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Judgments - Conor Medsystems Incorporated (Respondents) v Angiotech Pharmaceuticals Incorporated and others (Appellants)

HOUSE OF LORDS

SESSION 2007-08

[2008] UKHL 49

on appeal from: [2007]EWCA Civ 5

OPINIONS

OF THE LORDS OF APPEAL

FOR JUDGMENT IN THE CAUSE

Conor Medsystems Incorporated (Respondents) v Angiotech Pharmaceuticals Incorporated and others (Appellants)

Appellate Committee

Lord Hoffmann

Lord Scott of Foscote

Lord Walker of Gestingthorpe

Baroness Hale of Richmond

Lord Neuberger of Abbotsbury

Counsel

Appellants:

Antony Watson QC

Andrew Waugh QC

Colin Birss QC

(Instructed by Howrey LLP )

Comptroller General of Patents Solicitors (acting in place of Respondents):

Michael Tappin

Jessie Bowhill

(Instructed by Treasury Solicitors)

Hearing date:

6 and 7 MAY 2008

ON

WEDNESDAY 9 JULY 2008

HOUSE OF LORDS

OPINIONS OF THE LORDS OF APPEAL FOR JUDGMENT

IN THE CAUSE

Conor Medsystems Incorporated (Respondents) v Angiotech Pharmaceuticals Incorporated and others (Appellants)

[2008] UKHL 49

LORD HOFFMANN

My Lords,

1.  Angiotech Pharmaceuticals Inc, a Canadian company, and the University of British Columbia are joint proprietors of European patent 0 706 376 which claims, among other things, a stent coated with taxol for “treating or preventing recurrent stenosis". For convenience I shall call the patentees Angiotech. Conor Medsystems Inc (Conor), an American competitor, applied in both the United Kingdom and the Netherlands for revocation of the patent on the ground that the claimed invention was obvious. In the United Kingdom, before Pumfrey J and the Court of Appeal (Mummery, Tuckey and Jacob LJJ), it succeeded. In the Netherlands, before the District Court of The Hague (Robert van Peursem, Edgar Brinkman and Walter van Straalen) it failed. Angiotech appeals to your Lordships’ House and says that the Dutch court was right and that the patent should be declared valid.

2.  Since the decision of the Court of Appeal, Angiotech and Conor have reached a settlement. Conor does not oppose Angiotech’s appeal. But a patent confers proprietary rights in rem and the validity of a patent cannot be established simply by a judgment in default of opposition. Your Lordships therefore invited the Comptroller General of Patents to assist the court in presenting what appeared to him to be the arguments against the validity of the patent. The House followed the procedure adopted by the Court of Appeal in a similar situation in Halliburton Energy Services Inc v Smith International (North Sea) Ltd [2006] EWCA Civ 1715. Angiotech agreed to pay the Comptroller’s costs and the Comptroller instructed Mr Tappin to appear before the House. I have, as I am sure your Lordships will agree, found his written and oral submissions of great assistance.

3.  There is still no European Patent Court. A European patent takes effect as a bundle of national patents over which the national courts have jurisdiction. It is therefore inevitable that they will occasionally give inconsistent decisions about the same patent. Sometimes this is because the evidence is different. In most continental jurisdictions, including the European Patent Office (“EPO”), cross-examination is limited or unknown. Sometimes one is dealing with questions of degree over which judges may legitimately differ. Obviousness is often in this category. But when the question is one of principle, it is desirable that so far as possible there should be uniformity in the way the national courts and the EPO interpret the European Patent Convention (“EPC”). In this case, as Pumfrey J made clear in his judgment, there is a question of principle at stake. It is about how you identify the concept embodied in the invention which may constitute the “inventive step” for the purposes of article 56 of the EPC and section 1(1)(b) of the Patents Act 1977.

4.  The subject matter of the patent is a stent, a tubular metal scaffold inserted into an artery to keep it open. It is used in connection with angioplasty, one of the great modern advances in the treatment of sclerosis of the coronary arteries. A catheter carrying a balloon is inserted into the arterial system from outside (“percutaneously”), usually at the groin, and manoeuvred through the arteries to the point at which the coronary artery has become constricted or “stenosed". There the balloon is expanded to push back the artery walls and enlarge the channel. The insertion of a stent will prevent the walls from collapsing when the catheter and balloon are withdrawn.

5.  A serious problem with this form of intervention was that the injury caused to the inner layer of the artery by the insertion of the stent often produced an exaggerated healing response, characterised by the proliferation of smooth muscle cells forming new tissue which once again constricted the arterial channel. This is called restenosis. It affected between a third and a half of patients in whom stents had been inserted and no one knew what to do about it.

6.  There was however no shortage of suggestions and in 1993, more or less at the same time as the priority date of the patent in suit, a group of Dutch scientists of high repute in the field published a two-part article entitled Pharmacological Approaches to the Prevention of Restenosis Following Angioplasty: The Search for the Holy Grail? (Drugs 46(1) 18-52; 46(2) 249-262). Many people thought that the proliferation of smooth muscle cells in restenosis was analogous to the proliferation of cells in cancer tumours and might be treated by anti-proliferative drugs. Others favoured antithrombotic agents such as heparin, antiplatelet agents like aspirin, anti-inflammatories, calcium antagonists and lipid-lowering drugs. The article described two theories about how the process of restenosis took place. Both involved several stages at which different forms of pharmacological intervention might be appropriate.

7.  The summary at the start of the second part of the article, which dealt with future possibilities, said:

“[D]espite 15 years of clinical experience and research in the field of restenosis prevention, this has not yet resulted in the revelation of unequivocal beneficial effects of any particular drug. Other newer approaches likely to receive more attention in the future include anti-bodies to growth factors, gene transfer therapy and antisense oligonucleotides. Whether there is a feasible monotherapy, whether we have to focus on a drug combination, or whether we are only searching for the ‘Holy Grail’ remain to be answered.”

8.  Meanwhile in Vancouver, a young medical student named William Hunter was studying angiogenesis, the process by which capillary blood vessels grow, under a Dr Arsenault, who had made it his particular area of research. It occurred to Dr Hunter that one approach to unwanted cell proliferation might be the inhibition of angiogenesis, because most cell tissue cannot grow more than 200 or so microns without blood. (Tumour cells are different; they are notoriously able to grow without a supply of oxygen from the blood but they are not the normal cause of restenosis). In 1991, during his third year at medical school, Dr Hunter met Dr Machan, who had experience in cardio-vascular intervention and the use of stents. As a result of their discussions, they decided to try to find an anti-angiogenic agent which could be used to inhibit or prevent tissue growth in restenosis. To fund the research, Drs Hunter, Arsenault and Machan formed Angiotech and obtained a grant from the Science Council of British Columbia.

9.  They tested various drugs for anti-angiogenic properties by an assay using chick embryos (the chorioallantoic membrane or “CAM” assay). This was an established test, although perhaps not very sophisticated or discriminating. One of the drugs tested, in February 1993, was paclitaxel, a recently-discovered anti-proliferative derived from the Pacific yew tree, which was much in the news as a possible cancer treatment. Dissolved in cremophor for pharmacological use, it was marketed under the trade name of taxol. On the CAM assay, it appeared to have remarkable anti-angiogenic properties. Dr Hunter said it was effective to inhibit angiogenesis even in minute concentrations.

10.  On 19 July 1993 Angiotech applied for a US patent which is the priority document for the patent in suit. The title of the patent is “Anti-angiogenic compositions and methods of use” and the patent, at least as originally applied for, is by no means confined to their use on stents. The primary emphasis is on the use of anti-angiogenics for the treatment of cancer. This was a bold claim because most anti-angiogenics such as taxol were anti-proliferatives and their use for treating cancer was well known. But their use on stents comes next, as is made clear by the introductory paragraph of the description:

“The present invention relates generally to compositions and methods for treating cancer and other angiogenic-dependent diseases, and more specifically, to compositions comprising anti-angiogenic factors and polymeric carriers, stents which have been coated with such compositions, as well as methods for utilizing these stents and compositions.”

11.  In the European Patent Office, the patent was opposed after grant on the ground, among others, that use for cancer treatment was either not new or obvious. As a result of a decision of the Opposition Division, the claims for treating cancer and other diseases were abandoned and the patent confined to the use of taxol on stents. Claim 1 as amended was for a stent coated with taxol, claim 11 to a stent according to claim 1 for treating a “narrowing of a body passageway” and claim 12 for a stent according to claim 11 “for treating or preventing recurrent stenosis". It is this last claim which is in issue in these proceedings.

12.  The Angiotech stent has been a great commercial success. It has the largest share of the market in drug eluting stents, which have very considerably reduced the incidence of restenosis.

13.  The action for revocation was commenced by Conor on 18 February 2005. In its amended grounds of invalidity it was said that the alleged invention was obvious having regard to three items of prior art: PCT Patent Application WO 91/12779 (Wolff) PCT Patent Application WO 93/11120 (Kopia) and an abstract of a paper by Katsuda and others delivered at a symposium in Rome in 1988 (Katsuda). I shall return to the prior art at the end of this opinion.

14.  At the end of July and in early August 2005 Angiotech served reports from Professor Cumberland of Sheffield, an expert on cardio-vascular intervention, and Professor Calvert of Newcastle-on-Tyne, an oncologist. Conor’s experts were Professor Rogers, a cardio-vascular specialist at Harvard, and Professor Lemoine, an oncologist at Barts. A reading of these reports suggests that the only issue over which the experts proposed to lock horns at the trial was whether it would have been obvious at the priority date to coat a stent with taxol to prevent or treat restenosis. Professor Rogers said that he would have consulted an oncologist about a suitable anti-proliferative drug. Professor Lemoine said that taxol was at the time a highly publicised new drug for cancer treatment. He would have recommended it and Professor Rogers said he would have found it attractive. On the other side, Professor Cumberland said that he would have seen no reason to select taxol out of the huge variety of possible solutions then under consideration and Professor Calvert said that, on account of its toxic properties, he would actually have advised against it.

15.  That seemed a fairly straightforward issue and Angiotech no doubt prepared for trial clutching the Holy Grail paper as the best possible evidence that there was at the time no obvious solution to restenosis. But then events took a different turn. In a skeleton argument served at the end of September 2005, Mr Thorley QC, for Conor, denied that the inventive step disclosed by the specification was to coat the stent with taxol. It was, he said (at paragraph 62), much less precise; the inventive concept —

“purportedly resides in the idea of seeking to treat or prevent restenosis by coating a stent with a taxol/polymer composition. The disclosure is of no more than this. The idea is not shown to work (either in humans or in animals), nor to work to any particular extent, nor to work with any particular polymer nor with any particular amount of drug. The invention thus lies in the idea of trying some, one or more, taxol/polymer combinations to determine whether restenosis can thereby be treated. It is at this level of generality that inventiveness must be assessed.”

16.  On the basis that the patent taught no more than that taxol was worth trying, he submitted that it added nothing to existing knowledge. It was common ground that taxol was, like many other anti-proliferative drugs, worth a try. And that was obvious. It was not necessary for Conor to show that it was obvious actually to use taxol to treat restenosis because the patent did not teach that it would work.

17.  I shall say at once that in my opinion this argument was an illegitimate amalgam of the requirements of inventiveness (article 56 of the EPC) and either sufficiency (article 83) or support (article 84) or both. It is the claimed invention which has to involve an inventive step. The invention means prima facie that specified in the claim: see section 125(1) of the 1977 Act. In the present case, the invention specified in claim 12 was a stent coated with taxol. There was no dispute that this was a new product. The question should therefore simply have been whether it involved an inventive step. As in the case of many product claims, there was nothing inventive in discovering how to make the product. The alleged inventiveness lay in the claim that the product would have a particular property, namely, to prevent or treat restenosis. (Compare Pharmacia Corp v Merck & Co Inc [2002] RPC 775). So the question of obviousness was whether it was obvious to use a taxol-coated stent for this purpose. And this, as I have said, was the question to which the experts addressed themselves.

18.  Mr Thorley, however, sought to avoid this question by watering down the claimed invention by reference to what he said were inadequacies in the specification. It did not contain information about human or animal tests which showed that it would work or provide enough information about doses and so forth to enable the skilled person to work it. It was therefore nothing more than an idea that taxol might work and any skilled person would have known that.

19.  In my opinion, however, the invention is the product specified in a claim and the patentee is entitled to have the question of obviousness determined by reference to his claim and not to some vague paraphrase based upon the extent of his disclosure in the description. There is no requirement in the EPC or the statute that the specification must demonstrate by experiment that the invention will work or explain why it will work. As the Dutch court said (at paragraph 4.17):

“…it is not required in the view of the court that experimental data concerning such use of taxol stents in humans and the actual prevention of restenosis be included in the patent to further substantiate [the claim].”

20.  There seems to have been no dispute about what the experts thought the teaching of the patent to be. In cross-examination, Mr Thorley put to Professor Cumberland:

“Q. The teaching on page 12, lines 33-38 [of the patent in suit] , is that an anti-angiogenic composition can be used to treat restenosis. Correct, professor?

A. Either prevent or treat.

Q. Prevent or treat.”

21.  That speaks in general terms of anti-angiogenic compounds and it is true that the headline story in the specification was that preventing angiogenesis was the route by which one could prevent cell proliferation. But the specification also makes it clear that taxol is the favoured anti-angiogenic. Example 2, headed “Analysis of Various Agents for Anti-angiogenic Activity", describes the results of testing various anti-angiogenics by the CAM assay. It gives top marks to taxol:

“In summary, this study demonstrated that 48 hours after taxol application to the CAM, angiogenesis was inhibited. The blood vessel inhibition formed an avascular zone which was represented by three transitional phases of taxol’s effect. The central, most affected area of the avascular zone contained disrupted capillaries with extravasated red blood cells; this indicated that intercellular junctions between endothelial cells were absent. The cells of the endoderm and ectoderm maintained their intercellular junctions and therefore these germ layers remained intact; however, they were slightly thickened. As the normal vascular area was approached, the blood vessels retained their junctional complexes and therefore also remained intact. At the periphery of the taxol-treated zone, further blood vessel growth was inhibited which was evident by the typical redirecting or ‘elbowing’ effect of the blood vessels…Taxol-treated avascular zones also revealed an abundance of cells arrested in mitosis in all three germ layers of the CAM; this was unique to taxol since no previous study has illustrated such an event. By being arrested in mitosis, endothelial cells could not undergo their normal metabolic functions involved in angiogenesis. In comparison, the avascular zone formed by suramin and cortisone acetate do not produce mitotically arrested cells in the CAM; they only prevented further blood vessel growth into the treated area. Therefore, even though agents are anti-angiogenic, there are many points in which the angiogenesis process may be targeted.

We also observed the effects of taxol over the 48 hour duration and noticed that inhibition of angiogenesis occurs as early as 9 hours after application. … Also, we observed the revascularization process into the avascular zone previously observed. It has been found that the avascular zone formed by heparin and angiostatic steroids became revascularized 60 hours after application. In our study, taxol-treated avascular zones did not revascularize for at least 7 days after application implying a more potent long-term effect.”

22.  It is true that the specification said very little about the details of how or why taxol would be efficacious in preventing restenosis. It clearly saw the solution for restenosis in terms of preventing angiogenesis, but offered no proof that this was right. In cross-examination, Mr Thorley put to Professor Cumberland (Day 3, p.517):

“Q.  The disclosure that a compound is anti-angiogenic would be of no assistance to you in concluding whether that compound would actually work to inhibit the proliferation of smooth muscle cells?

A.  That is correct, at that time, yes.”

23.  That again meant that the patentee appeared to be at risk of a finding of insufficiency. On the other hand, if (as turned out to be the case) the invention did work, it would not matter why. The reason may have had nothing to do with anti-angiogenesis. The specification would be sufficient if, for whatever reason, taxol coated stents possessed the claimed property of preventing or treating restenosis.

24.  Likewise, Mr Thorley elicited a string of admissions from Professor Cumberland about whether the specification provided enough information to enable the skilled person to make a suitable stent:

“Q.  There is no data in this patent which demonstrates that any of those compounds actually worked to treat restenosis?

A. That is correct.

Q. The patent does not address the question of whether any of the compounds will inhibit the proliferation of smooth muscle cells?

A. That is correct.

Q. It does not address the question of whether local administration of any of the compounds will cause unmanageable side-effects?

A. I think that is correct, yes.

Q. The patent does not address the question of the dose of drug that will be needed to prevent or cure restenosis?

A. That is true.

Q. lt does not address the question of the period of time for which the drug should rest at the location in question?

A. True. That is correct.”

25.  At this point, Mr Waugh objected that these questions appeared to go to the question of sufficiency rather than obviousness. The judge disagreed, saying afterwards in his judgment (at paragraph 27) that this evidence showed that the disclosure was merely a speculative idea. In my opinion, however, Mr Waugh’s point was well taken. The questions had nothing to do with whether claim 12 involved an inventive step.

26.  In his judgment, Pumfrey J accepted Mr Thorley’s argument. He said:

“61.  In summary, therefore, the Claimant’s case is that it is sufficient for the purposes of invalidating the claims of the patent in suit that the interventional cardiologist, in consultation with someone of skill and experience in the field of anti-mitotic drugs of one sort or another, would see paclitaxel (taxol) as worth experimentation. The Patentees’ case is that the properties of taxol are such that the skilled person would not think that it was suitable for local administration in a drug-eluting stent. The Patentees’ contentions centre on the toxic character of taxol. It is therefore necessary at this point to deal with a particular question which has vexed this case. Is it sufficient for Conor to show that taxol is an obvious candidate for testing on a drug-eluting stent in addition to the material specifically identified in Wolff, or is it necessary to show that taxol is an obvious, or the obvious, material to use in a drug-eluting stent for administration to human beings? Put another way, is the patent vulnerable only if it can be shown that the skilled person would have an expectation of success sufficient to induce him to incorporate taxol in a drug-eluting stent, or is it sufficient that without any expectation of success he would test or screen taxol?

62.  In my judgment, this question is to be answered by assessing the contribution to the art disclosed by the specification. For the reasons that I have given above, I am satisfied that the disclosure of the specification is that taxol may be incorporated in a stent. It does not suggest that such a stent would be safe or that such a stent would work to prevent restenosis. I think it is fair to say that the sum of the disclosure of the specification is that taxol should be incorporated in a drug-eluting coating on a stent with a view to seeing whether it works to prevent restenosis and whether it is safe. If it is obvious to the skilled person that taxol should be incorporated in a drug-eluting coating on a stent with a view to seeing whether it prevents restenosis and is safe, then the claim is invalid, the specification having made no contribution to the art. It is obviously preferable to identify the correct question before assessing the evidence. In this case, the profound difference between the parties as to the nature of the inventive step has led them to identify as relevant very different factors.

64.  The claim is to a physical device, that is, to a stent upon which is a drug-eluting coating loaded with taxol and optionally with other active ingredients as well. If, as I consider is the case here, the specification provides directions to make such a stent, but provides no data or other material suggesting that such a stent is in fact suitable for the treatment of restenosis, then success in preventing restenosis is not, in my view, a relevant consideration when assessing the obviousness of constructing such a stent. I accept immediately that there must be some motive [for] making such a stent: but a sufficient motive is the testing of such a stent to see if it has potential in the treatment of restenosis. In the present case, therefore, I reject Mr Waugh’s contention that the definite object in view is the treatment or prevention of restenosis. The object in view is the testing of a taxol-loaded stent to see if it is of any use in the treatment or prevention of restenosis: that is all the specification provides.”

 
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