About SAFLII
Databases
Search
Terms of Use
RSS Feeds
South Africa: Supreme Court of Appeal
SAFLII
>>
Databases
>>
South Africa: Supreme Court of Appeal
>>
2014
>>
[2014] ZASCA 123
|
|
Pharma Dynamics (Proprietary) Limited v Bayer Pharma AG and Another (468/2013) [2014] ZASCA 123; [2014] 4 All SA 302 (SCA); 2014 BIP 69 (SCA) (19 September 2014)
THE
SUPREME COURT OF APPEAL OF SOUTH AFRICA
JUDGMENT
REPORTABLE
Case
No: 468/2013
In
the matter between:
PHARMA
DYNAMICS (PROPRIETARY)
LIMITED
.................................................
APPELLANT
and
BAYER
PHARMA AG (FORMERLY BAYER
SCHERING
PHARMA
AG)
.............................................................................
FIRST
RESPONDENT
BAYER
(PROPRIETARY)
LIMITED
........................................................
SECOND
RESPONDENT
Neutral
citation:
Pharma Dynamics (Pty) Ltd
v Bayer Pharma AG
(468/13)
[2014] ZASCA
123
(19 September 2014).
Coram:
Brand, Cachalia, Wallis, Mbha JJA
et
Mathopo AJA
Heard:
28 August 2014
Delivered:
19 September 2014
Summary:
Patents Act 57 of 1978
– whether appellant’s product
constitutes infringement of respondents’ patent –
counterclaim for revocation
of patent – whether invention for
which protection claimed in the patent involves an inventive step
required by
s 25(1)
of the Act – whether patent qualifies
as a true ‘divisional patent’ in terms of
s 37
of
the Act.
ORDER
On
appeal from:
The Court of the
Commissioner of Patents of South Africa (Pretorius J, sitting as
Commissioner of Patents):
The
appeal is dismissed with costs, including the costs of two counsel.
JUDGMENT
Brand
JA
(Cachalia, Wallis, Mbha JJA
et
Mathopo AJA concurring):
[1]
This is an appeal against the judgment and order of Pretorius J
sitting as the Commissioner of Patents. The first respondent,
Bayer
Pharma Aktiengesellschaft, formerly known as Schering AG, is the
patentee of South African Patent No 2004/4083 for an invention
entitled ‘Pharmaceutical combination of ethinylestradiol [EE]
and drospirenone [DSP] for use as a contraceptive’ (the
2004
patent). The second respondent, Bayer (Pty) Ltd, has been licenced to
use the invention in South Africa. They will jointly
be referred to
as ‘Bayer’. The appellant, Pharma Dynamics (Pty) Ltd
(Pharma) is a local distributor of generic pharmaceuticals.
[2]
As predicted by the concise description in its title, the 2004 patent
concerns a female combination oral contraceptive containing
the
active pharmaceutical ingredients, DSP and EE. It was filed in 2004
in terms of s 37 of the Patents Act 57 of 1978 (the
Act) as a
so-called ‘divisional patent’, based on patent 2002/1668,
as its ‘parent patent’. By virtue of
the provisions of
s 37, the priority date of the 2004 patent was ante-dated to 31
August 1999, which is the priority date
of its 2002 parent patent.
[3]
In March 2011, Pharma obtained approval from the Medical Control
Council to import and sell an oral contraceptive called Ruby.
This
product is the generic equivalent of the Yasmin product sold by Bayer
under the 2004 patent. Alleging that the sale of Ruby
constituted an
infringement of claim 1 of the 2004 patent, Bayer approached the
court a quo for an interdict and ancillary relief.
Pharma denied that
Ruby infringed the patent. It also denied that the 2004 patent was
valid and counterclaimed for its revocation.
The court a quo held,
however, that the 2004 patent was valid and that Ruby infringed it.
In consequence it granted the relief
claimed by Bayer and dismissed
Pharma’s counterclaim, in both instances, with costs of suit.
The present appeal against that
order is with the leave of the court
a quo.
[4]
The case for Pharma on appeal is that, properly interpreted, claim 1
of the patent in suit – which is the only claim relevant
–
does not include within its scope the allegedly infringing Ruby
product. For its attack on the validity of the patent,
Pharma relied
firstly on the ground that the invention claimed in the specification
of the patent lacks an inventive step, or,
in patent parlance, it
relied on the basis of obviousness. Secondly, Pharma contended that,
in any event, the 2004 patent is invalid
on the ground that it is not
a true ‘divisional’ of the 2002 parent patent. In
consequence, so Pharma’s contention
went, the 2002 patent
lacked novelty in the light of the disclosures in the 2002 patent.
Since all these contentions are largely
dependent on an
interpretation of the specification and especially claim 1 of the
2004 patent, I find it appropriate to reflect
on the broad principles
of patent interpretation as established by authority.
Foreign
judgments
[5]
However, before doing so, there is the matter of foreign judgments,
which attracted a fair deal of debate during argument before
us. It
appears that the patent in suit had been the subject of litigation in
various jurisdictions. Unsurprisingly Bayer referred
us to judgments
in the United Kingdom by the high court in
Gedeon Richter plc v
Bayer Schering Pharma AG
[2011] EWHC 583
(Pat) and the Court of
Appeal in
Gedeon Richter plc v Bayer Pharma AG
[2012] EWCA Civ
235
and in Australia by the Federal Court of Australia General
Division in
Generic Health (Pty) Ltd v Bayer Pharma AG
[2014]
FCAFC 73
where the patent in suit survived an attack based on the
premise that it lacked an inventive step. Pharma, on the other hand,
referred
us to the judgment of the Technical Board of Appeal of the
European Patent Office in
Bayer Pharma AG v Teva Pharmaceutical
Industries Ltd
(Case No 0598/12) where the application for the
revocation of the patent was upheld. But as I see it, we must decide
the matter
on the evidence before us. Helpful as these foreign cases
may be on matters of law, we can derive no guidance from them on
issues
of fact.
Approach
to Interpretation
[6]
This brings me back to the principles of interpretation. To begin
with, there is the tenet of patent construction which is encapsulated
in the oft quoted statement by Trollip JA in
Gentiruco AG v
Firestone SA (Pty) Ltd
1972 (1) SA 589
(A) at 614B-H that:
‘
.
. . [T]he rule of interpretation is to ascertain, not what the
inventor or patentee may have had in mind, but what the language
used
in the specification means, ie, what his intention was as conveyed by
the specification, properly construed . . . since he
is presumed to
have intended what his language means. To ascertain that meaning the
words used must be read grammatically and in
their ordinary sense . .
. The specification like any other document must be read as a whole.’
(See
also
Cipla Medpro (Pty) Ltd v Aventis Pharma SA and Related Appeal
2013 (4) SA 579
(SCA) para 14.)
[7]
Yet, established authority also reveals that the reference to ‘the
ordinary meaning of words’ must not be understood
as an
exercise in focusing on each word in isolation, but by viewing them
in the context of the patent as a whole (see eg
Aktiebolaget
Hässle & another v Triomed (Pty) Ltd
2003 (1) SA 155
(SCA) para 8). Essentially the same principle was expressed with
admirable clarity in the following statement by Lord Diplock in
Catnic Components Ltd & another v Hill & Smith Ltd
[1982]
RPC 182
(HL) at 242 – referred to with approval in the many
judgments of this court cited in
Aktiebolaget Hässle (
para
8):
‘
.
. . A patent specification should be given a purposive construction
rather than a purely literal one derived from applying to
it the kind
of meticulous verbal analysis in which lawyers are too often tempted
by their training to indulge. The question in
each case is: whether
persons with practical knowledge and experience of the kind of work
in which the invention was intended to
be used, would understand that
strict compliance with a particular descriptive word or phrase
appearing in a claim was intended
by the patentee to be an essential
requirement of the invention so that
any
variant would fall outside the monopoly claimed, even though it could
have no material effect upon the way the invention worked.'
[8]
Or, in the words of Corbett JA in
Multotec Manufacturing (Pty) Ltd
v Screenex Wire Weaving Manufacturers (Pty) Ltd
1983 (1) SA 709
(A) at 721C-E:
‘
.
. . The Court should always guard against too "textual" an
approach in the interpretation of claims in a patent specification.
It is true that it is in the claims that a patentee stakes out and
defines his monopoly; and that the claims must be looked at
in order
to determine whether an infringement has taken place. But by peering
too closely at the language of a claim the Court
may overlook an
infringement which takes the substance of the invention.’
[9]
Finally, with regard to interpretation, I start out from the
well-established premise, that a patent specification is a statement
by the patentee, addressed to those ‘skilled in the art’,
in which he informs them of what he or she claims to be the
essential
features of the invention for which a monopoly is claimed.
Consequently, a patent specification must be construed with
reference
to the state of knowledge of those skilled in the art at the time of
the priority date of the patent in issue. Accordingly,
in order to
enable the court to construe the specification properly, it must be
instructed by expert witnesses as to the state
of the art in the
field of the invention in order to place the court as near as may be
possible to the position of those skilled
members of the public to
whom it is addressed, as at the relevant date (see eg
Sappi Fine
Papers (Pty) Ltd v ICI Canada Inc (Formerly CIL INC)
[1992] ZASCA 58
;
1992 (3) SA
306
(A) at 318I-319E).
Background
[10]
For that purpose, two experts in the field were called to give
evidence at the trial, namely, Prof Martyn Davies on behalf
of Bayer
and Dr Peter Rue on behalf of Pharma. They were largely in agreement
that the addressees of the patent would be a broad
interdisciplinary
product formulation team of a pharmaceutical company, led by an
experienced scientist and including biological
pharmacologists,
toxicologists, clinicians and so forth. For the sake of brevity,
these addressees of the patent in suit were referred
to at the trial
and in argument as ‘the skilled formulator’. I propose to
follow that example. Broadly speaking, the
two experts were also in
agreement as to the state of the knowledge of that skilled formulator
as at the priority date, ie 31 August
1999. In this way the following
background had been established.
[11]
An active pharmaceutical ingredient (API) administered to humans
orally, passes down the gastro-intestinal tract and is absorbed
into
the bloodstream. For present purposes we can concentrate on two parts
of that tract, to wit, the stomach and the small intestine.
The
stomach is highly acidic with a generally accepted pH range of
between 1 and 3. The stomach lining is not designed for absorption.
The primary purpose of the stomach is after all not to absorb, but to
digest the ingested food. By contrast, the small intestine
is less
acidic – generally accepted as ranging from pH 5 to 7 –
and primarily designed for absorption into the bloodstream.
The API
can only be absorbed into the bloodstream once it is in solution, ie
once it has been dissolved. The quantity of API absorbed
into the
bloodstream and eventually becoming available at the point of the
human body where it is required for treatment of the
individual, is
said to be bioavailable. Bioavailability therefore describes the
quantity of the drug, expressed as a percentage
of the dose
administered, that becomes available for treatment.
[12]
Because of the arrangement of the gastro-intestinal tract, the API
must pass through the highly acidic conditions in the stomach
before
it reaches the small intestine where it can be absorbed, ie before it
becomes bioavailable. It stands to reason that the
longer the API
remains in the stomach, the more it will be affected by those
conditions. The skilled formulator would have been
aware that the
residence time of the API in the stomach might vary substantially.
With regard to a particular individual it would
be influenced by a
number of factors, including whether the individual had eaten or
fasted, the nature of the diet and so forth.
Moreover, apart from
this intra-individual variability, there would be inter-individual
variability in residence time. All in all
stomach residence may vary
between 30 minutes and 4,5 hours with a meantime of 90 minutes. If
the API is therefore immediately
released once it reaches the
stomach, it may spend anything between 30 minutes and 4,5 hours in
that highly acidic condition.
[13]
A formulator charged with a formulation for an API will invariably
conduct formulation tests in the laboratory, referred to
as in vitro
tests. These are, inter alia, aimed at establishing, among other
things, the solubility of the drug and its stability
under acidic
conditions. The rate of dissolution may be studied in vitro using
standard dissolution tests. Such tests are routinely
used in the
pharmaceutical industry. The ‘USP XXIII Paddle Method’
referred to in claim 1 of the 2004 patent –
to which I shall
presently return – is one of these standard methods of testing
the rate of dissolution, which any skilled
formulator would
understand.
[14]
As drugs administered orally need to dissolve in the
gastro-intestinal tract in order to be effective, drug candidates
that
exhibit poor solubility in vitro will be considered a risk for
development as they may show poor bioavailability in vivo, ie in
the
human body. The dissolution rate of a drug can, however, be
increased. So, for example, the particle size of the drug can be
reduced – known as micronisation – or the drug can be
dissolved and sprayed onto the surface of inert carrier particles.
Since these two methods of improving the rate of dissolution are
expressly referred to in the 2004 patent, I shall return to them
in
later discussion.
[15]
If an API is unstable in acidic conditions, ie if it is acid labile,
a significant portion of the drug may be degraded or isomerised
in
the stomach, which would in turn reduce its bioavailability. This
would of course be a contraindication for increasing the dissolution
rate of an API known to be acid labile. The reason for the ‘of
course’ is that the sooner the drug dissolves in the
acidic
conditions of the stomach, the more severe the influence of those
conditions will probably be. Moreover, given the potential
of both
intra and inter individual variability in stomach residence time, the
formulator would have to produce a formulation that
could cope with
the longest possible exposure to the acidic environment of the
stomach.
[16]
One way of overcoming the problem of isomerisation in the stomach is
to increase the dosage of API administered. That, however,
could
result in an overdose. The skilled formulator would have known that,
especially with reference to a drug which is used regularly,
as in
the case of a contraceptive, overdose could be particularly
detrimental to the user. Another way of resolving the problem
of acid
lability is to protect it from the acidic environment in the stomach
by means of an enteric coating. Enteric coatings act
as an
impermeable barrier around the API and prevent the acid content of
the stomach from coming into contact with the underlying
API. As at
the priority date, the skilled operator would have known that there
were a number of different enteric coatings available
for this
purpose.
[17]
Also well-known, since at least the 1960s, was the fact that DSP in
combination with EE could be used as a contraceptive. In
vitro tests
had shown, however, that DSP has the two features that presented a
particular challenge to formulators, namely that
it was both poorly
soluble and acid labile. Moreover, because it was destined for use as
a contraceptive, excessive dosage was
a potential problem, which
indicated small dosages. To add to the formulator’s difficulty,
a contraceptive has to be formulated
so that it is a 100 per cent
effective at inhibiting ovulation, given that the consequence of an
ineffective dose could be an unwanted
pregnancy. This added demand
does not present itself, for instance, with analgesics and
antibiotics. With DSP it was therefore
necessary to establish a
dosage which achieved this high degree of reliability. What the
formulator would have known in sum was
that in all these
circumstances, it was of cardinal importance to ensure, not only that
each tablet contained the right dosage
at the point of
administration, but also that as little as possible of the dosage was
not lost on its way to the site of absorption
in the small intestine.
[18]
The two experts who testified at the trial were generally in
agreement that the results of in vitro tests in themselves would
have
indicated a development of a small dosage of DSP with increased
solubility – also described as rapid dissolution –
eg by
way of micronisation, but protected from the acid in the stomach by
an enteric coating. The record of the in vitro tests
carried out by
Bayer in fact showed this. From here on, the two experts, however,
parted company. Dr Rue’s view was that
the skilled formulator
would not have decided to protect DSP with an enteric coating unless
and until the results of the in vitro
experiments had been confirmed
by in vivo tests on humans. Even with drugs known to be highly acid
labile, so he said, in vivo
tests are routinely conducted. The
reason, he said, was the known fact that one cannot accurately
predict the in vivo bioavailability
of the drug purely from in vitro
experiments. Accordingly, he concluded that despite the results of
the in vitro tests, the skilled
formulator would routinely have
performed an in vivo test with both enteric coated and uncoated DSP
at an early stage of the development
process. In vivo tests would
then have shown, as we now know with the experience of hindsight,
that good bioavailability could
be attained with DSP unprotected by
an enteric coating. Prof Davies, on the other hand, was of the view
that in the light of the
in vitro results, the skilled formulator
would have regarded in vivo tests with uncoated DSP as wasteful of
both time and money.
This is particularly so, because in vivo tests,
he said, are costly and time consuming. A skilled formulator would
therefore not
embark on this road with no expectation of success
which was what the in vitro experiments predicted.
[19]
How Bayer actually came to realise that DSP need not be protected by
an enteric coating, emerges from the ‘inventors’
story’
that derived from the documents referred to by both experts during
their evidence at the trial. In broad terms the
story went as
follows. During April 1983, Dr Johannes Tack, who later became the
Head of Pharmaceutical Development at Bayer –
but at that time,
still a junior researcher – was charged with the task of
developing an oral tablet formulation of one milligram
DSP. Results
of in vitro tests steered him in the direction of an enteric coating.
For the next four years scientists at Bayer
thus conducted
pre-formulation experiments with enteric coated DSP exclusively.
Results achieved by in vivo studies during this
period, both with
dogs and humans, were encouraging to the formulation team. Of some
concern to them, however, was the inter-subject
variation in these
results. To address the possibility that these variances could be
caused by the enteric coating that they used,
they decided to do what
was referred to in evidence as a three arm bioavailability test,
which was done during the first term of
1988.
[20]
Broadly speaking, the three arm test compared the bioavailability of
DSP when administered in three forms: (a) intravenously
– where
absorption plays no role; (b) through enteric coated tablets; and (c)
through tablets which were not enteric coated
at all, and the DSP is
thus immediately released in the stomach. Based on the results of in
vitro studies, the formulation team
clearly had no anticipation of
success for the uncoated formulation. However, the surprise came when
the bioavailability of the
uncoated formulation proved to be
statistically no different from that of the enteric coated drug.
[21]
What must also be borne in mind at this juncture is that, although
enteric coatings perform the positive function of protection
against
acid in the stomach, they had known disadvantages. First of these is
that it delays absorption until it is finally dissolved
in the small
intestine. Hence it also delays the onset of action of the drug. The
second and related problem is that the period
of delay would be the
subject of inter and intra-patient variability which is coupled to
the residence time of the protected drug
in the stomach. This again
is of particular significance with a drug intended for contraception
where it is undesirable to leave
large gaps in the sequence of
administration. In the light of these known disadvantages of an
enteric coating and consequent delayed
release of the drug, skilled
formulators of Bayer realised the benefits of an immediate release of
DSP. In consequence, the formulation
team at Bayer subsequently
redirected its research and development from coated to uncoated DSP,
which is the form in which its
Yasmin product was eventually
marketed.
[22]
In this light Prof Davies contended that the invention covered by the
patent is the following (p 2 137):
‘
The
very fact that against all expectations for a drug which is poorly
soluble such as drospirenone and which is acid labile, against
all
expectations that if you used a rapid dissolution, a formulation that
achieves a rapid dissolution, as per claim 1 of the 2004
specification . . . what you get is good bioavailability, in other
words, good absorption in vivo. That is against all expectation
due
to the acid lability of the drug. So that is the inventive step.’
And
at 2 504:
‘
There
was a research proposal which they [the formulating team at Bayer]
undertook, there was no expectation of success and they
found to
their surprise that they had a formulation which was rapidly
dissolving on a poorly soluble acid labile compound good
bioavailability in vivo against all experience, against all of the
scientific knowledge that they had and we still cannot understand
how
it works. . . .’
[23]
Dr Rue disagreed. In his view the fact that a rapidly dissolving
micronised form of DSP, known to be acid labile, would not
in fact
degrade in vivo would have been experimentally determined by the
skilled formulator through in vivo tests performed as
a matter of
routine at an early stage of the development. The three arm test
eventually conducted by Bayer, so he testified, should
have been done
as a matter of routine at an earlier stage. Had this been done, the
‘problem’ contemplated by Bayer
in the light of the in
vitro results, would routinely have been established to be no real
problem at all. His answer to Prof Davies’
view that the
invention, protected by the patent in suit served to resolve a
particular problem was therefore in short that the
skilled formulator
would have known at an early stage that the perceived problem was not
a real problem at all.
Infringement
[24]
Against this background I can now turn to the question: does Pharma’s
Ruby product constitute an infringement of claim
1 of the 2004
patent? In
Letraset Ltd v Helios Ltd
1972 (3) SA 245
(A) at
274G-H, the approach to this question was formulated as follows:
‘
The
determination of the question as to whether or not plaintiff has
proved an infringement of his patent turns upon a comparison
between
the article . . . involved in the alleged infringement and the words
of the claims in the patent. If the article or process
falls within
the ambit of the claims, properly construed; an infringement is
proved. But the article or process will not be regarded
as falling
outside the scope of the claims if such differences as the comparison
may disclose are not matters of any substance.
In making the
comparison the law looks at the essence of what is contained in the
claim and will not allow what is described as
the “pith and
marrow” of the protected invention to be pirated. The
evaluation of what is the substance or essence
of an invention is a
matter for the “good sense” of the judicial tribunal
seized with the enquiry.’
[25]
Claim 1 of the 2004 patent is formulated as follows:
‘
A
pharmaceutical composition comprising:
as
a first active agent drospirenone in an amount corresponding to a
daily dosage, on administration of the composition, of from
about 2
mg to 4 mg, and
as
a second active agent ethinylestradiol in an amount corresponding to
a daily dosage of from about 0.01mg to 0.05 mg,
together
with one or more pharmaceutically acceptable carriers or excipients,
wherein
at least 70% of said drospirenone is dissolved from said composition
within 30 minutes, as determined by USP XXIII Paddle
Method II using
water at 37ºC as the dissolution media and 50 rpm as the
stirring rate.’
[26]
It is common cause between the parties that this claim can be divided
up into the following five features or integers:
A
A pharmaceutical composition comprising:
B
as a first active agent drospirenone in an amount corresponding to a
daily dosage, on administration of the composition, of from
about 2
mg to 4 mg;
C
as a second active agent ethinylestradiol in an amount corresponding
to a daily dosage of from about 0.01mg to 0.05 mg;
D
together with one or more pharmaceutically acceptable carriers or
excipients; and
E
wherein at least 70% of said drospirenone is dissolved from said
composition within 30 minutes, as determined by USP XXIII Paddle
Method II using water at 37ºC as the dissolution media and 50
rpm as the stirring rate.
[27]
It was not in dispute that Pharma’s product includes integers
A-D of the claim. The debate therefore turned on integer
E. In broad
outline the debate went along the following lines: according to the
interpretation contended for by Bayer, the claim
includes within its
scope, DSP having the rapid dissolution rate specified in accordance
with a known method of determination without
an enteric coat, no
matter how that dissolution rate had been achieved. By contrast, the
interpretation relied upon by Pharma is
that the claim is limited to
the achievement of the specified rapid dissolution by way of
micronisation on DSP (or of the possible
alternative method of
dissolving DSP in a suitable solvent and spraying the solution onto
the surface of an inert carrier).
[28]
In this regard it is common cause that the DSP used in the
manufacture of Pharma’s Ruby product attains the dissolution
rate specified in integer E, but that it is not provided in
micronised form or dissolved in a solvent and then sprayed onto the
surface of inert carrier particles. Instead a solution containing the
DSP is added as a bulk liquid which is distributed uniformly
throughout the granules used in the formulation by means of a high
speed mixer or granulator. Hence it is clear that if the
interpretation
contended for by Bayer is accepted, Ruby falls within
the compass of integer E and hence of the claim – but not if
Pharma’s
interpretation of the claim is sustained.
[29]
Bayer’s case is that claim 1 protects the invention described
by Prof Davies. The contrary position taken by Dr Rue and
Pharma is
that if there was indeed an invention as described by Prof Davies -
which they denied – that is not the invention
covered by claim
1. Although directly contradictory, each party found support for its
interpretation in the body of the patent
specification, which reads
in relevant part, under the heading ‘Detailed disclosure of the
invention’:
‘
Drospirenone
. . . is a sparingly soluble substance in water and aqueous buffers
at various pH values. Furthermore, drospirenone
is rearranged to an
inactive isomer under acid conditions and hydrolysed under alkaline
conditions. To ensure good bioavailability
of the compound, it is
therefore advantageously provided in a form that promotes rapid
dissolution thereof.
It
has surprisingly been found that when drospirenone is provided in
micronized form . . . rapid dissolution of the active compound
from
the composition occurs in vitro (“rapid dissolution” is
defined as the dissolution of at least 70% over about
30 minutes . .
. of drospirenone from a tablet preparation containing 3 mg of
drospirenone in 900 ml of water at 37ºC determined
by the USP
XXIII Paddle Method using a USP dissolution test apparatus 2 at 50
rpm). Instead of providing the drospirenone in micronized
form, it is
possible to dissolve it in a suitable solvent, e.g. methanol or ethyl
acetate, and spray it onto the surface of inert
carrier particles
followed by incorporation of the particles containing drospirenone on
their surface in the composition.
Without
wishing to be limited to any particular theory, it appears that the
in vitro dissolution rate of drospirenone is connected
to the
dissolution rate in vivo resulting in rapid absorption of
drospirenone in vivo on oral administration of the compound. This
is
an advantage because isomerization of the compound in the gastric
environment and/or hydrolysis in the intestine is substantially
reduced, leading to a high bioavailability of the compound. . . .
The
composition of the invention may be formulated in any manner known in
the pharmaceutical art. In particular, as indicated above,
the
composition may be formulated by a method comprising providing
drospirenone and, if desired, ethinylestradiol in micronized
form in
said unit dosage form, or sprayed from a solution onto particles of
an inert carrier in admixture with one or more pharmaceutically
acceptable excipients that promote dissolution of the drospirenone
and ethinylestradiol so as to promote rapid dissolution . .
. on oral
administration.’
[30]
On Pharma’s construction of these paragraphs the ‘surprising
finds’ made were, that when DSP is provided
in micronised form
(or dissolved and sprayed onto the surface of the particles of an
inert carrier), rapid dissolution of the active
compound from the
composition in vitro is achieved. With regard to the contrary
interpretation contended for by Bayer – ie
that it covers the
invention described by Prof Davies – Pharma pointed out that
there is no indication that the ‘surprising
finds’ relate
to rapidly dissolving DSP leading to good bioavailability in vivo
without the need for it to be protected by
an enteric coating. In
fact, so Pharma argued, the specification does not even refer to the
subject of enteric coatings at all.
Its only topic of discussion is
the rapid dissolution of DSP and the two methods in which this can be
attained.
[31]
I do not believe, however, that this is how the skilled addressee
would understand the specifications. First of all, the fact
that
rapid dissolution could be achieved in vitro through one of the two
methods referred to, was well-known at the time. Indeed,
it was
common knowledge amongst those skilled in the art that the same
result could be achieved in at least five ways. Hence rapid
dissolution by these two methods could never have been understood by
those skilled in the art to constitute the ‘surprising
finds’.
What the ‘detailed disclosure’ teaches at the outset, as
I said, is that DSP is (a) sparingly soluble
in water and at the same
time, (b) unstable in an acidic environment, in that it rearranges
into an inactive isomer in these conditions
(ie that DSP is acid
labile). It then continues to explain that – despite (b) –
it has surprisingly been found that
when DSP is provided in a rapidly
dissolving form (which would ordinarily mean that both the solubility
and the risk of degradation
as a result of acid lability, were
increased) high bioavailability was nonetheless attained in vivo. To
the skilled operator, the
‘surprising find’ described
would therefore be, in my view, the invention described by Prof
Davies, which indeed came
as a surprise to Bayer’s development
team. It is true that all this is not explicitly stated in the
specification and that
no mention is made, for instance, of enteric
coatings. But as appears from the authorities I have referred to at
the outset, one
must read the specification through the eyes of a
person skilled in the field and avoid the undue focus on a literal
analysis in
which lawyers tend to indulge.
[32]
As I read it, there is therefore no basis upon which the limitation
proposed by Pharma can conceivably be read into the claim
of the
patent in the context of the specification. On the contrary, I think
the plain meaning of the claim read with the specification
goes the
other way. First of all it teaches that DSP can be provided in
micronised form or ‘instead’ that ‘it
is possible’
for the dissolution rate of integer E to be achieved through the use
of inert carrier particles. These are not
statements from which one
could infer that the claim should be limited to a particular method
of achieving a dissolution rate.
But what settles the matter, I
think, is the patentee’s express statement that ‘composition
of the invention may be
formulated in any manner known in the
pharmaceutical art’. This means that the composition of the
invention could be formulated
in any known manner that would achieve
the dissolution rate specified in integer E, which includes the
method employed in the formulation
of Pharma’s Ruby product.
[33]
In sum I therefore agree with the court a quo’s finding that
the skilled reader of the patent (reading it as a whole)
would accept
that claim 1 covers any method of achieving the dissolution rate of
integer E; that Pharma’s Ruby product therefore
falls within
the compass of the claim and consequently infringes the 2004 patent.
Inventive
step
[34]
This brings me to Pharma’s attack against the patent on the
basis that it lacked an inventive step. The challenge must
of course
be understood in the light of s 25(10) of the Act which requires
that, in order to be patentable, an invention must
‘involve an
inventive step’ in the sense that ‘it is not obvious to a
person skilled in the art, having regard
to any matter which forms,
immediately before the priority date of the invention, part of the
state of the art . . .’ As
explained by Plewman JA in
Ensign-Bickford (South Africa) (Pty) Ltd & others v AECI
Explosives and Chemicals Ltd
1999 (1) SA 70
(SCA) at 80H-J, a
structured approach to the alleged obviousness of an invention
involves the following enquiry:
‘
Four
steps are identified. They include or restate in part what has been
said above but may be taken to conveniently list the inquiries
to be
made:
(1)
What is the inventive step said to be involved in the patent in suit?
(2)
What was, at the priority date, the state of the art (as statutorily
defined) relevant to that step?
(3)
In what respect does the step go beyond, or differ from, that state
of the art?
(4)
Having regard to such development or difference, would the taking of
the step be obvious to the skilled man?’
[35]
As we know by now, the inventive step of the patent in suit contended
for by Bayer and supported by Prof Davies, lies in the
surprising,
counter-intuitive finding that DSP, despite being both acid labile
and poorly soluble, can be administered in a low
dosage (of 2 to 4
mg), having the rapid dissolution rate of claim 1 and yet give
sufficiently good bioavailability in vivo to be
effective. We also
know by now that the answer to this contention, as presented by Dr
Rue, was that the skilled formulator would
have determined
experimentally at an early stage of the development of the drug that,
despite DSP being acid labile, it does not
in fact degrade in vivo.
[36]
According to Dr Rue his thesis was supported by the state of the art
at the priority date which showed that in vivo tests were
conducted,
even with highly acid labile drugs. In this regard he relied in
particular on an article by two Swedish scientists,
A Pilbrant and C
Cederberg ‘Development of an oral formulation of omeprazole’
(1985) 108
Scand J Gastroenterol Suppl
which was published in
1985 (the Pilbrant article). The article relates to the development
of an oral formulation of the drug, omeprazole,
which is both poorly
soluble and highly acid labile. The article reflects that the authors
considered whether to use an immediate
release formulation of
omeprazole or an enteric coated one. As part of their research they
conducted in vivo tests, using the drug
in both protected and
unprotected formulations. The result of these in vivo tests
corresponded to what was foreshadowed by the
in vitro experiments:
more than half of the omeprazole in the uncoated dosage degraded in
the stomach. Although the Pilbrant article
supports Dr Rue in that it
evinces the performance of in vivo tests on a drug known to be acid
labile, the results of the Pilbrant
tests published in the article
teaches away from the use of an acid labile drug, like DSP, in
uncoated form. If anything,
the article would therefore, in my view,
persuade the skilled formulator in August 1999 to use an enteric
coating in preparing
any formulation containing DSP.
[37]
In addition to the Pilbrant article, Pharma sought to find support
for Dr Rue’s views in Bayer’s own internal documents.
Apart from the fact that these are not public documents and do not
therefore form part of the ‘state of the art’ as
defined
in s 25(6) of the Act, I believe they in fact do not support Dr
Rue’s thesis. According to Dr Rue, these documents
show that
Bayer conducted an in vivo experiment with unprotected DSP as a
matter of routine, albeit at a late stage of the development.
But
that is not how I understand the Bayer documents. On my
understanding, Bayer first spent about four years in the development
of DSP protected by an enteric coating before it did any in vivo
tests. Secondly, the in vivo tests were then conducted not so
much
with the view to establish the bioavailability of uncoated DSP but
for the purpose of establishing possible shortcomings in
the enteric
coating actually used, that the formulator team suspected of being
inefficient. In any event, it was not done, as Dr
Rue would have it,
as a matter of routine. In this light, I think the ‘inventor’s
story’ reflected in the Bayer
documents, was supportive of Prof
Davies’ views rather than those of Dr Rue.
[38]
As to the third inquiry contemplated in
Ensign-Bickford
, it
appears to be common cause that the development of DSP as an oral
contraceptive without an enteric coating went beyond and
was a step
different from the state of the art at the priority date. Dr Rue’s
thesis is that it fails the obvious test on
the fourth step of the
Ensign-Bickford
inquiry, in that the taking of this step would
be obvious to the skilled formulator after in vivo testing, which
would have been
done as a matter of routine. However, in evaluating
Dr Rue’s views, I believe they fall foul of at least two
well-established
principles in assessing obviousness. The first is
that one must guard against the dangers of hindsight or
ex post
facto
explanation of the invention (see eg
Gentiruco AG v
Firestone SA (Pty) Ltd
1972 (1) SA 589
(A) at 660G;
Roman
Roller CC & another v Speedmark Holdings (Pty) Ltd
[1995] ZASCA 78
;
1996 (1)
SA 405
(A) at 418I-J). It is all too easy after the event and with
the brilliance of hindsight, to say that a skilled formulator would
have arrived at the invention earlier by doing an in vivo test.
[39]
The second principle relates to Dr Rue’s view that it would
have been ‘obvious to try’ uncoated DSP, as a
matter of
routine, in an in vivo test. The principle is, however, that before
an invention will be found to be obvious on the ‘obvious
to
try’ basis, it must be established by expert evidence that
those skilled in the art would have carried out a test that
led to
the invention, not only because it was the obvious thing to do, but
also because they would consider that a reasonable possibility
existed that the test might lead to a useful result (see eg
B-M
Group (Pty) Ltd v Beecham Group Ltd
1978 BP 373 (T) at 405A-C).
In this case it seems that, in the light of the in vitro results, the
in vivo experiment that eventually
led to the unsuspected invention
did not seem to have the slightest hope of success before it was
actually done.
[40]
But what I find most unappealing about Dr Rue’s theory is that
it lacks any form of logical underpinning. It makes no
sense for a
formulator to take the time to do in vitro acid stability tests, and
then to ignore the results by proceeding to carry
out what are very
expensive and time-consuming clinical trials on humans. What his
proposition amounts to is that the skilled formulator
would have
conducted in vivo bioavailability tests regardless of the fact that
he or she had no expectation that the formulation
would not degrade
in the stomach and therefore to take a step which was strongly
contra-indicated. Stated somewhat differently:
that the skilled
formulator would disregard the considerable costs, delays and risks
associated with carrying out in vivo tests
in circumstances where the
formulator had no expectation whatsoever that the test might lead to
any useful result.
[41]
By contrast, I find the reasoning of Prof Davies far more persuasive
in its logical progression. In the light of this evidence
I agree
with the court a quo’s conclusion that Pharma had failed to
establish its attack on the patent in suit based on obviousness.
This
conclusion is also supported by the principle acknowledged in English
law, that an invention can lie in ‘finding out
that which those
in the art thought ought not to be done, ought to be done’
(
Dyson Technology Ltd v Samsung Gwangju Electronics Co Ltd
[2009]
EWHC 55
(Pat) at 154) or as it was formulated by Jacob LJ in a
passage cited in
Buhler AG v FP Spomax SA
[2008] EWHC 823
(Ch)
para 47:
‘
A
patentee who contributes something new by showing that, contrary to
the mistaken prejudice, the idea will work or is practical
has shown
something new. He has shown that an apparent “lion in the path”
is merely a paper tiger. Then his contribution
is novel and
non-obvious and he deserves his patent.’
Lack
of novelty
[42]
This brings me to Pharma’s further ground of attack against the
2004 patent, based on the proposition that it is not
a true
‘divisional’ of the 2002 patent and that it therefore
lacks novelty in the light of the disclosures made in
the 2002
patent. This ground is to be understood against the background of
s 37
of the
Patents Act which
provides:
‘
1.
Where at any time after an application had been lodged at the patent
office and before it is accepted, a fresh application is
made in the
prescribed manner by the same applicant in respect of part of the
matter disclosed in the first-mentioned application,
the registrar
may, on application made to him in the prescribed manner before that
application is accepted, direct that such fresh
application be
antedated to a date not earlier than the date on which the
first-mentioned application was so lodged.
2.
A patent granted on such fresh application shall not be revoked or
invalidated on the ground only that the invention claimed
in such
fresh application is not new having regard to the matter disclosed in
the first-mentioned application.’
[43]
It is common cause that the application for the 2004 patent was filed
under
s 37
before the 2002 patent had been accepted. Likewise it
is common cause that if it constituted a ‘fresh application’
as contemplated by the section, it would enjoy immunity against an
attack based on the disclosure of the 2002 patent by virtue of
s 37(2)
, but that if it was not, it would be open to that
attack. Pharma’s argument is that it was not a ‘fresh
application’
properly so called.
[44]
Bayer’s first answer to the attack is that, since the 2004
patent was granted as a divisional patent by the Registrar
of Patents
under
s 37
in the form it was sought, Pharma’s remedy was
to seek the setting aside of that decision in a review application
which it
never did. In support of this argument Bayer pointed out
that s 61 of the Act – which enumerates the grounds for
the
revocation of a patent – does not provide for the
revocation of a patent on the basis that it was wrongly registered as
a
‘divisional patent’ under s 37. In further support
of this argument, Bayer relied on the following statement by
this
court in
Clipsal Australia (Pty) Ltd & another v Trust
Electrical Wholesalers & another
2009 (3) SA 292
(SCA) para
9, which was made with reference to an analogous attack on the
registration of a ‘set of articles’ in terms
of the
Designs Act 195 of 1993
:
‘
If
the registrar has registered articles as a set when they in truth do
not form a set it is at best a matter for review but it
cannot be
raised as a defence to infringement or be a ground for revocation.’
[45]
I believe Bayer’s objection to be well-founded. At the same
time I hold the view that Pharma’s attack falls down
on its
merits as well. The procedure provided for in
s 37
is referred
to in patent parlance as ‘dividing out’ part of the
matter disclosed in the parent patent as a divisional
patent. The
divisional patent is antedated and runs for the same period as the
parent patent and claims priority from the same
date. Ultimately, the
two separate patents (the parent and the divisional) run in parallel
and for the same length of time.
[46]
The advantages of and requirements for divisional patents are
explained with remarkable clarity by Jacob LJ in
Napp
Pharmaceutical Holdings Ltd v Ratiopharm GmbH
and
Napp
Pharmaceutical Holdings Ltd v Sandoz Ltd
[2009] EWCA Civ 252
paras 7-15. With regard to the requirements for a divisional patent
he inter alia said:
‘
The
two patents have, for practical purposes, the same text because they
are “divisionals”. The differences lie in their
respective claims, and in variations of the text consequential upon
the dividing out process.’
And:
‘
So
what a patentee can do, having made an initial application, is to
apply for a divisional patent. Provided the subject-matter
of this
does not extend beyond the content of the earlier application, he can
get a free-standing patent for the divisional application.
Because
the date of filing is deemed to be that of the “parent”
as the jargon goes, a patentee cannot extend the period
of protection
by applying for a divisional.’
And:
‘
One
of the features of the divisional system is that each divisional must
have claims which are different: the patentee cannot have
the same
claim in different patents.’
[47]
Pharma’s first argument as to why the 2004 divisional
application was not a divisional patent as contemplated in
s 37
was that for all intents and purposes the body of the 2004 patent and
that of the 2002 patent is the same. As a matter of fact,
that is so.
But, I do not think that renders the objection valid. As explained by
Jacob LJ, the very idea of a divisional patent
is that it has for
practical purposes the same text as the parent. The invention
disclosed is the same. The difference between
the two lies in the
claim.
[48]
Pharma’s second argument rests on the proposition that the
claim of the 2004 patent is the same as the claim of the 2002
parent
claim. Or, stated in patent law jargon, that the two claims are
coterminous. As a matter of law, this cannot happen. That
much
appears, for instance, from the passage in the
Napp
case to
which I have referred (see also T D Burrell
South African Patent
and Design Law
3 ed (1999) para 2.62). But this time the argument
falls down on the facts. Claim 1 of the 2002 patent is expressly
limited to
DSP in micronised form. On the interpretation of claim 1
of the 2004 patent, contended for by Pharma, the two would indeed be
the
same. But I have already held that interpretation unsustainable.
In accordance with the contrary interpretation of the 2004 claim
contended for by Bayer – which I found to be correct –
this claim is broader than the 2002 parent claim, in that it
includes
DSP having the rapid dissolution rate specified in the claim, however
that dissolution rate had been obtained, which clearly
includes, but
is not confined to micronisation. This means that the two claims are
not coterminous. Following upon this, Pharma’s
further argument
was that
s 37
does not allow a divisional claim which is broader
than the parent claim. It sought to find support for this argument in
the statement
by Jacobs LJ in
Napp
(para 10) that ‘Provided
the subject matter of this [ie the divisional patent] does not extend
beyond the content of the earlier
[parent] application, he can get a
free-standing patent for the divisional application’. But I do
not believe that this statement
lends support to Pharma’s
argument. What Jacob LJ refers to is that the claim of the divisional
patent cannot be broader
than the invention disclosed in the body of
the parent patent. This would, after all, give rise to a ground of
revocation that
the claim is not fairly based on the matter disclosed
in the application (see s 61(f)(ii) of the Act).
[49]
Pharma’s final argument as to why s 37 should be construed
so as to exclude a divisional patent which claims broader
protection
than its parent, is that it could otherwise place the infringer of
both patents in an invidious position when licences
in respect of the
two patents were granted to different licensees. In this event, so
Pharma’s argument went, the infringer
could potentially be held
liable by two plaintiffs instead of one. I believe there are two
answers to this argument. First, I do
not think the position would be
any different if the divisional patent is narrower than the parent.
Secondly, the prejudice feared
by Pharma seems to be more apparent
than real. If the remedy sought by the two licensees is an interdict,
the two interdicts will
clearly overlap. If on the other hand, the
remedy sought is one in the form of damages, each licensee will be
confined to the amount
that he or she can establish. In the
circumstances, I find that Pharma’s attack of the patent on the
basis of novelty must
also fail.
Conclusion
[50]
For these reasons the appeal is dismissed with costs, including the
costs of two counsel.
___________
F
D J BRAND
JUDGE
OF APPEAL
APPEARANCES:
For
the Appellant: L Bowman SC and B du Plessis
Instructed
by:
Von
Seidels, Cape Town
c/o
Webbers, Bloemfontein
For
the Respondent: P Ginsburg SC and G Marriott
Instructed
by:
Adams
& Adams Inc, Pretoria
c/o
Honey Attorneys Inc, Bloemfontein