Beecham Group' Limited v. Bristol Laboratories Limited (Patent, Interlocutory injunction Ch.D., C.A.) IN THE HIGH COURT OF JUSTICE-CHANCERY DIVISION

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1 406 [No. 16] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [1967] Beecham Group' Limited v. Bristol Laboratories Limited IN THE HIGH COURT OF JUSTICE-CHANCERY DIVISION Before MR. JUSTICE LLOYD-JACOB 3rd, 6th, 7th and 8th March, and IN TIlE SUPREME CoURT OF JUDICATURE-COURT OF ApPEAL Before THE MASTER OF THE ROLLS (LORD DENNING) LORD JUSTICE DAVIES AND LORD JUSTICE RUSSELL 20th, 21st and 24th April, BEECHAM GROUP LIMITED v. BRISTOL LABORATORIES AND ANOTHER LIMITED Patent-Infringement-Interlocutory injunction-patent prima facie valid Manufacture of drug by patented process abroad and import into United Kingdom -whether patent infringed by such importation-colourable imitation-substance of invention taken-interlocutory injunction granted. 15 The plaintiffs were the owners of two patents covering the process of manufacture and the product known as 6-apa, or 6-aminopenicillanic acid (the penicillin nucleus). Though the defendants disputed the validity of these two patents, there was established a prima facie case of their validity. The plaintiffs also owned a further two patents covering the process for the manufacture of, and the product ampicillin, 20 which was a derivative made by acylating 6-apa. Ampicillin w'as found to have exceptional therapeutic value. The prima facie validity of these two patents was similarly established. The defendants were about to launch on the market in this country a product made in the United States by acylating 6-apa in the presence of acetone to produce a third product, hetacillin. However, the evidence established 25 that ampicillin was in fact formed just before it was turned into hetacillin, and that in use hetacillin reverted in the blood stream to ampicillin which was the effective curative agent. The plaintiffs' application for an interlocutory injunction was refused by Lloyd-Jacob, J., on the ground that he was unable to resolve on motion the issues of fact raised both as to validity and infringement. On appeal:- 30 Held, allowing the appeal, that if a person making a product overseas used as a principal part of his manufacture processes which would be infringing processes if performed here, and imported the product, he was guilty of infringement, for by so doing he deprived the patentee of the benefit at the invention. It was proved that hetacillin was equivalent to ampicillin, and there was recognised authority that 35 infringement was not avoided by trifling or unessential variations. Accordingly an interlocutory injunction would be granted. 5 10

2 407 [1967] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [No. 16] Beecham Group' Limited v. Bristol Laboratories Limited ;Saccharin: Corporation Ltd. v. Anglo-Continental Chemical Works Ltd. (1900) 17 R.P.C. 307; Saccharin Corporation Ltd. v. Reitmeyer & Co. (1900) 17 R.P.C. 606; Van per Lely N.V. v. Bamfords Ltd. [1963] R.P.C. 61 at 75, followed. This was a motion by the plaintiffs, Beecham Group Limited, for an interlocutory 5 injunction to restrain the defendants, Bristol Laboratories Limited and Bristol Myers Company, from infringing the plaintiffs' patents Nos. 870,396; 870,395; 873,049 and 902,703. The relevant facts and the arguments of counsel in the court of first instance appear sufficiently from the following judgment. Patrick Graham, Q.C., and Stephen Gratwick, instructed by Simmons & Simmons, 10 appeared for the plaintiffs. G. W. Tookey, Q.C., and G. D. Everington, instructed by Slaughter & May, appeared for the defendants. Lloyd-Jacob, J.-By this motion the plaintiffs seek an interim injunction to restrain the two defendants from infringing four letters patent. These letters patent are the result of a research programme which the plaintiffs undertook from about Shortly stated, the letters patent are as follows: No. 870,396 describes and claims a process for the preparation of 6-aminop'enicillanic acid (referred to in the evidence as 6-apa and sometimes called, I understand, penicillin nucleus) and the material when prepared by the process therein described. No. 870,395 is the preparation from that material, 6-apa, of the so-called semi 20 synthetic penicillin by an acylation reaction. The preferred product, known as ampicillin, is marketed by the plaintiffs under the brand name PENBRITIN, and the evidence shows that currently sells to a value of several million pounds a year. No. 873,049 is a development of that second specificationwherein certain specified amino substituted groups are employed for the acylation, and it covers in parti cular the penicillin derivative alpha-aminobenzyl penicillin. No. 902,703 is a further development, whereby the two optically isomeric forms of alpha-aminobenzyl penicillin can be separately prepared, and both the process and the product are claimed in that specification. The actual ampicillin which the plaintiffs market is the dextro epimer which, according to the evidence, appears to 30 be the more effective anti-bacterial agent of the two forms. The first defendants are an offshoot of the second defendants, a United States corporation, who, in the past, have had amicable relations with the plaintiffs. The American corporation is in fact licensed to operate in the United States of America under the corresponding United States patent. However, the prospect ot entering 35 upon the lucrative market in this country has persuaded them to enter upon the activity which is complained of in the present proceedings, and they have recently commenced to import from the United States and to market in this country an anti-bacterial agent of the semi-synthetic penicillin type, to which the name. of hetacillin has been applied and which is sold by the first defendants in this country 40 under the brand name VERSAPEN. In the manufacture of that material in the United States, the evidence show's that the makers follow the licensed process for preparing 6-apa and this they then acylate, but, instead of isolating and recovering the ampicillin so formed, they react it with acetone, a step' which is neither mentioned nor foreshadowed in any of the letters patent in suit, and as a result they produce this 45 hetacillin. The evidence asserts that when that hetacillin is introduced into the human body it will be hydrolised by the patient's metabolism and converted, so to speak, in vivo, to ampicillin, It is obvious, therefore, that the alleged acts of infringement are

3 408 [No. 16] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [1967] indirect in the sense that it cannot be said that they fall specifically within any claim of any of the letters patent. The argument on infringement is put in a number of different ways. First, it is said that because in its manufacture this hetacillin requires the exercise of the invention which is claimed in No. 870,396 (that is to say, it requires the initial 5 preparation of 6-apa as a fundamental step), the importation into the United Kingdom of a derivative therefrom is in fact an infringement of No. 870,396. Secondly, it is said a fortiori by the application to that material of the acetylation reaction, the subject of No. 870,395, then an additional step of infringement has taken place. 10. Thirdly, which is additional or alternative, it is asserted that this hetacillin is either a chemical or a medical or pharmaceutical equivalent of ampicillin and, by parity of reasoning with the mechanical oases, wherein it is the established law that the substitution of a mechanical equivalent has been held not to avoid infringement of a patent claim, these substances in the present case should be treated as 15 obvious alternatives of the material which is described and claimed in the specification. Fourthly (and if the facts in fact support it, it is possibly the strongest way of putting the act of infringement) it is said that the introduction into this material of acetone is a step of no genuine significance whatsoever, it serving only to obscure 20 the colourable quality of the imitative intention of these defendants who are out to secure, it is said, the real substance of the plaintiffs' invention. The defendants strenuously contest all four. In the course of developing their argument they have had occasion, at any rate on the face of it, to denigrate the value of the step which these four specifications embody. The plaintiffs themselves 25 assert that this was really a striking breakthrough in a very important field of activity, and there is no question that on the evidence they have the support of gentlemen who are very well known for their activity in this field. The defendants say that, properly regarded, if anything, it was only a very modest contribution, almost wholly foreshadowed by the work of two Japanese workers. In consequence, 30 these parties, who have been closely associated in the past, now find themselves substantially at ann's length. As to the first tw10 points, that is to say, the assertion that because hetacillin in its manufacture requires the preparation of 6-apa and additionally its acylation, they say that you have only got to look at these specifications which relate to that 35 to notice the absence of product claims therefor, and they assert that the process claims can only avail them within the realm to which the monopoly which they confer extends and, as it is conceded there is no alteration of either of those processes in this country, there is no act of infringement of which the plaintiffs can complain. 40 They say the objection, therefore, must be understood as not being one of operating in accordance with the patent monopoly, because that is territorially limited, but rather that of denying to the patentees the benefit of the monopoly which the grant of the letters patent confers upon them, namely, to secure to themselves the financial benefit of operating in accordance with the grant. 45 It is a fact that the books do contain cases wherein that alleged type of infringement (has been considered and has received the approval of, at any rate, two judgments of the Chancery Courts; but the defendants strongly question the applicability

4 409 [1967] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [No. 16] of those judgments in the present circumstances. I refer to Saccharin Corporation Ltd. v. Anglo-Continental Chemical Works Ltd. (1900) 17 R.P.C. 307, and Saccharin Corporation Ltd. v. Reitmeyer & Co. (1900) 17 R.P.C They urge that in any event the application of the principles therein set out require much closerconsidera- 5 tion of all the circumstances of their trading than can be properly undertaken on consideration of the affidavits filed on motion. They point out that, having regard to the re-statement of the law as it appears in the Act of 1949, authorities which dealt with the scope to be afforded to process claims may well have been substantially modified by the provisions in the Act with regard to freedom of patentees to 10 include product claims within their specification. As to the third point (that is to say, by parity of reasoning with the mechanical equivalent cases) they say that you can search the books and fail entirely to find any case wherein any court has accepted as an infringement a case wherein the mechanical equivalent is of all the characteristics set out in the claim, and that in 15 truth that doctrine has been confined, and has necessarily to be confined, to the cases wherein a substantially immaterial integer specified in the claim has been substituted by something which every person skilled in the art would have appreciated was its obvious and plain alternative. In consequence, it is said that this doctrine is applicable only to cases wherein there is a substitution of a non-essential feature 20 in the strict sense. When this is added to the submission which they urge, that, so far as the cases go, there has been no translation of that doctrine either to chemical or medical cases, they point out that there must be scope for very considerable argument indeed not only on the law, but also on the facts, before the court can proceed on the basis of the substitution of one particular chemical for another or 25 the introduction of one 'chemical reaction either as an alternative or as an additional step in the manufacture of these materials, and that it is quite undesirable that a point of that significance should be determined on motion, As to the fourth point, the colourable imitation point, they strenuously contest the basis upon which that is averred. They say that before this court is entitled to 30 assume an imitative intention such as would justify perhaps some elasticity in the application of the principles of patent jurisprudence, it is plainly reasonable that they are entitled to an opportunity to lead the fullest evidence and to develop the fullest argument in relation to what they have in fact done in the preparation of this material and its introduction into this country. They urge'-and to my mind 35 they urge with great force-that an interlocutory hearing of this sort is not a suitable opportunity wherein the court should be invited to arrive at a decision on points as significant as those I have formulated. It is certainly quite impossible for me to say at this stage that there is no substance in the objections Which they raise. Accordingly, I am not myself satisfied that the plaintiffs have established a sufficient 40 prima facie case of 'infringement of any or all of these four letters patent such as to justify me in making an order which would in fact stop altogether further dealing by the defendants in these materials. Having come to that conclusion, it is unnecessary for me to deal in any detail with the other two points which were argued in the case for really two reasons. 45 The first one, of course, is that it is very undesirable for the judge hearing the motion, when he is also likely to be the judge at the final hearing, to indicate even a prima facie view unless it is absolutely necessary he should do so. As I have already indicated, quite shortly, the validity of these letters patent is called into question in part, it being suggested that some earlier work by Mr. 50 Sakaguchi and his associate Mr. Murao had sufficiently foreshadowed the isolation

5 410 [No. 16] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [1967] of this so-called penicillin nucleus that thereafter the course of manufacture whereby it is obtained and its subsequent acylation to provide active penicillin did not provide an exercise for any inventive ingenuity. There is no question, if you look at the evidence, that there is strong support for the assertion the plaintiffs make that this was a very definite and marked break- 5 through in penicillin chemistry and that the citation can be attacked on the ground that, although it does in fact contain a representation of the graphical formula of 6-apa, it is put forward merely as a speculation and, further, that the identification of the physical characteristics of the substance to which that graphical formula refers quite plainly is not comparable with the actual characteristics of 6-apa. On 10 the other hand, it can be asserted that the disclosure was of sufficient significance to a skilled person in the art-and I refer in particular to Professor Chain-for him to make inquiries of the two Japanese gentlemen who were responsible for the publication and to make a determined effort on his part to receive materials and endeavour to repeat the treatment with their enzyme of one of the penicillins, the 15 name of which escape's me at the moment, which was the subject matter of this disclosure, It so happened that when he sought to repeat that Which the writers of the article asserted they had done, he had no success. He asserts-and he is entitled to assert on motion-i-that similar experience seems to have been found with other workers in the field. Quite what the truth of that is one cannot tell until one! hears 20 the whole of the evidence and determines it. Had I taken a different view on the question of infringement, I do not think it is likely that I should deny to the plaintiffs some relief merely on the ground of what is asserted with regard to the validity of these four specifications, The other point, of course, was the question of the balance of convenience. As 25 I think I have indicated during the course of the argument, if I was able to persuade myself that there was here a sufficient prima facie case established on validity and infringement of these letters patent, I cannot see that the court ought to deny to the plaintiffs the protection which the grant of these letters patent was intended to give to them merely because' the defendants have entered upon a commercial 30 programme which would involve them in very considerable 'expense and which, if brought to an abrupt halt, may possibly affect in some way their reputation and prestige in this country. That seems to me to be a risk which they took up/on themselves when they decided to start in this way. Anyway, for the reasons I have endeavoured to give, I find myself unable to 35 accede to the plaintiffs' motion for an injunction and I must dismiss the motion. Tookey-My Lord, I ask that the motion be dismissed with costs. Lloyd-Jacob, J.-I do not think I can do that, Mr. Tookey. There is undoubtedly a point to be argued. I think the costs of the motion should be costs in the cause. Tookey-If your Lordship pleases. 40 The plaintiffs appealed from this decision to the Court of Appeal, being represented as below. Graham, Q.C.-The plaintiffs object that the importation and sale of hetacillin in the United Kingdom constitutes an infringement of four of their patents, and in particular two of them, No. 870,396, which describes and claims a process of 6-45 aminopenicillanic acid (hereinafter referred to as o-apa), and No. 870,395 concerning a process to produce from 6-apa by acylation a semi-synthetic penicillin known as ampicillin. Hetacillin starts with 6-apa: then it is acylated, but instead of isolating

6 411 [1967] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [No. 16] and recovering ampicillin, the defendants react it with acetone. Thereby a compound of a different chemical formula is produced, but when hetacillin is introduced into the human body it will be hydrolised and produce ampicillin. The plaintiffs sell their ampicillin in 65 countries, their export amounts to 40 per 5 cent. of the United Kingdom's export of drugs. In the year ending 31st March 1965 the sales of ampicillin in the United Kingdom amounted to 6,000,000 and the export to 8,000,000. The second defendants have the exclusive licence to produce ampicillin in the United States subject to the right of the plaintiffs to sell o-apa there. The defendants have not applied for a compulsory licence in this country. The 10 patents are nine and six years old respectively, and they have never been successfully attacked. The isolation of the penicillin nucleus was a breakthrough in the antibiotic field. The sale of hetacillin would cause damage to the plaintiffs which could not be compensated by money. That damages are an inadequate remedy in such a case is shown by the Court of Appeal decision in Hoffman-La Roche & Co. A.G. v. 15 D.D.S.A. Pharmaceuticals Ltd. [1965] R.P.C. 503 and Hoffman-La Roche & Co. A.G. v. Inter-Continental Pharmaceuticals Ltd. [1965] R.P.C Hetacillin in an infringement of the plaintiffs' patents on the saccharin principle. Alternatively it is an infringement as a colourable imitation or as a chemical equivalent, for the following reasons :- (1) it infringes the patent for manufacture of 6-apa, 20 and the ampicillin patent because it is a basic derivative of 6-apa. (2) It is only a colourable imitation of ampicillin because it changes into ampicillin in the bloodstream. Importation into this country has been held to be an indirect infringement of the monopoly granted. The form of the grant is contained in the Fourth Schedule to the Patent Rules, 1958, to be found in Terrell on Patents (11th Edn.) para The question of validity of the patents is disposed of by the evidence of Professor Robinson and Professor Chain. As to infringement; the locus classicus is Saccharin Corporation Ltd. v. Anglo-Continental Chemical Works Ltd. (1900) 17 R.P.C. 307; see also paragraphs 364 and 365 of Terrell as to infringement by sale. This is a' different case from Wilderman v. F. M. Berk,& Co. Ltd. (1925) 42 R.P.C. 79 at Von Heyden v. Neustadt (1880) 14 Ch.D. 230 decided that importation ofan article which is the result of the use of a patented process is an infringement. It has been argued. by the defendants that the Saccharin oase was no longer good law because the Patents Act of 1949 amended the law relating to claims. The correctness of the Saccharin case was doubted by the Court of Appeal in an unreported case. 35 It was decided under the Patents Act, 1883 which provided that distinct claims as to the scope of the invention had to be made. It is said that one must now claim a product expressly. Under the 1919 Act one could only claim a new substance as made by a particular process. The Patents Act, 1949 went back to the former position. 40 The allegation of infringement on the basis of the Saccharin case is to be distinguished from infringement on the basis that there has been a colourable imitation. Under the Saccharin doctrine, the plaintiffs say that although the respondents acylate 6-apa to ampicillin outside the United Kingdom, they bring in hetacillin to this country and thereby deprive the appellants of the profit of their invention. On the 45 basis of colourable imitation. although hetacillin is ostensibly different from ampicillin, yet on realities it is only adisguised form of what is claimed, that is of ampicillin. The prohibition of infringement by colourable imitation is derived from Clark v. Adie (1877) 2 A.e. 315 at 320. It is clear from Kerr on Injunctions (6th Edn.) page 312, that the intention of the potential infringer is immaterial. The doc- 50' trine was affirmed recently in Van Der LeZy N.V. v. Bamfords Ltd. [1963] R.P.C. 61. The submission that hetacillin infringes by being a colourable imitation applies

7 412 [No. 16] REPORTS OF PATENT, DESIGN AND TRADE MARK. CASES [1967] strictly to claim 5 of patent No. 873,049, and claim 1 of No. 902,703. There is the same result, and it is for the same purpose. Hetacillin is the equivalent of ampicillin, with merely colourable differences. It is not here suggested that there has been a substitution of an integer of the claim, but rather a quite immaterial addition. The proposition that there may be infringement when the defendant has made additions 5 to what is claimed received its authority from Proctor v. Bennis (1887) 4 R.P.C. 333 at 353 and Wenham Gas Co. Ltd. v. Champion Gas Lamp Co. (1892) 9 R.P.C. 49 at 56. Tookey, Q.C.-The plaintiffs have alleged that Bristol in some way" jumped the gun" and has referred to the Hoffman-La-Roche cases in this respect. Those cases 10 have no relevance to the present case in which there is a genuine dispute as to infringement. In those cases there had been an application for a compulsory licence, and so the Comptroller " held the gun," in that such a licence had to be granted by him. Furthermore, there is no legal or moral objection to apply for a declaration of non-infringement under section 66, although it was suggested by the plaintiffs that IS the defendants should have done this. The plaintiffs' case is not that there has been direct infringement of any of their four patents, but that there has been infringement by virtue of the decision in the Saccharin case, and that there has been infringement by virtue of equivalence to what is claimed. It is to be noted that all their evidence on this asp'ect of infringe- 20 ment is medical, not chemical, evidence. Rodi and Weinenberger v. Henry Showell Ltd. [1966] R.P.C. 441 at 464 refers to the doctrine on equivalence derived from Clark v. Adie, and states the nlodern law. The court must decide what are the essential elements in a claim, and whether these have been taken by the infringer. If this applied to claim 1 of No. 873,049 for example, it is clear that the essential 25 features are not taken. Similarly with claim 5, which is a claim to a specific chemical compound. There is no claim in any of the four patents whose essential features have been taken. The Saccharin case [1900] 17 R.P.C. 307 was subsequently heard on appeal, but was settled before judgment was given [1901] 1 Ch, 414 at 418. Fletcher-Moulton on 30 Patents (1913 edn, at page 158) suggests that the views of the Court of Appeal were not the same as those of Buckley, J., in the court below. The Patents Act, 1949 requires that the claims shall define the scope of the invention claimed. The Saccharin case can no longer be good law in view of the requirements of this Act. On the question of validity, Sakaguchi and Murao disclosed the chemical structure of 6-apa, 35 claimed in claim 1 of No. 870,396. The second affidavit of Professor Scott states the basis of Bristol's attack on the validity of the four Beecham patents. To what monopoly are the plaintiffs entitled? They isolated the material and found out the melting point of 6-apa; they verified what the Japanese surmised. Can they get a monopoly for the product, however it is made? Such a claim would be a blocking claim. The 40 identical claim was refused in the United States on the strength of these Japanese documents. That is all they are entitled to on patent No. 870,396. The other patents are the result of routine research work. There is a serious dispute as to the validity of the claims of the patents on which the plaintiffs rely. Invalidity is apparent on the face of the evidence, in the light of which the plaintiffs were only entitled to a patent 4S for their process of manufacture of 6-apa, but not to claim the already known product per se however made. Claim 1 has the same wording as the cited Japanese paper. This case is far removed from the HofJman-La-Roche cases. There the Court of Appeal held that the attack on validity was highly speculative. As to infringement, the Saccharin case did not survive the Act of The first case on importa- 50 tion was Elmslie v. Boursier (1870) L.R.9 Eq There it was held that selling in

8 413 [1967] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [No. 16] this country an article manufactured abroad according to a British patent was a violation of the privileges granted by the patent. In Von Heyden v. Neustadt (1880) 14 Ch.D. 230 there were no claims either formal or informal. It was decided that the patent was wide enough to cover the imported product of the process for making 5 salicylic acid. The Patents Designs and Trade Marks Act of 1883 required claims to be inserted at the end of the complete specification. In the Saccharin case in 1900 it was held that it was wide enough to cover the importation of saccharin made abroad by the use of an intermediate produced in accordance with the process claimed in the patent. There were no product claims in the patent either to the intermediate 10 product or to the saccharin. The Patents and Designs Act, 1919 introduced section 38A into the Act of 1907, which provided that in the case of inventions relating to substances prepared by chemical processes, the specification must not contain claims to the substance except when produced by the special processes described and claimed. The Patents and Designs Act, 1932 amended. section 38A by substituting 15 for the words ~, by the special... processes... described and claimed," the words, by the "processes of manufacture particularly described and ascertained." The Patents Act, 1949 omitted section 38A, but the Act uses the expression" the invention... as claimed in any claim." See particularly sections 7 and 32. If the Saccharin case is good law, extraordinary results would follow. In order to 20 be safe one would have to see whether any substance used in manufacture was patented. The patent ought to say what is protected, otherwise: it is against the whole trend of patent law. Competitors should know what they are entitled to do. Section 66 of the Act of 1949 does not apply to anything which is not claimed. Sub-section (3) excludes attacks on validity, and does not therefore assist the defendants; see 25 Dunlop Rubber Co. Ltd. v. Long-life Battery Depot [1958] R.P.C On the balance of convenience; damages under a cross-undertaking are difficult to assess. The judge has exercised his discretion against the plaintiffs. It is not a case where the Court of Appeal ought to interfere. Graham, Q.C., in reply-hetacillin is an infringement of all three patents, of the 30 product as well as the process claims because it is a colourable imitation. Diplock, I...I.J., accepted in the Rodi and Weinenberger case the statement of Upjohn, L.J., in the Van der Lely N.V. v. Bamjords Ltd. [1961] R.P.C. 296, at 312 line 35. As to the Saccharin case principle: the Act of 1949 has not limited the extent of the grant. In order to change the law, clear words are necessary; per Lord Wright in Secretary 35 of State v. Bank of India [1938] 2 All E.R. 797, at 802, letter H. Lord Denning, M.R.-Beeeham Group Limited have produced in England a most valuable drug to combat disease. It is called ampicillin and is distributed under the trade name of PENBRITIN. It is covered by patents in this country and all over the world. The sales run into millions of pounds. In the United States of America 40 there is a company, Bristol-Myers Company, who under licence produce: this selfsame drug, ampicillin. Arrangements have been made between Beecham Group Limited and Bristol-Myers whereby the American Company exploit the market of the United States, Canada and many other countries. In January of this year the American Company through an English subsidiary, 45 Bristol Laboratories Limited, started to bring into this country for sale a rival drug which is oalled hetacillin. It is said to be as effective as ampicillin in combating diseases. It is made in America but is distributed here under the name VERSAPEN. Beeehams claim that hetacillin is an infringement of their patents for ampicillin. They aplply to the 'court for an interim injunction to prevent the sale of hetacillin 50 in this country. They say that, although made in the United States of America, it

9 414 [No. 16] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [1967] is made by processes which, if done here, would be infringing processes of their own patents: and on that account when it is brought into this country and sold here, it is an infringement of their patents. The first question is whether the English patents are valid. The American company have challenged the validity of those patents, even though they have been 5 working under them in the United States. The history is this: After penicillin itself was discovered during the last War, a great deal of research was done to try to isolate the penicillin nucleus. About 1950, some Japanese workers suggested a formula for the structure of the penicillin nucleus, but they did not succeed in isolating it. It was first isolated in 1957 and made available by research workers at 10 the Beecham Research Laboratories. Their discovery was acclaimed everywhere as a fundamental break-through in antibiotics. The penicillin nucleus is called by the scientists 6-aminopenicillanic acid. In this court for short we have called it 6-apa. By isolating it, the research workers opened the way to the making of a whole new series of penicillins which are known as semi-synthetic penicillins. 15 The research workers of the Beecham company patented their discovery. In 1958 they filed patents Nos. 870,395 and 870,396. These patented the process by which 6-apa was produced, and also the product itself, 6-apa. The validity of those patents has been challenged here today and is said to be a matter worthy of argument. But it seems to me that these patents have been recognised as valid for so long and in 20 so many countries that we should accept for present purposes that they are valid. Professor Chain, himself a Nobel Prizewinner (who was given the prize for discovering, with Sir Alexander Fleming and Sir Howard Florey, the curative properties of penicillin) said: "I have no hesitation in stating my conclusion that 6-apa was not isolated or available until the work of Doyle, Nayler and Robinson." Those 25 three were the Beecham research workers. It seems to me that there is a prima facie case of validity for those two patents. There are two more patents equally important. They cover a derivative which has special curative properties called ampicillin, The research workers found that by inducing a chemical reaction which is scientifically known as " acylating " the 30 6-apa, they could produce the drug called ampicillin, It is the subject of two patents. One of these, No. 873,049, in claim 1 claims a group' of penicillin derivatives in accordance with a specified formula: and in claim 5 a particular member of their group, alpha-amino-benzylpenicillin, which for short is called ampicillin. The other patent, No. 902,703, claims the discovery of the epimers, which are particularly 35 valuable in producing ampicillin of the most effective kind. Those two patents together cover a process for producing ampicillin, and the product itself. The validity of these patents also has been challenged here today. But these two patents also have been accepted so long and so widely that we should accept for present purposes that they are valid. Professor Chain said of these: 40 "The specific derivative of 6-aminop,eniciUanic acid, alpha-amino-benzylpenicillin could not have been predicted from the prior art. Still less could it have been predicted that that derivative would have particularly useful properties. Indeed, the discovery of this most valuable antibiotic resulted entirely and undisputedly from the work of Doyle, Nayler and Smith in the invention 45 which forms: the subject matter of British patent No. 873,049." On all these points Sir Robert Robinson, who is of the highest eminence himself, confirms the views of. Professor Chain. He describes ampicillin as a " highly important novel preparation." In my opinion we should assume prima facie the validity of these four patents. 50

10 415 [1967] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [No. 16] The next question is whether the English patents have been infringed by the importation and sale in this country of the drug hetacillin, Structurally it is a different product from ampicillin. But it is made by a process which is almost identical with the process for ampicillin, except for a small addition. In this drug 5 hetacillin you start again with this fundamental penicillin nucleus, 6-apa, and then you acylate it, so to speak, but with the addition of an acetone. The reaction of these chemicals together gives the product hetacillin, But, in the course of the chemical reaction, there is a point of time when there is ampicillin present just before it is turned into hetacillin. After the hetacillin is produced and used as a 10 medicine (by being injected or inserted into the bloodstream) the process is reversed. The hetaoillin in the blood turns into ampicillin, and then the ampicillin destroys the injurious germs in the system. It is the ampicillin which is really the curative. The result is this: first, hetacillin is made by processes which are essentially similar to the patent processes, the only difference being the addition of acetone. 15 Second, hetacillin has the same medical effects as ampicillin when it gets into the bloodstream. In this situation it is clear that if the hetacillin was manufactured in this country, it would be an infringement of the patent. But it was not made in this country. It was made in the United States and then brought over and sold here. Does this 20 infringe the patent? The law on this subject was stated by Buckley, J., in Saccharin Corporation Ltd. v. Anglo-Continental Chemical Works Ltd. [1901] 1 Ch. 414; (1900) 17 R.P.C The plaintiffs had a patent for a process for making a substance called orthotoluene-sulpho-chloride, It was very useful in making saccharin. The defendants 25 overseas used the self-same process of ortho-toluene-sulpho-chloride, they used it to make saccharin, and then Tmported the resulting saccharin into this country. Buckley, J., held that this importation was itself an infringement of the patent. He said (ibid, at 319, line 21) : " If the patented process were the last stage in the production of the article 30 sold, the importation and sale of the product would, in my opinion, plainly be an infringement. Does it make it any the less an infringement that the article produced and sold is manufactured by the use of the patented process which is subjected to certain other processes? In my opinion it does not. By the sale of saccharin, in the course of the production of which the patented process is 35 used, the patentee is deprived of some part of the whole profit and advantage of the invention, and the importer is indirectly making use of the invention." That was followed by Cozens-Hardy, J., in Saccharin Corporation Ltd. v. Reitmeyer,& Co. [1900] 2 Ch. 659; 17 R.P.C This view of the law was accepted by Tomlin, J., in Wilderman v. Berk,& Company Ltd. (1925) 42 R.P.C. 79, save that 40 he pointed out that the patented process must play a principal part in the final product. If the use overseas of the patented process was in an unimportant and trifling respect-playing a minor part in the whole product-s-then the importation and sale here would not be an infringement. He said: "In my judgment, each, case must be determined on its own merits by reference to the nature of the invention, 45 and the extent to which its employment played a part in the production of the article, the importation of which is complained of." Mr. Tookey urged us to say that those cases were no longer good law since the Patents Act of But, having studied the sections to which he has referred us, I cannot deduce from them any intention by the legislature to throw any doubt on 50 those cases. Prima facie these cases still represent the law in this country. If a

11 416 [No. 16] REPORTS OF PATENT, DESIGN AND TRADE MARK. CASES [1967] person, in making a product overseas, uses processes which would be infringing processes here-those processes being a principal part of the manufacture-s-and then imports the article into this country, he is guilty of an infringement. The reason is because, by using those processes overseas and bringing the product here to sell, he deprives the English patentee of the benefit of the 'invention. 5 The evidence here shows that in making hetacillin in the United States the defendants use a principal part of the processes which are protected here by the English patents. The importation and sale here is prima facie an infringement. There is a further point. A person is guilty of infringement if he makes what is in substance the equivalent of the patented article. He cannot get out of it by some 10 trifling or unessential variation. In Van Der Lely N.V. v. Bamiords Ltd. [1963] R.P.C. 61 at 75 Lord Reid, quoting James, L.J., said: " It has long been recognised that there' may be an essence or substance of the invention underlying the mere accident of form; and that invention, like every other invention, may be pirated by a theft in a disguised or mutilated 15 form, and it will be in every case a question of fact whether the alleged piracy is the same in substance and effect, or is a substantially new or different combination.' " On the evidence as it stands, there is ground for saying that hetacillin is medically equivalent to ampicillin, As soon as it is put into the human body, it doe's, after an 20 interval, by delayed action, have the same effect as ampicillin. In these circumstances I think there is a prima facie case for saying there was an infringement. The process is so similar and the product so equivalent that it is in substance the same as ampicillin. So I would hold, departing in this respect from the learned judge, that there is 25 prima facie evidence of infringement of these English patents by the importation and sale in this country of the drug hetacillin. That brings me to the last point, which is called the balance of convenience. Is it a case in which an interim injunction should be granted? We were told it may be two years and perhaps more before this case can come to trial. If the plaintiffs are 30 right, yet are granted no injunction, they will suffer greatly. Their market in this valuable drug may be captured, in part at least, by the drug hetacillin. Once doctors or patients get used to it, they will go on using it. But, on the other hand, the defendants have been to muoh expense in making all their arrangements for the importation and sale and in their advertising and marketing of hetaoillin. It would 35 be very damaging to them to have an injunction granted against them. On this point I follow the Hoffmann-La Roche cases (Hoffmann-La Roche & Co. A.G. and Geigy S.A. v. Intercontinental Pharmaceuticals Ltd. [1965] R.P.C. 226; and Hoffmann-La Roche & Co. A.G. v. D.D.S.A. Pharmaceuticals Ltd. [1965] R.P.C. 503) which were decided in this court. The defendants should not be allowed to "jump 40 the gun." They were warned beforehand that Beechams would take action. As soon as the defendants started selling hetacillin, Beechams lost no time. They applied for an injunction. I think they have acted speedily and have brought before us a sufficiently prima facie case to justify the grant of an interim injunction. I would allow the appeal and grant the injunction asked. 45 Davies, L.J.-I agree in every respect, and, although we are differing from the learned judge, feel I cannot usefully add anything.

12 417 [1967] REPORTS OF PATENT, DESIGN AND TRADE MARK CASES [No. 16] Russell, L. J.-The question is whether there is a prima facie case of, first of all, validity of the plaintiffs' patent and, secondly, infringement. As at present advised, I think there is a prima facie case under both heads. I add nothing on the question of validity. On infringement, here there seems to me to be a mere addition (which S I am prepared to accept is perhaps useful) to the plaintiffs' invention. The defendants' product is an antibiotic and nothing else. The fundamental essential of the defendants' product is the antibiotic ampicillin, which is the plaintiffs' invention. The application of acetone to ampicillin, in appropriate conditions of acidity, alters, it is true, the chemical composition of the defendants' product so as to make that 10 chemical composition different from that of ampicillin; but the process leaves, and deliberately leaves, the ampicillin, so to speak, latent, awaiting its necessarily intended re-emergence in the alkaline condition of blood or intestines. Thus, it seems to me the whole of the plaintiffs' invention is taken and incorporated in the defendants' antibiotic product and is the whole of the antibiotic element in the 15 defendants' product, On that broad ground it seems to me prima facie there is here a case of infringement. So far as balance of oonvenience is concerned, I think there is great force in the point which was put forward on behalf of the plaintiffs that it would be very 20 difficult as a practical matter for the plaintiffs to demand and insist upon a perpetual injunction at the trial, if over a period of what we have been told may be two to three years waiting for the trial to come on, the defendants are given free range to introduce their product in this market, because it would be said: Here is a company which is quite wrongly depriving sick people of a drug which their 25 doctors want to give to them under the trade name which is given alone to the defendants' product. I agree that this is a case in which an interlocutory injunction ought to go. Appeal allowed with costs. Leave to appeal to the House of Lords refused. F.G.