Status: Positive or Neutral Judicial Treatment

*1 Bristol-Myers Squibb Co. v Baker Norton Pharmaceuticals Inc.

In the Court of Appeal

23 May 2000

[2001] R.P.C. 1

Before: Lord Justice Aldous Lord Justice Buxton Mr Justice Holman

May 23, 20001

H1 Patent—Taxol—Second medical use—Industrial application—Whether a new method of treatmentor a new therapeutic purpose—Novelty—Obviousness—Sufficiency.

H2 Practice—Costs—Two defendants separately represented—Whether they should recover onlyone set of costs between them.

Patents Act 1977, sections 1(1), 2(1), (2), (6), 3, 4(2), (3).

European Patent Convention, Articles 52(1), (4), 54(5).

H4 Claim 1 of the patent in suit in an infringement action was as follows :

H5 “Use of taxol and sufficient medications to prevent severe anaphylactic reactions, formanufacturing a medicamentation for simultaneous, separate, or sequential application for theadministration of from 135 mg/m2 up to 175 mg/m2 taxol over a period of about 3 hours or lessas a means for treating cancer and simultaneously reducing neutropenia.”

H6 Taxol was known to interfere with cell division and the idea behind its use was to stop cancercells replicating. However, the effect on cancer cells was expected to go hand-in-hand withsuppression of other rapidly dividing cells particularly those producing the white blood cellsknown as neutrophils, an effect referred to as neutropenia. In early clinical trials with taxol manypatients developed severe hypersensitive (allergic) reactions. To minimise this, infusion times of24 hours were employed with premedication (a well-known technique) to reduce the danger ofreactions .

H7 Before the priority date, a lecture (the Winograd lecture) had publicly disclosed the initialstages of a new series of clinical trials comparing a 24-hour infusion with a 3-hour infusion usingtwo different dosages of taxol. With the premedication used, 3-hour infusion was shown to be asfeasible and as safe as 24-hour infusion. There was no disclosure, however, that neutropeniawas less .

H8 The acts complained of as infringements were clinical trials promoted by the first and thesecond defendants who provided the active ingredient and the instructions for its use. During thetrials women with ovarian cancer were treated *2 with premedication in an amount determined bythe doctor before infusion with taxol. In each case 175 mg/m2 of taxol was to be administeredintravenously every 21 days as a 3-hour infusion. The amount of taxol to be prescribed wasdetermined according to the patient's height and weight. During the infusion the patient wasmonitored for hypersensitive reaction.

H9 In the Patents Court the patent was found to be invalid on grounds of lack of novelty andobviousness (reported at (1999) R.P.C. 253), but in subsequently making an order for costs thejudge awarded the two defendants (who were separately represented) only one set of costsbetween them for all but the initial stages of the action. The proprietor of the patent appealed tothe Court of Appeal, and the defendants cross-appealed on the order for costs .

H10 The appellant submitted that claim 1 of the patent was an effective “Swiss-type” claim asallowed by the European Patent Office in Eisai/Second medical indication (Decision G05/83)based on the previously unknown suitability of taxol for treating cancer when infused in the

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claimed amount over 3 hours and the reduction of neutropenia. The appellant submitted that inany case novelty did not have to reside in a second or subsequent therapeutic use, relying uponMobil/Friction reducing additive (Decision G02/88).

H11 The respondents submitted that if claim 1 could derive novelty from Eisai that case had beenwrongly decided. They also submitted that the alleged infringements were treatments of humansby therapy which were matters not capable of industrial application under section 4(2) of thePatents Act 1977 (Article 52(4) EPC); if there was infringement the claim was invalid .

H12 Held, dismissing the appeal and allowing the cross-appeal :

H13 (1) Section 4(2) (Article 52(4) EPC) was not intended to excludepharmaceutical-preparations from being patentable. It had the limited purpose of ensuring thatthe actual use, by practitioners, of methods of medical treatment when treating patients shouldnot be subject to restraint or restriction by patent monopolies. The question was whether therestraint concerned a method of treatment as opposed to what was available for treatment.(paras 61–62)

Eisai/Second medical indication (Decision G05/83), (1985) O.J. E.P.O. 64, and Wyeth (John) &Brother Ltd's Application, (1985) R.P.C. 545 (Whitford and Falconer JJ.), referred to.

H14 (2) Second medical use (“Swiss-type”) claims must be limited to a therapeutic application orpurpose which was not only inventive but new. The decision in Eisai was justified by analogyfrom cases of first medical use, where patentability necessarily entailed the use of the substancefor a new and completely different purpose from that in relation to which it was already known.The relationship between the first and the second medical use must be of the same nature; thesecond medical use must be for an end-purpose distinctively different from the first, albeit alsomedical, purpose for which the substance was used. That followed also from the exclusion ofmethods of treatment from patentability. The novelty must lie, not in the method of use, but in thenew therapeutic purpose for which the substance was used. (paras 83–87, 109) .

Eisai/Second medical indication (Decision G05/83), (1985) O.J. E.P.O. 64, Wyeth (John) &Brother Ltd's Application, (1985) R.P.C. 545 (Whitford and Falconer JJ.), and Bristol-MyersSquibb Co. v. Yew Tree (Netherlands Court of Appeal, June 25, 1998), followed. *3

H15 (3) The Mobil case did not qualify or amplify the conclusion reached in Eisai. The decision inEisai was based on the interplay between Articles 52(4) and 54(5) EPC, whereas Mobildepended upon purposive construction of the claims so as to limit the claims to the product whenused. In the Mobil case, the claim to an additive in lubricating oil for reducing friction should beinterpreted as a claim to the product when used for reducing friction. Such a claim would benovel if the use had not previously been made available to the public. However, a Swiss-typeclaim could not be interpreted as relating to the product when used because that would constitutea method of treatment prohibited under Article 52(4) EPC. (paras 40–41)

Mobil/Friction reducing additive (Decision G02/88), (1990) E.P.O.R. 73, (1990) O.J. E.P.O. 9,explained.

H16 (4) In claim 1 of the patent in suit, the words “for treating cancer” when construed in contextmeant “suitable for trying to treat cancer”. What was suitable was a question of fact, not ofperception. If the drug had a beneficial effect in the treatment of cancer, it would be suitable: ifnot, it would not be. The words “simultaneously reducing neutropenia” meant inducing lessneutropenia than would have been induced by the previous medical practice of administration.(paras 21–22, 101–102)

H17 (5) The discovery that less neutropenia occurred during the 3-hour infusion than during a24-hour infusion was a discovery and not a second therapeutic use as considered in Eisai. Thedrug, the method of administration and the therapeutic purpose were exactly the same and theonly difference was the discovery that if the drug was infused over a shorter period anundesirable side-effect was less than it otherwise would have been while the therapeutic effectremained. That was not the discovery of previously unrecognised properties in the compound.(paras 42, 46, 110–112)

Eisai/Second medical indication (Decision G05/83), (1985) O.J. E.P.O. 64, and PharmaceuticalManagement Agency Ltd v. Commissioner of Patents, (2000) R.P.C. 24 (New Zealand Court ofAppeal) distinguished.

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H18 (6) The invention claimed in claim 1 was a method of treatment excluded from patentabilityby section 4(2) (Article 52(4) EPC). When analysed it was directed step by step to the treatment.The premedication was chosen by the doctor, and administered prior to the taxol according to thedirections of the doctor. The amount of taxol was selected by the doctor as was the time ofadministration. The actual medicament that was said to be suitable for treatment was produced inthe patient under supervision of the medical team. What the patent taught was not how tomanufacture a drug for use in the treatment of a patient, but how to treat the patient. Theinvention was not capable or susceptible of industrial application as required by section 1(1)(c)(Article 52(1) EPC). (paras 63, 93–94, 107)

H19 (7) Claim 1 lacked novelty. The Winograd lecture disclosed that taxol was suitable for tryingto treat cancer using a 3-hour treatment, and it contained clear and unmistakable directions tocarry out a 3-hour infusion which would have had the inevitable consequence of lessneutropenia. That was a mere discovery about an old use and was not patentable. (paras 45–46,88)

Dow Sequestering agent (Decision T958/90), (1994) E.P.O.R. 1, and AmericanCyanamid/Melamine derivates (Decision T279/93), (1999) E.P.O.R. 88, applied.

H20 (8) The Winograd lecture had disclosed the whole of the inventive nature of the claimedprocess. To try infusion over a 3-hour period in the way suggested had *4 been obvious. Theskilled man doing so would inevitably have discovered that less neutropenia was induced, andthat was not an inventive step. (paras 53, 98, 113)

H21 (9) (per Buxton L.J.). On the assumption that the patent sufficiently described whateverinvention was claimed, the claim was for no more than what had already been revealed byWinograd. A clinician would not have risked changing to 3-hour infusion on a mere assertion ofefficacy without specific data. (paras. 95–96)

H22 (10) The losing party should only be required to pay the costs reasonably incurred by theother party or parties. For parties to do other than instruct one set of solicitors and counsel toface a common enemy could result in an unreasonable expenditure of costs for which the losingparty should not pay. But it did not follow that successful defendants who were separatelyrepresented, even if they adopted a common approach, should invariably be deprived of part oftheir costs. What costs were reasonably incurred should be ascertained by the costs judge whocarried out the assessment, when any unreasonable duplication of expense and failure toco-operate could be seen and adjustments made accordingly. If there were evidence before thejudge that certain costs were not reasonably incurred, then they should be disallowed. (paras70–73)

H23 Observed,

H24 (1) (per Aldous L.J.) So as to decide issues of construction in a real context, it was helpful toconsider infringement even if the patent were to be held invalid. (para. 14)

H25 (2) (per Holman J.) Only with considerable hesitation should the judge's discretion as tocosts be interfered with; the mor so as it was the discretion of a specialist judge in a specialistfield who was sensitive to good practice in that field. His aim, which was to discourage multiplerepresentation by parties fighting a common enemy on a common cause, was to be applauded.(para. 116)

H26 The following cases were referred to in the judgments:

American Cyanamid/Melamine derivatives (Decision T279/93) (1999) E.P.O.R. 88.

Bristol-Myers Squibb v. Yew Tree (Netherlands Court of Appeal, The Hague, June 25, 1998).

Dow/Sequestering agent (Decision T958/90) (1994) E.P.O.R. 1.

Eisai/Second medical indication (Decision G05/83) (1985) O.J. E.P.O. 64.

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General Tire & Rubber Co. v. Firestone Tyre & Rubber Co. Ltd (1972) R.P.C. 457 (CA).

Hill v. Evans (1865) 4 De G.F. & J. 288, 31 L.J. Ch. 457 (Lord Westbury L.C.).

Hydropyridine (Decision X ZB 4/83) (1984) O.J. E.P.O. 26 (German Federal Court).

Merrell Dow Pharmaceuticals Inc. v. H.N. Norton & Co. Ltd (1996) R.P.C. 76 (HL).

Mobil/Friction reducing additive (Decision G02/88) (1990) E.P.O.R. 73, (1990) O.J. E.P.O. 93,469.

Nycomed/Contrast agent for imaging (Decision T655/92) (1998) E.P.O.R. 206, (1998) O.J.E.P.O. 17.

Pharmaceutical Management Agency Ltd v. Commissioner of Patents (2000) R.P.C. 24 (NewZealand Court of Appeal).*5

Wyeth (John & Brother Ltd's Application [1985] R.P.C. 545 (Whitford and Falconer JJ.).

H27 Representation

Andrew Waugh Q.C. and Justin Turner, instructed by Simmons & Simmons, appeared for theappellant. Simon Thorley Q.C. and Henry Whittle, instructed by Roiter Zucker, appeared forthe first respondents. Simon Thorley Q.C. and Roger Wyand Q.C., instructed by Bird & Bird,appeared for the second respondents.

H28 This was an appeal by Bristol-Myers Squibb Co. from the decision of Jacob J. in the PatentsCourt ([1999] R.P.C. 253) in an action against Baker Norton Pharmaceuticals Inc. and NaproBiotherapeutics Inc. for infringement of European Patent (U.K.) No. 0584001 with a counterclaim forrevocation of the patent, when the patent was held to be invalid and was ordered to be revoked. Therespondents cross-appealed from the judge's decision on costs (not included in the report at [1999]R.P.C. 253).

Aldous L.J.:

1 Bristol-Myers Squibb Company are the patentees of EP (U.K.) 0584001. They appeal against theorder and judgment of Jacob J. of August 20, 1998 whereby he held that the patent was invalid andordered its revocation. The respondents, Baker Norton Pharmaceuticals Inc. and NaproBiotherapeutics Inc. support the conclusion reached by the judge.

2 The patent claims priority from a patent application filed in the USA on August 3, 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 genericname, paclitaxel. Taxol was not new in 1992. It was identified in 1962 as part of a screeningprogramme for anti-tumour agents initiated by the U.S. National Cancer Institute (NCI). Its activeagent was first isolated in 1971 from the bark of the Pacific Yew and at about the same time it wasshown to have anti-tumour activity in mice. Further work was hampered because of difficulties withprocurement, extraction and isolation, but those difficulties have now to a substantial extent beenovercome by the development of semi-synthetic routes of manufacture. Taxol is poorly soluble, partlyfor that reason it was not at first possible to devise a formulation. That was overcome in 1980 and thatenabled animal studies to be carried out. By 1983 the NCI were in a position to apply for regulatory

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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 theappellants:

“During the initial days of the clinical development of paclitaxel severe hypersensitivity reactionsto paclitaxel occurred in many patients. After receiving just a few milligrams of paclitaxel, thesepatients started developing an acute reaction, including skin rash, shortness of breath, reductionof blood pressure and cardiac rhythm abnormalities, forcing interruption of the paclitaxelinfusion.”

4 The judge described how the trials progressed in this way2: *6

“As a result the NCI (who at the time were supplying the taxol) required all Phase I trials to havean infusion time of 24 hours initially (coming down to a minimum of six hours if there was noadverse reaction) and the use of premedication. The idea was to minimise the danger of toxicshock. The slower infusion rate meant that the body was not exposed to the taxol as quickly as inthe case of shorter infusion times and the use of premedication likewise reduced the danger ofshock. 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 andpremedication together, when it later proved that allergic reactions were becoming much less of aproblem, it was not clear whether this was due to the premedication, or the prolonged infusion ora combination of the two. None of this mattered at the time. The heart of the trials was to seewhether taxol really worked—particularly in refractory cases. Avoiding allergic reaction by usingboth 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 NCIconcentrated upon ovarian cancer and malignant melanoma particularly, but the melanomastudies gave results not as positive as had been hoped. By 1989 out of all the studies thenconducted (15 in all) only 427 patients had been treated. It was apparent that the NCI could notgo it alone. So it sought a commercial partner. It did so by a competition for a CollaborativeResearch 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 taxoland fund further clinical trials leading to an application for regulatory permission. Twentycompanies were interested, four were interested enough to enter the competition and it was BMSwhich was successful in January 1991. BMS tackled the problem of supplies and undertookresponsibility for all the trials outside the U.S. including in particular the Canadian/Europeanstudy 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 ofresearch and development of the appellants. That lecture was relied on by the respondents as thepublic disclosure which invalidated the patent. It was given at a major symposium in Amsterdam to anaudience estimated at 500. It will be necessary to consider the extent of disclosure made in thislecture, but at this stage of my judgment it is sufficient to outline what was said. Dr Winograddescribed the object and design of the study which was to evaluate the efficacy and safety of taxol inpatients with ovarian cancer which had previously been treated with platinum containingchemotherapy. He described how the Phase III studies had involved comprison of a 24-hourcontinuous infusion which had been used for the Phase II trials with a short time, 3-hour, continuousinfusion using two different dosages.

6 As was recounted by the judge, taxol interferes with cell division (mitosis). The idea behind its use isto stop the cancer cells replicating which they do rapidly. However it was well-known that other normalbody cells also replicate rapidly, in particular bone marrow cells. Bone marrow suppression istherefore an inevitable consequence of treating the body with chemotherapeutic agents that targetrapidly dividing cells. A fall in the white cell count with the consequent reduction of the bloodneutrophil count is known as neutropenia. It follows that neutropenia *7 is one of a number ofundesired, but inevitable, side effects of most forms of chemotherapy. It requires the patient's blood tobe regularly monitored to assess the degree of neutropenia which can be dangerous for obviousreasons. Since the mechanism of chemotherapeutic drugs on the cancer cells and the bone marrowis the same, there was a general expectation in the 1980s that the degree of neutropenia and thedegree of the effect on the cancer cells went hand-in-hand. The consequence of that was that those

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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”. Thespecification 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 cancerby McGuire et al . …

Unfortunately, taxol has extremely low solubility in water, which makes it difficult to provide asuitable dosage form. In fact, in Phase I clinical trials, severe allergic reactions were caused bythe emulsifiers administered in conjunction with taxol to compensate for taxol's low watersolubility; at least one patient's death was caused by an allergic reaction induced by theemulsifiers. Dose limiting toxicities include neutropenia, peripheral neuropthy, andhypersensitivity reactions.”

8 The specification then goes on to discuss the prior published documents concerning the use oftaxol. It continues in this way:

“The conflicting recommendations in the prior art concerning whether premedication should beused to avoid hyper-sensitivity reactions when using prolonged infusion durations, and the lack ofefficacy data for infusions done over a six hour period has led to the use of a 24-hour infusion ofhigh doses (above 170mg/m2) of taxol in a Cremoaphor EL emulsion as an accepted cancertreatment protocol.

Although it appears possible to minimise the side effects of administering taxol in an emulsion byuse of a long infusion duration, the long infusion duration is inconvenient for patients, and isexpensive 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 ortreatment clinic.

Thus, it is highly desirable to develop a taxol infusion protocol which would allow for recipients tobe treated on an out-patient basis. …

Even if infusion duration can not be shortened, it is also desirable to avoid the high dosages oftaxol presently believed necessary to have an antineoplastic effect, which induce a variety ofadverse side-effects, including respiratory distress, cardiovascular irregularities, flu-likesymptoms, gastrointestinal distress, hematologic complications, genitourinary effects,neuropathy, alopecia, and skin rashes.

Further, due to the extremely limited supply of taxol, and the high dosage *8 requirement for eachpatient, the demand for taxol greatly exceeds the supply.

Therefore, it is highly desirable to reduce taxol dosages, if possible, to both extend the supply oftaxol and reduce the toxic side effects of taxol. It is also highly desirable to decrease the timerequired 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 whichrequire less infusion time.

Therefore, it is a primary object of the present invention to provide new products containing taxolwhich allow to administer taxol over a shorter period of time than the present 6 to 24-hourinfusion 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 foradministration of taxol which reduce the amount of taxol administered to a patient, withoutsacrificing the antineoplastic effects desired by administering taxol.

It is yet a further object of the present invention to provide new products containing taxol for

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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 calleda “Detailed Description of the Invention”. There it is said:

“Despite the conventional understanding that it is necessary to infuse patients over a 24-hourperiod with high dosages of taxol (greater than 170mg/m2) following premedication to minimize oreliminate hypersensitivity responses, while obtaining the desired antineoplastic effect, it has beensurprisingly discovered that the new products containing taxol can be safely administered tocancer patients via infusions lasting 3 hours or less at dosages of 135mg/m2 to 175mg/m2. In apreferred embodiment, taxol is administered via an infusion having a duration of about threehours, with a taxol dosage of about 135mg/m2 or about 175mg/m2. Of great significance is asurprising discovery that the short term infusion causes less myelosuppression, which leads to alower incidence of infections and fever episodes ( e.g. , febrile neutropenia). Following thepreferred infusion schedules of the present invention provides an objective response rate ofgreater than 10 per cent for patients suffering from epithelial ovarian carcinoma, and preferablyan objective response rate of 14 per cent or greater for groups of at least 150 patients sufferingfrom ovarian carcinoma.

The surprising discovery that taxol could be safely administered via a short infusion ( e.g. , overabout 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 patientquality of life.

It has also been surprisingly discovered that lower taxol dosages, such as about 135mg/m2 canbe 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 [sic] ofthe specification, namely shortening infusion time and *9 reduction in dosage are said to have beenachieved by the invention. The discovery relied on is that short infusion times of about three hours ata dosage between 135mg/m2 to 175mg/m2 are effective and can be safely administered. It should benoted that the specification also refers to the “surprising discovery” that the short term infusion hasthe added advantage of less myelosuppression.

11 The specification goes on to give details of the OV.9 study that had been conducted on patientssuffering from ovarian cancer who had been previously treated with platinum. A high degree ofsuccess, greater than 10 per cent objective response, was found. This was said to be “trulyastonishing since responses to drug refractory ovarian carcinoma are extremely uncommon”. Thespecification concludes in this way:

“The success of the use of the new taxol products and infusion protocol of the present inventionin the treatment of ovarian cancer makes it readily apparent that antineoplastically effectivedosages of taxol can be infused over much shorter time periods than was previously believedpossible, 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 inventionmay 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 ofcancer 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 thepresent invention. In particular, by use of a 3-hour infusion of about 135mg/m2 taxol, followingpremedication, a substantial reduction results in the frequency of myelotoxicity and neuropathyassociated with the administration of taxol to patients suffering from cancer. Further, patients whoexhibits severe hypersensitivity reactions can be rechallenged with taxol after treating the HSRsymptoms by use of an infusion of about 24 hours or greater, preferably using a dosage of about135mg/m2 to about 175mg/m2. Preferably, colony stimulating factors are administered to assist inameliorating myelosuppression.

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The use of lower dosages of taxol to achieve antineoplastic results will allow for patients to betreated with the present limited supply of taxol. Further, depending upon the toxicities noted in apatient during treatment with taxol according to the present products and protocol, the duration ofinfusion can be extended or shortened, or the taxol dosage can be reduced or increased, thusproviding more flexibility in treating cancer with taxol. Further, patients capable of handling higherdoses of taxol can be administered up to about 275 mg/m2; should the patient encounter severetoxicity, such as a severe neuropathy, the products and protocol of the present invention allowsfor 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, formanufacturing a medicamentation for simultaneous, separate, *10 or sequential application forthe administration of from 135mg/m2 up to 175mg/m2 taxol over a period of about 3 hours or lessas a means for treating cancer and simultaneously reducing neutropenia.”

Infringement

13 A person infringes a patent if, but only if, he does within the U.K. any of the things specified insection 60 of the Patents Act 1977 without the consent of the proprietor of the patent. In this case therelevant things are contained in section 60(1)(b) and (2). They must be read subject to the exceptionin subsection (5).

“60. —Meaning of infringement.

(1) Subject to the provisions of this section, a person infringes a patent for an invention if, butonly if, while the patent is in force, he does any of the following things in the United Kingdom inrelation 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 UnitedKingdom when he knows, or it is obvious to a reasonable person in the circumstances, thatits 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 aninvention if … he supplies or offers to supply in the United Kingdom a person other than alicensee or other person entitled to work the invention with any of the means, relating to anessential element of the invention, for putting the invention into effect when he knows, or it isobvious 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 aninvention 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.”

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14 The judge did not come to any conclusion on infringement, perhaps because he had held thepatent invalid or because it was accepted, on the construction he had placed on the claim, that therewas infringement. However, I believe it is helpful in this case to consider infringement so as to decidethe issues of construction in a real context.

15 The Particulars of Infringement alleged that the defendants infringed by “(a) offering for use in theU.K. the method of the claims; and (b) acting in concert with those who have used the said method soas 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 andthe instructions for its use were provided”. There is also an allegation of infringement by the supplyand 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 Ord. 104, r. 11(1)(2)(a) they supplied *11 particulars of those trials which wereaccepted to set out, in sufficient detail, what happened.

17 At Guy's, the Royal Marsden and Hammersmith hospitals, women with ovarian cancer weretreated with premedication before infusion with taxol. The amount of premedication was determinedby the doctor. It was administered at 12 hours, six hours and one hour before infusion. The trial wasdesigned so that in every case 175mg/m2 of taxol was to be administered intravenously every 21 daysas a three-hour infusion. The amount was determined according to the patient's height and weightand was ordered by prescription. During the infusion the patient was monitored for hypersensitivereaction. Reductions from the starting dose to 130mg/m2 and then to 98mg/m2 took place for patientswhose recovery neutrophil blood counts were not satisfactory. Complete blood counts wereperformed 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 treatcancer”.3 Mr Thorley Q.C., counsel for the respondents, accepted that as correct. He drew attention tothe fact that the patent did not give any teaching of the extent of the effect that taxol would have onpatients. A medicament was suitable for trying to treat cancer if it had an effect on some patientseither by reducing the carcinoma or the extent or speed of growth. Upon that basis he accepted thatthere had been infringement if claim 1 was valid.

20 Mr Waugh Q.C., who appeared for the appellants, did not suggest that the judge was wrong in hisconstruction of the words “for treating cancer”. However, he submitted that the approach of the judgedid not reflect his construction in that it did not adequately take account of the requirement foreffective treatment. The patent disclosed that taxol was an effective treatment at the claimed rate andduration even though it was not successful in every case. That was the position in the trials alleged toinfringe. 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 incontext. The skilled addressee would realise that drugs which were suitable for treatment would notalways 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 thedrug 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 nostated amount from which reduction was to take place. He concluded that those words meant that themedicament had to be suitable for “reducing neutropenia as compared with what it would be ifadministration was for 24 hours”.4 I agree, but I would place a gloss upon his conclusion bysubstituting the words “lessening the amount of” instead of the word “reducing” for the reason, thattaxol 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 acceptthat the trials constituted infringement. *12

Validity

24 The respondents attacked the patent on three grounds. First that it was not new (see sections

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1(1)(a) and 2(1) and (2) of the 1977 Act)); second the invention did not involve an inventive step (seesections 1(1)(b) and 3 of the 1977 Act); third that it was not capable of industrial application (seesections 1(1)(c) and 4 of the Patents Act 1977). As those issues are to an extent interrelated it isconvenient 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 aresatisfied, 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 anytime before the priority date of that invention been made available to the public (whether inthe 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 personskilled in the art, having regard to any matter which forms part of the state of the art by virtueonly 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 industrialapplication 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 therapyor of diagnosis practised on the human or animal body shall not be taken to be capable ofindustrial application.

(3) Subsection (2) above shall not prevent a product consisting of a substance orcomposition being treated as capable of industrial application merely because it is inventedfor use in any such method.”

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25 The grounds of invalidity relied on require a decision as to whether the invention satisfied theconditions set out in the Act. To decide whether they were satisfied recourse has to be made to theclaims of the patent, in this case claim 1, as section 125 states that an invention of a patent shall betaken to be that specified in the claim. *13

Novelty

26 26. An invention is new unless it “has at any time before the priority date of the invention beenmade 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 inventionclaimed 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 toappreciate that two of the integers claimed had not been disclosed in the Winograd lecture; secondhe had failed to apply the right test, and third he had wrongly distinguished the decisions of theEnlarged Board in Eisai GR05/83 and Mobil Oil G02/88.

29 There can be no doubt that an invention can only have been made available to the public if thereare clear and unmistakable directions to do that which the patentee invented. As the Court of Appealsaid in the General Tire and Rubber Company v. The Firestone Tyre and Rubber Company Ltd [1972]R.P.C. 457 at 486:

“If, …, the prior publication contains a direction which is capable of being carried out in a mannerwhich would infringe the patentee's claim, but would be at least as likely to be carried out in away which would not do so, the patentee's claim will not have been anticipated, although it mayfail on the ground of obviousness. To anticipate the patentee's claim the prior publication mustcontain clear and unmistakable directions to do what the patentee claims to have invented: … Asignpost, however clear, upon the road to the patentee's invention will not suffice. The priorinventor must be clearly shown to have planted his flag at-the precise destination before thepatentee.”

30 Mr Waugh placed particular emphasis upon the well-known statement by Lord Westbury L.C. inHill v. Evans (1861) 4 DE G.F. & J. 288 at 301 5:

“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 purposesof practical utility, be equal to that given by the subsequent patent. The invention must be shownto have been before made known. Whatever, therefore, is essential to the invention must be readout of the prior publication. If specific details are necessary for the practical working and realutility 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 subsequentstatement 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 acomparison between the specification of the patent and the disclosure in the prior art. Thus, thestatement of the law as to novelty by Lord Westbury has to be read with that in mind and, when soread, is consistent with the *14 statement of the law by the Court of Appeal in General Tire. To thatstatement should be added the teaching of Lord Hoffmann in Merrell Dow Pharmaceuticals Inc. v.H.N. Norton & Co. Ltd [1996] R.P.C. 76 as to the effect of the 1977 Act. In that case novelty wasclaimed for the metabolite of terfenadine which was produced in the liver after consumption ofterfenadine. At the priority date terfenadine and its production was known by use and publication ofthe patent describing its production, but the metabolite had not been identified. The House of Lordsheld 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 notpurport 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.

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It is therefore part of the state of the art if the information which has been disclosed enables thepublic to know the products under its description sufficient to work the invention.”

32 He went on at 90 line 40 to conclude:

“In this case, knowledge of the acid metabolite was in my view made available to the public bythe terfenadine specification under the description ‘a part of the chemical reaction in the humanbody produced by the ingestion of terfenadine and having an anti-histamine effect’. Was thisdescription 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 orsynthesising the acid metabolite. But for the purpose of working the invention by making the acidmetabolite in the body by ingesting terfenadine, I think it plainly was. It enabled the public to workthe invention by making the acid metabolite in their livers. The fact that they would not have beenable to describe the chemical reaction in these terms does mean that they were not working theinvention. Whether or not a person is working a product invention is an objective factindependent 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 theterfenadine, he said page 91 line 26:

“Anticipation by disclosure, on the other hand, relies upon the communication to the public ofinformation which enables it to do an act having the inevitable consequence of making the acidmetabolite. The terfenadine specification teaches that the ingestion of terfenadine will produce achemical reaction in the body and for the purposes of working the invention in this form, this is asufficient description of the making of the acid metabolite. Under the description the acidmetabolite 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 aneffective treatment for cancer when administered over a period of 24 hours. Their case for noveltydepended upon the last part of claim 1, namely that the medicament was for administration at theclaimed dosage over about three hours as a means for treating cancer and simultaneously reducing*15 neutropenia. Thus the claim in broad terms was for the use of two known products to produce amedicament with the novelty relied on being provided by the alleged new application. The appellantssubmitted that such a claim was novel according to the principles laid down by the Enlarged Board inthe 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 theuse of a substance or composition for the manufacture of a medicament for a specified new andinventive therapeutic application. even in a case in which the process of manufacture as suchdoes 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 considerablediscussion amongst patent lawyers. Its importance was recognised by Whitford J. and Falconer J.who sat ien banc to decide whether it should be followed in this country. They held in John Wyeth andBrothers Ltd's Application and Schering Ag's Application [1985] R.P.C. 545 that it should be. Theyconcluded 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 theposition as it had developed in the courts of Convention States, the better view would be thatSwiss-type claims would not be patentable as they would lack novelty under the Patent Act 1977 andby parity of reasoning under the EPC. They went on to remind themselves that it was necessary tohave regard to the decisions of the courts of Member States of the EPC and also decisions of theEPO, particularly the enlarged board. Having referred in detail to the reasoning of the Enlarged Boardin Eisai, they held at page 567:

Page 12

“The approach of the Enlarged Board of Appeal to the question of the novelty requirement in aSwiss type use claim directed to a second or subsequent medical use may be summarised, itseems, as follows:

1. Because of the provisions of article 52(4) (first sentence) (which corresponds to section 4(2) ofthe 1977 Act), the normal type of use claim, whereby a new use of a known product may beprotected, is not open to pharmaceutical inventions directed to the use of medicaments in amethod of medical treatment.

2. However, no intention to exclude second (and subsequent) medical indications from patentprotection, 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 thelegislative history of the material articles thereof.

3. In that regard the Swiss-type of use claim now being considered is not prohibited by article52(4) and is capable of industrial application.

4. As to novelty, the Board consider that in the type of claim specifically provided for in article54(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 thenew pharmaceutical use. *16

5. Similarly, in the Swiss type of use claim directed to the use of a known pharmaceutical in themanufacture of a medicament, not novel in itself, for a novel second (or subsequent) therapeuticuse, the required novelty of the claimed process may be found in the new second (orsubsequent) 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, notwithstanding the opinion expressed earlier as to the better view of the patentability of such aSwiss type claim under the material provisions of the Act considered without regard to theposition, as it has developed under the corresponding provisions of the EPC, having regard tothe desirability of achieving conformity, the same approach should be adopted to the novelty ofSwiss-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 EnlargedBoard 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 newsecond (or subsequent) therapeutic use”. Mr Waugh submitted that claim 1 did relate to a secondtherapeutic use, namely use of taxol for the claimed period and in amount for the reduction ofneutropenia. He submitted that in any case novelty did not have to reside in a second or subsequenttherapeutic 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 infringementwere referred to by Lord Hoffmann in Merrell Dow. For the purposes of this case, it is necessary toappreciate what was actually decided and there is no need to become involved in the infringementdifficulties. The Enlarged Board summarised their conclusions in this way in paragraph 10.3 of theirdecision:

“… with respect to a claim to a new use of a known compound, such new use may reflect a newlydiscovered technical effect described in the patent. The attaining of such a technical effect shouldthen be considered as a functional technical feature of the claim ( e.g. the achievement in aparticular context of that technical effect). If that technical feature has not been previously madeavailable to the public by any of the means set out in article 54(2) EPC, then the claimedinvention is novel, even though such technical effect may have inherently taken place in thecourse 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 ofinvalidity. Thus prior use that did not make the invention available to the public could not invalidatethe invention. Similar reasoning was applied by the House of Lords in Merrell Dow. Secondly, a

Page 13

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 inlubricating oil for reducing friction should be interpreted as a claim to the product when used forreducing friction. Such a *17 claim would be novel if the use had not previously been made availableto the public. However it is relevant to note that similar reasoning cannot be applied in relation to aSwiss-type claim, as such a claim cannot be interpreted as relating to the product when usedbecause 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. Thedecision in Eisai was based upon the interplay between Articles 52(4) and 54(5) of the EPC; whereasMobil depended upon purposive construction of the claims so as to limit the claims to the productwhen 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 aclaim for a second therapeutic use. The medicaments in question were known to be suitable fortreating cancer. The remainder of the claim relates to the way that such a medicament was to beused. A similar conclusion was reached by the Dutch Court of Appeal in Bristol-Myers Squibb v. YewTree of June 25, 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 studywere to evaluate the efficiency and safety of taxol in patients with ovarian cancer previously treatedwith platinum containing chemotherapy. A two by two trial was used; long time infusion over 24 hoursversus a short time infusion over three hours using 135mg/m2 and 175mg/m2 doses. The lecturediscloses that the main impact on hypersensitivity was the premedication. The incidence of significanthypersensitivity reaction was said to be minimal with the premedication used. Thenon-hypersensitivity reactions were not more frequent in the three-hour arms which meant that thethree-hour arms were feasible and as safe as the 24-hour arms. Dr Winograd gave generalinformation as to the haematological toxicity showing that recovery occurred in almost all patients bythe 21-day period and only 10 out of the 270 courses needed to be delayed. His conclusion was thatthe three-hour infusion was as feasible and as safe as the 24-hour dose. This he said was animportant finding in view of the speed of infusion. He concluded his explanation of the trials in thisway:

“Responses were seen in all treatment arms. It is too early really to give you a breakdown of thatbecause the follow-up of the patients is relatively short and the overall response rate seems toobe in the ball park of what has … and again this is a multi-centre study; the overall responserate seems to be in the ball park of what has been published up to now and has been presentedin 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 claimedamount over a period of 3 hours. Secondly, 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 tobe suitable for treating cancer. Anybody listening to the lecture would have realised that thethree-hour arm of the trial had not shown adverse hypersensitivity and was safe and that a responsehad been shown which Dr Winograd categorised as in the ballpark of what had been published up tonow. *18 No doubt it would have been sensible to await the conclusion of the trials, but the lecturedisclosed that taxol was suitable for trying to treat cancer using a three-hour treatment.

46 The second submission depends upon the discovery that less neutropenia occurred during thethree-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 three-hour, 135mg/m2 infusion, described in the lectureand as such cannot impart novelty to the claim. As the judge held, the public could, using theinformation in the lecture, carry out the disclosed and claimed three-hour infusion with premedicationwithout the need of any information from the patent. Such a person would inevitably monitor thepatient's blood and would inevitably find the extent of neutropenia that occurred. The lecturecontained clear and unmistakable directions to carry out such a three-hour infusion and the resultwould inevitably be that which was claimed. The information given in the lecture enabled the public tocarry out an act which would have the inevitable consequence of less neutropenia. That conclusion is

Page 14

consistent with the attitude expressed by the Technical Boards in Dow Chemical Company T.90/0958and American Cyanamid T.93/0279. In my view the judge came to the right conclusion. Claim 1 lacksnovelty.

47 Mr Thorley submitted that if claim 1 could derive novelty from the Eisai or Mobil decisions, theywere wrongly decided. In a formidable attack upon Eisai, he criticised the way that the EnlargedBoard had interpreted Article 54(5) of the EPC and had failed to give proper effect to the view thathad been expressed at the Munich conference. He also drew attention to the Report of the FrenchCour 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 tothe correctness of Eisai were right and I decline to do so. However, it is relevant to point out that Eisaihas been applied by the EPO since at least 1985 and was accepted as correctly stating the law in1985 by the Patents Court in the John Wyeth case. It has also, I believe, been applied by themembers of the EPC, except perhaps France. There are therefore strong reasons for maintaining theview 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. MrThorley is correct that the issues raised in the House of Lords were not the same as those that arisein this case, but even so, it is unlikely that this Court would conclude that it was wrongly decided whenthe House of Lords did not so conclude.

Obviousness

50 The judge expressed his view in this way6:

“I finally come to obviousness. I think this is a very plain case. Winograd had disclosedthree-hour infusion with premedication was safe from the point of view of toxic shock. It wasunknown 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 ofthree-hour infusion you would surely test for neutropenia. As I have said blood tests *19 wereroutine in this sort of clinical trial. There simply cannot be any invention in pressing on with theOV.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. Hedrew attention to the evidence of Professor Calvert to the effect that the study disclosed in theWinograd lecture was unusual and that, until it was completed, no conclusion could have been drawnto adopt a three-hour infusion period. The obvious period of infusion was that which had been shownto be effective in the past, namely a six-to 24-hour infusion period. It was not obvious to carry out athree-hour infusion without evidence that it was effective. If he had attended the lecture, he would nothave been encouraged to use a three-hour infusion and would not risk changing without full resultsshowing that it would be effective.

52 Upon that evidence Mr Waugh submitted that the claimed three-hour infusion could not have beenobvious until it was known that the three-hour treatment was as effective as the 24-hour regimen andalso that it resulted in a reduction in neutropenia. Neither of those matters were disclosed in theWinograd lecture.

53 Of course Professor Calvert and others would not change from a 24-hour to a 3-hour treatmentwithout the results of the completed study. They would be treating patients with cancer and thereforewere subject to restraints that would not apply to normal manufacturing. Further, with the knowledgethat the study was nearly complete, they would not start new trials themselves as that would onlyresult in duplication for no useful purpose. But that does not mean that it was not obvious, in thesense of lacking invention, to carry out the trials which had been disclosed in the lecture in the waysuggested. There could be no invention in administering to a patient premedication and taxol with athree-hour infusion of the claimed amount as that was one of the arms of the trial disclosed in thelecture. If so, the amount of neutropenia was inevitable. In my view the judge came to the rightconclusion for the right reasons. Claim 1 was obvious.

Method of Treatment

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54 The judge rejected the attack upon the patent based upon sections 1 and 4 of the 1977 Act. Hesaid7:

“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 viewby the consideration that the Article 52(4) provision about methods of treatment is an exceptionto patentability and as an exception should be construed narrowly. As the Board of Appeal inHarvard/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 industrialapplication, which are new and which involve an inventive step. Any such exception must, asrepeatedly pointed out by the Boards of Appeal, be narrowly constructed ( cf. in particularT320/87, point 6 O.J. EPO 1990 76).’ *20

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 beconsidered. It is not so broad as to stop doctors using whatever they feel they need to treatpatients. If that were the purpose then one would not allow patents for medicines or medicalimplements at all. The purpose of the limitation is much narrower, merely to keep patent law frominterfering directly with what the doctor actually does to the patient. Patent monopolies arepermitted to control what he administers to, or the implements he uses on, the patient. Thethinking behind the exception is not particularly rational: if one accepts that a patent monopoly isa fair price to pay for the extra research incentive, then there is no reason to suppose that thatwould not apply also to methods of treatment. It is noteworthy that in the U.S. any such exceptionhas gone, and yet no-one, so far as I know, suggests that its removal has caused any trouble.”

55 Mr Thorley Q.C. who appeared for the respondents submitted the judge had not taken into accountthe full effect of the claim. In the present case, the claim was alleged to have been infringed by clinicaltrials 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 thetrials. The foundation of the allegations of infringement was the trials. They were treatments ofhumans by therapy. If there was infringement, the claim included within it matters that were notcapable 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 tocover treatment of humans. He drew attention to the words “use of taxol” and “sufficient medicationsto prevent severe anaphylactic reactions” which appears in claim 1. Those words required use of twosubstances “for manufacturing a medicament”. He submitted that they did not come together to formthe medicament except in the body of the patient which meant that the manufacture referred to in theclaim was part of the treatment. The amount of the premedication, its type and form of administrationwere all determined by the doctor as was the dosage of taxol which was determined according to thesize 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 oftreatment than claim 1 without use of the word “treatment”. He submitted that the claim, althoughlooking like a “Swiss-type” claim, was not of that type. Such claims, to use the words of the EnlargedBoard in Eisai, were “directed to the use of a substance or composition for the manufacture of amedicament for a specified new and inventive therapeutic application”. An example being one of theclaims in John Wyeth case at page 560 line 12:

“The use of an aromatase inhibitor for the manufacture of a medicament for the therapeuticand/or prophylactic treatment of prostatic hyperplasia.”

The novelty in such a claim resided in the second medical use, whereas claim 1 of the patent requiredcombination in the patient of two components selected by the doctor to carry out a treatment alsocontrolled by the doctor.

58 The judge construed the claim as being limited to the manufacture of the medicament to be used

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in treatment. He contrasted such manufacture with the *21 exclusion from patent protection ofmethods of treatment: an exclusion to prevent interference “directly with what the doctor actually doesto the patient”. Mr Thorley accepted the purpose of the exclusion and that, if the claim was limited tothe 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 theparts of the claim that required action by doctors and how the claim was alleged to be infringed. Ifthere was infringement as alleged, the claim had to be construed so as to include a method oftreatment.

59 Mr Waugh supported the conclusion and reasoning of the judge. The claim was to a medicamentmade up from premedication and taxol, but subject to limitations as to suitability for treatment ofcancer 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 claimsallowed 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 NycomedT655/92. Having re-read the reasons for decision of the Technical Board in that case, I have beenunable 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 humanis not different in essential context from a claim directed at a method of treatment. The difference isone of form and both are in conflict with section 4(2) (Article 52(4)). In my view the form of the claimcannot always be determinative. To decide what is determinative regard must be had to the purposeof 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 excludepharmaceutical preparations from being patentable. That has the result that restrictions can beimposed by patentees upon treatment. The section has the limited purpose of ensuring that the actualuse, by practitioners, of methods of medical treatment when treating patients should not be subject torestraint or restriction by patent monopolies. The difficulty is to decide whether the restraint concernsa 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 bychanging the treatment from a 24-hour infusion to three hours a similar effect was obtained with lessneutropenia. That was a discovery that a change in the method of treatment provided the result. Theclaim is an unsuccessful attempt to monopolise the new method of treatment by drafting it along thelines of the Swiss-type claim. When analysed it is directed step-by-step to the treatment. Thepremedication is chosen by the doctor, and administered prior to the taxol according to the directionsof the doctor. The amount of taxol is selected by the doctor as is the time of administration. The actualmedicament that is said to be suitable for treatment is produced in the patient under supervision ofthe medical team. It is not part of a manufacture. In my view Mr Thorley is correct. The inventionmade and claimed was a method of treatment precluded from patentability by section 4(2) (Article52(4)). That is emphasised by the way the allegations of infringement were pleaded. *22

Costs

64 The judge gave leave to appeal against his order for costs. He ordered the appellants to pay therespondents' costs. However with two exceptions he imposed a limitation that from February 6, “thefirst and second defendants shall recover only one set of costs between them, to be taxed as if onlyone firm of solicitors were acting for both parties and the parties were represented by one leading andone junior counsel, and how that one set of costs is split between the first and second defendants is amatter for them”.

65 His reasons were:

“It seems to me that the governing principle should be that where there are two or more partiesfighting a common enemy, unless there are special circumstances, the court should lean infavour of one set of costs. One can always say that the second party might be better off if theyhad their own particular legal team. I am not always sure that is true: too many cooks often spoilthe 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

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under pressure to agree there should be one set of lawyers to face the common enemy. I thinkthe 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 clearwhat 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, normallyonly 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 italternatively, half costs each, from either February 5, 1998 or February 9, 1998, when certainletters were written. I do not think anything turns on those letters, as such. The patentees havemisconstrued them because they do not amount to an admission of joint tortfeasorship asbetween BMS and Napro.

To my mind, February 1998 is not an unreasonable sort of date to take. I propose, therefore, toaward only one set of costs from then on. Whether the award should take the form of one set ofcosts or should take the form that each defendant only gets half its costs from that date is amatter upon which I will hear counsel.”

66 The respondents applied to adduce further evidence as they believed that the conclusion reachedby the judge had been taken upon incomplete facts which they could not have reasonably foreseen tohave been necessary to place before him. In this respect they referred to the skeleton of theappellants put forward for the hearing as to costs. That sought an order that one set of costs shouldbe ordered upon the basis that the exchange of correspondence between the parties showed thatthere was no issue of fact on infringement. That was rejected by the judge upon the basis that theletters 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, ofsubstance to the basic facts.

67 The impetus for the case was the petition for revocation of Napro which was served on theappellants on May 14, 1997. That proceeded up to the issue of the *23 summons for directions onOctober 22, 1997. The appellants were not content to have the issue of validity tried alone and onNovember 26, 1997 issued proceedings for infringement against Baker Norton. Subsequently thoseproceedings were amended to join Napro. The petition and the action and counterclaims wereconsolidated on January 16, 1998.

68 Although the clinical trials alleged to be infringements were joint trials, the respondents are in otherrespects in competition. It was therefore not surprising that they were initially represented by separatesolicitors and junior counsel and no complaint was made that that occurred. In fact, their cases oninfringement differed until the first day of the trial in that they adopted different attitudes in theadmissions 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 juniorcounsel, but with Mr Thorley leading upon their behalf. It was their belief that such was appropriatehaving regard to the potential conflict between them which had resulted in Mr Thorley being excludedfrom a consultation on one occasion.

70 In my view the governing principle enunciated by the judge is too broadly stated. The governingprinciple is that the losing party should only be required to pay the costs reasonably incurred by theother party or parties. No doubt parties should be under pressure only to instruct one set of lawyers toface a common enemy, as to do otherwise could result in an unreasonable expenditure of costs forwhich the losing party should not pay. But it does not follow that successful defendants, even if theyadopt 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 twodefendants. No complaint was made, nor could it have been made, that both instructed solicitors andcounsel to advise them and to serve defences. The complaint upheld by the judge was that sometimein February, before the trial in July 1998, that position changed and it became unreasonable for thedefendants to be represented by their own solicitors and counsel. That being so, it was notreasonable for the appellants to pay both sets of costs. What was it that meant that it wasunreasonable for one of the parties to continue to be separately represented? The judge did notanswer that question, except to say that he was not saying that the solicitors acted improperly. His

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conclusion depended upon what he thought was reasonable for the losing party to pay, not upon anassessment as to whether one of the respondents had acted unreasonably. That became evident inthe discussion after judgment when Mr Whittle, who appeared for the respondents, raised the difficultquestions as to how the respondents were to split the one payment of costs between them in theabsence of agreement. That resulted in the judge ordering that how the one set of costs was to besplit between them “was a matter for them”. Did he expect that if agreement was not reached, theactual split would have to be decided by litigation? I am not sure how that would be done as he didnot 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 beliable to pay one set of costs as that was the amount that it was reasonable for a claimant to pay. Idisagree. A losing claimant should ordinarily pay the costs reasonably incurred by the parties that hetakes proceedings against. What costs are reasonably incurred by one or more defendants should beascertained by the costs judge who carries out the assessment. Upon such an assessmentduplication and failure to co-operate can be *24 seen and adjustments made accordingly. To decidewhat costs were reasonably incurred by defendants by considering what costs a losing client shouldpay, amounts to pre-judging the results of a detailed assessment without considering the facts. Thejudge's conclusion involved, by implication, a decision that the costs of one or both of the respondentshad been unreasonably incurred. That could not have been inferred from the fact that they hadseparate solicitors and counsel and he had no evidence before him to enable him to reach thatdecision. No such conclusion could be reached without looking at the full picture which of coursewould 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 issuesbetween the parties on the wrong basis. Successful parties are ordinarily entitled to their costsreasonably incurred. If there be evidence before the judge that certain costs do not fall within thatcategory, then they should be disallowed. In this case there was no such evidence and therefore thematter had to be left to the costs judge when carrying out the detailed assessment. Of course it isalways open to the judge to draw attention in his judgment to matters which he believes requireparticular investigation during assessment. I would therefore substitute for the judge's orders as tocosts 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 wouldtherefore dismiss the appeal. I would allow the cross-appeal on costs.

Buxton L.J.:

75 I gratefully adopt the account of the facts set out by and the notation used by Aldous L.J. Like him,I would dismiss this appeal. Because of the importance of the issues involved, and in deference to thearguments addressed to us, I venture to add some words of my own. In view of the terms of section130(7) of the Patents Act 1977 I shall address the requirements of the EPC rather than thecorresponding sections of that Act. No argument was addressed to us to suggest that that was aninappropriate 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 thatsecond medical use claims were, in principle, patentable inventions. The argument envisaged at leastthe possibility that even first medical use claims may be excluded from patentability if the substanceused is already comprised in the state of the art; but that in any event second medical use claimswere not permitted by the EPC. For reasons that I will develop, I do not think that it is open to us toact on those criticisms, even if they were thought to have force; but it will usefully illuminate the termsand extent of the provisions of the EPC regarding medical use claims to consider the criticisms madeof 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 Boardrecognised (at para. 21) that in the normal industrial field— *25

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“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 useof 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 thecase 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 ofmedicaments is concerned, in respect of which the normal type of use claim is prohibited byArticle 52(4) EPC. In effect, in this case the required novelty for the medicament which forms thesubject-matter of the claim is derived from the new pharmaceutical use. It seems justifiable byanalogy to derive the novelty for the process which forms the subject-matter of the type of useclaim now being considered from the new therapeutic use of the medicament and thisirrespective of the fact whether any pharmaceutical use of the medicament was already known ornot.”

79 That reasoning was criticised on two grounds. First, and somewhat tentatively, the respondentssaid that the terms of the EPC did not envisage any sort of use-based claims at all in connection withpharmaceutical products, and therefore there was no allowable category of first medical use claimsfrom which the allowability of second medical use claims could be derived by analogy. The premise ofthat argument seems ill-founded. It is difficult to see what the proviso to Article 54(5) of the EPC istalking about if it does not envisage use-based claims of same sort. Second, however, a moresubstantial argument was advanced in relation specifically to second medical use claims. That wasthat as a matter of construction of the proviso the reference to the exclusion of a case where the useof the product in “any” method of treatment is within the state of the art meant that once the productwas “within the pharmacy” the doctor was free, without threat of infringement, to prescribe it forwhatever treatment seemed best to him.

80 An argument in similar form appears to have attracted the Patents Court in Wyeth: see [1985]R.P.C. 545 at p. 565, line 20. For my part, however, I did not find it persuasive. It is far from clear thatthe wording of Article 54(5) should be read, as the argument requires, as referring to any methodwhatsoever . It is at least equally understandable that the refrence to exclusion from the state of theart is simply to the method on the basis of which novelty is claimed. Indeed, if the aim were to excludefrom further patentability any substance already used in a medical application, Article 54(5) couldhave simply said so: provided that its use for any other method of treatment, etc., is not alreadycomprised in the state of the art. And once that objection is excluded, the Enlarged Board'sconclusion seems, with respect, irresistible that, if a product can claim novelty on the basis of thenovelty of its first medical use, then production for a novel second medical use must equally satisfythe requirements of the EPC. And since by Article 52(4) products for use in methods of medicaltreatment are not to be regarded, on that ground alone, as not susceptible of industrial application, itfollows, 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 *26 or compositionfor 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 knownprocesses using the same active ingredient.”

81 This may seem to be merely a roundabout way of seeking to patent a medical process, and onethat only doubtfully gives proper weight to the first sentence of Article 52(4). It is not, however, in myview 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] R.P.C. 76 at p. 82, line 25 asto the undesirability of departing from decisions of the EPO may strictly speaking not have been partof the ratio of that case, they are considered and reasoned guidance of a unanimous House, which Ido not think we are free to depart from. The same view of the standing of the decision of the EnlargedBoard in Eisai was taken. though without the benefit of the guidance in Merrell Dow, by the PatentsCourt sitting in banc in Wyeth.

The limits of second medical uses as recognised in Eisai

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82 The conclusion that we ought to adopt the approach of the Board in Eisai requires us to lookclosely 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 theseexpressions appearing to carry the same meaning.

83 It is important in this enquiry to remember the emphasis placed by the Board on justification byanalogy from cases of first medical use. Recognition of first medical use as a subject of patentabilitynecessarily entails the use of the substance for a new and completely different purposes from that inrelation to which it is already known. If the Board's analogy is to hold, therefore, the relationshipbetween the first and the second medical use must be of the same nature: the second medical usemust be for an end-purpose distinctively different from the first, albeit also medical, purpose for whichthe substance was used. That not only follows from the structure of the Board's argument, but alsofrom the need to respect the exclusion of methods for treatment from patentability. If the novelty canlie in the nature of use, rather than in the end-result at which that use aims, then it is indeed themethod of treatment on which patentability rests.

84 It is reasonable to infer that this distinction was assumed by the Enlarged Board when they spokeof new therapeutic use; and at least some specific indication of it is to be found in the account, atparagraph 17 of the ruling in Eisai, of the Hydropyridine 8 decision, where the problem, not criticisedas 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 aninvention involving the use of a substance, already known as a medicament, to treat an illnessnot 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 veryexperienced judges of the Patents Court in Wyeth, who expressed the question as involving— *27

“the allowability of claims directed to an invention based on the discovery of a second (orsubsequent) pharmaceutical use of a known substance or composition, already known for aparticular medical use (or particular medical uses), the new use being unconnected with thepreviously known use or uses.” [1985] R.P.C. 545 at p. 556, line 24, emphasis supplied”.

86 That was equally the view of the Court of Appeal of the Hague in Bristol-Myers Squibb v. YewTree, a case concerned with the patent in suit in our case, which, as cited by the judge at paragraph60,9 described a second medical indication as—

“an application of a substance for a different therapeutic purpose (for example to fight anotherillness or for prevention instead of cure)”.

87 The novelty of the second medical use, on which its patentability rests, must therefore be found inapplications that are new in the terms used in Wyeth and Yew Tree. The novelty cannot lie in themethod 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 newin the terms of Article 54 of the EPC as it was understood in Eisai. The inventive step is to find that inthe 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 methodof administering an existing treatment; it is not a new therapeutic purpose. The judge was right tohold, at paragraph 66,10 that

“This is not a case of a second or other medical use. It is a case of mere discovery about an olduse.”

The invention is therefore not patentable.

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89 That suffices to dispose of this appeal, but in view of the argument addressed to us I should go onand consider other points relating to industrial application; method of treatment; and prior disclosureand obviousness in the light, in particular, of the Winograd lecture. It will be noted that discussion of anumber of these issues may be distorted by the fact that the premise on which they proceed, that theinvention 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 formanufacturing a medicamentation.”

91 The judge held, at paragraph 50,11 that he did not accept the respondents' argument that— *28

“the claim amounts to merely a method of treatment. It is to the manufacture of the medicines tobe 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 patent”.

92 But the “manufacture” to which the patent in suit relates is significantly different from the operationthat was understood to be in issue in, for instance, Wyeth. In that case the Patents Court said, [1985]R.P.C. at p. 563, line 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 treatdisease B’ is, in reality, a claim to the method of manufacture of such a medicament by usingsubstance A in its manufacture. Such a claim, therefore, would seem clearly to be a claim to aninvention capable of industrial application.”

93 In relation to the patent in suit, however, the manufacture claimed is not the use of the activeingredient, paclitaxel, in the manufacture of taxol; but the mixing in the hospital pharmacy of taxol andother ingredients to produce the medium that is injected into the patient. It is that latter process that issaid to be susceptible of industrial application, under Article 52(1) of the EPC. I am afraid that I foundthat assertion to be, at best, artificial, and one that I do not think would have been made were it notfor the need to demonstrate that the invention is not of a method of treatment. We were told that themixing process could be, and in some cases was, sub-contracted outside the hospital; but that doesnot prevent it from being a long way away from anything that in normal parlance would be consideredan industrial application; or, for that matter, as under the old English law, “manufacture”. As my Lordhas described, the mixing is of amounts and types of premedication, and of amounts of taxol, alldetermined 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 thepatient, the doctor will, or at least may, administer the drugs according to the guidance contained inthe patent. But that merely underlines that what the patent teaches is not how to manufacture a drugfor use in the treatment of the patient, which would be in form at least a Swiss-type claim, but how totreat 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 notpatentable.

Prior disclosure

95 I agree with my Lord that there was sufficient prior disclosure in the Winograd lecture for claim 1 ofthe patent to lack novelty. Further, the judge was, with respect, right to reject the argument that thepatent was novel in that it taught, as Winograd did not, that three-hour infusion was effective in thetreatment of cancer. The judge said, at paragraph 6312:

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“Nor does the case get any better by saying that the prior art contained no information abouteffectivity at 3-hours. The patent does not either—the *29 mere assertion of effectivity being, asthe evidence on both sides accepted, one which the skilled man would not accept on the data inthe patent.”

96 Conspicuous amongst the evidence was that of the appellants' witness Professor Calvert. He saidthat 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 doessufficiently describe whatever invention it is that it claims, the claim is for no more than had alreadybeen revealed by Winograd.

Obviousness

98 The part of the invention said to be unknown at the time of the Winograd lecture was the reductionin neutropenia. But, for the reasons indicated by the judge, identification of that quality did not requireinventive skill over and above the skills already taught by Winograd, since the skilled man armed withthe latter information would or at least could press on with the trials, and in so doing inevitably find outthe facts about neutropenia. That would be a discovery, but not an inventive step. The whole of theinventive 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 hegives.

Holman J.:

100 I also agree that this appeal should be dismissed. I gratefully adopt my Lord, Aldous L.J.'saccount of the facts, and respectfully agree with the detailed reasoning of both my Lords; and I willstate 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 beparaphrased by some such words as “whilst inducing less neutropenia than would be induced if thetaxol was administered over a 24-hour period” (the reference to 24 hours reflecting the previousmedical practice).

102 As the judge said, the words “as a means of treating cancer” also need to be given a specialmeaning. The patent itself describes a 10 per cent response in patients suffering from drug refractoryovarian cancer as a “high degree of success” and “truly astonishing”. So, sadly, the words can onlyrefer 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 asinteger (3). *30

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 anaphylactic reactions

(2) for manufacturing a medicamentation for simultaneous separate or sequential application

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(3) for the administration of from 135mg/m2 up to 175mg/m2 taxol

(4) over a period of about three 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 overa 24-hour period.

105 A dosage of between 135mg/m2 and 175mg/m2 is in fact a lower dosage than was conventionallyadministered over a 24-hour period; and indeed one of the advantages asserted in the patent is that itenables lower dosages to be used of a drug which is in short supply, thereby making it available formore patients. However, Mr Waugh Q.C., on behalf of the appellants, expressly disclaimed that anysignificance attaches to that particular fact; or, in other words, to the content (as a discrete matter) ofwhat 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 casequite shortly.

107 I respectfully disagree with the view of the judge that this patent was not a claim to a method oftreatment of the human body by therapy. In my view it clearly was. The element of “manufacture” ofthe “medicamentation” referred to in the claim is simply the preparation in the hospital pharmacy, orsome other convenient place, of the taxol itself and suitable anti-anaphylactic premedication, and themeasuring of them into the amounts prescribed or specified by the clinician for a particular patent. MyLord, Aldous L.J. has already described the process. It is clear that the clinician must make a decisionas to, and prescribe, the actual quantities of premedication to be given to, and taxol to be infused intothe particular patient and as to the period of infusion. Among other possible variables, the clinicianhas to take into account the height and weight of the particular patient. Everything that happens asdescribed in claim 1 of the patent is, or ought to be, under the direction of the clinician. It is “a methodof 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) ofthe 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 medicaluse?

109 I respectfully agree with the analysis by my Lord, Buxton L.J. as to the limits of second medicaluse claims, the validity of which was recognised by the Enlarged Board in Eisai. The conclusion of theEnlarged 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 orpurpose which is not only inventive but new.

110 Mr Waugh Q.C. placed reliance upon the recent decision of the Court of Appeal of New Zealandin Pharmaceutical Management Agency Ltd v. Glaxo Group, in which judgment was given onDecember 17, 1999. but it does not seem to me to *31 assist him. In their analysis of Eisai, the Courtof 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 factthe situation, that the novelty as well as the inventiveness resides in the newly discoveredpurpose 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

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advantageous properties in a chemical compound, the obligation to make patent protectionavailable 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 theattempt to treat cancer, is exactly the same. The only difference is the discovery that if the drug isinfused over a shorter period an undesirable side-effect, neutropenia, is less than it otherwise wouldbe, while the therapeutic effect remains. No “previously unrecognised advantageous properties in[the] chemical compound” have been discovered. All that has been discovered (important though thatdiscovery is) is that if the compound is administered over a shorter period, one of its disadvantageousside-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 thecases 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 Winogradlecture had clearly disclosed that infusion over a period of about three hours or less was possible andsafe, and that the overall response rate seemed to be “in the ball-park of what has been published upto now”. The only integer which could be said to be novel is integer (6)—whilst inducing lessneutropenia than would be induced over a 24-hour period. That had certainly not been disclosed byWinograd. 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 tryinfusion over a three-hour period; and if he did do so, he would inevitably discover that lessneutropenia was induced.

114 In short, in my view, in so far as this claim was novel (inducing less neutropenia) it was alsoobvious 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 industrialapplication, and (ii) it lacks novelty, and (iii) it lacks an inventive step. The judge was right to order itsrevocation.

Costs

116 I also agree that the cross-appeal as to costs should be allowed for the reasons given by myLord, Aldous L.J. I would like to stress, however, that it is only after considerable hesitation that Iwould interfere with the judge's discretion as to *32 costs; the more so as it is the discretion of aspecialist judge in a specialist field who is sensitive to good practice in that field. Further, I applaudthe judge's aim which was to discourage multiple representation by parties fighting, as he put it, acommon enemy on a common cause. That said, the judge himself gave leave to appeal from hisorder as to costs. Further, I was persuaded by Mr Whittle, on behalf of Baker Norton, that in heavypharmaceutical patent actions of this kind the fact that two large drug companies are facing acommon 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 caselike this, thereby justifying that each party has its own legal advisers in the fray. The proper target ofthe judge should not have been separate representation as such, but any unreasonable duplication ofexpense by the two sets of representatives. The proper point at which to consider that is on detailedassessment by the costs officer, and not by the arbitrary order which the judge made.

1. Paragraph numbers in this judgment are as assigned by the court.

2. [1999] R.P.C. 253 at 261.

3. [1999] R.P.C. 253 at 270 line 50.

4. [1999] R.P.C. 253 at 270 line 38.

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5. Sub nom. Hills v. Evans, 31 L.J.Ch. 457 at 463.

6. [1999] R.P.C. 253 at 280.

7. [1999] R.P.C. 253 at 274.

8. Decision X ZB 4/83, [1984] O.J. E.P.O. 26 (German Federal Court).

9. [1999] R.P.C. 253 at 278.

10. [1999] R.P.C. 253 at 279.

11. [1999] R.P.C. 253 at 274 lines 5, 23.

12. [1999] R.P.C. 253 at 279.

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