The art of using secondary patents

to improve protection
Received (in revised form): 4th March, 2003

Michael Burdon
is Head of Olswang’s sector-focussed Biosciences team and a member of the Intellectual Property Group. His principal area of
expertise is patents, especially multijurisdictional disputes. Michael manages the legal requirements of and provides specialist
intellectual property and regulatory advice to, participants in all aspects of the biosciences industry. He serves on the
Intellectual Property Advisory Committee of the BioIndustry Association, is an associate member of the Chartered Institute of
Patent Agents and on the Editorial Board of Patent World. He regularly writes for specialist journals and chairs and speaks at
conferences and in the media about biosciences and intellectual property. He has been selected for inclusion in the
Euromoney Guide to the World’s Patent Law Experts as well as Law Business Research’s International Who’s Who of Patent
Lawyers. He is also ‘Highly Recommended’ in the UK Intellectual Property (Hard) category of PLC’s Global Counsel 3000.

Kristie Sloper
is an assistant solicitor in the Intellectual Property Group and a member of the Biosciences team. She works on a variety of
contentious intellectual property matters including patent, trademark, copyright and design right disputes. She has particular
experience of advising clients in the biotechnology and pharmaceutical sectors on a broad range of intellectual property and
regulatory matters.

Keywords patents, secondary patents, legal, patent protection, intellectual property,

pharmaceuticals

Abstract In an environment where there is ever increasing pressure on innovator

pharmaceutical companies to maximise return on investment and where share values
may be substantially affected by court decisions in patent litigation between
pharmaceutical innovators and generic companies, a key element of pharmaceutical life
cycle management strategies is to extend patent protection for as long as possible by
filing secondary patents to keep generics off the market. This paper considers the
approach taken by the UK courts to the enforcement of secondary patents, focussing on
recent decisions of the UK courts and attempting to draw some conclusions from the case
law as to the types of secondary patent that may be enforceable in the UK and the
implications of the case law for the development of a credible life cycle management
strategy.

INTRODUCTION steady decline. The annual number of new

There has been a great deal of publicity
during the first few months of 2003
concerning the current decline in
productivity, as measured by the number
of successful new chemical entities
reaching market, of the research and
development (R&D) departments of the
Michael Burdon
Partner, Olswang, innovator pharmaceutical companies.
90 High Holborn,
London WC1V 6XX, UK Despite a large increase in investment in
Tel: +44 (0)20 7208 8697
e-mail:
R&D, the number of new chemical
michael.burdon@olswang.com entities reaching the market has been in
chemical entities approved by the US’
FDA fell from an all-time high of 53 in
1996 to 24 in 2001. As at September 2002,
the number of new chemical entities
obtaining approval in 2002 was only 11.
Added to this problem of the dearth of
new drugs is the problem of patent
expiration and/or revocation of the patents
protecting existing brand-name drugs. A
number of high profile drugs lost patent
protection and fell open to generic

226 International Journal of Medical Marketing Vol. 3, 3 226–238 Henry Stewart Publications 1469–7025 (2003)
 The art of using secondary patents to improve protection
competition during 2001–2002; among
them, Eli Lilly’s PROZAC,
GlaxoSmithKline’s AUGMENTIN and
Akzo Nobel’s REMERON. Such loss of
protection often has a devastating effect on
sales and share price. Sales of Prozac fell 66
per cent following the loss of patent
protection and this shortfall led Eli Lilly to
reduce profit estimates three times in one
year.
It is clear that court decisions in the
USA, the UK and elsewhere in patent
litigation between pharmaceutical
innovators and generic companies can have
a substantial effect on share prices. This is
well illustrated by the case of PRILOSEC,
AstraZeneca’s ulcer drug. The patent on
the active ingredient in Prilosec,
omeprazole, expired in October 2001 in
the USA. The Supplementary Protection
Certificate protecting omeprazole in the
UK expired in April 2002. Prilosec, which
has annual global revenues of
approximately US$6bn a year, was widely
regarded as one of the best selling drugs in
the world. Following the expiry of patent
protection on omeprazole, AstraZeneca
sought to extend their period of
exclusivity and to keep generics off the
market using formulation patents for a
coating for an oral administration form of
Prilosec. Shares in AstraZeneca rose by 13
per cent, after a US court ruled that the
US formulation patents on the coating for
Prilosec were valid until 2007 and that
three of the four companies, which had
applied to sell generic versions of Prilosec,
were infringing these patents. The US
court found that the product of the fourth
company, Schwarz Pharma of Germany,
did not infringe these patents. Following
this ruling Schwarz Pharma’s shares soared
by 80 per cent. The unpredictability of
patent litigation however, is illustrated by
the fact that just 10 days later the UK
Court of Appeal found AstraZeneca’s UK
formulation patents for the coating on the
drug (known as Losec in the UK) to be
Henry Stewart Publications 1469–7025 (2003) Vol. 3, 3 226–238
invalid. As the UK accounted for only 4.3
per cent of worldwide sales of Losec, this
ruling did not have such a substantial effect
on AstraZeneca, but it still resulted in a
share price drop.
There is thus increasing pressure on
innovator pharmaceutical companies to
maximise the value obtained from each
product in view of the very high R&D
costs of pharmaceuticals. Development of
a ‘life cycle management’ strategy in
relation to successful products to ensure
that maximum value can be obtained has
therefore become increasingly important.
Life cycle management strategies
commonly include the tactical use of
patent litigation and the proactive strategic
use of the regulatory system. A key
element of any life cycle management
strategy however, is to extend patent
protection beyond the basic patent term
for as long as possible, by filing secondary
patents which are effective to keep generics
off the market.
This paper provides a brief consideration
of the different types of secondary patents
that may be available and considers the
approach taken by the courts to
enforcement of these types of patents. As
can be seen from the example given above
in relation to omeprazole, there may be
differences in the outcome of patent
litigation in different jurisdictions. Such
differences in outcome may result from a
number of factors including differences in
the substantive legislation (eg between the
UK and USA); differences in the
procedural requirements of each
jurisdiction; differences in the evidence put
before the courts in each jurisdiction and
differences in the approach of the courts to
interpretation of the relevant provisions of
the legislation.
This paper focuses primarily on recent
decisions of the UK courts and attempts to
draw some conclusions from the case law
as to the types of secondary patent that
may be enforceable in the UK and the
International Journal of Medical Marketing 227
Burdon and Sloper
implications of the case law for the
development of a credible life cycle
management strategy.
SECONDARY PATENTS
The process of converting a new chemical
entity into a marketable product involves a
great deal of research and investment.
During this research process, a number of
new and potentially patentable discoveries
may result. These discoveries may result in
‘secondary patents’, the aim of which is
generally to extend the period of patent
protection of the compound and therefore
extend the period of exclusivity during
which the product can be marketed free
from generic competition. Possible types
of secondary patent include:
. Composition patents
. Patents for new polymorphs
. Patents for new formulations
. Synthesis patents
. Patents for new therapeutic uses
. Patents for new treatment regimes
. Patents for metabolites/pro drugs.
As the aim in filing secondary patents is to
extend the period of exclusivity for the
product, such patents must be filed later
than the basic patents. This means that the
basic patent is generally prior art in
relation to the secondary patent. This may
give rise to difficulties in validity and
enforcement.
Set out below are summaries of some
recent decisions of the UK courts in
relation to some of the types of secondary
patents referred to above.
PATENTS FOR NEW
POLYMORPHS: SMITHKLINE
BEECHAM AND SEROXAT
There have been a number of cases
involving patents concerned with
SmithKline Beecham’s antidepressant
product paroxetine, which is marketed as
Seroxat in the UK (Paxil in the USA).
228 International Journal of Medical Marketing Vol. 3, 3 226–238
Seroxat is one of SmithKline Beecham’s
leading products.
Patent protection on the basic
compound paroxetine hydrochloride (for
which a Supplementary Protection
Certificate was obtained on the expiry of
the basic patent in the UK) expired in the
UK in January 1999. The patent in issue in
many of the recent disputes in the UK was
GB 2,297,550 which relates to the
anhydrous form of paroxetine
hydrochloride, its preparation and its use
as a therapeutic agent. The specification
described the invention as ‘paroxetine
hydrochloride anhydrate substantially free
of bound organic solvent’. SmithKline
Beecham’s Seroxat product is in fact
produced from a different form of
paroxetine hydrochloride, the
hemihydrate. Due to the existence of
patent protection on the hemihydrate and
other hydrated forms however, a number
of generic companies sought to develop
paroxetine hydrochloride products that
utilise the anhydrate form.
Set out below are summaries of some of
the recent decisions in this area.
SmithKline Beecham v Generics
(UK) Ltd (23rd October, 2001)
SmithKline Beecham applied for an
interim injunction restraining infringement
of GB 2,297,550 by Generics (UK). The
matter came before Mr Justice Jacob, who
granted the injunction. This case was
notable, as it was the first time that an
interim injunction had been granted in
patent proceedings in the UK for a
number of years and was therefore a
significant victory for the patentee.
In reaching his decision to grant an
interim injunction in that case, the judge
took into account the fact that the
defendant had known about the patent for
a long time and therefore could have taken
steps (by, eg applying for a declaration of
non-infringement, launching a petition to
revoke or inviting the claimant to sue) to
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 The art of using secondary patents to improve protection
clear its position prior to the intended
launch of its product. This decision places
a high burden on a generic company
planning to launch a product where that
company is aware of a competitor’s patent
and the possibility of infringement.
The proceedings between SmithKline
Beecham and Generics subsequently settled
before the matter came to a full trial.
BASF v SmithKline Beecham (12th
July, 2002)
BASF brought proceedings to revoke GB
2,297,550 on the grounds of anticipation
and/or obviousness. The main item of
prior art relied on was an earlier Beecham
Group patent application (the ‘407
application’), which was never published
by the UK Patent Office, but was
subsequently published in the files of a
later application (the ‘403 application’),
when that application was published by
the EPO.
The ‘407 application’ was concerned
with the preparation of crystalline
paroxetine hydrochloride. It describes the
production of three polymorphic forms:
the hemihydrate, the anhydrate and
paroxetine hydrochloride isopropanol
solvate. A method of preparation of the
anhydrate form is described. BASF alleged
that the patent was invalid for anticipation
and/or obviousness in relation to the ‘407
patent’.
Issues of construction arose in relation to
the meaning of the phrase ‘substantially
free of bound organic solvent’. The
specification sought to define this as ‘less
than the amount of propan-2-ol that
would remain solvated, ie bound, within
the crystal lattice of the product under
conventional vacuum oven drying
conditions’. The judge stated that he found
this issue of construction very difficult to
decide, but he concluded that this passage
was to be read as relating to any relevant
organic solvent or solvents, rather than
merely to propan-2-ol.
Henry Stewart Publications 1469–7025 (2003) Vol. 3, 3 226–238
The evidence showed that although at
the time the ‘407 application was prepared
it appeared that it was possible to produce
the anhydrate by following the method set
out in this application, subsequently (and
prior to the priority date of the patent) it
became impossible to reproduce the
teaching of the ‘407 application to produce
the anhydrate form. The judge found that
the experiments performed by the parties
in the course of the litigation failed to
establish that the anhydrate form could be
produced by this method. The result of
following the teaching of the ‘407 patent
was that a hydrated form of paroxetine
hydrochloride was produced. The court
held that the claim to paroxetine
hydrochloride substantially free of bound
organic solvent was therefore not
anticipated over the ‘407 patent.
Some, but not all, of the process claims
however, were found to be invalid on the
ground of obviousness. The judge stated
that the product claims would have to be
limited to the products of the valid process
claims.
Following this judgment, SmithKline
Beecham applied to amend the patent. The
amendment proceedings are continuing
and are due to be heard in July 2003. In
addition, both parties have appealed the
judgment. The appeal is due to be heard in
May 2003.
SmithKline Beecham v Apotex &
others (28th November, 2002)
Following their successful application for
an interim injunction against Generics in
October 2001, SmithKline Beecham
applied for a further interim injunction
restraining infringement of GB 2,297,550
by Apotex and others. The matter came
before Mr Justice Jacob in November
2002. By this date, the patent had been
held only partially valid by the decision of
Mr Justice Pumfrey in the action against
BASF in July 2002. The claim that
SmithKline Beecham sought to enforce
International Journal of Medical Marketing 229
Burdon and Sloper
against Apotex, Claim 11, however, was
one of the claims that had been held valid
by Mr Justice Pumfrey. SmithKline
Beecham argued that the defendants’
process infringed this claim and that an
interim injunction should be granted
restraining infringement pending trial.
The defendants argued that the judge
should not grant an injunction. They
raised a number of points. They stated that
their product did not infringe the claim;
that since the claimants were not
exploiting the patent (as their product in
fact involved the hemihydrate and not the
anhydrate form) they should not be
entitled to damages and therefore no
injunction should be granted; that since the
patent had been found only partially valid
and therefore required amendment, no
injunction should be granted; and that
damages would be an adequate remedy to
SmithKline Beecham, should infringement
be established at trial.
The judge rejected the defendants’
arguments, considering that it was
appropriate to grant an interim injunction
in all the circumstances. He reiterated his
comments in the earlier case against
Generics that the generic company should
take steps to clear its position prior to
launch of its product, stating that:
‘Where litigation is bound to ensue if the
defendant introduces his product he can avoid all
the problems of an interlocutory injunction if he
clears the way first. That is what the procedures
for revocation and declaration of non-
infringement are for’.
SmithKline Beecham v Apotex &
others (4th February, 2003)
This dispute came back before the court
on a matter relating to confidentiality of
test results and whether the results of tests
which had been conducted for the
purposes of the UK proceedings could be
disclosed or used outside those
proceedings.
230 International Journal of Medical Marketing Vol. 3, 3 226–238
SmithKline Beecham had asked the
defendants for samples of their product to
enable them to ascertain whether or not
they infringed the patent. The defendants
agreed to provide samples but wanted
access to the samples and the results of the
tests controlled by certain confidentiality
undertakings. SmithKline Beecham
objected to the draft undertakings because
they imposed restrictions on SmithKline
Beecham but allowed the defendants to
use the test results in any way they chose.
The undertakings were amended, but it
became apparent that the defendants
thought they could use the test results
provided for the purpose of these
proceedings by the claimants, in any way
they chose. The defendants submitted that
if the test results proved to be unhelpful to
them, then they could restrain SmithKline
Beecham from making use of the samples
or results outside the proceedings, but that
the defendants could use them in any way
they chose.
The court held that CPR Part 31.22
applied once the proceedings had
commenced. This rule states that a party to
whom a document has been disclosed may
use the document only for the purpose of
the proceedings in which it is disclosed,
except where — (1) the document has
been read to or by the court, or referred
to, at a hearing which has been held in
public, (2) the court gives permission, or
(3) the party who disclosed the document
and the person to whom the document
belongs agree.
SmithKline Beecham had submitted that
if the test results fell outside CPR 31.22,
then they could be used in the current US
proceedings, although they were generated
solely for the purpose of the UK
proceedings. The court held that the test
results came within CPR 31.22 and should
not be disclosed outside the UK
proceedings except where the parties
agreed or by order of the court.
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 The art of using secondary patents to improve protection
Synthon BV v SmithKline Beecham
(19th June, 2002; 31st July, 2002; 3rd
December, 2002)
Synthon brought an action for revocation
in relation to a further patent owned by
SmithKline Beecham relating to
paroxetine, GB 2,336,364. This patent
relates to paroxetine methansulphonate in
crystalline form.
Synthon had filed a patent application in
relation to paroxetine methansulphonate in
June 1997, prior to the priority date of
SmithKline Beecham’s patent in July 1998.
Synthon’s patent application was
unpublished at the priority date of
SmithKline Beecham’s patent. Under
section 2(3) of the Patents Act 1977
Synthon’s patent application was therefore
deemed to be prior art for the purposes of
a novelty attack but not for the purposes
of obviousness.
The Synthon patent application
described paroxetine methansulphonate, a
method of making it and an IR spectrum
characterising it. The main claim of
SmithKline Beecham’s patent was as
follows:
‘Paroxetine methansulphonate in crystalline form
having inter alia the following characteristic IR
peaks [list] and/or the following XRD peaks
[list]’
The key difficulty for Synthon was that
the product described in the Synthon
patent application had a different IR
spectrum to that set out in the SmithKline
Beecham patent. Synthon claimed that the
patent was anticipated by their prior
application. SmithKline Beecham argued
that Synthon had identified a different
polymorph since a different IR spectrum
was obtained. Synthon alleged that the IR
spectrum set out in their patent application
was erroneous and that if the method set
out in the patent application was repeated
the IR spectrums obtained would be those
set out in SmithKline Beecham’s patent.
Henry Stewart Publications 1469–7025 (2003) Vol. 3, 3 226–238
Their argument was in essence that there
was ‘only one paroxetine
methanesulphonate’, as the judge put it
and that this was disclosed by their prior
application.
Synthon made an application to the
court in June 2002 to determine the
admissibility of experiments carried out to
establish that following the method set out
in Synthon’s patent application would
produce a product having exactly the same
characteristics as those disclosed in the
patent in suit. SmithKline Beecham argued
that the results of these experiments were
irrelevant since the ‘inevitable result’ test
for anticipation could not apply where the
prior art was an unpublished patent
application which only constituted prior
art under the provisions of section 2(3).
They stated that in these circumstances the
application could only be novelty
destroying if this was clear on the face of
the application. The judge dismissed
SmithKline Beecham’s argument, stating
that it would be bizarre if there were two
sorts of novelty, one for actually prior
published applications and one for deemed
prior published applications. If the
inevitable result of using the process
described in Synthon’s application was a
product within the claims of the patent in
suit then experiments proving this were
both relevant and admissible. The matter
was appealed to the Court of Appeal, who
agreed with the judge. The experimental
evidence was therefore admitted.
The matter came to trial in October
2002 and judgment was given by Mr
Justice Jacob on 3rd December, 2002. The
judge found on a balance of probabilities
that Synthon was correct that there was
only one crystalline form of paroxetine
methansulphonate. He found on the
evidence that the Synthon experiment was
not repeatable. He considered however,
that if SmithKline Beecham’s patent
enabled crystals to be made in all the ways
it taught, so did Synthon’s patent
International Journal of Medical Marketing 231
Burdon and Sloper
application. Synthon’s patent application
was a general disclosure of a wide variety
of methods of making crystalline
paroxetine methansulphonate. SmithKline
Beecham’s later disclosure was an
equivalent wide disclosure. All that could
be said for SmithKline Beecham was that
the disclosure in their patent was to a
readier way of making the crystals, but the
disclosure in Synthon’s application was
clear enough and amounted to an
anticipation.
It was Synthon that first invented
paroxetine methansulphonate, including
the crystals of the SmithKline Beecham
form and Synthon gave enough
information as to how to make this
substance. The patent was therefore held
invalid and revoked.
FORMULATION PATENTS:
CAIRNSTORES LTD &
GENERICS (UK) LTD v
AKTIEBOLAGET HASSLE (6th
MARCH, 2002; 22nd OCTOBER,
2002) (OMEPRAZOLE)
The principal patent in issue in this case
concerned a formulation of an oral
preparation containing the drug
omeprazole, which inhibits the secretion of
acid in the stomach and is used in the
treatment of gastric ulcers. The basic
patent for omeprazole had expired but was
the subject of a Supplementary Protection
Certificate, which would expire in April
2002. Omeprazole is very sensitive to and
can be degraded by acid and therefore had
to be in a form which protected it during
its passage through the stomach, but which
allowed it to be released in the intestine.
The invention was a way of orally
administering the drug, which was
resistant to stomach acid but was
bioavailable in the intestines. The solution
to this problem in the patent had three
parts; the use of a separating layer, which
was water soluble or dispersible and the
232 International Journal of Medical Marketing Vol. 3, 3 226–238
use of alkali or alkaline salts in the
omeprazole core. The claimants applied to
revoke the patent on the basis of common
general knowledge and prior art.
Mr Justice Laddie held the patent should
be revoked on the following grounds:
1 The possibility of chemical interaction
between a new drug and each of the
excipients contemplated for use in the
dosage form, including the coating
material, would have been recognised
by the skilled formulator.
Compatibility tests would have been
carried out as a matter of course,
which would have shown
incompatibility between the
omeprazole and the coating material.
2 A soluble intermediate layer or coat
would have been expected to work by
the notional skilled man, or to be
sufficiently likely to work to warrant
trial. There was nothing that would
have deterred him from trying such a
separating layer. Therefore Claim 1
and all the remaining claims failed for
obviousness and the prior art (various
technical leaflets/books) relied on by
the claimants also rendered the claim
invalid for obviousness.
The defendant appealed to the Court of
Appeal. The main ground of appeal was
the judge’s conduct. The defendant alleged
that the conduct of the judge during the
cross examination of the defendant’s expert
had been such as to render the trial unfair.
In his judgment, the judge had rejected
much of this expert’s evidence and stated
that he had acted more as an advocate than
as an expert for the defendant and that his
evidence had become increasingly
unconvincing during the course of cross
examination. The Court of Appeal noted
that some of the questions asked by the
judge could be seen as not directed to
clarifying or amplifying an answer
previously given, but found that there was
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 The art of using secondary patents to improve protection
no doubt that when considered in context,
the judge’s part in the trial as a whole
could not be seen as such to render the
trial unfair. The appeal was dismissed.
SYNTHESIS PATENTS:
GENERICS BV v SMITH KLINE &
FRENCH LABORATORIES LTD
(EUROPEAN COURT OF
JUSTICE, 9th JULY, 1997)
(TAGAMET)
This decision of the European Court of
Justice is significant in that it was the first
decision to confirm that remedies for
patent infringement may extend beyond
the life of the patent itself. In this case the
ECJ confirmed that a post expiry
injunction did not amount to an unlawful
restraint of trade. The principle of this
decision was followed in the UK in the
case of Dyson v Hoover in 2001 where the
judge awarded a post-expiry injunction
against Hoover.
On 19th June, 1991, following an
application submitted on 4th September,
1973, SKF was granted a Netherlands
patent in respect of a manufacturing
process for a pharmaceutical preparation
having the generic name ‘cimetidine’,
which it marketed in the Netherlands
under the brand name ‘Tagamet’. That
patent expired on 4th September, 1993.
In October 1987 and October 1989,
Genfarma BV (‘Genfarma’) filed three
applications with the assessment board for
medicinal products (‘the CBG’) to register
200 mg, 400 mg and 800 mg cimetidine
tablets. Samples of those preparations were
submitted to the CBG with the
applications. Genfarma was granted
registration in January 1990 in respect of
the first two applications and in December
1992 in respect of the third. Genfarma
subsequently transferred those registrations
to Generics and, in June 1993, they were
entered under Generics’ name in the
register of pharmaceutical preparations.
Henry Stewart Publications 1469–7025 (2003) Vol. 3, 3 226–238
In August 1993, SKF applied to the
Dutch court for an injunction restraining
Generics, until November 1994, from
offering or supplying cimetidine on the
Netherlands market or transferring to
third parties the registrations relating to
that product.
SKF considered that the submission of
the samples of cimetidine preparation to
the CBG constituted an infringement of its
patent under Dutch law. In particular,
SKF referred to the judgment delivered by
the Supreme Court in Medicopharma v ICI,
in which it was held that submission to the
CBG of samples of a medicinal product
manufactured in accordance with a
patented process, by a person other than
the patentee, with a view to placing the
product on the market after the expiry of
the patent, was not covered by the
exemption in Article 30(3) of the relevant
Dutch law. That paragraph provides: ‘The
exclusive right does not extend to acts
undertaken solely for the purposes of an
examination of the patented object, which
must be taken to include a product directly
obtained by means of the application of
the patented process.’
SKF took the view, therefore, that
Generics could not have applied for the
registrations until after the expiry of the
patent on 4th September, 1993 and that
given the duration of the registration
procedure in the Netherlands, it would not
have obtained them for another 14
months. They therefore asked for the
injunction to be extended to 5th
November, 1994.
The Dutch courts referred to the ECJ
for a ruling as to whether the post-patent
expiry injunction constitutes a measure
which is prohibited by Article 30 of the
EC Treaty and which is not covered by
the exception contained in Article 36 of
the EC Treaty, as being a barrier to intra-
community trade.
The ECJ approved the decision of the
Dutch courts to grant the injunction,
International Journal of Medical Marketing 233
Burdon and Sloper
stating that if Generics had respected SKF’s
patent, they could not have submitted the
cimetidine samples until after the patent
expired. SKF would therefore have been
able to continue marketing its product
without competition from the generic
product for the period required to obtain
the marketing authorisation. The relief
imposed by the court, in so far as it sought
to place SKF in the position in which it
would have been in had its rights been
respected, could not be disproportionate.
NEW THERAPEUTIC USES
Article 52(4) of the European Patent
Convention states that methods of
treatment of the human or animal body by
surgery or therapy or diagnostic methods
practised on the human or animal body
shall not be regarded as inventions which
are susceptible of industrial application and
therefore shall not be patentable. This
provision however, goes on to state that
this exception does not apply to products,
in particular substances or compositions,
for use in any of these methods.
Article 54(5) in effect provides that first
medical uses of substances or compositions
will be patentable. This section states that
the use of a known compound for a
method of treatment may be patentable if
the use itself does not form part of the
state of the art. Novelty resides in the use
itself. Article 54(5) however, effectively
precludes a claim to a substance or
composition characterised by a medical
application if that product has already been
described for another medical use (‘further
medical use’ or ‘second medical use’
claims). The question therefore arose as to
whether such second (or subsequent)
medical use claims could be patentable in
any circumstances or whether this article
precluded the patentability of such claims.
In the EISAI case in 1985 (G 5/83) the
Enlarged Board of Appeal of the EPO
held that second medical use claims were
patentable. This decision was subsequently
234 International Journal of Medical Marketing Vol. 3, 3 226–238
followed by the English courts in Wyeth
& Schering’s Applications [1985] RPC
545. Novelty was held to reside in the new
second (or subsequent) use.
In order to claim an invention which
involves second or subsequent medical use
of a known substance or composition, it
has been necessary for the claims to be
expressed in a form known as ‘Swiss-type’
claims (because the EPO in EISAI
followed a precedent first set by the Swiss
Patent Office). ‘Swiss-type’ claims are
those directed to the use of a substance or
composition for the manufacture of a
medicament for a specified new and
inventive therapeutic application, ie ‘Use
of X for the manufacture of a medicament
for the treatment of Y’.
Article 54(5) is due to be amended
following the Diplomatic Conference held
in November 2000 at the EPO. The
amended article will specifically allow for
claims to second and further medical uses
of known substances or compositions and
therefore avoid the need for such claims to
be expressed as ‘Swiss-type’ claims.
Set out below are several recent cases
concerning claims to second medical uses.
Lilly ICOS v Pfizer (23rd January,
2002) (VIAGRA)
One of the most high profile cases
concerned the patent dispute between
Pfizer and Lilly ICOS in relation to
Pfizer’s second medical use patent covering
Viagra (sildenafil citrate).
In 1991 and 1992 Pfizer patented a series
of compounds, which exhibited selective
inhibition of phosphodiesterases (‘PDEs’).
The patented compounds included
sildenafil citrate. The patents stated that
these compounds were useful in the
treatment of angina and hypertension.
In 1992 and 1993 several research articles
were published, which suggested that an
inhibitor of PDEs would be useful in the
treatment of impotence and male erectile
dysfunction (MED).
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 The art of using secondary patents to improve protection
Pfizer applied for the patent in suit in
June 1994. This patent covered
substantially the same compounds,
including sildenafil citrate, which had been
patented in 1991 and 1992, but this time
claimed that the invention was the use of
those products as a treatment for
impotence and MED. The specification of
the patent stated that the compounds had
‘unexpectedly’ been found to operate as
inhibitors of PDEs and had the added
advantage of being capable of being
administered orally, thereby removing the
disadvantages associated with the common
treatments for impotence and MED,
which were administered by injection. The
main claim was drafted in the Swiss form.
The matter came before Mr Justice
Laddie in November 2000. Lilly ICOS
argued that the patent was invalid for
obviousness in view of the 1992–1993
articles. Pfizer argued that these articles did
not suggest the use of PDE inhibitors as an
oral treatment for impotence and that the
patent was inventive in this respect. The
judge found that the only difference
between the prior art and the claims in the
patent was the suggestion of oral use. He
held that this did not constitute an
invention. The patent was invalid for
obviousness and should therefore be
revoked. Pfizer appealed.
The Court of Appeal dismissed the
appeal. They held that the judge had
rightly held the patent to be invalid for
obviousness. Anyone reading the prior art
would have realised that PDE inhibitors
were likely to be effective in the treatment
of impotence and MED. There was
nothing inventive in trying them out for
that purpose. The Court of Appeal
rejected the argument that the judge’s
conclusion had been arrived at as a result
of hindsight reasoning, which was unfair
to inventors. The also found that while
there were reasons for doubting the ability
to administer orally a drug to treat MED,
this did not mean that it was inventive to
Henry Stewart Publications 1469–7025 (2003) Vol. 3, 3 226–238
decide to do so. Oral was the obvious
route of administration and there was
nothing in the specification that suggested
there was any difficulty to be overcome to
adapt the compound for oral use. If it was
obvious to try, success was within the
reach of the skilled person carrying out
routine procedures.
AHP v Novartis (27th July, 2000)
(RAPAMYCIN)
This case concerned a patent for the use of
rapamycin for inhibiting transplant
rejection in mammals. Rapamycin was a
known compound also known at the
priority date of the patent, to be useful as
an immunosuppressant. The patent claimed
a second medical use of rapamycin, namely
its use in the prevention of transplant
rejection. Claim 1 was drafted in Swiss
form as follows: ‘Use of rapamycin for the
preparation of a medicament for inhibiting
organ or tissue transplant rejection in a
mammal in need thereof’. Derivatives and
prodrugs of rapamycin were mentioned in
the title of the patent and in the
specification, but not in the claims.
Novartis’ alleged infringing product was
an immunosuppressant known as SDZ
RAD, a derivative of rapamycin. AHP
claimed that the patent covered the use of
rapamycin and derivatives of rapamycin,
which exhibited the same
immunosuppressive effect as rapamycin,
including SDZ RAD. Novartis contended
that the patent covered the use of the
compound rapamycin only and therefore
SDZ RAD did not infringe.
At the first instance hearing Mr Justice
Laddie concluded that the person skilled in
the art would understand the scope of the
patent to include such derivatives of
rapamycin as exhibited the same type of
inhibition to organ rejection as rapamycin
itself did. He therefore concluded that
Novartis’ product infringed the patent.
The Court of Appeal overturned Mr
Justice Laddie’s judgment. They concluded
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Burdon and Sloper
that the scope of protection of the patent
was limited to the use of rapamycin alone
and therefore there was no infringement.
They found that if Claim 1 had the
broader scope contended for by AHP,
then the specification would have been
insufficient, since to be sufficient the claim
must be enabled over its entire scope and
the skilled person should not be expected
to carry out research to ascertain how the
invention is to be performed. For the
patent to cover derivatives of rapamycin,
it would need to disclose how to perform
the invention with such derivatives.
Although the patent gave a starting point,
the skilled man was left to ascertain by
research which derivatives worked; an
enormous task since these derivatives
would need to be conceived, produced and
tested for their effect in the inhibition of
transplant rejection. The Court of Appeal
therefore concluded that the patent was
valid but not infringed.
Note that this case was slightly unusual
in that the parties had agreed between them
that the issues of infringement and
sufficiency should be heard separately from
the issues of novelty and obviousness. The
above decisions related to the case on
infringement and sufficiency only, the issues
of novelty and obviousness to be heard at a
later date. The parties subsequently settled
their dispute before the trial on novelty and
obviousness took place.
As is often the case with patent disputes,
parallel proceedings were also ongoing in
Germany and the Netherlands. The
District Court of the Hague on 29th
March, 2000 came to the same view later
reached by the English Court of Appeal in
this case, ie that the scope of the patent
was limited to the use of the compound
rapamycin itself and that Novartis’
derivative therefore did not infringe.
NEW TREATMENT REGIMES
As stated above in the discussion on second
medical use patents, Article 52(4) of the
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European Patent Convention excludes
methods of treatment of the human or
animal body by surgery or therapy or
diagnostic methods from patentability.
There are therefore difficulties in trying to
obtain a valid patent for new treatment
regimes in Europe. As can be seen from
the summaries set out below, the current
position in the UK is that claims to new
treatment regimes are likely to be seen as
claims to methods of treatment and
therefore unpatentable. In the case of Teva
v Merck, however, the judge expressed
some reservations as to whether this is in
fact the correct approach to take. It will be
interesting to see whether the Court of
Appeal follow their reasoning in Bristol
Myers Squibb v Baker Norton when this
question next comes before that Court.
Bristol Myers Squibb v Baker Norton
(23rd May, 2000) (TAXOL)
This case concerned Bristol Myers
Squibb’s taxol product, which is used in
the treatment of cancers, particularly breast
cancer and ovarian cancer. Taxol was a
natural product, which was known to
have anti-tumour activity prior to the
priority date of the patent. The use of
taxol however, was limited by its side-
effects, in particular neutropenia, a
reduction in the white blood cell count.
Bristol Myers Squibb filed a UK patent
in 1993 for the ‘use of taxol . . . for
manufacturing a medicament . . . for the
administration of 135–175 mg/m2 taxol
over a period of about 3 hours or less, as a
means of treating cancer and
simultaneously reducing neutropenia’.
Baker Norton contended that the patent
was invalid for lack of novelty and/or
inventive step, since the prior art had
suggested that taxol may be administered
over 3 hours (although the reduction in
neutropenia that might result from such
administration had not been explicitly
stated). They also alleged that the claim,
although drafted in Swiss form, was really
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 The art of using secondary patents to improve protection
a ‘method of treatment’ claim in disguise
and as such was unpatentable due to the
provisions of Article 52(4) EPC and the
corresponding provisions in the UK
Patents Act 1977 (s.4(2)).
The Court of Appeal upheld the view
of the High Court that the claim was in
effect a claim to a ‘method of treatment’
and therefore unpatentable, since the claim
to the use of taxol in a new treatment
regime did not disclose any new
therapeutic method. Following the EISAI
decision the Court of Appeal considered
that Swiss form claims were only valid
where they related to second or further
medical uses and the disclosure of a new
treatment regime as set out in this case did
not constitute a second or further medical
use. They also found that the claim in any
event lacked novelty since the inevitable
result of following the teaching in the
prior art was a reduction in neutropenia.
Teva Pharmaceutical Industries Ltd v
Merck & others (21st January, 2003)
(ALENDRONATE)
This case involved an application by three
drug companies for revocation of two
patents owned by Merck. Both patents
concerned a pharmaceutically active
compound called alendronate, a
biphosphonate. Alendronate is capable of
inhibiting bone resorption and as such can
be used to treat bone diseases such as
osteoporosis.
The first patent, which had a priority
date of 1982, claimed a pharmaceutical
composition containing as its active
ingredient alendronate or its salt with an
acceptable carrier or diluent. The patent
stated that the invention related especially
to pharmaceutical compositions suitable
for the treatment of urolithiasis and
capable of inhibiting bone resorption. A
number of matters were agreed to be
common general knowledge. These
included the fact that there was widespread
interest in the clinical use of
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biphosphonates to treat disorders of excess
bone destruction and that the oral
administration of three biphosphonates
(etidronate, clodronate and pamidronate)
had been shown to be clinically effective in
treating several medical disorders of excess
bone destruction, but that these
compounds had different efficacies and
there was room for a better therapy.
The claimants alleged that the patent
was invalid for lack of novelty, or
alternatively obviousness by reason of
‘Blum’, which was a process patent for
making alendronate suitable for
pharmaceutical preparations. They also
contended that the patent was invalid for
obviousness over ‘Kabatchnick’, which was
similar to Blum and detailed how to make
alendronic acid; and ‘Fleisch’, which
reviewed the history and mechanisms of
action of bisphosphonates and predicted
that further exploration of other types of
bisphosphonates could lead to fruitful
future development of the compounds.
The judge found that a skilled man, being
aware of the bisphosphonate pamidronate
and its efficacy in the treatment of medical
disorders of excess bone destruction,
would naturally read Blum as a proposal
to use alendronate as the active ingredient
in a pharmaceutical. The patent was
therefore invalid for lack of novelty and
obviousness over Blum. The patent was
also obvious over Kabatchnick, which
detailed how to make alendronic acid, as it
was common general knowledge that the
bisphosphonates had clinical uses.
Alendronate was also an obvious
compound to try after Fleisch. There
would be a high expectation of biological
activity and a very good chance of
increased activity over pamidronate.
The second patent had a priority date of
1997. Merck were seeking to amend this
patent to claim a new regime for
administering the drug to treat
osteoporosis. This involved the
administration of a 70 mg dose once
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Burdon and Sloper
weekly. The previous treatment regime
was 10 mg per day to be taken in a
particular manner, which led to problems
with GI disturbance and also problems in
compliance. The claimants argued that this
was a claim to a method of treatment of
the human body by therapy and therefore
incapable of industrial application under
section 4(2) of the Patents Act 1977. They
also alleged the patent lacked novelty and
was obvious over the prior art.
The judge considered that the inventive
concept of the patent was the preparation
of a medicament, which could be used in a
70 mg dosing regime. He stated that, but
for the Court of Appeal’s decision in
Bristol Myers Squibb v Baker Norton he
would not have held this to be a claim to a
method of treatment since the monopoly
covered the preparation of the dose to be
administered but not its actual
administration. Following the principle set
out in that case however, he considered
that he had no choice but to find this to be
a claim for a method of treatment and
therefore unpatentable. He also found the
second patent to lack novelty and to be
obvious in the light of the prior art.
CONCLUSIONS
It is clear from a consideration of the above
cases that secondary patents can be useful in
extending patent protection in certain cases.
Although it has often proved difficult to
maintain the validity of such patents before
the UK courts it is by no means impossible
and there have been some significant
victories for patentees in the UK courts in
cases involving secondary patents in recent
years. The use by SmithKline Beecham of
its secondary patents relating to Seroxat to
obtain interlocutory injunctions to keep
generics off the market in the SmithKline
Beecham v Generics and SmithKline Beecham
v Apotex cases described above, was
particularly significant.
It is clear that patents for novel
polymorphs may be valid and enforceable
238 International Journal of Medical Marketing Vol. 3, 3 226–238
and can be very useful in certain cases. The
Synthon case highlights the need to
consider carefully how much detail to
include in the specification, in order to
adequately characterise the novel
polymorph. In that case it was the
inclusion of the IR spectra in Synthon’s
earlier application which caused them
difficulties in establishing that this
application anticipated SmithKline
Beecham’s later application, although they
were ultimately successful in proving
anticipation at the trial.
In general it has proved difficult to
maintain the validity of formulation
patents before the courts. These patents
however, can be useful provided validity
can be shown and the new formulation is
an improvement over existing
formulations (otherwise the generics may
simply develop generic versions of older
formulations on which patent protection
has expired).
Second and subsequent medical uses of
compounds may also be patentable,
provided that the new use is sufficiently
novel in relation to the known medical
use(s). Claims to new treatment regimes
however, should be used with caution
since the current approach in the UK is
that such claims will generally be
considered to be claims to a method of
treatment and therefore excluded from
patentability under the provisions of the
EPC (and the corresponding provisions in
the Patents Act 1977).
Even where the final outcome of
proceedings is that the patent is held
invalid, the effect of the litigation will
have been to delay the generics’ entry to
the market. Fighting the litigation may
also have ‘warned off’ other generic
competition. In any event, for a successful
product, the benefit of even a short time
of additional proprietary sales may easily
outweigh the costs of patent litigation.
# Olswang
Henry Stewart Publications 1469–7025 (2003)