with Article 13 of the regulation,
might be different for the same product.
22.
Lastly, and for the reasons set out in points 41 to 43 and 48 to
50 of the Advocate General’s Opinion, it must be found that
neither the purpose of Article 19 nor the broad logic of the
regulation militate in favour of the interpretation put forward
by Pharmacia.”
MIT
42.
In Case C-431/04 Massachusetts Institute of Technology [2006] ECR I-4089 the
applicant had applied in Germany for an SPC for the product carmustine, either in
combination with a polymeric biodegradable matrix called polifeprosan or
alternatively on its own. The applicant relied on a marketing authorisation for the
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GSK v Comptroller
medicinal product Gliadel, which was used for the treatment of human brain tumours.
Gliadel comprised carmustine as its active ingredient and polifeprosan as an excipient.
Carmustine was a highly cytotoxic substance which was already covered by an earlier
marketing authorisation for the treatment of brain tumours with inert excipients.
Polifeprosan was a new excipient that enabled the slow release of carmustine from a
disc implanted in the cranium after surgical removal of the tumor, thereby permitting
the delivery of a higher but constant dose of carmustine. Accordingly to the applicant,
the combined use of carmustine and polifeprosan extended the life expectancy of
patients by several months. Polifeprosan was the subject of a patent which the
applicant relied on as the basic patent for the application.
43.
The application was refused by the Deutches Patent- under Markenamt (German
Patent and Trade Mark Office) on the basis that (i) no SPC could be granted for the
combination of carmustine and prolifeprosan since that was not a combination of
active ingredients within the meaning of Article 1(b); and (ii) no SPC could be
granted for carmustine on its own since the marketing authorization relied on was not
the first authorization to market carmustine contrary to Article 3(d). As I understand
it, the applicant appealed against holding (i), but not holding (ii). In these
circumstances the Bundesgerichtshof referred the following questions to the Court of
Justice:
“1.
Does the concept of ‘combination of active ingredients of a
medicinal product’ within the meaning of Article 1(b) of
Regulation [1768/92/EEC] 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 comprises
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)?”
44.
Advocate General Léger advised the Court of Justice to rule that Article 1(b) should
be interpreted as including a combination of an active ingredient (such as carmustine)
with an excipient which is necessary for the therapeutic efficacy of the active
ingredient (such as polifeprosan). He did so on the basis of the kind of teleological
approach to interpretation contended for by GSK in the present case, saying that this
was just the kind of costly innovation that the Regulation was designed to protect.
Nevertheless the Court of Justice declined to follow that advice, and ruled that such a
combination was not within the scope of Article 1(b) on its proper interpretation.
45.
The following passages in the Court’s judgment are particularly relevant to the
present issue:
“17.
In the absence of any definition of the concept of ‘active
ingredient’ in Regulation No 1768/92, the meaning and scope
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of those terms must be determined by considering the general
context in which they are used and their usual meaning in
everyday language (see, inter alia, Case 349/85 Denmark v
Commission [1988] ECR 169, paragraph 9, and Case C-164/98
P DIR International Film and Others v Commission [2000]
ECR I-447, paragraph 26).
18.
In this case, it is important to note that it is common ground, as
the file in this case shows, that the expression ‘active
ingredient’ is generally accepted in pharmacology not to
include substances forming part of a medicinal product which
do not have an effect of their own on the human or animal
body.
19.
In that regard, attention must be drawn to the fact that in point
11 of the Explanatory Memorandum to the Proposal for a
Council Regulation (EEC), of 11 April 1990, concerning the
creation of a supplementary protection certificate for medicinal
products (COM(90) 101 final), to which the French
Government referred in its oral observations, it is specified that
‘[t]he proposal for a Regulation therefore concerns only new
medicinal products. It does not involve granting a [SPC] for all
medicinal products that are authorised to be placed on the
market. Only one [SPC] may be granted for any one product, a
product being understood to mean an active substance in the
strict sense. Minor changes to the medicinal product such as a
new dose, the use of a different salt or ester or a different
pharmaceutical form will not lead to the issue of a new [SPC].’
20.
Therefore, the definition of ‘product’ in Article 1(b) of
Regulation No 1768/92 does not in any way conflict with that
referred to by the Commission in point 11 of that explanatory
memorandum.
21.
In fact, it is apparent from that memorandum that the
pharmaceutical form of the medicinal product, to which an
excipient may contribute, as noted by the Advocate General in
point 11 of his Opinion and the French Government at the
hearing, does not form part of the definition of ‘product’,
which is understood to mean an ‘active substance’ or ‘active
ingredient’ in the strict sense.
…
25.
In the light of the foregoing, the inevitable conclusion is that a
substance which does not have any therapeutic effect of its
own and which is used to obtain a certain pharmaceutical form
of the medicinal product is not covered by the concept of
‘active ingredient’, which in turn is used to define the term
‘product’.
GSK v Comptroller
THE HON MR JUSTICE ARNOLD
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26.
Therefore, the alliance of such a substance with a substance
which does have therapeutic effects of its own cannot give rise
to a ‘combination of active ingredients’ within the meaning of
Article 1(b) of Regulation No 1768/92.
27.
The fact that the substance without any therapeutic effect of its
own renders possible a pharmaceutical form of the medicinal
product necessary for the therapeutic efficacy of the substance
which does have therapeutic effects cannot invalidate that
interpretation.
28.
As shown by paragraphs 6 and 7 of this judgment, carmustine
is an active ingredient which must be combined with other
substances, in particular inert excipients, to be therapeutically
effective. More generally, as observed by the Advocate
General in point 11 of his Opinion and by the French and
Netherlands Governments, it is apparently not unusual for
substances which render possible a certain pharmaceutical
form of the medicinal product to influence the therapeutic
efficacy of the active ingredient contained in it.
29.
Thus, a definition of ‘combination of active ingredients of a
medicinal product’ which includes a combination of two
substances, only one of which has therapeutic effects of its own
for a specific indication, the other rendering possible a
pharmaceutical form of the medicinal product which is
necessary for the therapeutic efficacy of the first substance for
that indication, might, on any view, create legal uncertainty in
the application of Regulation No 1768/92, as the French
Government pointed out at the hearing. Whether a substance
without any therapeutic effect of its own is necessary for the
therapeutic efficacy of the active ingredient cannot, in this
case, be regarded as a sufficiently precise test.
30.
Moreover, such a definition is liable to prevent the attainment
of the objective referred to in the sixth recital in the preamble
to Regulation No 1768/92, in the words of which 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.
31.
In those circumstances, the answer to the questions referred
must be that Article 1(b) of Regulation No 1768/92 must be
interpreted so as not to include in the concept of ‘combination
of active ingredients of a medicinal product’ a combination of
two substances, only one of which has therapeutic effects of its
own for a specific indication, the other rendering possible a
pharmaceutical form of the medicinal product which is
GSK v Comptroller
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GSK v Comptroller
necessary for the therapeutic efficacy of the first substance for
that indication.”
46.
47.
The Court of Justice’s reasoning in these passages can be summarised as follows:
i)
the expression “active ingredient” was generally accepted not to include
substances forming part of a medicinal product which did not have an effect
(which in context must mean a therapeutic effect) of their own on the human
or animal body;
ii)
this understanding was consistent with paragraph 11 of the Explanatory
Memorandum in the Commission’s original Proposal for the Regulation,
indeed it was apparent from the Memorandum that “product” was understood
to mean an “active ingredient” in the strict sense;
iii)
accordingly, a substance which did not have any therapeutic effect of its own
and which was used to obtain a certain pharmaceutical form of the medicinal
product was not an “active ingredient”;
iv)
therefore an alliance of such a substance with one that did have a therapeutic
effect of its own was not a “combination of active ingredients”;
v)
it was immaterial that the substance without any therapeutic effect of its own
rendered possible a pharmaceutical form of the medicinal product necessary
for the therapeutic efficacy of the substance which did have a therapeutic
effect;
vi)
indeed, a test which involved considering whether a substance without any
therapeutic effect of its own rendered possible a pharmaceutical form of the
medicinal product necessary for the therapeutic efficacy of another substance
which did have a therapeutic effect would create legal uncertainty and inhibit
the attainment of a uniform solution at Community level.
Although the Court did not refer to its earlier judgment in Pharmacia, and Pharmacia
did not dictate the decision in MIT, the Court’s decision in MIT was consistent with
the earlier decision.
Yissum
48.
In Case C-202/05 Yissum Research and Development Company of the Hebrew
University of Jerusalem v Comptroller-General of Patents [2007] ECR I-2839 the
applicant applied for an SPC for the product calcitriol either alone or in combination
with an ointment base. The applicant relied upon (i) a second medical use patent, the
claims of which were directed to the use of calcitriol in topical treatment of skin
disorders including psoriasis, and (ii) a marketing authorization for Silkis ointment,
which comprised calcitriol as the active ingredient with various carriers and was
authorised for the topical treatment of psoriasis. The application was refused by the
Comptroller because there were two earlier marketing authorisations for medicinal
products containing calcitriol as the active ingredient, namely Calcijex and Rocaltrol.
Calcijex was authorised for the management of hypocalcaemia in patients undergoing
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GSK v Comptroller
dialysis for chronic renal failure. Rocaltrol was authorised for administration to
patients with chronic renal failure or post-menopausal osteoporosis.
49.
On the applicant’s appeal, I referred three questions to the Court of Justice ([2004]
EWHC 2880 (Pat)]). Two of those were subsequently withdrawn in the light of the
Court’s judgment in MIT. The remaining question was as follows:
“In a case in which the basic patent protects a second medical
application of a therapeutic agent what is meant by ‘product’ in
Article 1(b) of the Regulation and in particular does the
application of the therapeutic agent play any part in the
definition of ‘product’ for the purpose of the Regulation?”
50.
51.
The Court of Justice gave its answer to that question by reasoned order on the basis
that the answer to it could be clearly deduced from the existing case law, and in
particular Pharmacia and MIT. In its order the Court held:
“16.
As laid down in Article 1(b) of Regulation No 1768/92,
‘product’ means the active ingredient or combination of active
ingredients of a medicinal product.
17.
It is clear from Massachusetts Institute of Technology, and, in
particular, from paragraphs 19, 21, 23 and 24 of that judgment,
that the concept of ‘product’ referred to in Article 1(b) of
Regulation No 1768/92 must be interpreted strictly to mean
‘active substance’ or ‘active ingredient’.
18.
It follows that the concept of ‘product’ cannot include the
therapeutic use of an active ingredient protected by a basic
patent.
19.
Moreover, the same interpretation can be inferred from
paragraph 20 of the judgment in Case C-31/03 Pharmacia
Italia [2004] ECR I-10001, in which the Court held that ‘the
decisive factor for the grant of the certificate is not the intended
use of the medicinal product and … the purpose of the
protection conferred by the certificate relates to any use of the
product as a medicinal product without any distinction between
use of the product as a medicinal product for human use and as
a veterinary medicinal product’.
20.
Consequently, the answer to the question referred must be that
Article 1(b) of Regulation No 1768/92 is to be interpreted as
meaning that in a case where a basic patent protects a second
medical use of an active ingredient, that use does not form an
integral part of the definition of the product.”
It can be seen from this that the Court of Justice confirmed that the concept of
“product” in Article 1(b) of the Regulation was to be interpreted strictly and could not
include the therapeutic use of the active ingredient or even whether the medicinal
product was for human use or for veterinary use.
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GSK v Comptroller
Neurim
52.
In Case C-130/11 Neurim Pharmaceuticals (1991) Ltd v Comptroller-General of
Patents [2012] ECR I-0000 melatonin, a naturally occurring hormone, had been
marketed by Hoechst under the trade mark Regulin for regulating the seasonal
breeding activity of sheep pursuant to a patent applied for in 1987 and a marketing
authorisation granted in 2001 (“the Regulin MA”). Neurim marketed melatonin under
the trade mark Circadin for the treatment of insomnia in humans pursuant to a patent
applied for in 1992 and a marketing authorisation granted on 28 June 2007 (“the
Circadin MA”). Neurim applied to the UK Intellectual Property Office for an SPC in
respect of Circadin. The IPO refused the application on the ground that it did not
comply with Article 3(d) of the SPC Regulation since the Circadin MA was not the
first authorisation to place melatonin on the market, the Regulin MA was. I dismissed
Neurim’s appeal ([2010] RPC 22, [2010] RPC 22), but the Court of Appeal referred
five questions to the Court of Justice ([2011] EWCA Civ 228, [2011] RPC 19).
53.
The Court interpreted the first and third questions as asking, in essence, whether
Articles 3 and 4 of the SPC Regulation were to be interpreted as meaning that the
existence of an earlier marketing authorisation for a veterinary medicinal product
precluded the grant of an SPC for a different use of the same product. It answered
those questions as follows:
“23.
The reason given for the adoption of the SPC Regulation is the
fact that the period of effective protection under the patent is
insufficient to cover the investment put into pharmaceutical
research and the regulation thus sought to make up for that
insufficiency by creating an SPC for medicinal products (see
Medeva, paragraph 31, and Georgetown University and Others,
paragraph 25).
24.
It is apparent from paragraph 29 of the explanatory
memorandum to the proposal for a Council Regulation (EEC)
of 11 April 1990, concerning the creation of a supplementary
protection certificate for medicinal products (COM(90) 101
final), that, like a patent protecting a ‘product’ or a patent
protecting a process by which a ‘product’ is obtained, a patent
protecting a new application of a new or known product, such
as that at issue in the main proceedings, may, in accordance
with Article 2 of the SPC Regulation, enable an SPC to be
granted and, in that case, in accordance with Article 5 of the
regulation, the SPC confers the same rights as conferred by the
basic patent as regards the new use of that product, within the
limits laid down by Article 4 of that regulation (see, by
analogy, Medeva, paragraph 32, and order of 25 November
2011 in Case C-630/10 University of Queensland and CSL,
ECR I-0000, paragraph 38).
25.
Therefore, if a patent protects a therapeutic application of a
known active ingredient which has already been marketed as a
medicinal product, for veterinary or human use, for other
therapeutic indications, whether or not protected by an earlier
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GSK v Comptroller
patent, the placement on the market of a new medicinal product
commercially exploiting the new therapeutic application of the
same active ingredient, as protected by the new patent, may
enable its proprietor to obtain an SPC, the scope of which, in
any event, could cover, not the active ingredient, but only the
new use of that product.
26.
In such a situation, only the MA of the first medicinal product,
comprising the product and authorised for a therapeutic use
corresponding to that protected by the patent relied upon for
the purposes of the application for the SPC, may be considered
to be the first MA of ‘that product’ as a medicinal product
exploiting that new use within the meaning of Article 3(d) of
the SPC Regulation.
27.
In the light of all the above considerations, the answer to the
first and third questions is that Articles 3 and 4 of the SPC
Regulation are to be interpreted as meaning that, in a case such
as that in the main proceedings, the mere existence of an earlier
MA obtained for a veterinary medicinal product does not
preclude the grant of an SPC for a different application of the
same product for which an MA has been granted, provided that
the application is within the limits of the protection conferred
by the basic patent relied upon for the purposes of the
application for the SPC.”
54.
As I observed in AstraZeneca AB v Comptroller-General of Patents, Trade Marks and
Designs [2012] EWHC 2840 (Pat) at [52]-[53], the Court’s judgment in Neurim is
problematic for two reasons.
55.
First, it appears that the Court was intending to depart from its earlier judgments and
order in Pharmacia, MIT and Yissum. This is not clear, however, since it did not refer
to those decisions. Thus one does not know if those decisions are to be regarded as
having been overruled, or as qualified in some unspecified manner.
56.
Secondly, it does not appear that the Court was intending to depart from its earlier
judgments in Case C-195/09 Synthon BV v Merz Pharma GmbH & Co KGaA [2011]
ECR I-0000, [2012] RPC 3 and Case C-427/09 Generics (UK) Ltd v Synaptech Inc
[2011] ECR I-0000, [2012] RPC4, since it cited Synthon at [20]. It is not clear to me,
however, how Neurim is to be reconciled with those decisions. The reasoning which
the Court relied on in Neurim, namely that the research required to obtain a patent and
marketing authorisation for a second medical use of an active ingredient justifies the
grant of an SPC for the second medical use despite the fact that the same active
ingredient has already been lawfully marketed as a medicinal product, seems to me to
be equally applicable to Generics and Synthon.
Bayer CropScience
57.
Case C-11/13 Bayer CropScience is a recent reference from the German
Bundespatentgericht (Federal Patent Court) to the CJEU. In this case Bayer applied
for an SPC for isoxadifen. Isoxadifen is a so-called “safener”, a substance which is
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GSK v Comptroller
added to herbicides and other plant protection products to eliminate or reduce their
phytotoxic effects on certain plants. The safener works in combination with the
herbicide to allow beneficial application of the herbicide. Without the safener, in
many cases the herbicide would destroy the crop in addition to the weed or pest. The
question referred is whether a safener is an “active substance” within the meaning of
Article 1(3) and 1(8) of European Parliament and Council Regulation 1610/96/EC of
23 July 1996 concerning the creation of a supplementary protection certificate for
plant protection products (“the Plant SPC Regulation”), and hence eligible for an SPC
as a product under Article 3(1).
58.
The Federal Patent Court has set out a number of competing considerations in its
reference, while indicating its own provisional view in favour of refusing the
application.
59.
First, the language of the Plant SPC Regulation supports the view that a safener is an
active substance. In particular, “active substances” are defined under Article 1(3) of
the Plant SPC Regulation as “substances or microorganisms including viruses, having
general or specific action”. Furthermore, “plant protection products” are broadly
defined in Article 1(1) as products intended inter alia to protect plants against all
harmful organisms or to influence the life processes of plants (other than as a
nutrient).
60.
Secondly, however, MIT decided that a substance that is used to obtain a
pharmaceutical form of a medicinal product is not covered by the concept of an
“active ingredient” under the SPC Regulation, even if it renders possible the
therapeutic efficacy of the substance in the medicinal product which does have
therapeutic effects. This supports a strict interpretation of “active substance” which is
limited to substances which have a direct therapeutic effect or plant protection action
of their own. It also indicates that merely because the safener is an integral part of the
plant protection product, it does not thereby necessarily constitute an active substance.
61.
The Bundespatentgericht recognises, however, that a factual distinction can be drawn
between MIT and the facts before it, since the mechanism of action of a safener is
different from that of a biodegradable matrix. In particular, a safener appears to have a
more complex mechanism of action which is of more direct effect.
62.
Furthermore, by contrast, in Case C-420/10 Söll [2012] ECR I-0000 the CJEU ruled
that the concept of “biocidal products” under Article 2(1)(a) of European Parliament
and Council Directive 98/8/EC of 16 February 1998 concerning the placing of
biocidal products on the market (“the Biocidal Directive”) follows from the concept
of “active substance” as defined in Article 2(1)(d) of that Directive and includes
indirect action.
63.
Thirdly, European Parliament and Council Regulation 1107/2009/EC of 21 October
2009 concerning the placing of plant protection products on the market, which
replaces Directive 91/414/EEC, clearly distinguishes between the terms “active
substance” and “safener”. It indicates that active substances have general action
against harmful organisms or on plants, whereas safeners are added to the plant
protection product to influence its effects.
THE HON MR JUSTICE ARNOLD
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64.
GSK v Comptroller
It is reasonable to consider that “active substance” should have the same meaning
under the Plant SPC Regulation. In particular:
i)
Paragraph 66 of the Explanatory Memorandum to the Plant SPC Regulation
states expressly that the term “active substances” is taken from Directive
91/414/EEC.
ii)
There is repeated reference to Directive 91/414/EEC (now to be read as
Regulation 1107/2009/EC) in the Plant SPC Regulation.
iii)
There is a clear link or connection between the plant authorisation legislation
and the Plant SPC Regulation.
iv)
When Directive 91/441/EEC was repealed and replaced with Regulation
1107/2009/EC, the Plant SPC Regulation was not amended and the definition
of “active substance” under Article 1(3) remains unchanged.
65.
Fourthly, the substantive requirements for an authorisation of a safener are largely the
same as those for an active substance. It would be consistent with the objectives of the
Plant SPC Regulation to grant a certificate to compensate for the delay (and resulting
reduced period of patent protection) caused by such authorisation requirements.
66.
Finally, the lack of searchability of safeners, which do not appear on any databases of
active substances, suggests that they are not intended to be treated in the same way.
The issue in the present case
67.
The Deputy Director decided that, applying the reasoning of the Court of Justice in
MIT, AS03 was not an “active ingredient” within the meaning of Article 1(b) of the
SPC Regulation whether in its own right or in combination with the antigen contained
in Prepandrix because AS03 did not have a therapeutic effect on its own. AS03 did
not itself confer any immunity, whether against influenza or any other condition. The
fact that AS03 enhanced the therapeutic effect of the antigen, irrespective of the actual
antigen involved and the immunological protection sought, was not sufficient.
68.
GSK contends that the Deputy Director’s decision was wrong. Counsel for GSK
argued in summary as follows.
69.
First, he relied upon various paragraphs of the Explanatory Memorandum to the
Commission’s Proposal for Regulation 1768/92/EEC, and in particular paragraph 11,
as showing that it was intended to apply to all new products which were the subject of
innovative research save only for minor variants such as a new dose, the use of a
different salt or ester or a different pharmaceutical formulation.
70.
Secondly, he relied upon the primary purpose of the SPC Regulation, which was
described by the Court of Justice in Case C-482/07 AHP Manufacturing BV v Bureau
voor de Industriële Eigendom [2009] ECR I-7295 at [30] as follows:
“Regarding the objectives of Regulation No 1768/92, firstly, it
must be noted that the fundamental objective of the Regulation,
as set out in the first and second recitals in the preamble
thereto, is to ensure sufficient protection to encourage
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GSK v Comptroller
pharmaceutical research, which plays a decisive role in the
continuing improvement in public health (Case C-392/97
Farmitalia [1999] ECR I-5553, paragraph 19). In that regard,
the third and fourth recitals in the preamble give as a reason for
the adoption of the Regulation the fact that the period of
effective protection under the patent is insufficient to cover the
investment put into the pharmaceutical research. Regulation
No 1768/92 thus seeks to make up for that insufficiency by
creating an SPC for medicinal products. It seeks, in addition, to
confer supplementary protection on the holders of national or
European patents, without instituting any preferential ranking
amongst them (Biogen, paragraphs 26 and 27).”
71.
In this regard, counsel for GSK argued that giving effect to this purpose had been key
to the Court’s reasoning in Neurim and that that decision showed that Article 1(b)
should not be narrowly interpreted.
72.
Thirdly, he argued that the present case was to be distinguished from MIT. In this
regard, he argued that MIT was concerned with an excipient which had no
physiological effect on the body, whereas the present case was concerned with an
adjuvant which did have physiological effects on the body and which thereby
enhanced the therapeutic effect of the antigen.
73.
The Comptroller supports the Deputy Director’s decision. Counsel for the
Comptroller argued in summary as follows.
74.
First, she relied on the language of the SPC Regulation. In this regard she argued that
the SPC Regulation makes a clear distinction between a “medicinal product” and a
“product” (compare Article 1(a) with Article 1(b)). The former may have an effect on
a physiological function, but it is only the latter which can be the subject of an SPC.
As a consequence, although an adjuvant may fall within the definition of “medicinal
product”, it does not mean that that the adjuvant is an “active ingredient” or “product”
within the meaning of the SPC Regulation. If a substance with general and indirect
physiological effects - which could be positive or negative or might or might not be
related to the indication which was the subject of the marketing authorisation - also
fell within the concept of “active ingredient”, then it would result in a definition
which is too broad and uncertain, leading to divergent results in different Member
States.
75.
Secondly, she relied on the Court of Justice’s decision in MIT. In this regard, she
disputed that the present case could be distinguished from MIT. She pointed out that
the Court’s judgment made barely any reference to excipients, and that neither the
ruling nor the reasoning was confined to excipients. She argued that the ruling and the
reasoning were directly applicable to the present case. She also pointed out that in that
case the Court had been considering a situation in which the presence of the
polifeprosan was necessary to the therapeutic efficacy of the medicinal product. She
argued that, if inventive merit was the only consideration, the Court would have
reached the opposite conclusion.
76.
Thirdly, she relied on European Parliament and Council Directive 2001/83/EEC of 6
November 2001 on the Community Code relating to medicinal products. In this
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regard, she pointed out Directive 2001/83/EEC draws a clear distinction between
“active substances” on the one hand and “excipients” on the other. “Active substance”
is defined in Article 1(3a) as:
“Any substance or mixture of substances intended to be used in
the manufacture of a medicinal product and that, when used in
its production, becomes an active ingredient of that product
intended to exert a pharmacological, immunological or
metabolic action with a view to restoring, correcting or
modifying physiological functions or to make a medical
diagnosis.”
“Excipient” is defined in Article 1(3b) as:
“Any constituent of a medicinal product other than the active
substance and the packaging material.”
77.
Furthermore, the Directive expressly treats an adjuvant as a type of excipient. Thus
Annex 1, Part I, Module 3 to the Directive provides at section 3.2.2.1 as follows
(emphasis added):
“Description and composition of the finished medicinal
product
A description of the finished medicinal product and its
composition shall be provided. The information shall include
the description of the pharmaceutical form and composition
with all the constituents of the finished medicinal product, their
amount on a per-unit basis, the function of the constituents of:
—
the active substance(s),
—
the constituent(s) of the excipients, whatever their
nature or the quantity used, including colouring matter,
preservatives, adjuvants, stabilisers, thickeners,
emulsifiers, flavouring and aromatic substances, etc.,
—
the constituents, intended to be ingested or otherwise
administered to the patient, of the outer covering of the
medicinal products (hard capsules, soft capsules, rectal
capsules, coated tablets, films-coated tablets, etc.),
—
these particulars shall be supplemented by any relevant
data concerning the type of container and, where
appropriate, its manner of closure, together with details
of devices with which the medicinal product will be
used or administered and which will be delivered with
the medicinal product.”
THE HON MR JUSTICE ARNOLD
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78.
GSK v Comptroller
Counsel for the Comptroller argued that it is reasonable to consider that “active
ingredient” should have the same meaning in the SPC Regulation, for at least the
following reasons:
i)
There is repeated reference to Directive 2001/83/EC in the SPC Regulation.
ii)
The SPC Regulation sits at the interface between the regulatory and patent
systems, and serves to compensate for the delay involved in obtaining
marketing authorisations and the resulting effective loss in patent protection.
As a result, the protection is strictly limited to the product which has obtained
authorisation to be placed on the market as a medicinal product under the
Directive (see Recital (10) and Article 3(b)).
iii)
It would be perverse if a substance was not considered an active substance for
the purposes of regulatory approval, but was nevertheless considered an active
ingredient for the purposes of SPC protection.
iv)
Although the Directive has been amended on several occasions and the SPC
Regulation has been codified, no amendments have been made to the
definition in Article 1(b) or otherwise to indicate that the distinction that exists
between active ingredients and adjuvants within the regulatory framework
would not also apply to the SPC Regulation.
79.
In addition, counsel for the Comptroller pointed out that the then European Agency
for the Evaluation of Medicinal Products’ Note for Guidance on Requirements for the
Evaluation of New Adjuvants in Vaccines dated 25 April 2002 stated that “because
the adjuvant is not the active ingredient, it is an individual vaccine/adjuvant
combination which will be licensed”.
80.
Fourthly, she relied upon the other purposes of the SPC Regulation, reflected in
recitals (7)-(10), which the Court of Justice described in AHP as follows:
“35.
…
Second, Regulation No 1768/92, which was adopted on the
basis of Article 100a of the EEC Treaty (subsequently Article
100a of the EC Treaty, and now, after amendment, Article 95
EC), establishes, as is apparent from the sixth and seventh
recitals in the preamble thereto, a uniform solution at
Community level by creating an SPC which may be obtained
by the holder of a national or European patent under the same
conditions in each Member State. It thus aims to prevent 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 (see Case C-350/92 Spain v Council [1995]
ECR I-1985, paragraphs 34 and 35, and Case C-127/00 Hässle
[2003] ECR I-14781, paragraph 37).
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39.
81.
GSK v Comptroller
Thirdly, apart from the objective of adequate protection to
encourage research, Regulation No 1768/92 recognises, as is
apparent from the ninth recital in its preamble, the necessity, in
a sector as complex as the pharmaceutical sector, to take into
account all the interests at stake, including those of public
health (see Spain v Council, paragraph 38). For that purpose,
the SPC may not be granted for a period exceeding five years.
Similarly, the eighth recital in the preamble states that the
holder of both a patent and an SPC should be able to enjoy an
overall maximum of fifteen years of exclusivity from the time
the medicinal product in question first obtains authorisation to
be placed on the market in the Community.”
In this regard counsel for the Comptroller argued that in order to give effect to these
purposes it was necessary to interpret Article 1(b) strictly, as the Court of Justice had
done in MIT.
Conclusion
82.
As noted above, the parties are agreed that this issue should be referred to the Court of
Justice for a preliminary ruling. I also agree that this is necessary, for three reasons.
First, in the light of the arguments summarised above, I do not consider that the
answer is acte clair. Secondly, it is clear that there is a divergence of interpretation
between the different national authorities on this point. Thus the patent offices in
Austria, Italy, Luxembourg and Spain have granted SPCs in respect of both AS03 and
the combination of the antigen and AS03 based on the 918 patent, while the
Portuguese patent office has refused an SPC in respect of AS03 alone but granted one
in respect of the combination and the Swedish patent office, like the Deputy Director,
has refused both applications. In addition, the patent offices in Cyprus and Italy have
granted SPCs for the combination based on the 889 patent. Thirdly, the present case
raises a similar issue to the issue in Bayer CropScience.
83.
Accordingly, I shall refer the following questions to the Court of Justice:
84.
“1.
Is an adjuvant which has no therapeutic effect on its own, but
which enhances the therapeutic effect of an antigen when
combined with that antigen in a vaccine, an ‘active ingredient’
within the meaning of Article 1(b) of Regulation
469/2009/EC?
2.
If the answer to question 1 is no, can the combination of such
an adjuvant with an antigen nevertheless be regarded as a
‘combination of active ingredients’ within the meaning of
Article 1(b) of Regulation 469/2009/EC?”
In case it assists, I shall state my own view on these questions. While I acknowledge
the force of counsel for GSK’s argument that the primary purpose of the SPC
Regulation is to reward innovative research of the kind that led to the development of
AS03 and Prepandrix, I find the arguments presented by counsel for the Comptroller
more convincing. In particular, I consider that the SPC Regulation was intended to
provide a simple and predictable system that could be operated by the competent
THE HON MR JUSTICE ARNOLD
Approved Judgment
GSK v Comptroller
authorities of the Member States, and in particular the national patent offices, in a
uniform manner. To achieve those objectives, it is necessary to have bright-line rules.
Article 1(b) is such a rule. In my view the Court of Justice was correct to hold in
Pharmacia, MIT and Yissum that it should be strictly interpreted. The result of a strict
interpretation is to deny extended protection for what may well be meritorious
inventions, but the price of not adopting a strict interpretation is a level of uncertainty
and inconsistency which in my opinion is unacceptable. Accordingly, I would answer
both questions no.
85.
It is worth adding that, as counsel for the Comptroller pointed out, GSK may be able
to obtain an SPC for the antigen contained in Prepandrix based on the 889 patent and
the marketing authorisation for Prepandrix. Thus refusal of the appeal would not
necessarily leave GSK bereft of protection.
86.
Finally, I would observe that this is the third time in six months that I have had to
refer questions of interpretation of the SPC Regulation to the CJEU. I do so with
considerable regret. That this should be necessary demonstrates the dysfunctional
state of the SPC system at present. This is primarily due to the poor drafting of the
SPC Regulation and to the failure of the European Commission, Council and
Parliament to revise it to address the problems which have emerged. Matters have not
been assisted, however, by the fact that the Court of Justice’s recent case law
interpreting the SPC Regulation has not provided the level of clarity and consistency
that is required.