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Kirin-Amgen Inc and others (Appellants) v. Hoechst Marion Roussel Limited and others (Respondents). Kirin-Amgen Inc and others (Respondents) v. Hoechst Marion Roussel Limited and others (Appellants) (Conjoined Appeals)
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OPINIONS OF THE LORDS OF APPEAL FOR JUDGMENT IN THE CAUSE Kirin-Amgen Inc and others (Appellants) v. Hoechst Marion Roussel Limited and others (Respondents) Kirin-Amgen Inc and others (Respondents) v. Hoechst Marion Roussel Limited and others (Appellants) (Conjoined Appeals) ON THURSDAY 21 OCTOBER 2004 The Appellate Committee comprised: Lord Hoffmann Lord Hope of Craighead Lord Rodger of Earlsferry Lord Walker of Gestingthorpe Lord Brown of Eaton-under-Heywood HOUSE OF LORDSOPINIONS OF THE LORDS OF APPEAL FOR JUDGMENTIN THE CAUSEKirin-Amgen Inc and others (Appellants) v. Hoechst Marion Roussel Limited and others (Respondents)Kirin-Amgen Inc and others (Respondents) v. Hoechst Marion Roussel Limited and others (Appellants)(Conjoined Appeals)[2004] UKHL 46LORD HOFFMANN My Lords, The proceedings 1. Kirin-Amgen Inc ("Amgen"), a Californian pharmaceutical company, is the proprietor of a European patent (EP 0148605B2) relating to the production of erythropoietin ("EPO") by recombinant DNA technology. EPO is a hormone made in the kidney which stimulates the production of red blood cells by the bone marrow. The discovery by Amgen of a method of making EPO artificially for use as a drug was a significant advance in the treatment of anaemia, particularly when associated with kidney failure. Amgen market it under the name Epogen and the patent (which will expire on 11 December 2004) has been very profitable. 2. These appeals arise out of a dispute concerning both the validity and infringement of the patent between Amgen and two other pharmaceutical companies. Transkaryotic Therapies Inc ("TKT") is a Massachusetts corporation. It has also developed a method of making EPO, which it markets under the name Dynepo. It uses a process which it calls "gene activation" and the product been referred to in this appeal as "GA-EPO". Hoechst Marion Roussel Ltd ("Hoechst") is the English subsidiary of a well-known multinational pharmaceutical company which has been proposing to import GA-EPO into the United Kingdom. In three consolidated actions, Amgen claims that GA-EPO infringes the claims of the patent in suit and TKT and Hoechst claim a declaration of non-infringement and revocation of the patent. I shall for convenience refer to both Hoechst and TKT as "TKT" but it should be borne in mind that the only allegations of infringement in the United Kingdom arise out of the importation of the drug by Hoechst. 3. The science upon which recombinant DNA technology is based has been described in a number of judgments, not least in the admirable account given by Neuberger J in this case, much of which was reproduced verbatim by the Court of Appeal. I do not propose to repeat these passages but gratefully adopt them and will largely take them as read. The race for EPO 4. The technology for manufacturing proteins ("polypeptides") by the expression of recombinant DNA developed rapidly after the mid-1970s. The speed of development is illustrated by the decision of your Lordships' House in Biogen Inc v Medeva plc [1997] RPC 1, in which a recombinant method of making the antigens of a hepatitis virus was patented with a priority date of 22 December 1978 but was conceded to have been obvious by 21 December 1979. Pharmaceutical companies competed to be the first to plant the flag on some desirable protein. 5. EPO was a particularly elusive goal in the early 1980s because it was difficult to get hold of enough of the natural product to do the necessary research. To design the probes to find the gene, whether in a genomic or cDNA library, you first had to know the amino acid sequence of at least a part of the natural polypeptide. But the kidney makes such minuscule quantities that purified natural EPO was virtually unobtainable. In 1977 a team including Dr Takaji Miyake and Dr Eugene Goldwasser developed and published a protocol for purifying milligrams of EPO from large quantities of urine laboriously collected from patients suffering from aplastic anaemia: see Miyake et al, 252 J Biol Chem. 252 No 15, pp 5558-5564 (1977). Dr Goldwasser made some of this urinary EPO ("uEPO") available to Dr Rodney Hewick of Cal Tech, who tried to sequence 26 residues at the N terminus. (The protein has 165 residues). This information was published by Sue and Sytkowski in 80 PNAS USA, pp 3651-3655 (1983) but two of the residues were incorrectly identified. 6. The Amgen team trying to sequence the EPO gene was headed by (indeed, consisted largely of) Dr Fu-Kuen Lin. Dr Goldwasser was engaged as a consultant. He was able to make some uEPO available to Dr Lin, who designed a set of fully degenerate probes to hybridise with the DNA coding for two regions of the protein. As the kidney makes so little EPO, there was little prospect of obtaining mRNA for a cDNA library. So Dr Lin used his probes on the vast array of genes in a genomic library. Against the odds, he obtained three positives which enabled him to locate the EPO gene in the fall of 1983. He was then able by patient but conventional methods to identify the whole of its structural region, its introns, exons and splicing sites and a fair amount of the upstream and downstream sequences as well. He thus established the correct sequence of the amino acid residues which formed the protein and its leader sequence. 7. This information, first discovered by Dr Lin, was essential to any process for making EPO, whether by Amgen's method or TKT's. As one of the principal issues in the case is whether TKT's GA-EPO (which is chemically exactly the same as Amgen's Epogen) falls outside the claims of the patent in suit because of the difference in the way it is made, I shall at once describe in bare outline the two methods. There are some details on which special arguments were founded and I shall come back to these later. For the moment, however, a sketch will do. The two methods of making EPO 8. Once the sequence of the EPO gene had been discovered, it was possible to make it by methods of recombinant DNA technology which were well known in 1983. These are succinctly described in the specification of the patent in suit:
9. That is the way the patent in suit teaches how to make EPO. Dr Lin isolated the gene which coded for human EPO from a human donor cell and then introduced it into a mammalian cell in culture which had been derived from the ovary of a Chinese hamster (a "CHO cell"). As part of the hamster DNA, it expressed EPO. Of course it was not as simple as that. To get it into the DNA of the CHO cell, it had first to be incorporated into a bacterial plasmid vector. To improve the chances of expression, the gene's natural promoter was removed and a more powerful viral promoter substituted. To increase the rate of expression, cells in which the gene had been multiplied ("amplified") were selected by a technique which involved treating them with methotrexate. Indeed, the CHO cell had been chosen as host because it had a gene mutation which made it particularly suitable for amplification by methotrexate. But these were all tricks of the trade well known among practitioners of the art. The essence of the technique was that described in the passage from the specification which I have quoted, namely, the introduction of an exogenous DNA sequence coding for EPO into a host cell in which it would be expressed. 10. In TKT's gene activation method, the EPO is expressed in a human cell by an endogenous gene naturally present or by cells derived by replication from such a cell. Ordinarily, such a gene would not express EPO. Almost all human cells contain the full complement of DNA coding for all the proteins needed by the body ("the human genome") but each cell will express only those proteins which its particular tissue requires. The rest remain inactive, disabled by the absence of a suitable regulator which is needed to promote expression. The TKT technique involves introducing the necessary control sequence upstream of the EPO gene. The control sequence is accompanied by other bits of machinery (for example, to allow for amplification by methotrexate treatment) which it is for the moment unnecessary to describe. All this exogenous DNA has to be inserted into the human DNA at exactly the right point upstream of the EPO gene. This could not have been done at the time of the patent but can now be done by using a phenomenon called "homologous recombination". It is fully described by Neuberger J and I need say no more than that it enables TKT to activate or "switch on" the EPO gene in a human cell which would not ordinarily express that protein and then to select for commercial use those descendants of the manipulated cells in which the relevant genes have been amplified to produce a high level of expression. 11. The essential difference between Epogen and GA-EPO is that the former is made by an exogenous DNA sequence coding for EPO which has been introduced into an host cell and the latter is made by an endogenous DNA sequence coding for EPO in a human cell into which an exogenous upstream control sequence has been inserted. 12. With that introduction, we can now look at the patent. The specification explains the relevant science, the nature of EPO and the difficulties which stood in the way of identifying the gene. It then describes the methods which Dr Lin used to find the gene in the DNA of monkeys and humans and sets out the full sequences for both species in Tables V and VI respectively. In a series of 12 examples it describes what Dr Lin was able to do with this information, including in example 7 the expression of human EPO in COS-1 cells (not very successful because of difficulties about amplification and transience of expression) and in example 10 its expression in CHO cells (successful because of amplification by methotrexate.) There are 31 claims but we need concern ourselves only with claims 1, 19 and 26. To summarise them very briefly and leaving out qualifications to which I shall later return, they are for (1) a DNA sequence for use in securing the expression of EPO in a host cell, (19) EPO which is the product of the expression of an exogenous DNA sequence and (26) EPO which is the product of the expression in a host cell of a DNA sequence according to claim 1. Only claims 19 and 26 are alleged to have been infringed because TKT do not make any GA-EPO in this country. The alleged infringement is by importation. But claim 26 cannot be understood without first construing claim 1. 13. I shall now set out the precise terms of the three relevant claims. Claim 1 is for?
14. Claim 19 is for?
15. Finally, claim 26 is for?
16. Claims 2, 3, 5, 6 and 7 are all dependent on claim 1 in the sense that if the TKT method does not involve using a "DNA sequence for use in securing expression [of EPO] in a…host cell" within the meaning of claim 1, it would not infringe any of the other claims either. The decisions of the courts below17. The trial judge held that claim 19 was invalid (for insufficiency) but that claim 26 was valid and infringed. The Court of Appeal (Aldous, Hale and Latham LJJ) held that both claims were valid but that neither was infringed. Both sides appeal: Amgen against the decision that, as a matter of construction, the TKT process is not within the claims and TKT against the rejection of its attack on the claims for insufficiency and (in the case of claim 26) anticipation. I shall consider Amgen's appeal first. Extent of protection: the statutory provisions 18. Until the Patents Act 1977, which gave effect to the European Patent Convention ("EPC") there was nothing in any UK statute about the extent of protection conferred by a patent. It was governed by the common law, the terms of the royal grant and general principles of construction. It was these principles which Lord Diplock expounded in the leading case of Catnic Components Ltd v Hill & Smith Ltd [1982] RPC 183, which concerned a patent granted before 1977. But the EPC and the Act deal expressly with the matter in some detail. Article 84 specifies the role of the claims in an application to the European Patent Office for a European patent:
19. For present purposes, the most important provision is article 69 of the EPC, which applies to infringement proceedings in the domestic courts of all Contracting States:
20. In stating unequivocally that the extent of protection shall be "determined" (in German, "bestimmt") by the "terms of the claims" (den Inhalt der Patentansprüche) the Convention followed what had long been the law in the United Kingdom. During the course of the 18th and 19th centuries, practice and common law had come to distinguish between the part of the specification in which the patentee discharged his duty to disclose the best way of performing the invention and the section which delimited the scope of the monopoly which he claimed: see Fletcher-Moulton LJ in British United Shoe Machinery Co Ltd v A. Fussell & Sons Ltd (1908) 25 RPC 631, 650. The best-known statement of the status of the claims in UK law is by Lord Russell of Killowen in Electric and Musical Industries Ltd v Lissen Ltd (1938) 56 RPC 23, 39:
21. The need to set clear limits upon the monopoly is not only, as Lord Russell emphasised, in the interests of others who need to know the area "within which they will be trespassers" but also in the interests of the patentee, who needs to be able to make it clear that he lays no claim to prior art or insufficiently enabled products or processes which would invalidate the patent. 22. In Germany, however, the practice before 1977 in infringement proceedings (validity is determined by a different court) was commonly to treat the claims as a point of departure ("Ausgangspunkt") in determining the extent of protection, for which the criterion was the inventive achievement ("erfinderische Leistung") disclosed by the specification as a whole. Likewise in the Netherlands, Professor Jan Brinkhof, former Vice-President of the Hague Court of Appeals, has written that the role of the claims before 1977 was "extremely modest": see Is there a European Doctrine of Equivalence? (2002) 33 IIC 911, 915. What mattered was the "essence of the invention" or what we would call the inventive concept. The Protocol 23. Although the EPC thus adopted the United Kingdom principle of using the claims to determine the extent of protection, the Contracting States were unwilling to accept what were understood to be the principles of construction which United Kingdom courts applied in deciding what the claims meant. These principles, which I shall explain in greater detail in a moment, were perceived as having sometimes resulted in claims being given an unduly narrow and literal construction. The Contracting Parties wanted to make it clear that legal technicalities of this kind should be rejected. On the other hand, it was accepted that countries which had previously looked to the "essence of the invention" rather than the actual terms of the claims should not carry on exactly as before under the guise of giving the claims a generous interpretation. 24. This compromise was given effect by the "Protocol on the Interpretation of Article 69":
25. It is often said, on the basis of the words "a position between these extremes", that the Protocol represents a compromise between two different approaches to the interpretation of claims. But that is not quite accurate. It is a protocol on the interpretation of article 69, not a protocol on the interpretation of claims. The first sentence does deal with interpretation of the claims and, to understand it, one needs to know something about the rules which English courts used to apply, or impose on themselves, when construing not merely patents but documents in general. The second sentence does not deal with the interpretation of claims. Instead, it makes it clear that one cannot go beyond the claims to what, on the basis of the specification as a whole, it appears that "the patentee has contemplated". But the last sentence indicates that, in determining the extent of protection according to the content of the claims but avoiding literalism, the courts of the Contracting States should combine "a fair protection for the patentee with a reasonable degree of certainty for third parties." 26. Both article 69 and the Protocol are given effect in United Kingdom law, in relation to infringement, by sections 60 and 125 of the Act. Section 60 provides that a person infringes a patent if he does various things in the United Kingdom "in relation to the invention" without the consent of the proprietor of the patent. Section 125 defines the extent of "the invention":
The English rules of construction 27. As I indicated a moment ago, it is impossible to understand what the first sentence of the Protocol was intending to prohibit without knowing what used to be the principles applied (at any rate in theory) by an English court construing a legal document. These required the words and grammar of a sentence to be given their "natural and ordinary meaning", that is to say, the meanings assigned to the words by a dictionary and to the syntax by a grammar. This meaning was to be adopted regardless of the context or background against which the words were used, unless they were "ambiguous", that is to say, capable of having more than one meaning. As Lord Porter said in Electric & Musical Industries Ltd v Lissen Ltd (1938) 56 RPC 23, 57:
28. On the other hand, if the language of the claim "in itself" was ambiguous, capable of having more than one meaning, the court could have regard to the context provided by the specification and drawings. If that was insufficient to resolve the ambiguity, the court could have regard to the background, or what was called the "extrinsic evidence" of facts which an intended reader would reasonably have expected to have been within the knowledge of the author when he wrote the document. 29. These rules, if remorselessly applied, meant that unless the court could find some ambiguity in the language, it might be obliged to construe the document in a sense which a reasonable reader, aware of its context and background, would not have thought the author intended. Such a rule, adopted in the interests of certainty at an early stage in the development of English law, was capable of causing considerable injustice and occasionally did so. The fact that it did not do so more often was because judges were generally astute to find the necessary "ambiguity" which enabled them to interpret the document in its proper context. Indeed, the attempt to treat the words of the claim as having meanings "in themselves" and without regard to the context in which or the purpose for which they were used was always a highly artificial exercise. 30. It seems to me clear that the Protocol, with its reference to "resolving an ambiguity", was intended to reject these artificial English rules for the construction of patent claims. As it happens, though, by the time the Protocol was signed, the English courts had already begun to abandon them, not only for patent claims, but for commercial documents generally. The speeches of Lord Wilberforce in Prenn v Simmonds [1971] 1 WLR 1381 and Reardon Smith Line Ltd. v Yngvar Hansen-Tangen [1976] 1 WLR 989 are milestones along this road. It came to be recognised that the author of a document such as a contract or patent specification is using language to make a communication for a practical purpose and that a rule of construction which gives his language a meaning different from the way it would have been understood by the people to whom it was actually addressed is liable to defeat his intentions. It is against that background that one must read the well known passage in the speech of Lord Diplock in Catnic Components Ltd v Hill & Smith Ltd [1982] RPC 183, 243 when he said that the new approach should also be applied to the construction of patent claims:
31. This was all of a piece with Lord Diplock's approach a few years later in The Antaios [1985] AC 191, 201 to the construction of a charterparty:
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