Merck Sharp & Dohme Corp v Clonmel Healthcare Ltd [2019] IEHC 814 (29 November 2019)
BAILII is celebrating 24 years of free online access to the law! Would you
consider making a contribution?
No donation is too small. If every visitor before 31 December gives just £1, it
will have a significant impact on BAILII's ability to continue providing free
access to the law.
Thank you very much for your support!
[New search]
[Printable PDF version]
[Help]
THE HIGH COURT
COMMERCIAL
[2019] IEHC 814
[ 2018 No. 3485 P.]
BETWEEN
MERCK SHARP & DOHME CORP
PLAINTIFF
AND
CLONMEL HEALTHCARE LIMITED
DEFENDANT
JUDGMENT of Mr. Justice Denis McDonald delivered on 29 November, 2019
Table of Contents
The issues to be decided
1. These proceedings were commenced by the plaintiff against the defendant seeking relief
in relation to the alleged infringement of the plaintiff’s rights under Supplementary
Protection Certificate (“SPC”) no. 2005/2001 granted in 2005 in respect of a cholesterol-
reducing medicinal product comprising a combination of two active ingredients namely
ezetimibe and simvastatin. Ezetimibe is a member of a class of compounds known as
azetidinones. As described in more detail below, simvastatin is a statin. In response to
the plaintiff’s claim, the defendant raised a counterclaim in which it challenged the validity
of the SPC on three grounds. This judgment addresses the invalidity claim. The issues
raised by the defendant are as follows:-
(a) In the first place, the defendant contends that the SPC breaches Article 3 (a) of
Regulation (EC) No. 469/2009 (“the SPC Regulation”) on the ground that the
combination of ezetimibe and simvastatin is not protected by the underlying patent
“and/or was not the core inventive advance to which the …Patent pertained” (to
quote from para. 6 (a) of the Particulars of Objection annexed to the counterclaim).
The patent in question is described in more detail in para. 2 below and is referred
to in this judgment as the “599 patent”;
(b) Secondly, it is claimed that, in breach of Article 3 (c) of the SPC Regulation, the
only compound protected by the 599 Patent (which the defendant contends is solely
ezetimibe) was already the subject matter of an earlier SPC granted in 2003. In
addition, during the course of the hearing, this contention appears to have been
expanded to also make the case that, if the 599 patent protects the combination of
ezetimibe and simvastatin, that combination had previously been the subject of the
earlier SPC granted in 2003 (described further below). In those circumstances, it is
contended that the 2005 SPC is not valid; and
(c) Thirdly, the defendant claims that the marketing authorisation for the combination
was not the first marketing authorisation for such combination and that, in the
circumstances, the SPC was granted contrary to the provisions of Article 3 (d) of
the SPC Regulation.
Background
2. The plaintiff is the holder of Irish Patent 0 720 599 (“the 599 patent”) which was granted
by the European Patent Office (“EPO”) on 19th May, 1999 with a priority date of 21st
September, 1993. The patent relates to a treatment for atherosclerosis. There is no
dispute between the parties that the 599 patent covers a number of azetidinone
compounds including ezetimibe. There is equally no dispute between the parties that
ezetimibe inhibits the resorption of cholesterol (known to be a cause of atherosclerosis) at
the brush border of the intestinal villus in the small intestine. The mode of action of
ezetimibe is different to that of other cholesterol lowering agents such as HMG-CoA
reductase inhibitors commonly known as statins (including simvastatin) which act by
increasing the breakdown of cholesterol in the liver. As described further below, there are
also a number of other agents (each with their own mode of action) which are used to
treat elevated levels of cholesterol.
3. In 2003, a marketing authorisation was granted in respect of a medicinal product under
the trade name Ezetrol pursuant to national measures implementing Directive
2001/83/EC (“the Medicinal Products Directive”) which permitted the marketing of 10mg
tablets of ezetimibe for the following therapeutic indications namely:-
(a) In the case of primary hypercholesterolemia, the tablets were to be administered
with an “HMG-CoA reductase inhibitor (statin) or alone” as adjunctive therapy to
diet for use in patients with primary (heterozygous familial and non-familial)
hypercholesterolemia. It should be noted that heterozygous familial
hypercholesterolemia occurs where the relevant gene is inherited from one parent
alone.
(b) For homozygous familial hypercholesterolemia, the tablets were to be administered
with a statin and were indicated for use in patients with this condition. By way of
explanation, homozygous hypercholesterolemia occurs where a child inherits the
relevant gene from both parents.
(c) For homozygous sitosterolemia, the tablet was indicated for use in patients with
this condition. In other words, the tablet was to be administered alone for this
condition. I should explain that homozygous sitosterolemia is an inherited disorder
of sterol metabolism in which an excess of plant sterols is absorbed and not enough
is excreted.
4. In circumstances where a marketing authorisation was granted for ezetimibe (on the
terms set out above), the plaintiff was in a positon to apply for the grant of an SPC. In
2003, an SPC was issued in respect of ezetimibe. This is the SPC on which the defendant
relies in support of its case under Article 3 (c) of the SPC Regulation.
5. Subsequently in 2005, a new marketing authorisation was issued to the plaintiff in respect
of a medicinal product with the trade name Inegy. This was in respect of tablets
containing a combination of ezetimibe and simvastatin. The authorisation extended to
four specific compositions namely 10 mg ezetimibe and 10 mg simvastatin, 10 mg
ezetimibe and 20 mg simvastatin, 10 mg ezetimibe and 40 mg simvastatin and 10 mg
ezetimibe and 80 mg simvastatin. According to the clinical particulars set out in the
marketing authorisation, the therapeutic indications for this combination were:-
(a) In the case of primary hypercholesterolemia, Inegy was indicated as adjunctive
therapy to diet for use in patients with primary (heterozygous familial and non-
familial) hypercholesterolemia or mixed hyperlipidaemia where use of a
combination product is appropriate.
(b) For homozygous familial hypercholesterolemia, Inegy was indicated as adjunctive
therapy to diet for use in patients with this condition.
6. Thereafter, the SPC, the subject matter of these proceedings was issued in 2005. It was
issued in respect of ezetimibe or a pharmaceutically acceptable salt of ezetimibe in
combination with “a cholesterol biosynthesis inhibitor such as simvastatin”.
7. It should also be noted that simvastatin was previously the subject of Irish Patent No.
51478 which was filed on 2nd February, 1981. Simvastatin also had the benefit of an
SPC. However, that SPC expired on 5th May, 2003.
The SPC Regulation
8. In order to understand the issues which the defendant raises in relation to the validity of
the SPC, it is necessary to refer, at this point in broad terms, to the provisions of the SPC
Regulation. Under Article 3 (a) of the SPC Regulation, an SPC may only be granted where
the product, the subject matter of the SPC is protected by “a basic patent in force”. As
noted above, the defendant maintains that the combination of ezetimibe and simvastatin
is not protected by the 599 patent and/or that it was not the “core inventive advance to
which the 599 Patent pertained”. According to the evidence adduced on behalf of the
defendant, the patent does not disclose anything about a combination product comprising
ezetimibe and simvastatin. The defendant claims that the patent does not teach that
there is any advantage to taking ezetimibe and simvastatin in the same tablet compared
to taking a medicinal product containing ezetimibe alone and another medicinal product
containing simvastatin alone. The defendant maintains that the innovation of the patent
is the demonstration that the different structure of the compounds represented by
formula 1 (which are represented in the patent and which include ezetimibe) can be made
in a pure form. According to the defendant, the combination of ezetimibe and simvastatin
does not represent a separate invention. The defendant also maintains that combination
treatment with lipid lowering compounds belonged to the state of the art in the early
1990s (i.e. before the priority date of September 1993) such that the combination could
not, of itself, be considered to be an invention. In order to resolve this issue, it will be
necessary to consider the terms of the 599 Patent in some detail. It will also be
necessary to consider the case law of the Court of Justice (“the CJEU”) in relation to what
is meant by the words used in Article 3 (a) namely that: “the product is protected by a
basic patent in force”. The case in relation to Article 3 (a) is addressed in detail in paras.
43 to 95 below.
9. Under Article 3 (c) of the SPC Regulation, an SPC cannot be granted if the product (the
proposed subject of the SPC) has already been the subject of a previous SPC. In this
case, the defendant has pleaded in its particulars of objection, that the compound
protected by the 599 Patent (which it contends was confined to ezetimibe) was already
the subject of the 2003 SPC. In addition, during the course of the hearing, the defendant
maintained that the combination product has also been the subject of the SPC granted in
respect of Ezetrol. This is largely on the basis that (a) the marketing authorisation for
Ezetrol required the 10 mg tablets containing ezetimibe to be administered with a statin
for patients suffering from homozygous familial hypercholesterolemia and (b) that,
thereafter, the Ezetrol SPC was granted on foot of that authorisation. In those
circumstances, the defendant contends that Article 3 (c) prohibited the grant of the SPC
in issue in these proceedings (i.e. the SPC granted on foot of the Inegy marketing
authorisation). The case in relation to Article 3 (c) is considered in detail in paras. 96 to
103 below and also 124 and 125 below.
10. Insofar as Article 3 (d) is concerned, it makes clear that, if an SPC is to be granted, the
relevant marketing authorisation under the Medicinal Products Directive must be the first
such authorisation to place the product on the market as a medicinal product. For this
purpose, Article 1 (b) defines a “product” as:-
“The active ingredient or combination of active ingredients of a medicinal product”.
11. In turn, Article 1 (a) defines a “medicinal product” as:-
“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”.
12. Insofar as Article 3 (d) is concerned, the defendant argues that the marketing
authorisation in respect of Inegy is not the first authorisation to place the combination
product on the market as a medicinal product. The defendant argues that the first such
authorisation was that issued in respect of Ezetrol. As noted in para. 3(b) above, this
argument proceeds on the basis that, according to para. 4.1 of the clinical particulars
relating to the Ezetrol authorisation, ezetimibe was required to be administered with a
statin for use in patients with homozygous familial hypercholesterolemia. The defendant
submits, accordingly, that the combination of ezetimibe and simvastatin was authorised
by the 2003 authorisation. The defendant makes the case that, in those circumstances,
the requirements of Article 3 (d) are not satisfied in the case of the Inegy marketing
authorisation issued in 2005. The case in relation to Article 3 (d) is addressed in paras.
104 to 123 below.
Atherosclerosis
13. Before proceeding to consider the legal issues in more detail, it may be helpful, at this
point, to briefly describe the role which cholesterol is generally believed to have in the
development of atherosclerosis which is the relevant medical condition for present
purposes. It would be impracticable to set out, in this judgment, all of the expert
evidence that was given in the course of the hearing. The best that can be done is to set
out a broad overview which, I hope, will be sufficient to identify the relevant features of
the factual background against which the legal issues fall to be determined. Insofar as
atherosclerosis is concerned, the disease arises as a consequence of the accumulation of
atherosclerotic plaques in the inner layers of artery walls. This leads to the gradual
narrowing of blood vessels. Atherosclerosis is typically asymptomatic especially in the
early stages. Patients may only become aware of the condition after clinical complications
occur such as a heart attack or a stroke.
14. One of the risk factors for the development of atherosclerosis is the presence of low-
density lipoproteins (“LDL”) in the blood. Human blood plasma contains a series of
lipoprotein classes (including LDL, high density lipoprotein (“HDL”) and very low-density
lipoprotein (“VLDL”)) which act as transport vehicles for fat molecules such as
triglycerides, cholesterol and a number of other lipid species in the blood. Although
cholesterol is essential for the human body (in that cholesterol is a building-block for cell
membranes) an excessive supply of lipid molecules (exogenous) or an excess of
biosynthesis of lipid molecules (endogenous) may exceed the body’s demands. As a
consequence, it is believed that this can lead to the accumulation of atherosclerotic
plaques. There are a number of reasons why LDL may be elevated. These include an
increased supply of saturated fatty acids. Another risk factor is a genetic disorder of the
lipoprotein metabolism as observed in familial hypercholesterolemia.
The development of cholesterol treatments
15. In circumstances where high concentrations of LDL are generally associated with an
enhanced risk of atherosclerotic disease, attempts have been made over the years to
develop treatments designed to reduce LDL levels in a patient’s blood. Again, it is
important to identify, in broad terms, the relevant treatment background that existed as
of the priority date of the patent. While there was disagreement between the experts as
to when combination therapy was first used for the treatment of hypercholesterolemia,
there was general agreement between the experts on both sides about the development
of a number of monotherapies for the treatment of LDL cholesterol. According to Prof. Dr.
Winfried Marz (“Prof. Marz”) who gave evidence on behalf of the defendant, one of the
first active ingredients observed to reduce both cholesterol and triglycerides in humans
was nicotinic acid (e.g. niacin). The reduction effected by treatment with nicotinic acids
were associated with a decrease in lipoprotein synthesis, resulting in a drop in LDL levels.
However, Prof. Marz gave evidence that side effects were frequently observed with
administration of these acids.
16. A further treatment used to reduce LDL levels comprised bile acid sequestrants (also
referred to as ion-exchange resins). These agents act by binding bile acids within the
intestinal lumen, interfering with their reabsorption and increasing their excretion. As a
consequence, bile acid synthesis is stimulated in the body, requiring an increased amount
of cholesterol in the liver. According to Prof. Marz, cholestyramine is an example of such
an agent which was found to be highly effective in treatment. However, one of the
downsides was that it was not well tolerated by many patients.
17. Another agent which was used in the early 1990s consisted of fibrates. According to Prof.
Marz, clorfibrate and its derivatives were amongst the most commonly used agents for
cholesterol reduction at that time.
18. Another treatment comprised the use of plant sterols. These target the intestinal
absorption of exogenous (principally dietary) and endogenous (biliary) cholesterol and
they thus act to lower serum levels of LDL.
19. Finally, statins (also known as HMG-CoA reductase inhibitors) had been developed as a
therapy as early as the 1980s. Statins are, in general, more effective and better
tolerated compared to many of the compounds mentioned above. Statins were first
authorised for use by humans in the United States. According to the evidence, they were
first authorised for use in Ireland in January 1990 which coincides with the date when
they were first authorised in Germany. However, even in advance of the date of
authorisation, the use of statins was recommended. This was acknowledged by Prof. Dr.
Gerd Assmann (“Prof. Assmann”) (who was called as an expert on behalf of the plaintiff)
on Day 7 of the hearing. The professor explained that the LDL cholesterol lowering
effects of statins was such that it was unjustifiable to delay their application since, to do
so, would expose significant numbers of patients to myocardial infarction. Prof. Assmann
also explained that it was not until the publication of the Scandinavian Simvastatin
Survival Study (known as the “4s study”) in November 1994 that it was demonstrated
that long term treatment with simvastatin, in high risk individuals, not only lowered non-
fatal myocardial infarction but also total mortality. Prof. Assmann described the 4s study
as an “absolute breakthrough study”. In turn, Prof. Marz accepted that the 4s study was
a “landmark study” which showed for the first time that statins could not only reduce
cardiovascular events but also total mortality. Nonetheless, it is clear that from all of the
evidence that I heard in the course of the hearing and from the many papers that were
produced in the course of the evidence, that statins were already in use as a cholesterol
treatment well in advance of the priority date of the 599 patent and also well in advance
of the 4s study. As of the priority date of the 599 patent, several statins were already
commercially available on the market including lovastatin and simvastatin. Others (such
as atorvastatin) were in development at that time.
20. As noted above, the 599 patent dealt with a different treatment for hypercholesterolemia
namely a class of compounds known as azetidinones which includes ezetimibe. The
background to the invention disclosed in that patent is set out in paras. 0001 to 0008 of
the patent. In para. 0001, the invention is stated to relate to hydroxy-substituted
azetidinomes which are useful as hyporcholesterolemic agents in the treatment and
prevention of atherosclerosis. The same paragraph says that the invention also relates to
the combination of such an azetidinone and a cholesterol biosynthesis inhibitor (which
would include statins).
Combination therapy
21. It would be a mistake to think, however, that the concept of a combination of two
cholesterol inhibitors was first disclosed in the 599 patent. The evidence very clearly
establishes that, by the priority date of the patent, combination therapy was both known
and in use. While there was a dispute on the evidence as to the extent to which
combination therapy was in use at this time, there can be no doubt that the idea of
combination therapy was not new at the priority date.
22. Paragraph 0008 of the patent itself refers to a pre-existing paper by Illingworth published
in “Cardiology” in 1989 which suggested that combination therapy involving an HMG CoA
reductase inhibitor (i.e. a statin) and a bile acid sequestrant has been demonstrated to be
more effective in human patients than either agent in monotherapy. In the summary at
the beginning of the Illingworth paper, the author states:-
“Combined therapy with drugs which have different mechanisms of action can be
effectively used in the treatment of patients with severe hypercholesterolaemia or
combined hyperlipidaemia; for the former group, combinations which use bile acid
sequestrants, HMG CoA reductase inhibitors and nicotinic acid are the most
effective”.
23. Paragraph 0008 of the patent also refers to a paper by Witzum published in November
1989 which mentions combination therapy for individuals suffering from heterozygous
familial hypercholesterolemia or severe hypercholesterolemia. The author states that in
such cases:-
“A combination of two or occasionally even three medications will be required to
achieve ideal LDL cholesterol values. Fortunately, effective combinations are
available …”.
The author also states, at an earlier point in the paper, that “dramatic” results could be
achieved by a combination of a bile acid sequestrant and a statin such as Lovastatin.
24. Similar statements had been made in publications as early as 1987. For example, in a
paper presented in the European Heart Journal in 1987 authored by a prestigious study
group from the European Atherosclerosis Society (co-chaired by Prof. Assmann) the
following was stated:-
“Monotherapy is preferred, but resistant familial hypercholesterolaemia not
infrequently requires treatment with two drugs possessing different modes of
action”.
25. This paper in the European Heart Journal was an important document at the time. It
represented the distilled knowledge of a wide range of experts in atherosclerosis including
the late Prof. Risteard Mulcahy who was well known in this jurisdiction. According to Prof.
Marz, the European Heart Journal is addressed to the entire medical community and is a
“really important” journal. In addition, Prof. Assmann confirmed that the article
represented the consensus view of approximately 30 of the most recognised experts in
Europe on issues including the risk and benefit of cardiovascular drugs.
26. According to Prof. Assmann in the course of his evidence on Day 7 of the trial, the
advantage of two drugs with different modes of action is that they may have an additive
effect. The expert evidence on both sides also suggested that, where a combination of
two inhibitors was used, the doses of the individual components of the combination could
be lower thus reducing the risk of unwanted side effects.
27. I do not propose to here identify each of the papers which were discussed in the course of
the evidence at the trial. They included a paper published in “Cardiology” in 1990 by
Prof. Willem Erkelens in 1990, a further paper by Prof. Assmann published in May 1989 in
the American Journal of Cardiology, an article by Akira Endo published in the Journal of
Lipid Research and a paper by Caroline J. Lintott and others published in the Medical
Journal of Australia in October 1991. The paper authored by Caroline Lintott addressed
simvastatin in particular and described a combination of simvastatin with bezafibrate as a
“potentially useful drug combination”. The paper by Erkelens also addressed statins. It
contained a section providing practical advice (which Prof. Marz, on Day 4 of the hearing,
suggested was addressed to medical practitioners) in the following terms:-
“The HMG CoA reductase inhibitor lovastatin is reportedly used by 1 million patients
in the USA, and the use of simvastatin in Europe may reach this number in the
coming years. The reported lack of serious adverse effects in widespread use and
the paucity of adverse effects in clinical trials suggest that HMG CoA reductase
inhibitors might be appropriate first-line drugs for the treatment of
hypercholesterolemia, despite the fact that no data on long-term side effects are
yet available. In my opinion, HMG CoA reductase inhibitors of which simvastatin is
the most potent on a weight basis should be used as first-line therapy in
heterozygous FHC. If this monotherapy fails to achieve an adequate reduction of
the cholesterol level, cholestyramine or cholestipol should be added, initially in
doses much lower than the recommended maximum doses of 8 and 10g ….
respectively. …” (Emphasis added)
By way of explanation, cholestyramine is a bile acid sequestrant. So is cholestipol.
28. In the 1989 article by Prof. Assmann, he also drew attention to the possible use of
combination therapy in cases where both triglyceride and cholesterol levels remain
elevated. In such cases, Prof. Assmann suggested that a combination of lipid-lowering
agents may be appropriate. He continued:
“Suggested combinations include a bile acid sequestrant and a fibrate, or
alternatively, an HMG CoA reductase inhibitor”.
29. In the 1992 article by Akira Endo, the author observed that statins (in particular lovastin,
simvastatin and pravastatin) had been approved and marketed in many countries and
were now well established as effective and safe cholesterol-lowering drugs used by many
patients. In the course of the paper, the author refers to studies undertaken as early as
1983 and 1984 in Japan which showed that a combination of mevastatin and
cholestyramine in patients with heterozygous familial hypercholesterolemia was reduced
by as much as 50-60% by the combination without serious side effects. A similar rate of
reduction was found in studies involving a combination of lovastatin and cholestipol. The
author reported that this combination enhanced the control of LDL while permitting the
use of smaller doses of both drugs.
30. However, Prof. Assmann, in his written statement submitted in these proceedings in July
2018, maintained that by the early 1990s, the “theoretical combination” of various
cholesterol inhibitors was based on “very limited clinical findings” and, in light of “fairly
severe side effects and lack of appropriate safety and efficacy data” such combinations
and “other similar experimental combinations” were seen as a “a last resort for the small
population of patients with severe hypercholesterolemia…” and would “certainly not have
been considered state of the art for a GP at that time”.
31. The evidence of Prof. Assmann was flatly contradicted by the evidence of Prof. Marz. In
his witness statement delivered in response to Prof. Assmann in October 2018 Prof. Marz
said that, depending on the individual patient’s needs for reduction of LDL cholesterol, it
was established practice in the 1990s to administer more than one active ingredient to
achieve target cholesterol levels. According to Prof. Marz, this was not only well
documented in the literature but was also in agreement with his personal experience. In
his evidence at the hearing, he explained that if monotherapy did not work, combination
therapy would be applied and he said that the most frequent combination that was used
was one involving a statin with a bile acid sequestrant. In this context, Prof. Marz
referred not only to the scientific literature discussed above but also to a number of
further articles co-authored by Prof. Assmann himself in a journal distributed to every
general practitioner in Germany. The journal in question was “Deutsches Arzteblatt”
(which I will refer to as the “German Medical Journal”). The first such article was
published in 1987 and did not address combination therapy as such. However, it is clear
from the text of the article that it was addressed to general practitioners. The article also
stressed the importance of screening patients in respect of lipid levels at regular intervals
by general practitioners.
32. Subsequently, in 1988, a further article was published in the German Medical Journal
again co-authored by Prof. Assmann which provided more detailed recommendations for
diagnosis and management of hyperlipidaemia patients. These were the
recommendations made by the European Atherosclerosis Society (in which Prof. Assmann
played a prominent role). As described in para 25 above, the recommendations of that
society represented the synthesis of the views of 30 experts drawn from all around
Europe. The introduction to the article stated that the recommendations were directed to
all practising physicians and should be particularly helpful for those doctors working in
primary care and in certain specialist units. Detailed recommendations were given in
relation to the treatment of patients with elevated levels of cholesterol. These included
dietary recommendations. If changes in diet did not succeed, drug therapies were
recommended. In the case of Group D patients (namely patients with elevated levels of
cholesterol and triglycrides) the paper recommended a number of treatments including
some combinations.
33. The article in 1988 was followed up by an even more detailed article published in the
German Medical Journal in April 1990 (again co-authored by Professor Assmann) which
contained similar recommendations. The paper also contained a number of useful
questions and answers including, at para. 29, a question as to which combinations of lipid
lowering agents were recommended and which were not recommended. The answer
given to this question was in the following terms:-
“Ion exchange resins are often used with nicotinic acid derivatives or fibrates. This
results in further reduction of serum cholesterol, triglycerides and LDL cholesterol,
while HDL cholesterol increases.
The combination of HMG-CoA reductase inhibitors with fibrates or nicotinic acid
derivatives should be avoided due to the myopathy-rhabdomyolysis risk.
The combination of ion exchangers with cholesterol synthesis inhibitors (HMG-CoA
reductase inhibitors) results in a dramatic reduction of LDL cholesterol by up to 50
percent”.
34. The reference in that answer to “ion exchangers” is another name for bile acid
sequestrants. It will be recalled that, in the paper by Akira Endo, the author referred to
studies involving such a combination going back to the 1980s. In my view, the articles
clearly demonstrate that significant efforts were made in the period between 1988 and
1990 to educate general practitioners in Germany as to the recommended treatments for
hypercholesterolemia and to inform general practitioners of the treatments available
including combination therapy. General practitioners were not told that combination
therapy should only take place in specialist clinics. In my view, the sheer extent of the
guidance given to general practitioners in Germany strongly supports the evidence given
by Prof. Marz that combination therapy was in use in Germany among general
practitioners in 1992. In this context, I do not believe that the evidence goes so far as to
suggest that it was undertaken by a majority of general practitioners at that time.
However, the evidence satisfies me that it was undertaken by some general practitioners
and that it was also available in specialist clinics. I appreciate that the plaintiff has
sought to undermine the evidence of Prof. Marz in this regard by reference to evidence
that he gave in the course of proceedings in Norway. It was suggested to Prof. Marz
during the course of cross examination that, in proceedings which took place in Oslo, Prof.
Marz had said it was not common for a general practitioner to use combination therapy
for the treatment of hyperlipidaemia. However, in response, Prof. Marz explained that his
evidence in Norway related to a period after the priority date of the patent when stronger
statins became available such as Atorvastatin which led to a shift back to monotherapy.
He also explained that his impression (formed during interaction with general
practitioners) was that a percentage of them were involved in combination therapy during
the late 1980’s and in the period before the priority date. While the evidence of Prof.
Marz on this issue lacked detail, it seems to me that, in light of the way in which general
practitioners were educated by the German Medical Journal, at least some of them must
have been involved in combination therapy. The very fact that the 1990 article published
in the German Medical Journal had a series of questions and answers supports this
position. It appears to me to be obvious that the very reason why the Journal included
these questions and answers was to assist general practitioners in their decision making
in relation to appropriate treatment for their hyperlipidaemic patients.
35. Notwithstanding that these articles in the German Medical Journal are clearly directed to
general practitioners and notwithstanding the very clear advice given in these articles,
Prof. Assmann, in his replying witness statement and in his oral evidence, sought to
maintain the positon that combination therapy was not undertaken in general practice
and was reserved for severe cases of hypercholesterolemia treated in specialist clinics.
Remarkably, he offered no satisfactory explanation as to why he did not bring to the
attention of the court, in his first witness statement, the approach taken by the European
Atherosclerosis Society or the three papers co-authored by him and published in the
German Medical Journal. I was unimpressed by the explanation given by Prof. Assmann
for not drawing these journals to the attention of the court. They were clearly relevant to
the pre-priority date practice of the medical community in Germany about which he had
purported to give evidence in his first witness statement. When he was cross examined
on Day 8 as to why he had not made reference to these papers, his answer, rather glibly,
was:-
“okay, that’s easy to explain. Because I was not asked to comment [on] my own
papers or the European Heart Journal papers. All of that came up after the
discussion with Prof. Marz. So he brought up these arguments and tried to
outbalance my statement …”.
36. In my view, Prof. Assmann, as an expert, clearly should have brought these papers to the
attention of the court in his own witness statement. It is unsatisfactory that an expert
would not bring such manifestly relevant materials to the attention of the court and
should only address them after they have been raised by an expert on the other side.
Given that these journals were clearly addressed to general practitioners, and given that
the journals did not themselves suggest that combination therapy was limited to
specialised clinics, the journals are plainly of relevance to the issue which falls for
consideration in these proceedings in relation to Article 3 (a) of the SPC Regulation. It is
particularly difficult to understand how Prof. Assmann, as a co-author of the articles, did
not address them of his own volition. At this point, it should be noted that the defendant
has strongly questioned the independence of Prof. Assmann’s testimony. The defendant
does so not merely on the basis that these relevant materials were not brought to the
attention of the court in the professor’s first witness statement but also on the basis of
the somewhat combative and, at times, unhelpful conduct of Prof. Assmann while giving
evidence. In addition, the defendant draws attention to the professor’s involvement with
the proprietor of the 599 patent (Schering Plough) in relation to ezetimibe. In this
context, it emerged during the course of Prof. Assmann’s cross-examination that he had
been on the advisory board of Schering Plough at the time when the 599 patent was filed
and that he had had “lots of discussions” with the inventor, Dr. Harry Roger Davis (albeit
that these related to the Niemann-Pick protein described in para. 28 below rather than to
the subject matter of the patent). In the course of his evidence on Day 8, Prof. Assmann
said that he did not reveal this relationship previously because he thought it was
“irrelevant”. Of course, prior involvement of that kind does not necessarily out rule the
giving of expert evidence by someone in Prof. Assmann’s position. However, the
professor’s failure to disclose it or to even consider it to be a relevant matter to be
disclosed raises serious questions about his understanding of the role of an expert
witness.
37. For completeness, it should also be noted that, in response to the evidence given by Prof.
Marz in relation to the advice to German general practitioners in the German Medical
Journal, Prof. Assmann also relied upon concerns from some clinicians, at the time, that
lowering cholesterol does not reduce overall mortality. He referred, inter alia, to an
advertisement which appeared in the same edition (i.e. the 1990 edition) of the German
Medical Journal as the last of the articles described above which raised this issue and
suggested:-
“The results of the long-term cholesterol studies do not come to a conclusion
whether lowering the cholesterol is harmful or if the side effects of the treatment
resulted in the increased number of deaths. In any case the cholesterol reduction
was not beneficial.
I have to say that I find it somewhat surprising that an expert would rely on an
advertisement of this kind. The advertisement extolled the continued use of milk, butter,
cheese, eggs and meat as an integral part of a healthy diet. It should be noted that the
advertisement was published by the central marketing organisation of the German
agribusiness industry. Prof. Assmann also referred to the views expressed by Prof.
Michael Oliver of London who published material to similar effect in the Lancet in 1991.
However, it emerged in the course of the cross-examination of Professor Assmann that
Prof. Oliver had participated in the meetings with the other experts in the European
Atherosclerosis Society which produced the consensus papers which ultimately fed into
the articles published in the German Medical Journal. There was no addendum or
qualification added to the papers published by the Society which reflected any objection
or dispute on the part of Prof. Oliver. Moreover, it is clear from Prof. Assmann’s evidence
that, in any event, he himself regarded Prof. Oliver as an outlier on the issue and as a
“non-believer” who did not share in the more generally held view.
The development of the combination in issue
38. While the relevance of his evidence is questioned by the defendant (for the reason that it
relates to events post the priority date of the patent) it should be noted that Dr. Harry
Roger Davis Jnr. gave evidence about the development of ezetimibe and of the
subsequent experiments done which ultimately identified the utility, efficacy and relative
safety of the combination of ezetimibe and simvastatin. Dr. Davis was a member of a
group of researchers at Schering Plough that developed ezetimibe and later discovered its
molecular target in the human body namely the intestinal sterol transporter Niemann-Pick
C1-Like 1 protein (“NPC”). As I understand it, NPC acts as a cholesterol-sensing receptor
and is responsible for cellular cholesterol absorption. It is found in the intestine and in
the liver.
39. Several years after the patent was granted, Dr. Davis was involved in the carrying out of
experiments relating to combinations of one of the azetidinone compounds covered by the
599 patent with statins. Dr. Davis explained that, at the outset, he did not know what
the azetidinone compounds would do in combination with statins. The first experiment
carried out involved a compound covered by the 599 patent which was given an internal
name “Schering 48461”. Early experiments with animals suggested that a combination of
Schering 48461 and statins synergistically lowered cholesterol. However, in the course of
the experiments carried out, there was a drug-drug interaction with lovastatin which
precluded it from further development. The experiments in question were carried out on
dogs. When the experiments with the Schering 48461 compound proved problematic, the
investigators turned to a number of backup compounds covered by the patent including
ezetimibe. Ultimately, it was ezetimibe that, in the words of Dr. Davis, “eventually made
it to market”.
40. Dr. Davis explained that, in the course of his investigations, he combined ezetimibe with
five or six different statins that were on the market or that were coming on the market
and he ensured that ezetimibe did not interfere with the drug metabolism of those statins
or have a drug-drug interaction.
41. Dr. Davis, in his evidence, also explained that it took twelve years of research to figure
out how the mechanism of action of ezetimibe works. He explained that this point was
not actually reached until 2003. Dr. Davis confirmed, under cross-examination, that
ezetimibe itself was not first synthesised until 1994 and the first clinical studies in relation
to ezetimibe in humans was in 1996.
42. As noted above, early experiments with animals suggested that a combination of an
azetidinone compound and a statin worked synergistically. Ultimately, however, this did
not transpire to be so in humans. Dr. Davis confirmed that the effect of the combination
in humans was found to be additive rather than synergistic. Dr. Davis also confirmed
that, at the time of these tests, Schering Plough did not have within its stable any of the
statins that were being tested. In fact, Dr. Davis explained that, for the purposes of the
studies in dogs, he “actually bought the drugs from the pharmacy … and ground them up
and fed them to the dogs…”. Dr. Davis was not entirely sure when the dog studies took
place involving ezetimibe and simvastatin but he thought that they commenced
somewhere between 1994 and 1996 and was completed by 1997.
The case made by the defendant in relation to Article 3 (a)
43. As noted in para. 8 above, the defendant maintains that the combination of ezetimibe and
simvastatin is not protected by the 599 patent and/or that it was not the “core inventive
advance to which the 599 Patent pertained”. The principal argument made by the
defendant in support of this contention is encapsulated in para. 6.22 of the defendant’s
closing written submissions in which the case is made that a skilled person reading the
599 Patent with the benefit of common general knowledge (in particular, common general
knowledge in relation to combination therapy as at the priority date of the patent) would
not deduce from the references in the patent to combining a compound of Formula 1 with
a statin that such a combination is an independent innovation (as distinct from the
compounds of Formula 1 simpliciter which include ezetimibe). The defendant submitted
that, in effect, the 599 Patent says nothing other than: “here is a new drug to be used in
the treatment and prevention of high cholesterol that will join the pool of other such
drugs already being used for this purpose, including statins, with which it can be
combined”.
44. In order to understand the legal basis for this argument, it will be necessary to address
some of the case law of the Court of Justice (“CJEU”) including the decision of the Grand
Chamber in Case C-121/17 Teva v. Gilead. Both sides have sought to rely on that
decision in support of their respective positons in relation to the Article 3 (a) issue. The
plaintiff strenuously argues, by reference to the decision of the CJEU in that case and by
reference to some of its previous decisions, that a product will be protected by a basic
patent in force (within the meaning of Article 3 (a)) where the product is expressly
mentioned in the claims of the patent. The plaintiff contends that, here, the 599 Patent
expressly contains a claim in respect of the combination in issue and that, as a
consequence, the combination of ezetimibe and simvastatin is protected by the patent for
the purposes of Article 3 (a). If the plaintiff is correct in that contention, that would be
sufficient, of itself, to resolve the Article 3 (a) issue and it would not be necessary to
consider any of the other arguments that arise in relation to Article 3 (a). It therefore
makes sense to address this issue first. If I find against the plaintiff in relation to that
issue, it will then be necessary to consider some of the other arguments that arise.
However, before doing so, it is necessary, at this point, to consider the terms of the 599
Patent itself. It is also important to bear in mind, in considering the patent, the argument
made by the defendant that it is not sufficient that the patent should make a claim in
relation to a combination. The defendant urges that, on the basis of the decision in Teva
v. Gilead, the relevant combination must fall within the ambit of an invention the subject
of the patent.
Relevant terms of the 599 Patent
45. As noted briefly above, para. 0001 of the patent records that the invention relates to
hydroxy-substituted azetidinones used as hypocholesterolemic agents in the treatment
and prevention of atherosclerosis and also to “the combination of a hydroxy-substituted
azetidinone of this invention and a cholesterol biosynthesis inhibitor for the treatment and
prevention of Atherosclerosis.”
46. The same paragraph says that the invention also relates to a process for preparing
hydroxy-substituted azetidinone. Thereafter, again as briefly described previously,
reference is made in para. 0008 to the articles by Witzum and Illingworth which both
address combination therapy. Paragraphs 0001 to 0008 are all under the heading
“BACKGROUND OF THE INVENTION”. The defendant places some emphasis on the fact
that, as noted above, the articles by Witzum and Illingworth both refer to combination
therapy and that the patent itself acknowledges that this forms part of the relevant
background.
47. Paragraphs 0009 to 0019 contain a summary of the invention. Paragraph 0009 refers to
the novel compounds of the present invention represented by Formula 1 or
pharmaceutically acceptable salts of such compounds. In para. 0014, it is stated that the
invention also relates to a method of lowering the serum cholesterol level in a mammal by
administering an effective amount of a compound of Formula 1. The same paragraph
again uses the phrase “a compound of the present invention”.
48. Thereafter, para. 0016 provides as follows:-
“The present invention also relates to a method of reducing plasma cholesterol
levels and to a method of treating or preventing atherosclerosis, comprising
administering to a mammal in need of such treatment an effective amount of a
combination of a hydroxy-substituted azetidinone cholesterol absorption inhibitor of
Formula 1 and a cholesterol biosynthesis inhibitor. That is, the present invention
relates to the use of a hydroxy-substituted azetidinone cholesterol absorption
inhibitor of Formula 1 for combined use with a cholesterol biosynthesis inhibitor
(and, similarly, use of a cholesterol biosynthesis inhibitor for combined use with a
hydroxy-substituted azetidinone cholesterol absorption inhibitor of Formula 1) to
treat or prevent atherosclerosis or to reduce plasma cholesterol levels”.
49. Paragraph 0017 is in similar terms but, rather than referring to a combination, it deals
with a kit comprising, in one container, an effective amount of the relevant Formula 1
compound and, in a separate container, an effective amount of a biosynthesis inhibitor in
a pharmaceutically acceptable carrier.
50. A detailed description of the invention is given at paras. 0020 to 0133. For present
purposes, it is sufficient to refer to a small number of those paragraphs. The first such
paragraph which is relevant to combinations is para. 0028 which expressly mentions the
possibility of a combination with, among other inhibitors, simvastatin. Paragraph 0028
provides as follows:-
Cholesterol biosynthesis inhibitors for use in the combination of the present
invention include HMG CoA reductase inhibitors such as lovastatin, pravastatin,
fluvastatin, simvastatin and CI-981”.
51. Paragraph 0028 refers to a number of other potential combination partners but concludes
by stating that the preferred HMG CoA reductase inhibitors are lovastatin, pravastatin,
fluvastatin, and simvastatin.
52. Paragraph 0029 provides that the compounds of Formula 1 can be prepared by known
methods but a number of such methods are then set out in considerable detail. No
equivalent information is provided in relation to the preparation of any combination of any
of the Formula 1 compounds with a statin.
53. Subsequently, at para. 0061, the patent states that compounds of the invention lower
serum lipid levels (in particular serum cholesterol levels) by inhibiting the intestinal
absorption of cholesterol and reducing the formation of liver cholesteryl esters in animal
models.
54. In the following number of paragraphs, a method of treating the in vivo activity of the
compounds of Formula 1 can be determined by following a procedure derived from trials
in hamsters.
55. Paragraph 0065 and following paragraphs deal with dosage. Paragraph 0065 deals with
dosage of Formula 1. Paragraph 0066 deals with dosages of combinations and sets out
typical daily doses depending on body weight. Paragraph 0066 also makes clear that
precise dosages are a matter for the treating clinician. Clearly, the patent envisages that
the clinician will use his or her general knowledge and expertise for that purpose. In this
context, para. 0066 provides:-
“The exact dose of any component of the combination to be administered is
determined by the attending clinician and is dependent on the potency of the
compound administered, the age, weight, condition and response of the patent”.
56. Paragraph 0068 identifies that, where plasma cholesterol levels are to be treated with a
combination of active ingredients, these ingredients may be administered separately.
Paragraph 0068 states that, in such circumstances, the invention also relates to
combining separate pharmaceutical compositions in “kit form”. The same paragraph
explains that a kit is contemplated where two separate units are combined, a cholesterol
biosynthesis inhibitor and a hydroxyl substituted azetidinone cholesterol absorption
inhibitor. Paragraph 0069 to 0130 all deal with examples of preparing compounds of
Formula 1. These paragraphs take up the next eleven pages of the patent. Having
described the method of manufacture of the compounds of Formula 1, para. 0132 of the
patent then deals with cholesterol biosynthesis inhibitors. Counsel for the defendant
placed some emphasis on the language of this paragraph and suggested that the
paragraph shows clearly that simvastatin could not be considered to be part of the
invention. He argued that the skilled addressee is informed at para. 0132 that
representative formulations comprising cholesterol biosynthesis inhibitors (which are not
confined to statins) are well known in the art and that the dosage is a matter that can be
adjusted by reference to the knowledge of the skilled addressee. This is an argument
which is not directly relevant to the issue as to whether it is sufficient to simply claim a
combination in the claims of a patent. Nonetheless, it is important to note it at this point
since it is relevant to the case made by the defendant as to the extent of protection
provided by the 599 Patent. For completeness, para. 0132 is in the following terms:-
“Representative formulations comprising a cholesterol biosynthesis inhibitor are
well known in the art. It is contemplated that where the two active ingredients are
administered as a single composition, the dosage forms disclosed above for
substituted azetidinone compounds may readily be modified using the knowledge of
one skilled in the art”.
57. The claims of the patent include a claim in relation to ezetimibe (which is covered by
Claim 8). Claim 9 refers to combinations in the following way:-
“A pharmaceutical composition for the treatment or prevention of Atherosclerosis,
or for the reduction of plasma cholesterol levels, comprising an effective amount of
a compound as claimed in any one of claims 1 to 8 alone or in combination with a
cholesterol biosynthesis inhibitor, in a pharmaceutically acceptable carrier”.
58. Claim 12 claims a process for preparing a pharmaceutical composition comprising the
admixing of a cholesterol biosynthesis inhibitor and a compound within any one of Claims
1 to 8 with a pharmaceutically acceptable carrier. However, it should be noted that there
is no description given in the patent itself of any process of admixture. Claims 12 – 13
both make claims in respect of combination use. Claim 15, consistent with para. 0068
deals with the kit comprising separate containers in a single package for use in
combination comprising, in one container, the cholesterol biosynthesis inhibitor and, in a
second container, a pharmaceutical composition comprising an effective amount of the
Formula 1 compound.
59. It is clear from Claim 16, that, when the patent speaks of cholesterol biosynthesis
inhibitors, it is not confining itself to statins. Claim 16 is in the following terms:-
“A pharmaceutical composition of any of claims 9,12 or 15 wherein the cholesterol
biosynthesis inhibitor is selected from the group comprising of HMG CoA reductase
inhibitors, squalene synthesis inhibitor and squalene epoxidase inhibitors”.
60. This is confirmed by the terms of Claim 17 which contains a list of named biosynthesis
inhibitors including simvastatin (among other statins) together with a number of other
inhibitors. Claim 17 is in the following terms:-
“A pharmaceutical composition of Claim 16 wherein the cholesterol biosynthesis
inhibitor is selected from the group consisting of lovastatin, pravastin, fluvastatin,
simvastatin, CI-981, DMP-565, L-659, 699, squalestatin 1 and NB-598”.
As I understand it, NB-598 is not a statin but a squalene epoxidase inhibitor.
The argument of the plaintiff based on the claims of the patent
61. While it is essential to keep in mind that the onus of proof of invalidity rests on the
defendant, it is convenient at this point to address the argument made by the plaintiff
that, once the combination has been the subject of a specific claim in the patent, that is a
complete answer to the defendant’s case.
62. The case made by the plaintiff derives some support from a number of decisions of the
CJEU which predate the decision in Teva v. Gilead including the decision in Case C-322/10
Medeva v. Comptroller General of Patents, Designs and Trade Marks [2011] ECR I-12095.
The “key role” of the claims was also emphasised by the CJEU in Case C-493/12 Eli Lilly v.
Human Genome Sciences Inc. Similar views were also expressed in a number of other
decisions but it is unnecessary to list them all. The critical decision for present purposes
is Teva v. Gilead. The facts giving rise to that decision have previously been described by
me in paras. 95-100 of my judgment in Gilead Sciences Inc v. Teva BV [2019] IEHC 683
and I therefore do not propose to repeat that material here. It is sufficient to record that
the patent in issue related to a treatment for the HIV retrovirus. A number of compounds
were claimed in the patent including a nucleotide reverse transcriptase inhibitor called
tenofovir disoproxil (“TD”). The patentee (Gilead) subsequently obtained an SPC in
respect of a combination sold under the brand name Truvada which contained two anti-
retroviral agents namely TD and emtricitabine (“FTC”). The issue was whether that
combination could be said to be protected by the patent in question. Claim 27 of that
patent did not claim FTC by name but it was suggested that the reference to “other
therapeutic ingredients” in Claim 27 of the patent would be construed by the skilled
person as referring to FTC. Claim 27 was in the following terms:-
“A pharmaceutical composition comprising a compound according to any one of
claims 1-25 together with a pharmaceutically acceptable carrier and optionally
other therapeutic ingredients”.
63. There is an obvious factual distinction between that patent and the 599 patent. The latter
specifically contemplates, in claims 16 and 17, that one or more of the Formula 1
compounds will be combined with a named statin, a squalene synthesise inhibitor or a
squalene epoxidase inhibitor. More particularly, simvastatin is specifically identified as
one of the statins with which the Formula 1 compound can be combined. Thus, if the
plaintiff is correct in its submission that a product will be protected by a basic patent
where it is expressly mentioned in the claims of that patent, there would be a good basis
to dismiss the defendant’s counterclaim founded on Article 3 (a). The defendant,
however, argues that the submission made by the plaintiff is not consistent with the
approach taken by the CJEU in Teva v. Gilead.
64. In Teva v. Gilead, the CJEU devised a comprehensive two stage test to assist in
determining whether a product is protected by a basic patent for the purposes of Article 3
(a). As outlined above, the plaintiff argues that this test was not intended to apply where
an identified combination is specifically claimed in the patent. The plaintiff argues that
the test is confined to cases where one of the components of the combination is not
specifically identified in the claims of a patent. The plaintiff placed particular emphasis in
this context on what was said by the CJEU in para. 37 of the judgment which is in the
following terms:-
“37. Therefore, a product cannot be considered to be protected by a basic patent in
force within the meaning of Article 3 (a) … unless the product which is the subject
of the SPC is either expressly mentioned in the claims of that patent or those claims
relate to that product necessarily and specifically”. (Emphasis added).
65. The plaintiff argues that, in that paragraph, the CJEU, very clearly, made a distinction
between those cases (such as the present) where a product is expressly mentioned in the
claims of a patent and cases such as Teva v. Gilead itself, where a product (or a
component of the product) is not expressly mentioned in the claims. The plaintiff draws
attention to the use of the word “or” in para. 37 of the judgment (as highlighted in para.
64 above). The plaintiff submits that the balance of the judgment (in which the two stage
test is set out) is solely concerned with the latter case and is of no relevance to the 599
Patent.
66. In support of its position, the plaintiff also relies on a number of other observations in the
judgment of the CJEU. In particular, the plaintiff draws attention to para. 32 which refers
to Article 69 of the European Patent Convention (“EPC”) and the Protocol (which, in broad
brush summary, emphasise the importance of the claims of a patent). The plaintiff
derived further support for this argument from what was said by the CJEU in para. 35 of
its judgment where, again referring to Article 69 of the EPC, the CJEU noted that the
extent of the protection conferred by a European patent is determined by the claims.
67. In addition, the plaintiff placed some emphasis on what was said by the CJEU at para. 34
of its judgment where, referring to the Eli Lilly case, the CJEU said:-
“…the Court has repeatedly emphasised the key role played by the claims for the
purpose of determining whether a product is protected by a basic patent…”.
68. While I can see how the plaintiff has come to make that argument, I do not believe that it
is correct. I have reached that conclusion for a number of reasons:-
(a) In the first place, the question posed by the referring court to the CJEU in Teva v.
Gilead was framed by Arnold J. in very broad terms. It simply asked the CJEU to
identify the criteria for deciding whether a product is protected by a basic patent in
force for the purposes of Article 3 (a). Because of the concerns expressed by
Arnold J. as to a lack of clarity in the law arising from previous decisions of the
CJEU, a Grand Chamber was assembled in order to provide definitive guidance.
The judgment of the Grand Chamber addresses the broad question posed and
seeks to clarify the law in relation to the meaning and effect of Article 3 (a).
(b) Secondly, I cannot see any basis in the judgment to suggest that the CJEU intended
that all of its judgment from para. 38 onwards is confined to cases where the
relevant combination is not expressly mentioned in the claims of a patent. On the
contrary, para. 38 of the judgment commences with the words “For that purpose…”.
Those words seem to me to refer back to the entire of what was said in the
preceding paragraph (i.e. para. 37). I can see nothing in the language used in
para. 38 of the judgment to support the suggestion that the CJEU only intended to
refer back to the second part of para. 37 (i.e. the part dealing with cases where the
relevant combination is not expressly mentioned in the claims of a patent);
(c) Thirdly, it is clear from the text of para. 38 that the CJEU was mindful of the
requirements of Article 69 of the EPC that the description and drawings of the basic
patent must be taken into account. One does not look solely at the claims. In that
paragraph, the CJEU stated:-
“…the description and drawings of the basic patent must be taken into
account, as stipulated in Article 69 of the EPC read in the light of the
Protocol…, where that material shows whether the claims of the basic patent
relate to the product which is the subject of the SPC and whether that
product in fact falls under the invention covered by that patent”. (Emphasis
added).
(d) Fourthly, and most importantly, the CJEU, in paras. 39-41 of its judgment,
emphasised the underlying objective of the SPC Regulation which is to compensate
for the delay in the commercial exploitation of an invention. The CJEU highlighted,
in stark terms, that it would be contrary to the objective of that Regulation to grant
an SPC for a product which does not fall under the invention covered by the patent.
The CJEU stressed that the purpose of the additional period of exclusivity is to
encourage research and to ensure that the investment in research is appropriately
compensated. If an SPC were to be granted for a product which does not fall within
the ambit of the invention covered by the patent, then the SPC would not relate to
the results of the research claimed under that patent. In addition, the CJEU
invoked Recital 10 to the preamble to the SPC Regulation which refers to the need
to take into account all the interests at stake including those of public health. The
court stated that, to accept that an SPC could grant to the holder of the patent
protection which goes beyond the scope of the invention it covers would be
contrary to the requirement to balance the interests of the pharmaceutical industry
and those of public health. All of these considerations led the CJEU to say, in para.
43 of the judgment:-
“43. Accordingly, having regard to the objectives pursued by [the SPC
Regulation], the claims cannot allow the holder of the basic patent to enjoy,
by obtaining an SPC, protection which goes beyond that granted for the
invention covered by that patent. Thus for the purposes of the application of
Article 3(a) of that regulation, the claims of the basic patent must be
construed in the light of the limits of that invention, as it appears from the
description and the drawings of that patent.” (Emphasis added).
(e) In my view, it is critically important, to have regard to the rationale expressed by
the CJEU in paras. 38-43 of its judgment. Those paragraphs illustrate the concern
of the CJEU to ensure that an SPC should not be granted for a product which does
not fall within the invention covered by the patent. The paragraphs also stress that
the claims of the basic patent must be construed in the light of the limits of that
invention. That rationale and concern are equally applicable whether or not a
product is expressly mentioned in the claims of the patent. If the plaintiff’s
interpretation of the judgment is correct, it would have the bizarre consequence
that the concerns expressed by the CJEU in those paragraphs could be readily
sidestepped by those patentees who had taken the course of assiduously listing
expressly in the claims of the relevant patent a large range of products or
combinations of products even where those claims went beyond the limits of the
underlying invention. In my view, the approach suggested by the plaintiff would
subvert the rationale expressed by the CJEU in its judgment in Teva v. Gilead. I
therefore cannot accept the approach which the plaintiff suggests. Accordingly, I
have come to the conclusion that the test set down in Teva v. Gilead must be
applied in this case in order to determine whether the combination of ezetimibe and
simvastatin is protected by the 599 patent.
The Teva v Gilead test
69. As noted above, there are two parts to the test laid down by the CJEU in Teva v. Gilead.
These are:-
(a) As set out in para. 47 of the judgment, the first element considers whether the
product which is the subject of the SPC necessarily falls under the invention
covered by the patent. The approach to be taken in considering that question is set
out in para. 48 of the judgment where the CJEU made clear that it is necessary to
consider the matter from the perspective of the person skilled in the art and to ask
whether such a person can understand, without any doubt, on the basis of their
general knowledge, and in the light of the description and drawings of the
invention, that the product to which the claims of the basic patent relate is “a
specification required for the solution of the technical problem disclosed by that
patent”. The language quoted is not, subsequently, replicated by the CJEU in its
specific answer to the question posed by Arnold J. The answer given by the CJEU to
that question is set out in para. 57 of the judgment and the language used there
refers to whether the active ingredient: “must necessarily, in the light of the
description and drawings of that patent, fall under the invention covered by that
patent”. Similar language emphasising the importance of the invention is used
elsewhere in the judgment. In my view, as I previously noted in my judgment in
Gilead v. Teva, the approach taken by the CJEU is invention focussed rather than
claims focussed. While the claims are important, a product will not be considered
to be protected by a basic patent for the purposes of Article 3 (a) unless it falls
within the ambit of an invention the subject of that patent.
(b) The second limb of the test is set out in para. 49 of the judgment where the CJEU
explained that, for the purposes of assessing whether a product falls under the
invention covered by a basic patent, account must be taken exclusively of the prior
art at the filing date or priority date of the patent “such that the product must be
specifically identifiable by a person skilled in the art in the light of all the
information disclosed by that patent”.
70. In my judgment in Gilead v. Teva I have sought to analyse, in more detail, the judgment
of the CJEU. It is therefore unnecessary to repeat that analysis here. For the reasons
explained in that judgment, I take the view that the reference to “prior art” must be read
in context. As set out in para. 128 of my judgment in Gilead v. Teva, it seems to me to
be clear that the CJEU envisaged that, in assessing the state of general knowledge as of
the priority date in a patent, one cannot have regard to any materials which only came
into existence after the priority date. In my view, the CJEU has made it clear that, in a
case of this kind, in assessing common general knowledge as of the filing date or priority
date of a patent, it is impermissible to have regard to material which came into existence
after those dates. In my judgment in Gilead v. Teva, I also addressed the question of
whether the CJEU had intended to lay down a “core inventive advance” test. I took the
view (which I continue to hold) that it would be unsafe to consider that the CJEU had laid
down such a test. Since my judgment was given in that case, a similar view has been
expressed by Advocate General Hogan in Joined Cases C-650/17 and C-114/18 Royalty
Pharma at paras. 50-54. As the Advocate General noted in para. 53 of his opinion, at no
point in Teva v. Gilead did the CJEU refer to the concept of “core inventive advance”. In
light of the approach taken by the CJEU, I took the view in Gilead v Teva that I should
decide the case by reference to the language used more consistently in the CJEU
judgment, i.e. by reference to whether the product in question falls within the ambit of
the “invention covered by [the] patent”. That is the approach which I believe should also
be taken in this case.
The role of the “skilled person”
71. It is important to keep in mind that the CJEU test involves a consideration of the issue by
reference to the standpoint of the skilled person. That is consistent with the general
approach taken to the construction of patents as explained by Clarke J. (as he then was)
in Rambaxy Laboratories Ltd v. Warner-Lambert Co. [2007] IEHC 256 at paras. 3.9-3.10
as follows:-
“3.9 The other key concept involved in the construction of the patent is that it must be
approached from the standpoint of what has been described in the authorities as
the ‘skilled addressee’. The skilled addressee is taken to be a person … with
practical knowledge and experience of the kind of work in which the invention was
intended to be used …It is common case that I should attempt to read the patent
and construe it in the way in which the so called skilled addressee would have done
so.
3.10 The knowledge which will be attributed to the notional skilled addressee is the
knowledge that any worker in the area concerned would be expected to have as
part of their general knowledge. … The knowledge is that which a skilled addressee
would have had as of the ‘priority date’ …. It is, therefore, agreed between the
parties that I should approach the construction of this patent on the basis of the
common general knowledge that would have been available to a person working in
the field … as of that date. …”.
72. At a later point in his judgment in that case, Clarke J. drew an analogy between the
approach to be taken in construing a patent and the approach taken by the courts in
construing a contract. In both cases, the relevant context (or factual matrix) is relevant.
At para. 3.25 of his judgment, Clarke J. observed that there was no “magical difference”
between the proper approach to the construction of a patent, on the one hand, or any
other document intended to effect legal obligations and entitlements (such as a contract),
on the other hand. At para. 3.23-3.24 he explained his reason for taking this approach.
While he stressed the fundamental importance of the nature of the document itself, he
drew attention to the need for a court, in a contractual context, to know the relevant
factual background. He then suggested that a similar approach should be taken in the
context of a patent. In particular, he said at paras 3.23-3.24:-
“3.23 a court may need to know the overall context of the circumstances leading to the
negotiation of the contract in the first place. This is because the contract should be
construed in the way in which a reasonable and informed person entering into a
contract of that type would be likely to interpret it. That person will not come to the
interpretation of the contract with a blank mind. The contractual negotiations will
commence against a particular factual backdrop and the parties will be seeking to
advance their commercial interests against that factual back drop.
3.24 The position of the skilled addressee in relation to a patent is, in reality, in my view,
no more than a special case of that generality. The equivalent, in a commercial
context, of the skilled addressee may be the person who understands the overall
context within which the contract is entered into and who is, thus, in a position to
interpret properly any terminology used. The skilled addressee also has his
counterpart in the bystander by reference to whom implied terms may be found to
exist.”
Who is the skilled person for the purposes of the 599 Patent?
73. In the course of making its case, the defendant argued that the skilled addressee, for the
purposes of the 599 Patent, was the general practitioner. In making this case, the
defendant referred to the articles in the German Medical Journal (summarised above) and
to the evidence of Prof. Marz to the effect that general practitioners were involved in
combination therapy. While I accept that there was evidence that general practitioners
were, at least to some extent, involved in combination therapy, I do not believe that it
could be suggested that combination therapy was part of the day to day general practice
of all or most general practitioners as of the priority date of the patent. I do not believe
that the evidence goes that far. Prof. Marz was not able to give any detail as to the
extent to which it was in use at that level. On the basis of the evidence which I have
heard, I believe that it is reasonable to conclude that there were some general
practitioners who were involved in combination therapy. However, the evidence suggests
that combination therapy was more likely to be encountered among specialist clinicians
involved in the treatment of atherosclerosis. Ultimately, I do not believe that very much
turns on the extent to which combination therapy was used by general practitioners.
What is clear is that combination therapy was in use as at the priority date, the most
common form being a combination of a statin and a bile acid sequestrant. It is also clear
that, as of the priority date, general practitioners were educated as to the existence of
combination therapy for more difficult cases of hypercholesterolemia. The articles
published in the German Medical Journal demonstrate this. I reject the evidence of Prof.
Assmann that, as of the priority date, combination therapy was still “theoretical” or that it
was used only for a small number of patients. In my view, that evidence flies in the face
of the contemporaneous materials placed before the court, including the German Medical
Journal. I should add that I do not believe that any useful purpose would be served by
attempting to resolve all of the other matters in dispute between Prof. Marz and Prof.
Assmann. They do not appear to me to be crucial to the issues that I have to decide.
74. It would be unreal, however, to believe that the skilled person would be represented
solely by clinicians of that kind. Professor Klaveness, a medicinal chemist, who gave
evidence on behalf of the plaintiff suggested that the skilled addressee would comprise a
group of scientists interested in or involved in the development of cholesterol lowering
drugs which would include scientists involved in medicinal chemistry, biology and clinical
science. The plaintiff makes the point that, under cross examination, Professor Klaveness
was not significantly challenged in relation to this evidence. That may well be so.
However, I must form my own view in relation to the identity of the skilled addressee
through whose eyes I must construe the patent. I am not bound by the evidence of any
particular expert. The question of construction of the patent is ultimately a matter for the
court.
75. In my view, as with most patents dealing with a pharmaceutical compound, the skilled
addressee will comprise a team. That team will include a clinician familiar with the
treatment of atherosclerosis (including the use of combination therapy for that purpose)
and also an appropriately qualified medicinal chemist. There are elements of the patent
that could only properly be understood by an appropriately qualified chemist. There are
other elements of the patent which would require a clinician’s skills. Thus, for example,
para. 0066 of the patent that is dealing with dosages in the context of combination
therapy envisages that the exact dose of any component of such a combination will be
determined by the attending clinician.
The application of the first limb of the Teva v. Gilead test
76. Bearing in mind that the nature of the skilled addressee (as described above) I must now
consider whether the combination of ezetimibe and simvastatin, on the basis of the
general knowledge of such a skilled addressee, and in the light of the description and
drawings of the invention in the 599 Patent, necessarily falls under the invention covered
by the patent.
77. In considering that issue, I must bear in mind that the patent is to be construed against
the relevant factual backdrop. As noted earlier, the patent itself treats the existence of
combination therapy as part of the relevant factual context. Paragraph 0008 (contained
in the first section of the patent dealing with the “background of the invention”)
specifically mentions combination therapy involving a statin and a bile acid sequestrant.
It explains that such combination therapy has been demonstrated to be more effective in
human hyperlipidemic patients than either agent in monotherapy. The papers by Witzum
and Illingworth are specifically referenced in this context. In addition, I bear in mind, as
part of the relevant factual backdrop, the extensive literature which existed in relation to
combination therapy involving combinations of various kinds of cholesterol inhibitors. In
particular, it is clear from the publications of the European Atherosclerosis Society and the
publications by Prof. Assmann in the German Medical Journal that, by the priority date of
the patent, combination therapy (in particular combination therapy involving statins) was
already well recognised and established for certain types of cholesterol treatments. This
is also supported by the evidence of Prof. Marz who said that, at the priority date, he was
using combination therapy to treat patients. He was also receiving referrals from general
practitioners who were doing likewise. I do not believe, however, that his evidence
establishes that, in 1992, it was common for general practitioners to use combination
therapy themselves. As noted in para. 73 above, Prof. Marz was unable to provide any
detail to support that suggestion.
78. As correctly stated in para. 6.21 of the defendant’s closing witness submissions, this was
the backdrop against which the 599 patent disclosed the compounds of Formula 1. The
defendants made the case that those compounds were being introduced into a world
where:-
(a) Lipid lowering drugs were used in combination with other lipid lowering drugs. This
contention is consistent with the evidence.
(b) The choice of which lipid lowering drugs should be combined with other lipid
lowering drugs was informed by whether the respective partner drugs would have
different modes of action. This is also largely consistent with the evidence although
there was some controversy as to whether a combination with a new “first in class”
drug such as ezetimibe would be undertaken. This is an issue which I address in
more detail in paras. 88 -91 below.
(c) Statins were a well-established therapy in the treatment of hypercholesterolemia
and were already recommended in the context of a number of combinations. This
contention is well supported by the evidence which was adduced in the course of
the hearing.
79. Against that background, the defendant argues that a skilled person reading the 599
Patent with the benefit of this common general knowledge would not deduce from the
references to combinations involving a compound of Formula 1 (such as ezetimibe) with a
statin (such as simvastatin) that the combination (as distinct from the compounds of
Formula 1) could be said to be an independent innovation.
80. In my view, there is considerable force in this submission on the part of the defendant.
This is especially so when one comes to consider the terms of the patent itself. The
patent provides very significant detail in relation to the compounds in Formula 1.
However, it is devoid of detail in relation to any of the potential combinations between
compounds in Formula 1 and any of the combination partners identified in the patent. In
this context, I do not wish to suggest that it is a necessary requirement for the validity of
a patent that the patent should demonstrate by experiment that a claimed invention will
work or that it is necessary to explain why it will work. As Barrett J. observed in
Boehringer Ingelheim [2017] IEHC 495 at para. 165 no particular information or test data
is required of a patent so long as the disclosure is plausible. However, on a reading of the
599 Patent, the absence of data in relation to the combination is striking. In contrast,
there is very significant detail in relation to the compounds in Formula 1. When read
against the factual backdrop (summarised above), the lack of detail in relation to the
combination provides significant support for the case made by the defendant that, the
skilled addressee, would not deduce from the references to combinations that such
combinations were an independent innovation (i.e. independent of the innovative
compounds comprised in Formula 1).
81. The defendant’s case also derives significant support from the evidence given by
Professor Hegarty. Professor Hegarty is a former professor of organic chemistry at
University College Dublin. He is not a medicinal chemist. Nor is he a patent expert. He
did not profess to be either of those things. He was entirely frank and objective in his
evidence. Of the four expert witnesses who gave evidence in relation to the patent, he
was by far the most impressive. His evidence both under direct examination and cross-
examination was clear, straight forward, authoritative and frank. He did not prevaricate or
dissemble. He clearly had the necessary scientific background to understand the patent
and, in particular, the chemistry described in the patent. This understanding was
demonstrated by him very clearly in the course of his evidence.
82. Under cross-examination, Prof. Hegarty confirmed that he did have occasion to consider
patents. He readily admitted that he did not know whether a patent in respect of a drug
was required to contain test data. That is, in any event, a legal issue.
83. Although Prof. Hegarty is not a medicinal chemist, he was clearly in a position to read and
understand the patent. His extensive expertise as an organic chemist allowed him to
understand all of the chemistry. He explained that he was asked to review the patent by
the solicitors for the defendant. At that point, he was told nothing about the facts of the
case. After he carried out his review, he reported to the defendant’s solicitors to the
effect that the focus of the patent was on the family of compounds represented by
Formula 1. He made no reference to the claimed combination. On receipt of his views,
the defendant solicitors asked him to explain what the patent said about the combination
of a hydroxy-substituted azetidinone and a cholesterol biosynthesis inhibitor. He
reviewed the patent again and expressed the view that he did not think the reference to
this combination was a particularly important element of the patent. He explained that
this was because all of the testing of the biological activities was limited to the
compounds within Formula 1. His view was that the patent contains only very superficial
information about combinations and does not contain any experimental data or any
information beyond what he described as “cursory references”. He also observed that
there was no data in the patent to show the usefulness of the claimed combination. His
views (as summarised in the preceding two sentences) are entirely correct as a reading of
the 599 patent will confirm.
84. Insofar as the drawings are concerned, Prof. Hegarty drew attention to the fact that,
although there are a large number of drawings in the patent, the structure of a
cholesterol biosynthesis inhibitor is not shown anywhere in the patent and, even more
importantly, the structure of a combination of a hydroxy-substituted azetidinone and a
cholesterol biosynthesis inhibitor is likewise not shown anywhere in the patent.
85. He communicated these views to the solicitors for the defendant who, only at that stage,
gave him basic details of the proceedings and asked him to review the patent again and
to provide his opinion on what it said about the combination of ezetimibe and simvastatin.
In response, he observed that there was no experimental data in the patent in relation to
any combination product, no information as to whether any testing of the combination of
ezetimibe and any statin was carried out, whether in vivo or otherwise (and that this was
in contra-distinction to the information provided in relation to the compounds within
formula 1). Likewise, there was no data (experimental or otherwise) or information in the
patent which shows, discloses or teaches that administering ezetimibe and simvastatin
together to a patient has any effect. In addition, there was no data or information to
suggest that one of the components of the combination would assist the efficacy of the
other. The patent provides no information or data as to whether the combination of
ezetimibe and any statin is better, worse or the same as using ezetimibe alone.
86. In these circumstances, Prof. Hegarty expressed the view that the combination of
ezetimibe and simvastatin could not be considered to be the innovation of the patent. In
his view, the innovation is the demonstration that the different structure of the
compounds represented by formula 1 (which are represented in the patent and which
include ezetimibe) can be made in a pure form together with the results of the in vivo
testing of those compounds. He expressed the view that the combination of ezetimibe
and simvastatin does not represent a separate invention and there is no evidence
whatever in the patent that the combination is efficacious at all.
87. Prof. Klaveness (the medicinal chemist who gave evidence on behalf of the plaintiff)
disagreed with Professor Hegarty. In his witness statement and in his evidence, Professor
Klaveness drew attention to a number of patents relating to potential new drug
substances “that contain some phrases relating to the option to combine drug substances
with additional drugs”. He suggested that this was in general use in patent documents.
With regard to Prof. Hegarty’s view that the combination of ezetimibe and simvastatin
could not be considered to be the innovation in the patent, Prof. Klaveness disagreed. His
response was that the combination “is a topic raised several times throughout the whole
document and I read the 599 Patent to include this invention. The combination was at
priority date new and inventive and has been shown to be useful. Based on the extensive
description of the combination invention in the whole patent and my understanding of
patentability criteria, my view is that this is an invention in the 599 patent.” Prof.
Klaveness also suggested that it was unsurprising that the patent should only provide
detailed information in relation to the new compounds disclosed in it. His evidence was
that it was “natural” that the focus of the inventors should be on the synthesis of various
new compounds and on the evaluation of biological efficacy in a relevant model (which, in
the case of the 599 Patent was an in vivo model using hamsters).
88. However, Prof. Klaveness did not justify his view that the extensive references to a
combination in the patent meant that the combination was itself an innovation. When he
came to give evidence, he advanced a proposition (which had not been put in these terms
to any of the witnesses who gave evidence on behalf of the defendant) that a combination
of a new drug with an existing drug (whatever that might be) is an invention. This is a
point that was also taken up, very strongly, in the plaintiff’s submissions. It was argued
on behalf of the plaintiff that the 599 patent told the skilled addressee that there was an
entirely new, first in class molecule which could be used in reducing LDL cholesterol and
therefore to treat atherosclerosis and that it could be combined with a statin also for the
purposes of treating atherosclerosis. The plaintiff maintains that the skilled addressee did
not know – other than from the 599 Patent – that this new first in class molecule could be
combined with a statin to treat atherosclerosis. The plaintiff maintains that the skilled
addressee would also know that putting an entirely new drug into the human body with
an existing drug may not result in the hoped-for efficacy and may even result in toxic
effects.
89. I do not believe that the approach suggested by the plaintiff is correct. In the first place,
as counsel for the defendant urged during the course of his closing submissions, the
addition of an existing compound to a novel compound cannot, without more, make the
combination an invention in itself. If that was all that was required, it would mean that
an SPC would automatically be available for any combination product containing a
combination of a novel product disclosed in a patent and a pre-existing product available
off the shelf. Having regard to the approach taken by the CJEU in Teva v. Gilead, a
product will only be protected by a basic patent for the purposes of the SPC Regulation
where the product falls within the limits of the invention, the subject of the patent in
issue.
90. I appreciate that Prof. Klaveness sought to suggest in his evidence (and in particular in
para. 194 of his witness statement) that the combination at the priority date was new and
inventive and that it “has been shown to be useful”. However, as was clear from the
evidence of Dr. Davis, the combination of ezetimibe and simvastatin was only
demonstrated to be efficacious several years after the priority date. It is clear from the
decision of the CJEU in Teva v. Gilead (at para. 50) that it is impermissible to have regard
to developments which have taken place since the priority date or filing date of a patent.
In this case, the 599 Patent must therefore be construed by reference to the state of
knowledge that existed as of the priority date. Neither side is entitled to draw attention
to post-priority date material. There is nothing in the patent itself to suggest that the
combination, to use the words of Professor Klaveness, “has been shown to be useful”. On
the contrary, as previously noted, all of the relevant chemical data and testing data in the
patent relates to the compounds within formula 1.
91. Moreover, there is a very obvious tension between the positon taken by Professor
Klaveness that it is understandable that the patent should only include data in relation to
a first in class compound and the case made by the plaintiff that the combination of two
different compounds (namely ezetimibe and simvastatin) with different modes of action
must itself be novel. If that combination is itself novel, then, having regard to the
approach advocated by Professor Klaveness, it is surprising that the “inventor” of the
combination would not provide some level of data akin, at least to some extent, to the
data supplied in relation to the first in class compound.
92. It is also striking that when Prof. Klaveness was asked, in the course of cross-
examination, to explain why the combination disclosed in the patent should be regarded
as an innovation, his principal response was to point to the “very many different places in
the document” where combinations are mentioned. That falls far short of identifying an
invention. The mere fact that combinations are mentioned in the patent does not mean
that the combination must, ipso facto, be treated as an invention. It is clear from the
approach taken by the CJEU in Teva v. Gilead that is necessary to identify what is an
invention. The fact that a patent makes a claim in relation to a product or that it makes
mention of a product is not enough in itself. I should have thought that, if Prof.
Klaveness genuinely believed that the combination was an invention, he would readily
have been able to explain why this was so. I regret to say that, in my view, Prof.
Klaveness provided no satisfactory explanation as to why he considered the combination
to be an innovation in itself.
93. It is true that he suggested, in the course of cross-examination, that:
“The combination aspect is not just added in a line or a few sentences … but it is
through all the documents. That’s why I look at it and I understand that this
concept, and I can go to the lab or it is possible to perform such combination study
if you would like to do it”.
94. At the conclusion of his evidence, I asked him to explain what he meant when he said
that it is possible to perform some combination studies by reference to the patent. I
asked him why he would need to refer to the patent to carry out such studies. I assumed
that, in his response, Prof. Klaveness would explain why it was essential to refer to the
patent. However, his answer was telling. His answer was, simply, that ezetimibe is
protected by the patent. He accepted that the statin was already available but he
explained that ezetimibe was subject to the 599 patent. Thus, Prof. Klaveness did not
identify anything in the patent itself which, from a scientific perspective, required
consideration. His concern was that, from a legal perspective, ezetimibe was protected
by the patent. Again, that seems to me to undermine any suggestion that the
combination per se was an innovation of the patent.
My conclusion in respect of Article 3 (a)
95. In light of the matters discussed in paras. 76 to 94 above, I have come to the conclusion
that the combination of ezetimibe and simvastatin is not an invention covered by the
patent. On the contrary, it seems to me that, by reference to the detailed information
contained in the patent and the drawings contained in the patent and in light of the
factual context described in paras. 21 to 37 above, the invention relates to the Formula 1
compounds. There is nothing in the evidence or in the materials before the court to
explain how the combination can be said to be an invention in itself. Having regard to the
approach taken by the CJEU in Teva v. Gilead, the fact that the patent makes claims in
relation to the combination is not sufficient of itself. For the patent to protect the
combination, the combination must itself be an invention covered by the patent. On the
basis of my reading of the patent (informed by the evidence which I have heard in the
course of the hearing and the materials put in evidence) I believe that the case made by
the defendant that the combination was not an independent innovation itself is correct. In
the circumstances, there is no need to apply the second limb of the Teva v. Gilead test.
Accordingly, I must hold that the combination is not protected by the 599 patent within
the meaning of Article 3 (a) of the SPC Regulation. The defendant is therefore entitled,
on that ground, to a declaration that the SPC is invalid and must be revoked.
The case made under Article 3 (c)
96. In light of the findings which I have made in relation to the defendant’s case under Article
3 (a), it is not strictly speaking necessary for me to consider the case made under Article
3 (c) or Article 3 (d). Nonetheless, lest I am wrong in my conclusion in relation to Article
3 (a) I will, for completeness, address both the case made under Article 3 (c) and also the
case made under Article 3 (d).
97. The first point to be made about Article 3 (c) is that if I am correct in my conclusion that
the only products which are protected under the 599 Patent are the azetidinones
(including ezetimibe) then the defendant must also succeed in its counterclaim made on
the basis of Article 3 (c). As noted in para. 4 above, an SPC was issued in respect of
ezetimibe in 2003. As a consequence, the provisions of Article 3 (c) (under which an SPC
cannot be granted if the product has already been the subject of a previous SPC) would
prohibit the grant of the SPC in issue in these proceedings. However, if I am wrong in my
conclusion that ezetimibe is the only relevant product protected by the 599 Patent, then it
is necessary to consider the alternative case made by the defendant during the course of
the hearing that the combination product has already been the subject of the SPC granted
in respect of Ezetrol. That case does not appear to me to be pleaded. However, if I have
correctly understood the submissions made by counsel on behalf of the defendant, that is
nonetheless a case which the defendant seeks to make. In his closing submissions,
counsel for the defendant spoke of the case under Article 3 (c) “segueing” into the case
under Article 3 (d). I will, for completeness, address this alternative case. As I
understand it, the defendant makes this case on the basis that:
(a) The marketing authorisation for Ezetrol required the 10mg tablets containing
ezetimibe to be administered with a statin for patients suffering from
homozygous familial hypercholesterolemia; and
(b) that, thereafter the Ezetrol SPC was granted.
98. On that basis, the defendant argues that the combination of ezetimibe and a statin such
as simvastatin had previously been the subject of the Ezetrol SPC and that accordingly
Article 3 (c) prohibited the grant of the SPC in issue in these proceedings. In making this
case, the defendant relies on the terms of the marketing authorisation granted in 2003 in
respect of Ezetrol. As described in para. 3 above, the marketing authorisation for Ezetrol
required that the ezetimibe tablets should be administered with a statin in the case of
patients suffering from homozygous famial hypercholesterolemia. Since the 2003 SPC
was granted on the basis of this marketing authorisation, the argument appears to be
that, even if the product here is to be regarded as the combination of ezetimibe and
simvastatin, that product was already the subject of the 2003 SPC. The factual basis for
this element of the defendant’s counterclaim is therefore substantially the same as the
factual basis for the case made by it under Article 3 (d). It therefore seems to me to be
more appropriate to turn first to the Article 3 (d) element of the counterclaim before
reaching any final conclusion in relation to the case made by reference to Article 3 (c).
99. Before turning to the case made under Article 3 (d), it is necessary, however, to address
some of the legal issues that were debated in the context of Article 3 (c). In particular, it
is necessary to address the contention of the plaintiff that it may be necessary to make a
reference to the CJEU for guidance in relation to Article 3 (c). This submission appears to
proceed on the basis that, in the event that I were to uphold the defendant’s case as to
what product is protected for the purposes of Article 3 (a), that opens up a gap or
dichotomy between the nature of the “product” protected under Article 3 (a), on the one
hand, and Article 3 (c), on the other. The plaintiff points to a decision of the High
Regional Court of Dusseldorf which suggests that a reference to the CJEU might well be
necessary on this point. In my view, there is no need for a reference in this case. In the
first place, it seems to me that there can be no difference between the “product” for the
purposes of Article 3 (a) on the one hand and Article 3 (c) on the other. It is quite clear
from Article 1 (b) that “product” has a consistent meaning throughout the SPC
Regulation. As noted in para. 10 above, Article 1 (b) defines a “product” as: “The active
ingredient or combination of active ingredients of a medicinal product”. That is the
relevant definition for the purposes of both Article 3 (a) and Article 3 (c).
100. Secondly, I can see no dichotomy in the case made by the defendant. The defendant
makes the simple case that, for the purposes of both Article 3 (a) and 3 (c), the “product”
protected by the 599 Patent is ezetimibe alone (along with the other azetidinones covered
by the patent). The same case is made under Article 3 (c). However, an alternative case
is made that, if the “product” protected by the 599 patent for the purposes of Article 3 (a)
is the combination, then the defendant makes the case summarised in para. 97 above. In
other words, the defendant would, for the purposes of making that argument, treat the
“product” as the combination of ezetimibe and simvastatin.
101. Secondly, while the plaintiff seeks to suggest that there may be a difference in approach
taken by the CJEU under Article 3 (a) and Article 3 (c), I cannot accept that there is such
a difference in approach. It seems to me that, following the decision of the CJEU in Teva
v. Gilead, the task of the court is clear. While the CJEU may, in previous case law, have
referred to the “core inventive advance” of a patent in the context of Article 3 (c), I do
not believe that there is any scope to take the view, subsequent to the decision of the
CJEU in Teva v. Gilead, that this continues to the relevant test. While Teva v. Gilead
addressed the meaning of “product” in the context of Article 3 (a), the court referred back
to some of the decisions in which Article 3 (c) had been considered. I cannot identify any
basis in the judgment in Teva v. Gilead to suggest that the CJEU had in mind that a
different approach should be taken in relation to the meaning of the word “product” in the
context of Article 3 (a) to its meaning in Article 3 (c).
102. Thirdly, in light of the conclusion which I have reached in relation to Article 3 (a), it
cannot be said that it is necessary to make a reference to the CJEU. To make a
reference, in these circumstances, would amount, in substance, to a request to the CJEU
to make a determination on a moot issue. While I propose to address the case made
under Article 3 (c) for completeness, there would be no basis for me to make a reference
to the CJEU on an issue which, strictly speaking, does not require to be addressed in
order to reach a conclusion on the counterclaim.
103. As noted in para. 98 above, I propose, before going further in relation to Article 3 (c) to
address the case made by the defendant by reference to Article 3 (d).
The case made under Article 3 (d)
104. For the defendant to succeed in relation to Article 3 (d), it would be necessary to
demonstrate that the marketing authorisation in respect of Inergy is not the first
authorisation to place the combination product on the market as a medicinal product. As
noted in para. 12 above, the defendant argues that the first such authorisation was that
issued in respect of Ezetrol. This argument proceeds on the basis that, according to the
Ezetrol authorisation, ezetimibe was required to be administered with a statin for use in
patients with homozygous familial hypercholesterolemia. In this context, para. 4.1 of the
relevant Summary of Product Characteristics (“SmPC”) for Ezetrol states, with regard to
homozygous familial hypercholesterolemia:-
“Ezetrol co-administered with a statin, is indicated as adjunctive therapy to diet for
use in patients with HoFH. Patients may also receive adjunctive treatments …”
(Emphasis added).
105. The defendant also draws attention to the dosage instructions in para. 4.1 of the Ezetrol
SmPC which states that the recommended dose of ezetimibe is 10mg tablets “used alone
or with a statin”. The same section of the SmPC states that if the 10mg are used in
combination with a statin therapy, the dosage instructions for that particular statin should
be consulted.
106. The defendant also highlights the text of the Ezetrol SmPC dealing with clinical trials
involving co-administration of ezetimibe with a statin. The relevant table in the SmPC
identifies that the quantities of statin tested with ezetimibe were 10mg, 20mg, 40mg and
80mg.
107. In turn, the SmPC for Inergy relates to precisely similar dosages. Paragraph 1 of the
SmPC identifies that the dosages are 10mg of ezetimibe with, respectively, 10mg, 20mg,
40mg or 80mg of simvastatin.
108. In addition, the clinical trials described in the SmPC for Inergy involved co-administered
ezetimibe and simvastatin “equivalent to INEGY”. The trials did not feature the
combination product as such.
109. Expert evidence was called by both sides in relation to the Article 3 (d) issue. I am not all
convinced that expert evidence is either necessary or admissible in relation to a legal
issue of this kind. Nonetheless, the evidence was of some utility in teasing out some of
the issues that arise in the context of Article 3 (d). In support of this part of its case, the
defendant called an expert witness namely Dr. Birka Lehmann who, in the course of her
career, worked at the German Federal Institute for Drugs and Medical Devices and also
worked, on secondment, as a regulatory expert with the European Commission. In her
written statement and in her evidence, Dr. Lehmann noted that para. 4.1 of the Ezetrol
SmPC made the co-administration of ezetimibe with a statin “mandatory”. She also gave
evidence to the effect that the marketing authorisation for the Ezetrol product covered the
co-administration of ezetimibe with a statin such as simvastatin. She suggested that,
from a regulatory point of view, the authorisation for Ezetrol constituted an authorisation
for the (non-fixed) combination of ezetimibe and simvastatin for the treatment of
hypercholesterolemia. Dr Lehmann also noted that the majority of the clinical studies
described in the Ezetrol SmPC related to the co-administration of ezetimibe with a statin
(including simvastatin).
110. Dr Lehmann noted that the clinical studies described in the SmPC for Inegy were based
on the co-administration of ezetimibe and simvastatin rather than on any combination
tablet. At para. 38 of her witness statement Dr. Lehmann stated:-
“…all essential clinical studies regarding the efficacy of the combination product
INEGY as well as the studies that are the basis for the EZETROL authorization were
conducted with a combination of active ingredients being administered wherein
simvastatin and ezetimibe were administered in parallel in the form of the mono
products i.e. ezetimibe was administered in its own separate tablet and simvastatin
was administered in its own separate tablet. The authorization for INEGY therefore
contains no additional scientific findings compared to the data in the authorization
for EZETROL. Therefore, the INEGY product (the fixed dose single combination
tablet) does not show any surprising added value in any way exceeding the mere
parallel administration of the active ingredients as separate individual tablets being
co-administered.”
111. Prof. Dr. Vincenzo Salvatore (“Prof. Salvatore”) gave evidence on behalf of the defendant.
In the course of his evidence Professor Salvatore stated that there is a very clear
difference, in regulatory terms, between a treatment comprising a combination of two
different products administered together, each containing a specific active ingredient and
a treatment comprising a product which contains both active ingredients in one. He
accepted that a physician may well prescribe a combination of two medicinal products
(both of which have been granted a separate marketing authorisation) but he maintained
that “the scenario is different” when a single medicinal product is subsequently launched
containing a combination of the two active ingredients in question. The latter requires a
separate marketing authorisation. The individual marketing authorisations for both of the
“mono” products do not allow for a sale of a combination product containing the two
active ingredients. Prof. Salvatore expressed the view that Inegy is a combination
product consisting of two separate and independent active ingredients (namely ezetimibe
and simvastatin) and that accordingly it was required to have a separate and independent
marketing authorisation from those granted in respect of ezetimibe (i.e. the Ezetrol
marketing authorisation) and the independent marketing authorisation issued in respect
of simvastatin. Against that backdrop, Prof. Salavatore expressed the opinion that the
marketing authorisation for Ezetrol is incapable of constituting the first authorisation to
place a combination product containing ezetimibe and simvastatin on the market.
112. Under cross-examination, Prof. Salvatore acknowledged that, in the context of
homozygous familial hypercholesterolemia, a patient treated with a 10mg tablet of
ezetimibe under the Ezetrol marketing authorisation would also be treated by a statin co-
administered with the ezetimibe tablet. He also accepted that prior to the grant of the
marketing authorisation in respect of Inegy, the dose ranges for simvastatin were 10mg,
20mg, 40mg and 80mg. Professor Salvatore accepted that, under the Inegy marking
authorisation, the amount of ezetimibe does not change. It remains at 10mg. He also
accepted that the amount of the simvastatin does not change. It is still at the same
strength of 10, 20, 40 and 80 mg respectively. From the perspective of a patient, Prof.
Salvatore accepted that if the patient was already being treated with ezetimibe under the
Ezetrol marketing authorisation together with simvastatin, the patient would receive the
very same active ingredients under the Inegy marketing authorisation. Professor
Salvatore also accepted that, under the Ezetrol marketing authorisation, there was no
doubt that, in the case of homozygous familial hypercholesterolemia, the authorisation
was to use ezetimibe with a statin.
113. On behalf of the plaintiff, it has been submitted that a therapeutic indication which
provides that Ezetrol can or should be administered with a statin (without indication of the
exact statin) cannot transform the marketing authorisation for Ezetrol into a marketing
authorisation for ezetimibe and simvastatin. The plaintiff placed significant reliance on
Article 1 (2) (a) of the Marketing Authorisation Directive which defines a medicinal
product as: “any substance or combination of substances presented as having properties
of treating or preventing disease in human beings…”.
114. The plaintiff submitted that, in circumstances where a marketing authorisation is in
respect of “any substance or combination of substances …”, it cannot be suggested that
the Ezetrol marketing authorization was granted in the context of a co-administration.
The plaintiff also placed emphasis on the fact that a co-administration contemplated by
the Ezetrol marketing authorization was not limited to simvastatin or even the four statins
identified in the clinical data. The relevant text (quoted above) simply said that it was to
be used in combination with a statin. The Ezetrol authorization does not direct what
statin a physician might use. The plaintiff makes the case that the co-administration
cannot be equated to a medicinal product authorized by the Medicinal Products Directive
and that, as a consequence, the Ezetrol authorisation could not constitute the first
authorisation to place the combination of ezetimibe and simvastatin on the market for the
purposes of Article 3 (d). The plaintiff drew attention, inter alia, to the decisions of the
Court of First Instance in Paris and a court in Oslo in support of this proposition. The
plaintiff also relied on the decision of Lewison J. (as he then was) in Yeda v. Comptroller
(which I examine in more detail below) Lewison J. held that the concept of “product” for
the purposes of the SPC Regulation does not include the therapeutic use of an active
ingredient. In that case, the relevant marketing authorisation was in respect of a named
product. The authorisation made clear that, in certain circumstances, the named product
was to be used in combination with another agent. Lewison J. came to the conclusion
that the only “product” that was authorised for the purposes of the SPC Regulation was
the named product. The authorisation could not be interpreted as an authorisation for the
combination notwithstanding that the authorisation contemplated that the named product
would be used, in certain circumstances, in combination with the additional agent.
My findings in relation to Article 3 (d)
115. In my view, the starting point for the analysis of this issue is Article 3 (b). Under Article 3
(b), an SPC cannot be granted unless: “a valid authorisation to place the product on the
market as a medicinal product has been granted in accordance with [the Medicinal
Products Directive] …”. It is significant that Article 3 (b) focusses on an authorisation for
a product. Article 3 (b) must be read in conjunction with the definitions of “product” in
Article 1 (b) (set out in para. 10 above) and the definition of “medicinal product” in Article
1 (a) (set out in para. 11 above).
116. In contrast to the definition of “medicinal product”, the definition of “product” is confined
to the active ingredient of a medicinal product or to a combination of such active
ingredients. This was highlighted by the CJEU in Case-431/04 Massachusetts Institute of
Technology. In that case, the CJEU also drew attention to the fact that there is no
definition in the SPC Regulation of “active ingredient”. The CJEU explained in para. 17 of
the judgment that, in the absence of such a definition, the meaning and scope of “active
ingredient” must be determined by considering the general context in which those words
are used and their usual meaning in everyday language. At para. 18 of the judgment, the
CJEU explained that it is generally accepted in pharmacology that an active ingredient will
not include substances forming part of a medicinal product which do not have an effect of
their own on the human or animal body.
117. Thus, for the purposes of Article 3 (b) (and in turn for the purposes of Article 3 (d)) the
“product” to be considered is solely the active ingredient (or where appropriate the
combination of active ingredients) which are the subject of a marketing authorisation.
Crucially, for the purposes of Article 3 (d), the authorisation must be the first
authorisation to “place the product on the market as a medicinal product” (emphasis
added). The question in this case is whether the Ezetrol authorisation was an
authorisation to place the combination product comprising two active ingredients namely
ezetimibe and simvastatin on the market as a medicinal product. That word “product” is
to be given a strict definition. That was made clear by the CJEU in the Massachusetts
Institute of Technology case. It is also clear from the decision of the CJEU in Case C-
31/03 Pharmacia Italia SpA (and re-affirmed in Case C-202/05 Yissum Research and
Development v. Comptroller-General of Patents) that the decisive factor is not the
intended use of a medicinal product but the product itself. In making that finding in the
Pharmacia Italia case the CJEU placed particular reliance on (a) the definition of “product”
in Article 1 (b) quoted in para. 10 above; (b) the fact that Article 3 (b) also refers to a
valid authorisation “to place a product on the market…” (emphasis added); and (c) the
provisions of Article 4 which make it clear that the protection conferred by an SPC is to
extend only to the product covered by the marketing authorisation for the corresponding
medicinal product. Article 4 expressly states the SPC: “shall extend only to the product
covered by the authorisation to place the corresponding medicinal product on the
market…”.
118. The approach taken by the CJEU was subsequently applied by Lewison J. in the Yeda
Research case mentioned in para. 114 above. There, the relevant patent related to a
combination treatment for cancer. The treatment involved the use of two active
ingredients, one of which was cytotoxic (i.e. it killed the cancer cells) while the other was
cytostatic (i.e. it stopped the replication of the cancer cells but did not itself kill the cells).
The cytostatic agent in the combination was known as cetuximab (also known by the
trade name Erbitux). The cytotoxic agent was irinotecan. The relevant authorisation in
that case was granted in respect of the medicinal product “Erbitux-cetuximab”. In the
clinical particulars of the authorisation, it was expressly stated that Erbitux was indicated
in combination with irinotecan for the treatment of patients with a particular type of
cancer where treatment with irinotecan as a monotherapy had failed. The authorisation
described the dosage of Erbitux and also stated that, for the dosage of the “concomitant
irinotecan” reference should be made to the product information for the latter and the
dosages for that product must be followed. The patentee applied (inter alia) for an SPC in
respect of a product which was described in the application as “cetuximab in combination
with irinotecan”. This was refused by the Patents Office on the basis that, contrary to
Article 3 (b), the application was based on an authorisation for cetuximab alone. The
hearing officer drew attention to the fact that the medicinal product is clearly identified as
Erbitux (the active ingredient of which was cetuximab). The hearing officer took the view
that this was distinguishable from how the product is used. He also drew attention to the
lack of any detail in relation to irinotecan in the marketing authorisation.
119. On appeal to the English High Court, counsel for the applicant submitted that the data
about Irinotecan were incorporated by reference into the marketing authorisation with the
consequence that, on its true interpretation, it authorised the combination of cetuximab
and Irinotecan. That submission chimes quite closely to the case made by the defendant
in these proceedings. This argument was rejected by Lewison J. who said, at para. 26:-
“…article 1 of the decision [of the hearing officer] plainly identifies the medicinal
product, ‘Erbitux – cetuximab’ as the subject-matter of the authorisation. No other
medicinal product is identified. The direction to enter that product in the
Community Register of Medicinal Products is to the same effect. Article 3 specifies
the form of the labelling and package leaflet. The outer packaging makes no
mention of irinotecan at all. The package leaflet contains two brief mentions of
irinotecan in explaining how cetuximab is used. The summary of the product
characteristics likewise contains brief mentions of irinotecan in explaining how
cetuximab is used. But as the case law shows, how a medicinal product is used
does not form part of the identification of the product itself. In my judgment the
brief references to irinotecan in explaining how cetuximab is used are wholly
insufficient to amount to a marketing authorisation of a product consisting of both
cetuximab and irinotecan. ...”
120. As counsel for the defendant emphasised, there is significantly more information about
statins in the Ezetrol marketing authorisation than appears to have been contained in the
authorisation considered by Lewison J. in relation to irinotecan. The Ezetrol marketing
authorisation contains extensive information in relation to clinical trials relating to the co-
administration of ezetimibe with a statin. The trials related to four different statins
namely atorvastatin, simvastatin, pravastatin and lovastatin. However, as in the Yeda
Research case, the Ezetrol marketing authorisation informs the reader to refer to the
SmPC for the “particular statin” when ezetimibe is to be administered with a statin.
Furthermore, all of the data dealing with the pharmacokinetic properties of the product
relate to ezetimibe.
121. Moreover, it seems to me that the fundamental reason why Lewison J. came to the
conclusion quoted above was that the manner in which a medicinal product is used does
not form part of the identification of the product itself. That conclusion is consistent with
the case law of the CJEU discussed in paras. 116 to 117 above. The case law of the CJEU
is binding on me. The decision in Yeda Research is a useful illustration of the application
of the principles laid down in the case law of the CJEU. There is a very clear parallel
between the facts in Yeda Research and the facts in issue in these proceedings. In Yeda
Research, the use of Erbitux in combination with irinotecan was expressly indicated for
the treatment of patients with a particular form of cancer after failure of irinotecan as a
monotherapy. Similarly, in the case of the Ezetrol marketing authorisation, the co-
administration was indicated for use in patients with homozygous familial
hypercholesterolemia. I cannot see any distinction, in substance, between the
therapeutic indication in Yeda Research and the therapeutic indication for homozygous
familial hypercholesterolemia under the Ezetrol marketing authorisation. What the latter
does is to require that a statin should be co-administered with the ezetimibe product.
That clearly relates to the manner in which ezetimibe is to be used in such cases. It is to
be used in conjunction with a statin. It therefore seems to me to fall squarely within the
principle laid down in Pharmacia Italia and in Yissum Research. Just as in Yeda Research,
the product is identified in the SmPC as Ezetrol. That product comprises ezetimibe
exclusively. The statin is not part of the product authorised. Any such statin required its
own authorisation with its own SmPC. The qualitative and quantitative composition of the
product authorised by the authorisation refers only to ezetimibe and the various
excipients. The pharmaceutical form relates only to the Ezetrol tablet. The fact that, in
the case of homozygous familial hypercholesterolemia, the Ezetrol product was to be used
in conjunction with a statin does not make that combination the subject of the
authorisation for the purposes of the SPC Regulation. While Prof. Salvatore accepted that
there was “no doubt” that the authorisation was to use Ezetrol with a statin in such cases,
use is not sufficient in itself to bring the relevant statin within the ambit of the product
authorised by the marketing authorisation. The case law of the CJEU makes that clear.
122. I can find nothing in the submissions made by the defendant in this case which
adequately addresses the effect of the case law of the CJEU. In the circumstances, I am
compelled to conclude that the case under Article 3 (d) has not been made out insofar as
the defendant contends that the combination of ezetimibe and simvastatin should be
regarded as authorised by the Ezetrol marketing authorisation.
123. Nor has the defendant sufficiently explained how it can plausibly be suggested that the
Ezetrol authorisation extends in particular to a combination of ezetimibe and simvastatin.
As noted above, the terms of the authorisation refer solely to a statin without identifying
any particular statin. While it is, of course, the case that simvastatin is one of the statins
which were the subject of clinical trials discussed in the SmPC, the relevant text of the
therapeutic indications for homozygous familial hypercholesterolemia does not confine
itself in any way to simvastatin. Thus, the effect of the defendant’s argument would be
that any combination of ezetimibe and any statin should be regarded as the subject of the
Ezetrol marketing authorisation. I do not believe that the authorisation for Ezetrol can be
construed in that way. On the contrary, the marketing authorisation is specific to the
product Ezetrol. The sole active ingredient of which is ezetimibe.
The impact of the Article 3 (d) finding on the case made under Article 3 (c)
124. As noted in para. 9 above, an SPC cannot be granted if the product (the proposed subject
of the SPC) has already been the subject of a previous SPC. If ezetimibe is the only
relevant product protected by the 599 patent, then it is clear that an SPC was previously
granted in respect of ezetimibe. That SPC was granted in 2003 following the granting of
the Ezetrol marketing authorisation. To that extent, the defendant’s counterclaim on the
basis of Article 3 (c) must succeed.
125. However, if I have correctly understood the position, the defendant also maintains that, if
it be the case that the combination product is protected by the 599 patent, the SPC
granted on foot of the Ezetrol marketing authorisation means that the SPC, the subject
matter of these proceedings, is not the first SPC granted in respect of the combination.
126. As noted previously, I do not believe that this element of the defendant’s case has been
pleaded. A serious question therefore arises as to whether the defendant was entitled to
make any such argument. In any event, in light of my finding in the context of Article 3
(d) that the Ezetrol marketing authorisation is not in respect of the combination product,
it seems to me that this alternative case of the defendant must fail.
Conclusion
127. In light of the findings which I have made above, it seems to me that the defendant’s
counterclaim under Article 3 (a) of the SPC Regulation must succeed. The SPC must
accordingly be revoked. It seems to me to be unnecessary in the circumstances to make
any order in respect of the defendant’s pleaded counterclaim insofar as Article 3 (c) is
concerned.
128. On the other hand, in light of the findings which I have made in paras. 120 – 123 above,
it seems to me that the counterclaim of the defendant, insofar as it relies on Article 3 (d)
in respect of the combination of ezetimibe and simvastatin must be dismissed. Similarly,
insofar as the defendant makes an alternative case under Article 3 (c) in relation to the
combination of ezetimibe and simvastatin, it seems to me that this case (although not
pleaded) must also be dismissed.
129. I will, of course, hear counsel as to the form of the order to be made. I will also hear
counsel in relation to costs or in relation to any other issues that may arise.
130. Finally, it should be noted that neither side made any application to defer this judgment
pending publication of the decision of the CJEU in Royalty Pharma.
Result: The SPC was held to be invalid and was revoked
BAILII:
Copyright Policy |
Disclaimers |
Privacy Policy |
Feedback |
Donate to BAILII
URL: http://www.bailii.org/ie/cases/IEHC/2019/2019IEHC814.html
