BAILII is celebrating 24 years of free online access to the law! Would you
consider making a contribution?
No donation is too small. If every visitor before 31 December gives just £1, it
will have a significant impact on BAILII's ability to continue providing free
access to the law.
Thank you very much for your support!
[New search]
[Printable RTF version]
[Help]
Case No: 98/1390/A3, 98/7637/A3
IN THE SUPREME COURT OF JUDICATURE
COURT OF APPEAL (CIVIL DIVISION)
ON APPEAL FROM CHANCERY DIVISION
MR JUSTICE JACOB
Royal Courts of Justice
Strand, London, WC2A 2LL
Tuesday 23rd May 2000
B e f o r e :
LORD JUSTICE ALDOUS
LORD JUSTICE BUXTON
and
MR JUSTICE HOLMAN
|
Bristol-Myers
Squibb Company
|
Plaintiff/Appellant
|
|
v
|
|
|
(1) Baker Norton Pharmaceuticals Inc
(2) Napro Biotherapeutics Inc
__________________________________
(Transcript of the Handed Down Judgment of
Smith Bernal Reporting Limited, 180 Fleet Street
London EC4A 2HD
Tel No: 0171 421 4040, Fax No: 0171 831 8838
Official Shorthand Writers to the Court)
__________________________________
|
Defendants/
Respondents
|
Andrew
Waugh QC and Justin Turner (instructed by Simmons and Simmons for the
Appellant)
Simon Thorley QC and Henry Whittle (instructed by Roiter Zucker for the
First Respondent)
Simon Thorley QC and Roger Wyand QC (instructed by Bird & Bird for
the Second Respondent)
__________________________________
Judgment
As Approved by the Court
Crown Copyright ©
LORD JUSTICE ALDOUS:
1. Bristol-Myers Squibb Company are the patentees of EP (UK) 0584001. They
appeal against the order and judgment of Jacob J of 20th August 1998 whereby he
held that the patent was invalid and ordered its revocation. The respondents,
Baker Norton Pharmaceuticals Inc and Napro Biotherapeutics Inc support the
conclusion reached by the judge.
2. The patent claims priority from a patent application filed in the USA on
3rd August 1992. It is entitled "Use of taxol for the manufacture of a
medicament for the treatment of cancer".
3. Taxol is the trade mark of the appellants, but I will use it in this
judgment instead of the generic name, paclitaxel. Taxol was not new in 1992.
It was identified in 1962 as part of a screening programme for anti-tumour
agents initiated by the US National Cancer Institute (NCI). Its active agent
was first isolated in 1971 from the bark of the Pacific Yew and at about the
same time it was shown to have anti-tumour activity in mice. Further work was
hampered because of difficulties with procurement, extraction and isolation,
but those difficulties have now to a substantial extent been overcome by the
development of semi-synthetic routes of manufacture. Taxol is poorly soluble,
partly for that reason it was not at first possible to devise a formulation.
That was overcome in 1980 and that enabled animal studies to be carried out.
By 1983 the NCI were in a position to apply for regulatory permission to try
the drug in humans. Initial trials, known as the Phase 1 trials, were started
in 1984. Problems soon emerged. In the words of Dr Canetta of the
Pharmaceutical Research Division of the appellants:
"During the initial days of the clinical development of paclitaxel severe
hypersensitivity reactions to paclitaxel occurred in many patients. After
receiving just a few milligrams of paclitaxel, these patients started
developing an acute reaction, including skin rash, shortness of breath,
reduction of blood pressure and cardiac rhythm abnormalities, forcing
interruption of the paclitaxel infusion."
4. The judge described how the trials progressed in this way:
"As a result the NCI (who at the time were supplying the taxol) required all
Phase I trials to have an infusion time of 24 hours initially (coming down to a
minimum of six hours if there was no adverse reaction) and the use of
premedication. The idea was to minimise the danger of toxic shock. The slower
infusion rate meant that the body was not exposed to the taxol as quickly as in
the case of shorter infusion times and the use of premedication likewise
reduced the danger of shock. It was not known at the time what caused the shock
- the taxol or the solvent (Cremophor) or both. Premedication was a well-known
technique. Having used slower infusion and premedication together, when it
later proved that allergic reactions were becoming much less of a problem, it
was not clear whether this was due to the premedication, or the prolonged
infusion or a combination of the two. None of this mattered at the time. The
heart of the trials was to see whether taxol really worked - particularly in
refractory cases. Avoiding allergic reaction by using both slow infusion and
premedication enabled this to be done.
Thus it was that taxol entered Phase II trials to discover what tumour types it
affected. The NCI concentrated upon ovarian cancer and malignant melanoma
particularly, but the melanoma studies gave results not as positive as had been
hoped. By 1989 out of all the studies then conducted (15 in all) only 427
patients had been treated. It was apparent that the NCI could not go it alone.
So it sought a commercial partner. It did so by a competition for a
Collaborative Research and Development Agreement. Notice of the competition was
given in August 1989. The selected partner was to have exclusive rights to NCI
data and would have to provide taxol and fund further clinical trials leading
to an application for regulatory permission. Twenty companies were interested,
four were interested enough to enter the competition and it was BMS which was
successful in January 1991. BMS tackled the problem of supplies and undertook
responsibility for all the trials outside the U.S. including in particular the
Canadian/European study early results from which led to the patent in suit.
This was called the "OV.9" study."
5. The initial stages of the OV.9 study were described in a lecture by Dr
Winograd the director of research and development of the appellants. That
lecture was relied on by the respondents as the public disclosure which
invalidated the patent. It was given at a major symposium in Amsterdam to an
audience estimated at five hundred. It will be necessary to consider the
extent of disclosure made in this lecture, but at this stage of my judgment it
is sufficient to outline what was said. Dr Winograd described the object and
design of the study which was to evaluate the efficacy and safety of taxol in
patients with ovarian cancer which had previously been treated with platinum
containing chemotherapy. He described how the Phase III studies had involved
comparison of a 24 hour continuous infusion which had been used for the Phase
II trials with a short time, 3 hour, continuous infusion using two different
dosages.
6. As was recounted by the judge, taxol interferes with cell division
(mitosis). The idea behind its use is to stop the cancer cells replicating
which they do rapidly. However it was well-known that other normal body cells
also replicate rapidly, in particular bone marrow cells. Bone marrow
suppression is therefore an inevitable consequence of treating the body with
chemotheraputic agents that target rapidly dividing cells. A fall in the white
cell count with the consequent reduction of the blood neutrophil count is known
as neutropenia. It follows that neutropenia is one of a number of undesired,
but inevitable, side effects of most forms of chemotherapy. It requires the
patient's blood to be regularly monitored to assess the degree of neutropenia
which can be dangerous for obvious reasons. Since the mechanism of
chemotherapeutic drugs on the cancer cells and the bone marrow is the same,
there was a general expectation in the 1980's that the degree of neutropenia
and the degree of the effect on the cancer cells went hand-in-hand. The
consequence of that was that those strategies that maximised tumour treatment
were also thought to increase myelosuppression.
The Patent
7. The invention of the patent is directed to the use of products containing
taxol for cancer therapy and "more particularly is directed to improvements in
the use of taxol in the treatment of cancer". The specification describes the
background to the invention. It states:
"Taxol is a naturally occurring compound which has shown great promise as an
anti-cancer drug. For example, taxol has been found to be an active agent
against drug-refractory ovarian cancer by McGuire et al. ....
Unfortunately, taxol has extremely low solubility in water, which makes it
difficult to provide a suitable dosage form. In fact, in Phase I clinical
trials, severe allergic reactions were caused by the emulsifiers administered
in conjunction with taxol to compensate for taxol's low water solubility; at
least one patient's death was caused by an allergic reaction induced by the
emulsifiers. Dose limiting toxicities include neutropenia, peripheral
neuropathy, and hypersensitivity reactions."
8. The specification then goes on to discuss the prior published documents
concerning the use of taxol. It continues in this way:
"The conflicting recommendations in the prior art concerning whether
premedication should be used to avoid hyper-sensitivity reactions when using
prolonged infusion durations, and the lack of efficacy data for infusions done
over a six hour period has led to the use of a 24-hour infusion of high doses
(above 170 mg/m2) of taxol in a Cremophor EL emulsion as an accepted
cancer treatment protocol.
Although it appears possible to minimise the side effects of administering
taxol in an emulsion by use of a long infusion duration, the long infusion
duration is inconvenient for patients, and is expensive due to the need to
monitor the patients for the entire 6 to 24-hour infusion duration. Further,
the long infusion duration requires that patients spend at least one night in a
hospital or treatment clinic.
Thus, it is highly desirable to develop a taxol infusion protocol which would
allow for recipients to be treated on an out-patient basis. ....
Even if infusion duration can not be shortened, it is also desirable to avoid
the high dosages of taxol presently believed necessary to have an
antineoplastic effect, which induce a variety of adverse side-effects,
including respiratory distress, cardiovascular irregularities, flu-like
symptoms, gastrointestinal distress, hematologic complications, genitourinary
effects, neuropathy, alopecia, and skin rashes.
Further, due to the extremely limited supply of taxol, and the high dosage
requirement for each patient, the demand for taxol greatly exceeds the
supply.
Therefore, it is highly desirable to reduce taxol dosages, if possible, to both
extend the supply of taxol and reduce the toxic side effects of taxol. It is
also highly desirable to decrease the time required to administer taxol to
patients to minimize patient discomfort and expense.
Thus, there is a need for products containing taxol for administration of less
taxol and/or which require less infusion time.
Therefore, it is a primary object of the present invention to provide new
products containing taxol which allow to administer taxol over a shorter period
of time than the present 6 to 24-hour infusion protocols, while minimizing
toxic effects induced by the administration of taxol.
It is another object of the present invention to provide new products
containing taxol for administration of taxol which reduce the amount of taxol
administered to a patient, without sacrificing the antineoplastic effects
desired by administering taxol.
It is yet a further object of the present invention to provide new products
containing taxol for administration of taxol which utilizes both lower dosages
of taxol and shorter infusion periods, without sacrificing the antineoplastic
benefits of the administration of taxol."
9. After giving a summary of the invention the specification comes at page 5
line 10 to what is called a "Detailed Description of the Invention". There it
is said:
"Despite the conventional understanding that it is necessary to infuse patients
over a 24-hour period with high dosages of taxol (greater than 170
mg/m2) following premedication to minimize or eliminate
hypersensitivity responses, while obtaining the desired antineoplastic effect,
it has been surprisingly discovered that the new products containing taxol can
be safely administered to cancer patients via infusions lasting 3 hours or less
at dosages of 135 mg/m2 to 175 mg/m2. In a preferred
embodiment, taxol is administered via an infusion having a duration of about
three hours, with a taxol dosage of about 135 mg/m2 or about 175
mg/m2. Of great significance is a surprising discovery that the
short term infusion causes less myelosuppression, which leads to a lower
incidence of infections and fever episodes (e.g., febrile neutropenia).
Following the preferred infusion schedules of the present invention provides an
objective response rate
of greater than 10% for patients suffering from
epithelial ovarian carcinoma, and preferably an objective response rate of 14%
or greater for groups of at least 150 patients suffering from ovarian
carcinoma.
The surprising discovery that taxol could be safely administered via a short
infusion (e.g., over about 3 hours) means that it will now be possible to
administer taxol on an out-patient basis, saving patients the time and expense
of yet another hospitalization while improving patient quality of life.
It has also been surprisingly discovered that lower taxol dosages, such as
about 135 mg/m2 can be administered via infusions having about
3-hours, and still be antineoplastically effective."
10. It is not surprising that the desired ends, set out in the passage quoted
above from page 3 of the specification, namely shortening infusion time and
reduction in dosage are said to have been achieved by the invention. The
discovery relied on is that short infusion times of about 3 hours at a dosage
between 135 mg/m2 to 175 mg/m2 are effective and can be
safely administered. It should be noted that the specification also refers to
the "surprising discovery" that the short term infusion has the added advantage
of less myelosupression.
11. The specification goes on to give details of the OV.9 study that had been
conducted on patients suffering from ovarian cancer who had been previously
treated with platinum. A high degree of success, greater than 10% objective
response, was found. This was said to be "truly astonishing since responses to
drug refractory ovarian carcinoma are extremely uncommon". The specification
concludes in this way:
"The success of the use of the new taxol products and infusion protocol of the
present invention in the treatment of ovarian cancer makes it readily apparent
that antineoplastically effective dosages of taxol can be infused over much
shorter time periods than was previously believed possible, without inducing
severe hypersensitivity reactions or inducing fatal anaphylactic shock. Thus,
it is contemplated that the infusion protocol of the new products of the
present invention may be utilized to treat solid tumours and leukemias, such as
but not limited to lung cancer, breast cancers, and ovarian cancers. It is to
be understood that treatment of different forms of cancer may require the
adjustment of the taxol dosage to have optimal efficacy.
The foregoing clearly establishes that taxol is both safe and effective in the
treatment of cancer, such as ovarian cancer, when administered with the
products and according to the protocol of the present invention. In
particular, by use of a 3-hour infusion of about 135 mg/m2 taxol,
following premedication, a substantial reduction results in the frequency of
myelotoxicity and neuropathy associated with the administration of taxol to
patients suffering from cancer. Further, patients who exhibits severe
hypersensitivity reactions can be rechallenged with taxol after treating the
HSR symptoms by use of an infusion of about 24 hours or greater, preferably
using a dosage of about 135 mg/m2 to about 175 mg/m2.
Preferably, colony stimulating factors are administered to assist in
ameliorating myelosuppression.
The use of lower dosages of taxol to achieve antineoplastic results will allow
for more patients to be treated with the present limited supply of taxol.
Further, depending upon the toxicities noted in a patient during treatment with
taxol according to the present products and protocol, the duration of infusion
can be extended or shortened, or the taxol dosage can be reduced or increased,
thus providing more flexibility in-treating cancer with taxol. Further,
patients capable of handling higher doses of taxol can be administered up to
about 275 mg/m2; should the patient encounter severe toxicity, such
as a severe neuropathy, the products and protocol of the present invention
allows for reducing the dosage."
12. There follow nine claims of which claim 1 is the only one that is
relevant:
"1. Use of taxol and sufficient medications to prevent severe anaphylactic
reactions, for manufacturing a medicamentation for simultaneous, separate, or
sequential application for the administration of from 135 mg/m2 up
to 175 mg/m2 taxol over a period of about 3 hours or less as a means
for treating cancer and simultaneously reducing neutropenia."
Infringement
13. A person infringes a patent if, but only if, he does within the UK any of
the things specified in section 60 of the Patents Act 1977 without the consent
of the proprietor of the patent. In this case the relevant things are
contained in section 60(1)(b) and (2). They must be read subject to the
exception in subsection (5).
"60. - Meaning of infringement.
(1) Subject to the provisions of this section, a person infringes a patent for
an invention if, but only if, while the patent is in force, he does any of the
following things in the United Kingdom in relation to the invention without the
consent of the proprietor of the patent, that is to say -
...
(b) where the invention is a process, he uses the process or he offers it for
use in the United Kingdom when he knows, or it is obvious to a reasonable
person in the circumstances, that its use there without the consent of the
proprietor would be an infringement of the patent;
...
(2) Subject to the following provisions of this section, a person (...) also
infringes a patent for an invention if ... he supplies or offers to supply in
the United Kingdom a person other than a licensee or other person entitled to
work the invention with any of the means, relating to an essential element of
the invention, for putting the invention into effect when he knows, or it is
obvious to a reasonable person in the circumstances, that those means are
suitable for putting, and are intended to put, the invention into effect in the
United Kingdom.
...
(5) An act which, apart from this subsection, would constitute an infringement
of a patent for an invention shall not do so if -
(a) it is done privately and for purposes which are not commercial;
(b) it is done for experimental purposes relating to the subject-matter of the
invention."
14. The judge did not come to any conclusion on infringement, perhaps because
he had held the patent invalid or because it was accepted, on the construction
he had placed on the claim, that there was infringement. However I believe it
is helpful in this case to consider infringement so as to decide the issues of
construction in a real context.
15. The Particulars of Infringement alleged that the defendants infringed by
"(a) offering for use in the UK the method of the claims; and (b) by acting in
concert with those who have used the said method so as to be joint tortfeasors
therewith". The actual acts relied on were clinical trials at certain
hospitals "which were promoted by the first and the second Defendants and by
whom the active ingredient and the instructions for its use were provided."
There is also an allegation of infringement by the supply and offer to supply
of an essential element.
16. The first respondents accepted that they had promoted clinical trials
using taxol supplied by them. In accordance with Order 104 rule 11(1)(2)(a)
they supplied particulars of those trials which were accepted to set out, in
sufficient detail, what happened.
17. At Guy's, the Royal Marsden and Hammersmith hospitals women with ovarian
cancer were treated with premedication before infusion with taxol. The amount
of premedication was determined by the doctor. It was administered at 12
hours, 6 hours and one hour before infusion. The trial was designed so that in
every case 175 mg/m2 of taxol was to be administered intravenously
every 21 days as a 3-hour infusion. The amount was determined according to the
patient's height and weight and was ordered by prescription. During the
infusion the patient was monitored for hypersensitive reaction. Reductions
from the starting dose to 130 mg/m2 and then to 98 mg/m2
took place for patients whose recovery neutrophil blood counts were not
satisfactory. Complete blood counts were performed at regular intervals during
the treatment.
18. At Guy's a similar trial was carried out for women with measurable breast
cancer.
19. The judge construed the words "for treating cancer" as meaning "suitable
for trying to treat cancer". Mr Thorley QC, counsel for the respondents,
accepted that as correct. He drew attention to the fact that the patent did
not give any teaching of the extent of the effect that taxol would have on
patients. A medicament was suitable for trying to treat cancer if it had an
effect on some patients either by reducing the carcinoma or the extent or speed
of growth. Upon that basis he accepted that there had been infringement if
claim 1 was valid.
20. Mr Waugh QC, who appeared for the appellants, did not suggest that the
judge was wrong in his construction of the words "for treating cancer".
However he submitted that the approach of the judge did not reflect his
construction in that it did not adequately take account of the requirement for
effective treatment. The patent disclosed that taxol was an effective
treatment at the claimed rate and duration even though it was not successful in
every case. That was the position in the trials alleged to infringe. Thus the
words "for treating cancer" meant suitable for effective treatment of cancer.
21. I have no doubt that the judge was right. The words "for treating cancer"
have to be construed in context. The skilled addressee would realise that
drugs which were suitable for treatment would not always be successful.
However drugs which had no effect were not suitable. The phrase means
"suitable for trying to treat cancer". What is suitable is a question of fact,
not one of perception. If the drug has a beneficial effect in the treatment of
cancer it will be suitable. If not, it will not be.
22. The judge concluded that the words "as a means for ... simultaneously
reducing, neutropenia" have to be read purposively in the light of the fact
that taxol causes neutropenia and there was no stated amount from which
reduction was to take place. He concluded that those words meant that the
medicament had to be suitable for "reducing neutropenia as compared with what
it would be if administration was for 24 hours". I agree, but I would place a
gloss upon his conclusion by substituting the words "lessening the amount of"
instead of the word "reducing" for the reason, that taxol causes neutropenia
and therefore cannot reduce it.
23. If the claim is considered in the way that I and the judge have construed
it, the respondents accept that the trials constituted infringement.
Validity
24. The respondents attacked the patent on three grounds. First that it was
not new (see sections 1(1) (a) and 2(1) and (2) of the 1977 Act);); second the
invention did not involve an inventive step (see sections 1(1)(b) and 3 of the
1977 Act); third that it was not capable of industrial application (see
sections 1(1)(c) and 4 of the Patents Act 1977). As those issues are to an
extent interrelated it is convenient to set out at the outset the relevant
parts of the sections of the Act.
"Patentable inventions.
1.(1) A patent may be granted only for an invention in respect of which the
following conditions are satisfied, that is to say -
(a) the invention is new;
(b) it involves an inventive step;
(c) it is capable of industrial application;
...
Novelty.
2.(1) An invention shall be taken to be new if it does not form part of the
state of the art.
(2) The state of the art in the case of an invention shall be taken to
comprise all matter (whether a product, a process, information about either, or
anything else) which has at any time before the priority date of that invention
been made available to the public (whether in the United Kingdom or elsewhere)
by written or oral description, by use or in any other way.
....
Inventive step.
3. An invention shall be taken to involve an inventive step if it is not
obvious to a person skilled in the art, having regard to any matter which forms
part of the state of the art by virtue only of section 2(2) above (and
disregarding section 2(3) above).
Industrial application.
4.(1) Subject to subsection (2) below, an invention shall be taken to be
capable of industrial application if it can be made or used in any kind of
industry, including agriculture.
(2) An invention of a method of treatment of the human or animal body by
surgery or therapy or of diagnosis practised on the human or animal body shall
not be taken to be capable of industrial application.
(3) Subsection (2) above shall not prevent a product consisting of a
substance or composition being treated as capable of industrial application
merely because it is invented for use in any such method."
25. The grounds of invalidity relied on require a decision as to whether the
invention satisfied the conditions set out in the Act. To decide whether they
were satisfied recourse has to be made to the claims of the patent, in this
case claim 1, as section 125 states that an invention of a patent shall be
taken to be that specified in the claim.
Novelty
26. An invention is new unless it "has at any time before the priority date of
the invention been made available to the public" (see sections 1(1)(a), 2(1)
and (2) of the 1977 Act).
27. In the present case the respondents submitted that the Winograd lecture
had made the invention claimed in claim 1 available to the public. The judge
accepted that submission.
28. The appellants submitted that the judge had erred in three respects.
First he had failed to appreciate that two of the integers claimed had not been
disclosed in the Winograd lecture; second he had failed to apply the right
test, and third he had wrongly distinguished the decisions of the Enlarged
Board in Eisai GR05/83 and Mobil Oil GO2/88.
29. There can be no doubt that an invention can only have been made available
to the public if there are clear and unmistakable directions to do that which
the patentee invented. As the Court of Appeal said in the General Tire and
Rubber Company v The Firestone Tyre and Rubber Company Limited and others
[1972] RPC 457 at 486:
"If, ... , the prior publication contains a direction which is capable of being
carried out in a manner which would infringe the patentee's claim, but would be
at least as likely to be carried out in a way which would not do so, the
patentee's claim will not have been anticipated, although it may fail on the
ground of obviousness. To anticipate the patentee's claim the prior
publication must contain clear and unmistakable directions to do what the
patentee claims to have invented: .... A signpost, however clear, upon the
road to the patentee's invention will not suffice. The prior inventor must be
clearly shown to have planted his flag at the precise destination before the
patentee."
30. Mr Waugh placed particular emphasis upon the well-known statement by Lord
Westbury LC in Hill v Evans (1861) 4 DE G.F. & J. 288 at 301:
"There is not, I think, any other general answer that can be given to this
question other than this: - that the information to the alleged invention given
by the prior publication must, for the purposes of practical utility, be equal
to that given by the subsequent patent. The invention must be shown to have
been before made known. Whatever, therefore, is essential to the invention
must be read out of the prior publication. If specific details are necessary
for the practical working and real utility of the alleged invention, they must
be found substantially in the prior publication.
Apparent generality, or a proposition not true to its full extent, will not
prejudice a subsequent statement which is limited and accurate, and gives a
specific rule of practical application."
31. In 1861 patent specifications did not have claims and therefore novelty
had to be decided by a comparison between the specification of the patent and
the disclosure in the prior art. Thus the statement of the law as to novelty
by Lord Westbury has to be read with that in mind and when so read is
consistent with the statement of the law by the Court of Appeal in General
Tire. To that statement should be added the teaching of Lord Hoffmann in
Merrell Dow Pharmaceuticals Inc v H.N. Norton & Co Ltd [1996] RPC 76
as to the effect of the 1977 Act. In that case novelty was claimed for the
metabolite of terfenadine which was produced in the liver after consumption of
terfenadine. At the priority date terfenadine and its production was known by
use and publication of the patent describing its production, but the metabolite
had not been identified. The House of Lords held that the claim lacked
novelty. Lord Hoffmann said at page 89 line 12:
"My Lords, I think that on this point the Patents Act 1977 is perfectly clear.
Section 2(2) does not purport to confine the state of the art about products to
knowledge of their chemical composition. It is the invention which must
be new and which must therefore not be part of the state of the art. It is
therefore part of the state of the art if the information which has been
disclosed enables the public to know the products under its description
sufficient to work the invention."
32. He went on at page 90 line 40 to conclude:
"In this case, knowledge of the acid metabolite was in my view made available
to the public by the terfenadine specification under the description 'a part of
the chemical reaction in the human body produced by the ingestion of
terfenadine and having an anti-histamine effect'. Was this description
sufficient to make the product part of the state of the art? For many
purposes, obviously not. It would not enable anyone to work the invention in
the form of isolating or synthesising the acid metabolite. But for the purpose
of working the invention by making the acid metabolite in the body by ingesting
terfenadine, I think it plainly was. It enabled the public to work the
invention by making the acid metabolite in their livers. The fact that they
would not have been able to describe the chemical reaction in these terms does
mean that they were not working the invention. Whether or not a person is
working a product invention is an objective fact independent of what he knows
or thinks he knows about what he is doing."
33. Having rejected the argument that the invention had been made available by
use of the terfenadine, he said page 91 line 26:
"Anticipation by disclosure, on the other hand, relies upon the communication
to the public of information which enables it to do an act having the
inevitable consequence of making the acid metabolite. The terfenadine
specification teaches that the ingestion of terfenadine will produce a chemical
reaction in the body and for the purposes of working the invention in this
form, this is a sufficient description of the making of the acid metabolite.
Under the description the acid metabolite was part of the state of the art."
34. The appellants accept that taxol had by the priority date been made
available to the public as an effective treatment for cancer when administered
over a period of 24 hours. Their case for novelty depended upon the last part
of claim 1, namely that the medicament was for administration at the claimed
dosage over about 3 hours as a means for treating cancer and simultaneously
reducing neutropenia. Thus the claim in broad terms was for the use of two
known products to produce a medicament with the novelty relied on being
provided by the alleged new application. The appellants submitted that such a
claim was novel according to the principles laid down by the Enlarged Board in
the Eisai case which concluded in paragraph 23 of their reasons:
"... the Enlarged Board considers that it is legitimate in principle to allow
claims directed to the use of a substance or composition for the manufacture of
a medicament for a specified new and inventive therapeutic application, even in
a case in which the process of manufacture as such does not differ from the
known processes using the same active ingredient."
35. A claim of the type considered to be legitimate by the Enlarged Board has
become known as a "Swiss-type" claim.
36. The conclusion reached in Eisai was at the time and has since been
the subject of considerable discussion amongst patent lawyers. Its importance
was recognised by Whitford J and Falconer J who sat in banc to decide whether
it should be followed in this country. They held in John Wyeth and Brothers
Ltd's Application and Schering AG's Application [1985] RPC 545 that
it should be. They concluded that there could not be any objection to the
patenting of inventions in the Swiss-type form, if the statutory requirement of
novelty could be met. They concluded that, without regard to the position as
it had developed in the courts of Convention States, the better view would be
that Swiss-type claims would not be patentable as they would lack novelty under
the Patents Act 1977 and by parity of reasoning under the EPC. They went on to
remind themselves that it was necessary to have regard to the decisions of the
courts of Member States of the EPC and also decisions of the EPO, particularly
the Enlarged Board. Having referred in detail to the reasoning of the Enlarged
Board in Eisai, they held at page 567:
"The approach of the Enlarged Board of Appeal to the question of the novelty
requirement in a Swiss type use claim directed to a second or subsequent
medical use may be summarised, it seems, as follows:
1. Because of the provisions of article 52(4) (first sentence) (which
corresponds to section 4(2) of the 1977 Act), the normal type of use claim,
whereby a new use of a known product may be protected, is not open to
pharmaceutical inventions directed to the use of medicaments in a method of
medical treatment.
2. However, no intention to exclude second (and subsequent) medical
indications from patent protection, other than by a purpose-limited claim
(under the provisions of article 54(5), corresponding to section 2(6) of the
1977 Act) is to be deduced from the terms of the EPC or the legislative history
of the material articles thereof.
3. In that regard the Swiss-type of use claim now being considered is not
prohibited by article 52(4) and is capable of industrial application.
4. As to novelty, the Board consider that in the type of claim specifically
provided for in article 54(5), namely, a purpose-limited product claim to a
known substance or composition for a first (and, therefore, novel)
pharmaceutical use, the required novelty for the claim is to be found in the
new pharmaceutical use.
5. Similarly, in the Swiss type of use claim directed to the use of a known
pharmaceutical in the manufacture of a medicament, not novel in itself, for a
novel second (or subsequent) therapeutic use, the required novelty of the
claimed process may be found in the new second (or subsequent) therapeutic use.
That approach to the novelty of the Swiss type of use claim directed to a
second, or subsequent, therapeutic use is equally possible under the
corresponding provisions of the 1977 Act and, not withstanding the opinion
expressed earlier as to the better view of the patentability of such a Swiss
type claim under the material provisions of the Act considered without regard
to the position, as it has developed under the corresponding provisions of the
EPC, having regard to the desirability of achieving conformity, the same
approach should be adopted to the novelty of Swiss-type of claim now under
consideration under the material provisions of the Act."
37. The patent judges in the John Wyeth case correctly summarised the
approach of the Enlarged Board and I believe that they came to the right
conclusion in the cases before them.
38. Mr Thorley rightly, in my view, emphasised that novelty in a Swiss-type
claim resided in "the new second (or subsequent) therapeutic use". Mr Waugh
submitted that claim 1 did relate to a second therapeutic use, namely use of
taxol for the claimed period and in amount for the reduction of neutropenia.
He submitted that in any case novelty did not have to reside in a second or
subsequent therapeutic use as had been made clear by the Enlarged Board in the
Mobil case.
39. The difficulties that arise from the decision of the Enlarged Board in the
Mobil case on infringement were referred to by Lord Hoffmann in
Merrell Dow. For the purposes of this case, it is necessary to
appreciate what was actually decided and there is no need to become involved in
the infringement difficulties. The Enlarged Board summarised their conclusions
in this way in paragraph 10.3 of their decision:
"... with respect to a claim to a new use of a known compound, such new use may
reflect a newly discovered technical effect described in the patent. The
attaining of such a technical effect should then be considered as a functional
technical feature of the claim (e.g. the achievement in a particular context of
that technical effect). If that technical feature has not been previously made
available to the public by any of the means set out in article 54(2) EPC, then
the claimed invention is novel, even though such technical effect may have
inherently taken place in the course of carrying out what has previously been
made available to the public."
40. That conclusion depended upon two strands of reasoning. First, that prior
use was not a ground of invalidity. Thus prior use that did not make the
invention available to the public could not invalidate the invention. Similar
reasoning was applied by the House of Lords in Merrell Dow. Second a
purposive construction of the claim according to the Protocol on Interpretation
was required. Thus claims should in appropriate circumstances be interpreted
as being limited to the technical effect, namely the physical activity. It
followed that in the case being considered, the claim to an additive in
lubricating oil for reducing friction should be interpreted as a claim to the
product when used for reducing friction. Such a claim would be novel if the
use had not previously been made available to the public. However it is
relevant to note that similar reasoning cannot be applied in relation to a
Swiss-type claim, as such a claim cannot be interpreted as relating to the
product when used because that would constitute a method of treatment which is
prohibited under the EPC.
41. I do not believe that the Mobil case qualifies or amplifies the
conclusion reached in Eisai. The decision in Eisai was based
upon the interplay between Articles 52(4) and 54(5) of the EPC; whereas
Mobil depended upon purposive construction of the claims so as to limit
the claims to the product when used together with an application of Article
52(2).
42. Against that background of law, I turn to claim 1. The judge was right to
conclude that it was not a claim for a second therapeutic use. The medicaments
in question were known to be suitable for treating cancer. The remainder of
the claim relates to the way that such a medicament was to be used. A similar
conclusion was reached by the Dutch Court of Appeal in Bristol-Myers Squibb
v Yew Tree of 25th June 1998. It follows that the reasoning in Eisai
does not apply.
43. The transcript of the Winograd lecture discloses that the objects and
design of the OV. 9 study were to evaluate the efficiency and safety of taxol
in patients with ovarian cancer previously treated with platinum containing
chemotherapy. A two by two trial was used; long time infusion over 24 hours
versus a short time infusion over 3 hours using 135 mg/m2 and 175
mg/m2 doses. The lecture discloses that the main impact on
hypersensitivity was the premedication. The incidence of significant
hypersensitivity reaction was said to be minimal with the premedication used.
The non-hypersensivity reactions were not more frequent in the 3 hour arms as
compared to the 24 hour arms which meant that the 3 hour arms were feasible and
as safe as the 24 hour arms. Dr Winograd gave general information as to the
haematological toxicity showing that recovery occurred in almost all patients
by the 21 day period and only 10 out of the 270 courses needed to be delayed.
His conclusion was that the 3 hour infusion was as feasible and as safe as the
24 hour dose. This he said was an important finding in view of the speed of
infusion. He concluded his explanation of the trials in this way:
"Responses were seen in all treatment arms. It is too early really to give you
a breakdown of that because the follow-up of the patients is relatively short
and the overall response rate seems to be in the ball park of what has ... and
again this is a multi-centre study; the overall response rate seems to be in
the ball park of what has been published up to now and has been presented in
the previous presentation."
44. Mr Waugh submitted that claim 1 contained two novel features over the
Winograd lecture. First there was no disclosure that taxol was suitable for
treating cancer when infused in the claimed amount over a period of 3 hours.
Second that there was no disclosure of reduction of neutropenia.
45. In my view the judge was right to reject the first submission. The claim
requires the medicament to be suitable for treating cancer. Anybody listening
to the lecture would have realised that the 3 hour arm of the trial had not
shown adverse hypersensitivity and was safe and that a response had been shown
which Dr Winograd categorised as in the ballpark of what had been published up
to now. No doubt it would have been sensible to await the conclusion of the
trials, but the lecture disclosed that taxol was suitable for trying to treat
cancer using a 3 hour treatment.
46. The second submission depends upon the discovery that less neutropenia
occurred during the 3 hour infusion than during a 24 hour infusion. That was
not mentioned in the lecture, but it was, as I have already pointed out, a
discovery not a second therapeutic use as considered in Eisai. Further
it is an inevitable consequence of the 3 hour, 135 mg/m2 infusion,
described in the lecture and as such cannot impart novelty to the claim. As
the judge held, the public could, using the information in the lecture, carry
out the disclosed and claimed 3 hour infusion with premedication without the
need of any information from the patent. Such a person would inevitably
monitor the patient's blood and would inevitably find the extent of neutropenia
that occurred. The lecture contained clear and unmistakable directions to
carry out such a 3 hour infusion and the result would inevitably be that which
was claimed. The information given in the lecture enabled the public to carry
out an act which would have the inevitable consequence of less neutropenia.
That conclusion is consistent with the attitude expressed by the Technical
Boards in Dow Chemical Company T.90/0958 and American
Cyanamid T.93/0279. In my view the judge came to the right conclusion.
Claim 1 lacks novelty.
47. Mr Thorley submitted that if claim 1 could derive novelty from the
Eisai or Mobil decisions, they were wrongly decided. In a
formidable attack upon Eisai, he criticised the way that the Enlarged
Board had interpreted Article 54(5) of the EPC and had failed to give proper
effect to the view that had been expressed at the Munich conference. He also
drew attention to the Report of the French Cour de Cassation(1993) which may
support his submission.
48. It is not necessary to come to any concluded view as to whether Mr
Thorley's submissions as to the correctness of Eisai were right and I
decline to do so. However, it is relevant to point out that Eisai has
been applied by the EPO since at least 1985 and was accepted as correctly
stating the law in 1985 by the Patents Court in the John Wyeth case. It
has also, I believe, been applied by the members of the EPC, except perhaps
France. There are therefore strong reasons for maintaining the view expressed
by the patent judges in the John Wyeth case.
49. As to Mobil, this was considered in depth and applied by the House
of Lords in Merrell Dow. Mr Thorley is correct that the issues raised
in the House of Lords were not the same as those that arise in this case, but
even so, it is unlikely that this Court would conclude that it was wrongly
decided when the House of Lords did not so conclude.
Obviousness
50. The judge expressed his view in this way:
"I finally come to obviousness. I think this is a very plain case. Winograd had
disclosed three-hour infusion with premedication was safe from the point of
view of toxic shock. It was unknown how efficacious the three-hour treatment
was, save for Winograd's hint that there were "responses in all arms". But
there was every motive to find out. And in further testing of three-hour
infusion you would surely test for neutropenia. As I have said blood tests were
routine in this sort of clinical trial. There simply cannot be any invention in
pressing on with the OV. 9 trial and finding out about the comparative levels
of neutropenia."
51. Mr Waugh submitted that the judge had approached the question of
obviousness wrongly. He drew attention to the evidence of Professor Calvert to
the effect that the study disclosed in the Winograd lecture was unusual and
that, until it was completed, no conclusion could have been drawn to adopt a 3
hour infusion period. The obvious period of infusion was that which had been
shown to be effective in the past, namely a 6 to 24 hour infusion period. It
was not obvious to carry out a 3 hour infusion without evidence that it was
effective. If he had attended the lecture, he would not have been encouraged
to use a 3 hour infusion and would not risk changing without full results
showing that it would be effective.
52. Upon that evidence Mr Waugh submitted that the claimed 3 hour infusion
could not have been obvious until it was known that the 3 hour treatment was as
effective as the 24 hour regimen and also that it resulted in a reduction in
neutropenia. Neither of those matters were disclosed in the Winograd lecture.
53. Of course Professor Calvert and others would not change from a 24 hour to
a 3 hour treatment without the results of the completed study. They would be
treating patients with cancer and therefore were subject to restraints that
would not apply to normal manufacturing. Further, with the knowledge that the
study was nearly complete, they would not start new trials themselves as that
would only result in duplication for no useful purpose. But that does not mean
that it was not obvious, in the sense of lacking invention, to carry out the
trials which had been disclosed in the lecture in the way suggested. There
could be no invention in administering to a patient premedication and taxol
with a 3 hour infusion of the claimed amount as that was one of the arms of the
trial disclosed in the lecture. If so, the amount of neutropenia was
inevitable. In my view the judge came to the right conclusion for the right
reasons. Claim 1 was obvious.
Method of Treatment
54. The judge rejected the attack upon the patent based upon sections 1 and 4
of the 1977 Act. He said:
"50. Nor do I accept that on his construction the claim amounts to merely a
method of treatment. It is to the manufacture of the medicines to be used in
that treatment. I am reinforced in that view by the consideration that the
Article 52(4) provision about methods of treatment is an exception to
patentability and as an exception should be construed narrowly. As the Board of
Appeal in Harvard/Oncomouse T0015/90 [1990] O.J. EPO 476 said, speaking of
another exception:
"Art. 53(b) is an exception, for certain kinds of inventions, to the general
rule under Art. 52(1): that European patents ´shall be' granted for all
inventions which are susceptible of industrial application, which are new and
which involve an inventive step. Any such exception must, as repeatedly pointed
out by the Boards of Appeal, be narrowly constructed (cf. in particular
T320/87, point 6 O.J. EPO 1990 76)."
51. A like approach is indicated in Plant Genetic Systems/Glutamine Synthetase
Inhibitors ((T356/93) [1995] O.J. EPO 545. There is also the limited purpose of
the exception to be considered. It is not so broad as to stop doctors using
whatever they feel they need to treat patients. If that were the purpose then
one would not allow patents for medicines or medical implements at all. The
purpose of the limitation is much narrower, merely to keep patent law from
interfering directly with what the doctor actually does to the patient. Patent
monopolies are permitted to control what he administers to, or the implements
he uses on, the patient. The thinking behind the exception is not particularly
rational: if one accepts that a patent monopoly is a fair price to pay for the
extra research incentive, then there is no reason to suppose that that would
not apply also to methods of treatment. It is noteworthy that in the U.S. any
such exception has gone, and yet no-one, so far as I know, suggests that its
removal has caused any trouble."
55. Mr Thorley QC who appeared for the respondents submitted the judge had not
taken into account the full effect of the claim. In the present case, the
claim was alleged to have been infringed by clinical trials at hospitals. It
was alleged that the respondents had offered the method of the claim for use,
acted in concert with those carrying out the trials and supplied taxol to the
hospitals for use in the trials. The foundation of the allegations of
infringement was the trials. They were treatments of humans by therapy. If
there was infringement, the claim included within it matters that were not
capable of industrial application and therefore it was invalid.
56. Mr Thorley also submitted that an analysis of the claim demonstrated that
it was drafted so as to cover treatment of humans. He drew attention to the
words "use of taxol" and "sufficient medications to prevent severe anaphylactic
reactions" which appears in claim 1. Those words required use of two
substances "for manufacturing a medicament". He submitted that they did not
come together to form the medicament except in the body of the patient which
meant that the manufacture referred to in the claim was part of the treatment.
The amount of the premedication, its type and form of administration were all
determined by the doctor as was the dosage of taxol which was determined
according to the size of the patient and how the treatment was progressing.
57. Mr Thorley submitted that it was difficult to envisage a claim more
closely written to a method of treatment than claim 1 without use of the word
"treatment". He submitted that the claim, although looking like a "Swiss-type"
claim, was not of that type. Such claims, to use the words of the Enlarged
Board in Eisai, were "directed to the use of a substance or composition
for the manufacture of a medicament for a specified new and inventive
therapeutic application". An example being one of the claims in John Wyeth
case at page 560 line 12:
"The use of an aromatase inhibitor for the manufacture of a medicament for the
therapeutic and/or prophylactic treatment of prostatic hyperplasia."
The novelty in such a claim resided in the second medical use, whereas claim 1
of the patent required combination in the patient of two components selected by
the doctor to carry out a treatment also controlled by the doctor.
58. The judge construed the claim as being limited to the manufacture of the
medicament to be used in treatment. He contrasted such manufacture with the
exclusion from patent protection of methods of treatment: an exclusion to
prevent interference "directly with what the doctor actually does to the
patient." Mr Thorley accepted the purpose of the exclusion and that, if the
claim was limited to the manufacture of the medicine to be used in the
treatment, it did not offend section 4 of the Act. However he submitted that
the judge had failed, when considering the claim, to take into account the
parts of the claim that required action by doctors and how the claim was
alleged to be infringed. If there was infringement as alleged, the claim had
to be construed so as to include a method of treatment.
59. Mr Waugh supported the conclusion and reasoning of the judge. The claim
was to a medicament made up from premedication and taxol, but subject to
limitations as to suitability for treatment of cancer and to achieve a
particular result. The activity of manufacture, although chosen by the doctor,
was the function of the pharmacist. There was no difference in the form of
claim 1 to the claims allowed in Eisai and in the John Wyeth
case, save for the features which were said to provide novelty. It
followed that if such claims did not offend section 4(2) (Article 54(2)), claim
1 did not either.
60. To support his submissions Mr Waugh relied on the decision of the
Technical Board in Nycomed TO 655/92. Having re-read the reasons for
decision of the Technical Board in that case, I have been unable to discern any
statement of principle which assists Mr Waugh's submissions.
61. As was pointed out in Eisai a claim directed to the use of a
substance for the treatment of a human is not different in essential context
from a claim directed at a method of treatment. The difference is one of form
and both are in conflict with section 4(2) (Article 52(4)). In my view the
form of the claim cannot always be determinative. To decide what is
determinative regard must be had to the purpose of the legislation as expressed
in the 1977 Act interpreted to be consistent with the EPC.
62. As pointed out in the John Wyeth case, section 4(2) (Article 52(4))
was not intended to exclude pharmaceutical preparations from being patentable.
That has the result that restrictions can be imposed by patentees upon
treatment. The section has the limited purpose of ensuring that the actual
use, by practitioners, of methods of medical treatment when treating patients
should not be subject to restraint or restriction by patent monopolies. The
difficulty is to decide whether the restraint concerns a method of treatment as
opposed to what is available for treatment.
63. In my view the form of claim 1 does not disguise its effect. The
invention was the discovery that by changing the treatment from a 24 hour
infusion to 3 hours a similar effect was obtained with less neutropenia. That
was a discovery that a change in the method of treatment provided the result.
The claim is an unsuccessful attempt to monopolise the new method of treatment
by drafting it along the lines of the Swiss-type claim. When analysed it is
directed step-by-step to the treatment. The premedication is chosen by the
doctor, and administered prior to the taxol according to the directions of the
doctor. The amount of taxol is selected by the doctor as is the time of
administration. The actual medicament that is said to be suitable for
treatment is produced in the patient under supervision of the medical team. It
is not part of a manufacture. In my view Mr Thorley is correct. The invention
made and claimed was a method of treatment precluded from patentability by
section 4(2) (Article 52(4)). That is emphasised by the way the allegations of
infringement were pleaded.
Costs
64. The judge gave leave to appeal against his order for costs. He ordered
the appellants to pay the respondents costs. However with two exceptions he
imposed a limitation that from 6th February "the first and second defendants
shall recover only 1 set of costs between them, to be taxed as if only one firm
of solicitors were acting for both parties and the parties were represented by
one leading and one junior counsel, and how that one set of costs is split
between the first and second defendants is a matter for them".
65. His reasons were:
"It seems to me that the governing principle should be that where there are two
or more parties fighting a common enemy, unless there are special
circumstances, the court should lean in favour of one set of costs. One can
always say that the second party might be better off if they had their own
particular legal team. I am not always sure that is true: too many cooks often
spoil the broth. Even assuming that a party might be slightly better off,
unless there is a real conflict, genuinely justified by separate sets of
lawyers, I think the better view is the parties should be under pressure to
agree there should be one set of lawyers to face the common enemy. I think the
court should be reluctant to grant two sets of costs.
Often the position may be that initially separate sets of costs are justified
before it is fully clear what the issues are and that the issues are indeed
common. Such was the position, for example, under the old patents extension
cases where opponents, however many there were, normally only received one set
of costs shortly after the opposition had been entered.
In this case, the patentees suggest that there should be only one set of costs
or, as they put it alternatively, half costs each, from either 5th February
1998 or 9th February 1998, when certain letters were written. I do not think
anything turns on those letters, as such. The patentees have misconstrued them
because they do not amount to an admission of joint tortfeasorship as between
BMS and Napro.
To my mind, February 1998 is not an unreasonable sort of date to take. I
propose, therefore, to award only one set of costs from then on. Whether the
award should take the form of one set of costs or should take the form that
each defendant only gets half its costs from that date is a matter upon which I
will hear counsel."
66. The respondents applied to adduce further evidence as they believed that
the conclusion reached by the judge had been taken upon incomplete facts which
they could not have reasonably foreseen to have been necessary to place before
him. In this respect they referred to the skeleton of the appellants put
forward for the hearing as to costs. That sought an order that one set of
costs should be ordered upon the basis that the exchange of correspondence
between the parties showed that there was no issue of fact on infringement.
That was rejected by the judge upon the basis that the letters had been
misconstrued and therefore there was some justification for the respondents'
submission that they were taken by surprise. But the extra evidence adds
little, if anything, of substance to the basic facts.
67. The impetus for the case was the petition for revocation of Napro which
was served on the appellants on 14th May 1997. That proceeded up to the issue
of the summons for directions on 22nd October 1997. The appellants were not
content to have the issue of validity tried alone and on 26th November 1997
issued proceedings for infringement against Bristol-Myers Squibb and Napro.
Subsequently those proceedings were amended to join Napro. The petition and
the action and counterclaims were consolidated on 16th January 1998.
68. Although the clinical trials alleged to be infringements were joint
trials, the respondents are in other respects in competition. It was therefore
not surprising that they were initially represented by separate solicitors and
junior counsel and no complaint was made that that occurred. In fact their
cases on infringement differed until the first day of the trial in that they
adopted different attitudes in the admissions that they made as to whether they
had been joint tortfeasors as alleged.
69. At every stage the respondents have been represented by two firms of
solicitors and two junior counsel, but with Mr Thorley leading upon their
behalf. It was their belief that such was appropriate having regard to the
potential conflict between them which had resulted in Mr Thorley being excluded
from a consultation on one occasion.
70. In my view the governing principle enunciated by the judge is too broadly
stated. The governing principle is that the losing party should only be
required to pay the costs reasonably incurred by the other party or parties.
No doubt parties should be under pressure only to instruct one set of lawyers
to face a common enemy as to do otherwise could result in an unreasonable
expenditure of costs for which the losing party should not pay. But it does
not follow that successful defendants, even if they adopt a common approach,
should be invariably deprived of part of their costs.
71. In the present case the appellants chose to fight the issues of
infringement and validity against two defendants. No complaint was made, nor
could it have been made, that both instructed solicitors and counsel to advise
them and to serve defences. The complaint upheld by the judge was that
sometime in February, before the trial in July 1998, that position changed and
it became unreasonable for the defendants to be represented by their own
solicitors and counsel. That being so, it was not reasonable for the
appellants to pay both sets of costs. What was it that meant that it was
unreasonable for one of the parties to continue to be separately represented?
The judge did not answer that question, except to say that he was not saying
that the solicitors acted improperly. His conclusion depended upon what he
thought was reasonable for the losing party to pay, not upon an assessment as
to whether one of the respondents had acted unreasonably. That became evident
in the discussion after judgment when Mr Whittle, who appeared for the
respondents, raised the difficult questions as to how the respondents were to
split the one payment of costs between them in the absence of agreement. That
resulted in the judge ordering that how the one set of costs was to be split
between them "was a matter for them". Did he expect that if agreement was not
reached, the actual split would have to be decided by litigation? I am not
sure how that would be done as he did not give them liberty to apply to him for
that purpose.
72. Mr Waugh supported the judge's conclusion that from February 1998 the
appellants should only be liable to pay one set of costs as that was the amount
that it was reasonable for a claimant to pay. I disagree. A losing claimant
should ordinarily pay the costs reasonably incurred by the parties that he
takes proceedings against. What costs are reasonably incurred by one or more
defendants should be ascertained by the costs judge who carries out the
assessment. Upon such an assessment duplication and failure to co-operate can
be seen and adjustments made accordingly. To decide what costs were reasonably
incurred by defendants by considering what costs a losing client should pay,
amounts to pre-judging the results of a detailed assessment without considering
the facts. The judge's conclusion involved, by implication, a decision that
the costs of one or both of the respondents had been unreasonably incurred.
That could not have been inferred from the fact that they had separate
solicitors and counsel and he had no evidence before him to enable him to reach
that decision. No such conclusion could be reached without looking at the full
picture which of course would be done by the costs judge on a detailed
assessment.
73. I would discharge the costs order made by the judge upon the basis that he
approached the issues between the parties on the wrong basis. Successful
parties are ordinarily entitled to their costs reasonably incurred. If there
be evidence before the judge that certain costs do not fall within that
category, then they should be disallowed. In this case there was no such
evidence and therefore the matter had to be left to the costs judge when
carrying out the detailed assessment. Of course it is always open to the judge
to draw attention in his judgment to matters which he believes require
particular investigation during assessment. I would therefore substitute for
the judge's orders as to costs an appropriate order for the costs of the
respondents to be paid by the appellants.
Conclusion
74. The judge rightly concluded that the patent was invalid and ordered its
revocation. I would therefore dismiss the appeal. I would allow the
cross-appeal on costs. LORD JUSTICE BUXTON:
75. I gratefully adopt the account of the facts set out by and the notation
used by Aldous LJ. Like him, I would dismiss this appeal. Because of the
importance of the issues involved, and in deference to the arguments addressed
to us, I venture to add some words of my own. In view of the terms of section
130(7) of the Patents Act 1977 I shall address the requirements of the EPC
rather than the corresponding sections of that Act. No argument was addressed
to us to suggest that that was an inappropriate course, either generally in
this appeal or in any particular case.
"Swiss-type" claims and the ruling of the Enlarged Board in Eisai
76. The respondents argued that the Board in Eisai had misinterpreted
the EPC in concluding that second medical use claims were, in principle,
patentable inventions. The argument envisaged at least the possibility that
even first medical use claims may be excluded from patentability if the
substance used is already comprised in the state of the art; but that in any
event second medical use claims were not permitted by the EPC. For reasons
that I will develop, I do not think that it is open to us to act on those
criticisms, even if they were thought to have force; but it will usefully
illuminate the terms and extent of the provisions of the EPC regarding medical
use claims to consider the criticisms made of the Enlarged Board's
interpretation of them in Eisai.
77. It will be convenient first to remind ourselves of the reasoning in
Eisai. The Enlarged Board recognised (at para 21) that in the normal
industrial field
"a new use for a known product can be fully protected as such by claims
directed to that use. That is in fact the appropriate form of protection in
such cases as the new and non-obvious use of the known product constitutes the
invention."
78. But that direct approach might be thought to be precluded by the
provisions of Article 52(4) in the case of products for use in medical
treatment. The Board therefore said that
"Article 54(5) EPC provides an exception to this general rule, however, so far
as the first use of medicaments is concerned, in respect of which the normal
type of use claim is prohibited by Article 52(4) EPC. In effect, in this case
the required novelty for the medicament which forms the subject-matter of the
claim is derived from the new pharmaceutical use. It seems justifiable by
analogy to derive the novelty for the process which forms the subject-matter of
the type of use claim now being considered from the new therapeutic use of the
medicament and this irrespective of the fact whether any pharmaceutical use of
the medicament was already known or not."
79. That reasoning was criticised on two grounds. First, and somewhat
tentatively, the respondents said that the terms of the EPC did not envisage
any sort of use-based claims at all in connection with pharmaceutical products,
and therefore there was no allowable category of first medical use claims from
which the allowability of second medical use claims could be derived by
analogy. The premise of that argument seems ill-founded. It is difficult to
see what the proviso to Article 54(5) of the EPC is talking about if it does
not envisage use-based claims of some sort. Second, however, a more
substantial argument was advanced in relation specifically to second medical
use claims. That was that as a matter of construction of the proviso the
reference to the exclusion of a case where the use of the product in "any"
method of treatment is within the state of the art meant that once the product
was "within the pharmacy" the doctor was free, without threat of infringement,
to prescribe it for whatever treatment seemed best to him.
80. An argument in similar form appears to have attracted the Patents Court in
Wyeth: see [1985] RPC at p565,20. For my part, however, I did not find
it persuasive. It is far from clear that the wording of Article 54(5) should
be read, as the argument requires, as referring to any method whatsoever.
It is at least equally understandable that the reference to exclusion from
the state of the art is simply to the method on the basis of which novelty is
claimed. Indeed, if the aim were to exclude from further patentability any
substance already used in a medical application, Article 54(5) could have
simply said so: provided that its use for any other method of treatment,
etc, is not already comprised in the state of the art. And once that objection
is excluded, the Enlarged Board's conclusion seems, with respect, irresistible
that, if a product can claim novelty on the basis of the novelty of its first
medical use, then production for a novel second medical use must equally
satisfy the requirements of the EPC. And since by Article 52(4) products for
use in methods of medical treatment are not to be regarded, on that ground
alone, as not susceptible of industrial application, it follows, as the Board
said in paragraph 23 of the report in Eisai, that
"it is legitimate in principle to allow claims directed to the use of a
substance or composition for the manufacture of a medicament for a specified
new and inventive therapeutic application, even in a case in which the process
of manufacture as such does not differ from known processes using the same
active ingredient."
81. This may seem to be merely a roundabout way of seeking to patent a medical
process, and one that only doubtfully gives proper weight to the first sentence
of Article 52(4). It is not, however, in my view open to us to use such doubts
as a ground for not applying Eisai at all. That is because, although
the observations of the House of Lords in Merrell Dow [1996] RPC at
p82,25 as to the undesirability of departing from decisions of the EPO may
strictly speaking not have been part of the ratio of that case, they are
considered and reasoned guidance of a unanimous House, which I do not think we
are free to depart from. The same view of the standing of the decision of the
Enlarged Board in Eisai was taken, though without the benefit of the
guidance in Merrell Dow, by the Patents Court sitting in banc in
Wyeth.
The limits of second medical uses as recognised in Eisai
82. The conclusion that we ought to adopt the approach of the Board in
Eisai requires us to look closely at what Eisai in fact decided;
and in particular at what was meant by in Eisai by new "pharmaceutical"
use; new "therapeutic" use; and new "therapeutic application": all of these
expressions appearing to carry the same meaning.
83. It is important in this enquiry to remember the emphasis placed by the
Board on justification by analogy from cases of first medical use. Recognition
of first medical use as a subject of patentability necessarily entails the use
of the substance for a new and completely different purpose from that in
relation to which it is already known. If the Board's analogy is to hold,
therefore, the relationship between the first and the second medical use must
be of the same nature: the second medical use must be for an end-purpose
distinctively different from the first, albeit also medical, purpose for which
the substance was used. That not only follows from the structure of the
Board's argument, but also from the need to respect the exclusion of methods
for treatment from patentability. If the novelty can lie in the nature of use,
rather than in the end-result at which that use aims, then it is indeed the
method of treatment on which patentability rests.
84. It is reasonable to infer that this distinction was assumed by the
Enlarged Board when they spoke of new therapeutic use; and at least some
specific indication of it is to be found in the account, at paragraph 17 of the
ruling in Eisai, of the Hydropyridine decision, where the
problem, not criticised as being stated in too limited terms, was said to be
whether
"a provision in terms of Article 52(4) EPC stands in the way of patent
protection in respect of an invention involving the use of a substance, already
known as a medicament, to treat an illness not previously treated by
means of that substance [emphasis supplied]."
85. That was also certainly the understanding of the nature of second medical
use claims of the very experienced judges of the Patents Court in Wyeth,
who expressed the question as involving
"the allowability of claims directed to an invention based on the discovery of
a second (or subsequent) pharmaceutical use of a known substance or
composition, already known for a particular medical use (or particular medical
uses), the new use being unconnected with the previously known use or
uses." [1985] RPC at p556,22, emphasis supplied.
86. That was equally the view of the Court of Appeal of the Hague in
Bristol-Myers Squibb v Yew Tree, a case concerned with the patent in
suit in our case, which, as cited by the Judge at paragraph 60, described a
second medical indication as
"an application of a substance for a different therapeutic purpose (for example
to fight another illness or for prevention instead of cure)."
87. The novelty of the second medical use, on which its patentability rests,
must therefore be found in applications that are new in the terms used in
Wyeth and Yew Tree. The novelty cannot lie in the method of use,
but in the new therapeutic purpose for which the substance is used.
The patent in suit
88. Judged by the test just set out, I cannot agree that the patent in suit
claims an invention that is new in the terms of Article 54 of the EPC as it was
understood in Eisai. The inventive step is to find that in the use of
taxol for the treatment of cancer three-hour infusion, when compared with
longer infusion, achieves antineoplastic effect with reduced myelosuppression.
That is an improvement in the method of administering an existing treatment; it
is not a new therapeutic purpose. The Judge was right to hold, at paragraph
66, that
"This is not a case of a second or other medical use. It is a case of mere
discovery about an old use."
The invention is therefore not patentable.
89. That suffices to dispose of this appeal, but in view of the argument
addressed to us I should go on and consider other points relating to industrial
application; method of treatment; and prior disclosure and obviousness in the
light, in particular, of the Winograd lecture. It will be noted that
discussion of a number of these issues may be distorted by the fact that the
premise on which they proceed, that the invention is patentable, is not
established.
Industrial application and method of treatment
90. The patent claims
"Use of taxol and sufficient medications to prevent severe anaphylactic
reactions for manufacturing a medicamentation."
91. The Judge held, at paragraph 50, that he did not accept the Respondents'
argument that
"the claim amounts to merely a method of treatment. It is to the manufacture
of the medicines to be used in that treatment....the purpose of the limitation
[in Article 52(4) of the EPC] is... merely to keep patent law from interfering
with what the doctor actually does to the patient."
92. But the "manufacture" to which the patent in suit relates is significantly
different from the operation that was understood to be in issue in, for
instance, Wyeth. In that case the Patents Court said, [1985] RPC at
p563,13:
"Mr Laddie, for the Comptroller, submitted, and we agree, that a claim in the
Swiss form....although in the form 'The use of substance A in the manufacture
of a medicament to treat disease B' is, in reality, a claim to the method of
manufacture of such a medicament by using substance A in its manufacture. Such
a claim, therefore, would seem clearly to be a claim to an invention capable of
industrial application."
93. In relation to the patent in suit, however, the manufacture claimed is not
the use of the active ingredient, paclitaxel, in the manufacture of taxol; but
the mixing in the hospital pharmacy of taxol and other ingredients to produce
the medium that is injected into the patient. It is that latter process that
is said to be susceptible of industrial application, under Article 52(1) of the
EPC. I am afraid that I found that assertion to be, at best, artificial, and
one that I do not think would have been made were it not for the need to
demonstrate that the invention is not of a method of treatment. We were told
that the mixing process could be, and in some cases was, sub-contracted outside
the hospital; but that does not prevent it from being a long way away from
anything that in normal parlance would be considered an industrial
application; or, for that matter, as under the old English law, "manufacture".
As my Lord has described, the mixing is of amounts and types of premedication,
and of amounts of taxol, all determined by the doctor in relation to the
specific patient. It is in reality not a self-standing operation, but
subordinate and incidental to the doctor's treatment of the patient. True it
is that, in treating the patient, the doctor will, or at least may, administer
the drugs according to the guidance contained in the patent. But that merely
underlines that what the patent teaches is not how to manufacture a drug for
use in the treatment of the patient, which would be in form at least a
Swiss-type claim, but how to treat the patient: which is the teaching that the
Swiss-type claim is designed to avoid.
94. The invention in the patent in suit is, therefore, of a method of medical
treatment, which is not patentable.
Prior disclosure
95. I agree with my Lord that there was sufficient prior disclosure in the
Winograd lecture for claim 1 of the patent to lack novelty. Further, the Judge
was, with respect, right to reject the argument that the patent was novel in
that it taught, as Winograd did not, that three-hour infusion was effective in
the treatment of cancer. The Judge said, at paragraph 63:
"Nor does the case get any better by saying that the prior art contained no
information about effectivity at 3-hours. The patent does not either-the mere
assertion of effectivity being, as the evidence on both sides accepted, one
which the skilled man would not accept on the data in the patent."
96. Conspicuous amongst the evidence was that of the appellants' witness
Professor Calvert. He said that the disclosure in the Winograd lecture would
not have caused 3-hour infusion to be adopted:
"Without specific data as to efficacy or at least results relating time to
progression of the tumour, the clinician would not risk changing to infusing
paclitaxel over 3 hours."
97. But the patent itself discloses no such data or teaching. On the
assumption that the patent does sufficiently describe whatever invention it is
that it claims, the claim is for no more than had already been revealed by
Winograd.
Obviousness
98. The part of the invention said to be unknown at the time of the Winograd
lecture was the reduction in neutropenia. But, for the reasons indicated by
the Judge, identification of that quality did not require inventive skill over
and above the skills already taught by Winograd, since the skilled man armed
with the latter information would or at least could press on with the trials,
and in so doing inevitably find out the facts about neutropenia. That would be
a discovery, but not an inventive step. The whole of the inventive nature of
the process had already been disclosed by Winograd.
Costs
99. I agree with my Lord that the cross-appeal on costs should be allowed for
the reasons that he gives.
MR JUSTICE HOLMAN:
100. I also agree that this appeal should be dismissed. I gratefully adopt
my Lord, Aldous LJ's account of the facts, and respectfully agree with the
detailed reasoning of both my Lords; and I will state my own reasons and
conclusions in summary form.
The Claim in the patent
101. Injecting a patient with taxol does not reduce neutropenia. It causes or
induces it. So the words "and simultaneously reducing neutropenia" at the end
of Claim 1 of the patent must mean and be paraphrased by some such words as
"whilst inducing less neutropenia than would be induced if the taxol was
administered over a 24 hour period" (the reference to 24 hours reflecting the
previous medical practice).
102. As the judge said, the words "as a means of treating cancer" also need to
be given a special meaning. The patent itself describes a 10% response in
patients suffering from drug refractory ovarian cancer as a "high degree of
success" and "truly astonishing." So, sadly, the words can only refer to the
attempt to treat. I would adopt the judge's paraphrase of "trying to treat"
cancer.
103. In analysing the integers of Claim 1, I would sub-divide into two parts
what the judge identified as integer (3).
104. Analysed in that way, and adopting the above paraphrases, the integers of
Claim 1 are:
(1) Use of taxol and sufficient medications to prevent severe anaphylatic
reactions
(2) for manufacturing a medicamentation for simultaneous separate or
sequential application
(3) for the administration of from 135 mg/m² up to 175 mg/m²
taxol
(4) over a period of about 3 hours or less
(5) as a means of trying to treat cancer
(6) whilst inducing less neutropenia than would be induced if the taxol was
administered over a 24 hour period.
105. A dosage of between 135 mg/m² and 175 mg/m² is in fact a lower
dosage than was conventionally administered over a 24 hour period; and indeed
one of the advantages asserted in the patent is that it enables lower dosages
to be used of a drug which is in short supply, thereby making it available for
more patients. However, Mr Waugh QC, on behalf of the appellants, expressly
disclaimed that any significance attaches to that particular fact; or, in
other words, to the content (as a discrete matter) of what I have identified as
integer (3).
The validity of the patent
106. Having thus analysed the integers of the Claim, I can now summarise my
own view of this case quite shortly.
107. I respectfully disagree with the view of the judge that this patent was
not a claim to a method of treatment of the human body by therapy. In my view
it clearly was. The element of "manufacture" of the "medicamentation" referred
to in the Claim is simply the preparation in the hospital pharmacy, or some
other convenient place, of the taxol itself and suitable anti-anaphylatic
premedication, and the measuring of them into the amounts prescribed or
specified by the clinician for a particular patient. My Lord, Aldous LJ has
already described the process. It is clear that the clinician must make a
decision as to, and prescribe, the actual quantities of premedication to be
given to, and taxol to be infused into the particular patient and as to the
period of infusion. Among other possible variables, the clinician has to take
into account the height and weight of the particular patient. Everything that
happens as described in Claim 1 of the patent is, or ought to be, under the
direction of the clinician. It is "a method of treatment" within section 4(2)
of the Patents Act 1977 and Article 52(4) of the EPC and, accordingly, not
"capable" or "susceptible" of "industrial application" as required by section
1(1)(c) of the Act and Article 52(1) of the Convention.
108. Is the Claim saved by its apparent Swiss-type formulation and as a claim
to a second medical use?
109. I respectfully agree with the analysis by my Lord, Buxton LJ as to the
limits of second medical use claims, the validity of which was recognised by
the Enlarged Board in Eisai. The conclusion of the Enlarged Board, as
expressed in the last paragraph (numbered 23) of their decision, clearly refers
to "a specified new and inventive therapeutic application." So there must be a
therapeutic application or purpose which is not only inventive but new.
110. Mr Waugh QC placed reliance upon the recent decision of the Court of
Appeal of New Zealand in Pharmaceutical Management Agency Limited v Glaxo
Group and others, in which judgment was given on the 17 December 1999. But
it does not seem to me to assist him. In their analysis of Eisai, the
Court of Appeal of New Zealand said, at paragraph [38] of their judgment, that:
"The step necessary to render Swiss-type claims acceptable would be to
recognise what is in fact the situation, that the novelty as well as the
inventiveness resides in the newly discovered purpose for which the
medicament is to be used." [my emphasis]
At paragraph [65] they said:
"Once it is accepted that there can be new invention in the discovery of
previously unrecognised advantageous properties in a chemical compound,
the obligation to make patent protection available must apply." [my
emphasis]
111. In the present case, however, the drug, taxol, is exactly the same; the
method of administration, by injection and infusion, is exactly the same; and
the therapeutic application or purpose, namely the attempt to treat cancer, is
exactly the same. The only difference is the discovery that if the drug is
infused over a shorter period an undesirable side-effect, neutropenia, is less
that it otherwise would be, while the therapeutic effect remains. No
"previously unrecognised advantageous properties in [the] chemical compound"
have been discovered. All that has been discovered (important though that
discovery is) is that if the compound is administered over a shorter period,
one of its disadvantageous side-effects will be less than it otherwise would
be.
112. In my view this is not a second medical use claim of the kind validated
by Eisai or any of the cases that were drawn to our attention in which
the principle of Eisai has been applied.
113. I turn next to novelty and obviousness. In my view there was clearly
nothing novel about integers (1) to (5) of the Claim. The contents of them
were all part of the prior state of the art. The Winograd lecture had clearly
disclosed that infusion over a period of about three hours or less was possible
and safe, and that the overall response rate seemed to be "in the ball-park of
what has been published up to now." The only integer which could be said to be
novel is integer (6) - whilst inducing less neutropenia than would be induced
over a 24 hour period. That had certainly not been disclosed by Winograd. But
in my view it was, for the reasons given by the judge and my Lords, "obvious."
Winograd had given to the person skilled in the art all the information he
needed in order to try infusion over a three-hour period; and if he did do so,
he would inevitably discover that less neutropenia was induced.
114. In short, in my view, insofar as this Claim was novel (inducing less
neutropenia) it was also obvious and did not involve an inventive step.
115. So in my judgment the patent is invalid on the grounds that (i) it is not
capable of industrial application, and (ii) it lacks novelty, and (iii) it
lacks an inventive step. The judge was right to order its revocation.
Costs
116. I also agree that the cross-appeal as to costs should be allowed for the
reasons given by my Lord, Aldous LJ. I would like to stress, however, that it
is only after considerable hesitation that I would interfere with the judge's
discretion as to costs; the more so as it is the discretion of a specialist
judge in a specialist field who is sensitive to good practice in that field.
Further, I applaud the judge's aim which was to discourage multiple
representation by parties fighting, as he put it, a common enemy on a common
cause. That said, the judge himself gave leave to appeal from his order as to
costs. Further, I was persuaded by Mr Whittle, on behalf of Baker Norton, that
in heavy pharmaceutical patent actions of this kind the fact that two large
drug companies are facing a common enemy does not, as he put it, "make them
friends." Many important commercial decisions, and the consequential effect
upon other potential litigation, may lurk just below the surface of a case like
this, thereby justifying that each party has its own legal advisers in the
fray. The proper target of the judge should not have been separate
representation as such, but any unreasonable duplication of expense by the two
sets of representatives. The proper point at which to consider that is on
detailed assessment by the costs officer, and not by the arbitrary order which
the judge made.
Order:
(1) The Appeal dismissed
(2) European Patent (UK) No. 0,584,001 be Revoked
(3) The Respondent's cross appeal be allowed and paragraph 3 of the order of
the Honourable Mr Justice Jacob dated Thursday the 1st day of
October 1998 be set aside
(4) The Appellant shall pay the first Defendant/Respondent's costs of the
action and counterclaim, and shall pay the Petitioner/ Second Defendants/
Respondent's costs of the petition, and the action and counterclaim such costs
to be assessed if not agreed.
(5) The appellant should pay the Respondents costs of the appeal and cross
appeal such costs to be assessed if not agreed
(6) That the revocation of European Patent (UK) No. 0,584,001 referred to in
paragraph (2) above to be stayed [pending the determination of an application
by the Appellants to leave to petition the House of Lords and thereafter, if
granted, until final determination of such appeal]
(7) Permission to Appeal to the House of Lords to be refused.
(Order does not form part of the approved judgment)
BAILII:
Copyright Policy |
Disclaimers |
Privacy Policy |
Feedback |
Donate to BAILII
URL: http://www.bailii.org/ew/cases/EWCA/Civ/2000/169.html
