Vericore Ltd v Vetrepharm Ltd & Anor

This is the application by Vericore Ltd (“Vericore”) to amend the claims to its patent GB 2,270,261. The validity of the patent was challenged in the Patent Office by the respondents, Vetrapharm Ltd and Alpharma (together referred to as “Alpharma”). In a decision dated 18 March 2002, Mr Dennehey, Divisional Director, acting on behalf of the Comptroller, held that the original claims 1 and 4 of the patent were not novel in the light of certain of the pleaded prior art and that, even had they been novel, all the claims were obvious. The latter decision was appealed to the Patents Court. By a judgment dated 6 February of this year, I dismissed the appeal.

Although in his decision Mr Dennehey expressed the preliminary view that there was unlikely to be anything inventive which could be salvaged from the patent, he gave Vericore permission to apply to amend. The issue of amendment was stayed pending the outcome of the appeal. Now that the appeal has been dismissed, Vericore seeks to take advantage of the opportunity given to it to apply for amendment.

The patent is concerned with providing a solution to the problem of sea lice infestation which can be of particular concern where high densities of salmonid fish, particularly salmon, are to be found. Thus it is of particular application to salmon being farmed in sea cages. The technical field of the patent is described in the early parts of Mr Dennehey’s decision which are repeated in my judgment of February of this year. The solution offered is to use pyrethrum, a known insecticide extracted from Chrysanthemum flowers, and related synthetic compounds, collectively referred to as pyrethroids. Two known synthetic pyrethroids are cypermethrin and alphacypermethrin. Pyrethroids are toxic chemicals. They can kill fish. As with many insecticides and pharmaceuticals, it is necessary to administer the active agent at a concentration which is high enough to kill the parasite but below the level at which it will kill or significantly harm the host.

The nature of the invention is described in the following words in the patent:-

“Accordingly, the invention provides the use of a pyrethroid pesticide, preferably cypermethrin or alphacypermethrin, for the manufacture of a composition for treatment of sea lice infestation in salmon or other sea fish in a seawater environment.”

The patent as litigated before Mr Dennehey and me contained 14 claims. Only four of them were said to be independently valid. For present purposes it is only necessary to refer to three of them:-

“1.

Use of a pyrethroid pesticide for the manufacture of a composition for the treatment of sea lice infestation in seawater fish in a seawater environment.

6.

Use of a pyrethroid pesticide in water for the manufacture of a treatment suspension for salmon suffering from sea lice infestation.

9.

A composition when used for controlling sea lice infestation in salmon which comprises a pyrethroid pesticide suspended in water.”

These claims read onto the description of the invention in the specification. In particular, the specification describes how the pyrethroids could be administered to fish. The relevant passages are as follows:

“Certainly, it is particularly surprising that alphacypermethrin is highly effective when administered orally. Good results at dosage rates equivalent to 0.005 mg/litre in water have been found whereas the dosage rate for dichlorvos [a prior art pesticide] to give equivalent results is of the order of 1 mg/litre.

The active ingredients used according to the present invention are preferable administered to the salmon or other fish in their feed but they could be added as a water or bath treatment to the fish.

The active ingredient can be used in suspension or emulsified concentrate form or as a solid formulation (e.g. powder or granules) of a particle size typically in the range 10 to 10³ microns. The range of suspension concentrate formulations is suitably 10 – 250 g active ingredient per litre, and powder or granular formulations typically being 1.0 to 2.5% w/w pre-mixes added to finished feed.

Accordingly the invention also extends to the use of a pyrethroid pesticide in water for the manufacture of a treatment suspension for salmon suffering from sea lice infestation, and to a food composition suitable for salmon, characterised in the in (sic) addition to food ingredients it contains (sic) a pyrethroid pesticide.

Suitably the active ingredient is administered orally, for example in feed to achieve a dose range of …, and is added to baths at a range of between 0.001 and 0.5 ppm by weight of pyrethroid pesticide to water (i.e. between 0.001 and 0.5mg of active ingredient of pesticide in 1 kg of water).” (patent pages 2 – 3)

The specification then goes on to a section entitled “Examples illustrating the Invention”. There are four such examples. The first two are described as in vitro tests. They use very dilute “working solutions”. The latter were obtained by adding emulsified concentrate of the pyrethroid to absolute ethyl alcohol and subsequently mixing that mixture with seawater. The other two experiments are described as in vivo tests. Once again, the “solutions” used for dosing the seawater in the sea cages were prepared by adding concentrate of the pyrethroid to absolute alcohol before introducing it into the seawater.

The findings of invalidity made by Mr Dennehey were based on three pieces of prior art which were referred to, and shall be referred to in this judgment, as D1, D2 and D9. They are, respectively, “Chemotherapy of Sea Lice Infestations in Salmonids: Pharmacological, Toxicological and Therapeutic Properties of Established and Potent Agents”, a DSc thesis of a Dr Horsberg and his wife, Dr Tonje Høy, “New Pesticide for Salmon Lice – promising trial using pyrethrum”, a published summary of a presentation given by Mr Jens Holm and Mr Per Jakobsen on 16 January 1990 as part of the 1990 Annual Meeting Seminar on Fish Health in Norway and“Alternative Chemical Treatments to Sea Lice”, the published text of a presentation at the Irish Salmon Grower’s Association Annual Conference and Trade Exhibition given by the same Messrs Holm and Jakobsen together with Ms K. Boxaspen.

Four new claims are proposed to replace the original fourteen. In the end the arguments concentrated on the first one:

“Use of a pyrethroid pesticide for the manufacture of a composition for the treatment of sea lice infestation in seawater fish in a seawater environment, wherein the composition is an emulsified concentrate”.

The claim is in this form because, in the light of the provisions of s 4(2) of the Patents Act, 1977, it is not possible to claim a method of treating fish. The invention therefore has to be expressed in “Swiss form”, that is to say as a product suitable for use in such treatment or use of a substance to make such a product. In this case the claim is in the latter form. Thus the product is identified as “a composition [which is] an emulsified concentrate”. That product is “for the treatment of sea lice infestation”. The alleged invention is “the use of a pyrethroid for the manufacture of” such a composition.

In determining the scope of the claim it is necessary to bear in mind that the word “for” in the expression “for the treatment of sea lice infestation” means “suitable for”. This is consistent with the judgment of the Court of Appeal in Coflexip SA v Stolt Comex Seaway Ms Ltd [2000] EWCA Civ 242 and the earlier authorities, Adhesive Dry Mounting Co Ltd v Trapp [1910] 27 RPC 341 and Instituform Technical Services v Inliner UK [1991] RPC 83. Thus the use of a pyrethroid for the manufacture of a composition which is suitable for treating sea lice is covered by the patent.

The scope of the claim is central to the question of amendment. Mr Hacon, who appears for Alpharma, argues that in the context of the specification, the claims will cover, amongst other things, the treatment of sea lice infested fish by placing them in seawater which contains a suspension of pyrethroid. This is the type of treatment which was covered by the original claims, and expressly in claims 6 and 9, and which have been held already to be invalid. Mr Young QC, who appears for Vericore, accepts that, if the claims covers the use of suspensions of pyrethroid, they are invalid. However, he says that they do not. They only cover treating the fish by putting them in seawater in which the pyrethroid is distributed as an emulsion.

To understand this point it is useful to have in mind some basic technology. As Dr Horsberg, who gave evidence on behalf of Alpharma, explains, depending on its solubility in water, a drug can be administered in an aqueous medium (such as seawater) in one of three ways. First it can be in the form of a solution. The drug is dissolved in the water. Second, it can take the form of a suspension. This means that the drug substance is dissolved in the water volume to its saturation point (i.e. to the point at which no more is able to be dissolved) and the excess amount is suspended in the water in the form of small crystals. It will be appreciated that, in the latter state, much of the drug will be distributed throughout the water in the form of very fine solid particles. Third, it can take the form of an emulsion. In this case the drug is dissolved partly in the water and partly it is dissolved in small droplets of a poorly water-soluble vehicle (e.g. an oil) dispersed in the water by a detergent. Thus a suspension is a solid-in-liquid system while an emulsion is a liquid-in-liquid system. A common example of an emulsion is a vinaigrette dressing consisting of vinegar and oil shaken together. Neither of these liquids is soluble in the other but an emulsion can be made by shaking them together vigorously. In most cases vinaigrettes are unstable emulsions, readily separating out into an oil layer and a vinegar layer. This can be reduced or eliminated by addition of a suitable detergent.

There is no dispute that all the pyrethroids have very low solubility in water. That means that to get them dispersed in seawater they either have to be in the form of an emulsion or a suspension. With this in mind it is possible to return to consider the disclosure in the patent.

In the passages from the specification set out above, the patentee indicates that the pyrethroid ingredient can be used in suspension, or emulsified concentrate form or as a solid. However this does not expressly explain how the active ingredient is dispersed in the seawater at the time the fish are treated. In particular, although the specification refers to the use of an emulsified concentrate, this does not mean that the pyrethroid exists in the seawater as an emulsion. This can be explained by reference to the examples in the patent which have been described above. There is no suggestion that the pyrethroid-containing emulsified concentrate can be used directly in that form. It will be far too toxic for the fish. As its name explains, it is a concentrate. It is an intermediate which will be used to produce the very low concentration dispersion of the pyrethroid in seawater which is needed for the treatment process. An emulsified concentrate can be used either to make an emulsion in water or a suspension. All of the examples in the patent illustrate the latter. In all of them emulsified concentrate containing a pyrethroid was mixed with ethyl alcohol. This was then added to seawater. In example 1, for example, 1cc of concentrate was added to 24 cc of ethyl alcohol and that was then mixed with 975 cc of seawater. There is no dispute as to what the result of this would be. The pyrethroid would go into solution in the ethyl alcohol. However, as soon as it was mixed with sea water the ethyl alcohol would be dispersed in it and the pyrethroid would precipitate in the form of very small solid crystals. In other words, it would form a suspension. It is, no doubt, for this reason that original claims 6 and 9 refer to the use of suspensions of pyrethroid to treat the fish.

The consequence is as follows. First, the fact that the proposed claims refer to the use of an emulsified concentrate of pyrethroid for the treatment of sea lice infestation does not mean that the treatment itself must be in form of an emulsion. An emulsified concentrate which is used to produce a suspension of the pyrethroid in the sea water is a “composition for the treatment of sea lice infestation in seawater”. This is not only consistent with the use of the word “for”, but it is consistent with the disclosure in the specification. Indeed, all the examples are said in the specification to illustrate the invention. They are all cases where the emulsified concentrate is used to produce a suspension in the sea water.

In my view the construction advanced by Mr Young is untenable. Not only does the claim not purport to define the form in which the pyrethroid is dispersed in the sea water at the time of treatment but, were he right, all the examples in the specification would be highly misleading. If the invention is limited to the creation of an emulsion in the sea water, none of the examples illustrate that even though they are said to illustrate the invention. Indeed, there is no express description or disclosure anywhere in the specification of the creation of an emulsion in the sea water used to treat the fish.

It follows that the proposed amended claims include products which generate a suspension of pyrethroid for treatment of the fish. As noted above, if this is so, the claims will be invalid. For this reason I will refuse the application to amend.

In the light of this finding it is not necessary to consider an alternative argument advanced by Mr Hacon to the effect that the proposed claims, if construed in the way advanced by Mr Young, should fail on the ground that they add matter to the patent.

Strictly it is also not necessary to consider the further argument that, were Mr Young’s construction to be correct, the claims would still fail for obviousness. However, because this matter may go further and, in relation to this issue, evidence, including oral testimony, was given, it is appropriate to set out briefly my conclusions on this issue.

The starting point is that the invention covered by the claims is restricted, in substance, to the use of an emulsion of pyrethroid to treat the fish. Since, for the reasons set out in the decision of Mr Dennehey and my judgment on appeal from that decision, the use of pyrethroids to treat salmonid fish was both anticipated and obvious over prior art D1, D2 and D9, the issue I have to consider is whether the use of an emulsion in sea water as the method of delivery of the active ingredient is inventive over the same prior art.

Mr Hacon says the use of an emulsion would have been the obvious method of delivery at the priority date. Dr Horsberg, an acknowledged expert in this field, gave evidence in support. His expert’s report contains the following passage:

“The teaching of Prior Art D1, D2, and D9

14.

From the above, it is my clear opinion that the use of an emulsion for testing a compound of low solubility in water was a well known and obvious approach to take. If the solubility is high, a formulation as a solution is normally preferred. As synthetic pyrethroids are very slightly soluble in water, a formulation that resulted in a solution of the active ingredient at the required concentration in the bath would be unlikely to be an option, and an emulsion would therefore be an obvious choice. This approach to formulation was standard practice and would have been well known to fish health specialists, who would have been familiar with the use of dichlorvos, and was therefore a part of the common general knowledge of fish health specialists.”

This evidence was not shaken in cross-examination. Dr Horsberg struck me as a fair and balanced witness.

Vericore relied on the evidence of Mr Soutar. He also struck me as an honest and fair witness. His response to the above paragraph in Dr Horsberg’s expert’s report is as follows:

“10.

Furthermore, as Professor Horsberg states in paragraph 14 of his Report, the synthetic pyrethroids are only very slightly soluble in water and therefore an emulsion would be an obvious choice of formulation. I would agree with this, absent the teaching of D2 and D9. I would add that this also applies to pyrethrum and so the skilled person would have believed that the Austevoll team would have concentrated their work on emulsions until they had exhausted that line of experimentation.”

The reference to the Austevoll team in the last part of that passage is a reference to the Norwegian Marine Aquaculture Station Austevoll, a research organisation in which the work reported in prior art D2 and D9 was conducted.

Mr Soutar’s position was that D2 and D9 would have deterred the notional skilled addressee in the field from following the obvious route of using an emulsion. He did not make the same point in relation to Dr Horsberg’s thesis, D1, but Mr Young argued that, because the latter cross referred to D2, the two documents should be read together. If that was done the deterrent passages in D2 became incorporated into D1. This led to a dispute as to whether it was permissible to read these two documents together. Mr Hacon said it was an illegitimate mosaic. Mr Young disputed that. It is not necessary to resolve this issue. For the purpose of this judgment I will assume that Mr Young is right and D1 and D2 can be read together. On this basis, I do not need to consider the disclosure of D1.

Mr Young’s argument and Mr Soutar’s evidence can be explained by reference to D2. The content of this document was discussed fully in Mr Dennehey’s decision. It is not necessary to repeat it all here. In substance it discloses what it describes as a new pesticide for salmon lice, namely pyrethrum. It includes the following passages:

“PYRETHRUM, a neuroactive mixture of pyretrins, is an effective pesticide. Introductory tests at the Marine Aquaculture Station Austevoll have shown that this substance can be toxic to fish if emulsified (finely distributed in water). However, this problem has been averted and the fish can now be deloused without the risk of dying because the salmon louse has a lipid layer in its outer shell, while the salmon’s slimy outer layer is water soluble. By allowing the salmon to hop through a layer of oil containing the fat soluble pyrethrum, we found that we could get pyrethrum into the salmon louse in effective concentrations, while leaving the fish unaffected. …

In the following, we present the results of one of several tests carried out at the Marine Aquaculture Station Austevoll in the autumn of 1989, which in our opinion demonstrates pyrethrum’s potential. The treatment method described here is probably not optimal. A number of optimisation tests will hopefully be carried out at the Marine Aquaculture Station Austevoll in 1990.”

Mr Soutar says Austevoll must have discovered that the use of an emulsion did not work. Hence the first sentence in the passage quoted in the preceding paragraph. This would have been understood by the reader who would also have understood this to be the reason why Austevoll decided to use the unusual treatment method which involved making the fish hop through an oil layer. Thus the reader would be taught that emulsions would not work and he would not try them.

Dr Horsberg did not read D2 in the same way. Perhaps the biggest difference between the two witnesses in relation to the contents of D2 was in relation to their understanding of what Austevoll had done. As can be seen from the end of the extract from Mr Soutar’s witness statement, he thought that the document was consistent with the Austevoll team having “concentrated their work on emulsions until they had exhausted that line of experimentation.” Dr Horsberg thought that most unlikely. He thought it much more likely that the reader of the document would conclude that Austevoll had done very little work and was trailing its preliminary results, probably in the hope of generating sponsorship for more detailed experiments.

On this point, I think Dr Horsberg’s view is more likely to accord with the view of the notional addressee. The first paragraph on page 2 of the document refers to Austevoll having carried out “promising tests” which had led to the discovery of a “promising new pesticide for salmon lice”, namely pyrethrum. The passage dealing with the tests conducted using an emulsion were “introductory”. It is difficult to read this as suggesting that the authors had concentrated their work on emulsions until that line of experimentation was exhausted, as suggested by Mr Soutar. It is to be noted that D2 does not state that such exhaustive tests were conducted.

Furthermore, even if D2 contains an implicit warning signal in relation to the use of emulsions, it is far from a definitive statement not to try them. All it says is that “this substance [i.e. pyrethrum] can be toxic to fish”. It does not say that pyrethrum is always toxic in this form. I accept Mr Hacon’s suggestion that any such warning would not be firm enough to deter a worker in the field from trying to use the most obvious treatment method, namely an emulsion.

Mr Soutar’s evidence in relation to this topic cannot be divorced from his own personal experiences. As I said in Pfizer Ltd’s Patent [2001] FSR 201, paragraph 62, the notional skilled man in the art, unlike real people, has no personal idiosyncratic preferences or dislikes. What became clear during the course of his cross-examination was that, even before he read D2 or D9, Mr Soutar was predisposed against the use of emulsions. As I understood him, he accepted that in this respect he differed from many others in the art. In my view, in this respect he differed from the notional skilled addressee. I think his reading of D2 and D9 as containing strong advice against using emulsions was attributable largely to his own dislike of this type of delivery system. I do not think the notional addressee would have read this prior art in the same way. It follows that the skilled addressee who was interested in taking the teaching of the prior art forward would have tried using an emulsion as the delivery vehicle for the pesticide. Furthermore it should be noted that D2 and D9 were only concerned with experiments on natural pyrethrum. He would have considered using synthetic pyrethroids. Once again, in relation to that category of insecticides, there is nothing in the prior art which would have led the skilled addressee to the confident expectation that an emulsion would not work. Absent that, he would have tried it out.

It follows that, even were the proposed claims limited in the way suggested by Mr Young, they would be not allowable because they would be invalid for obviousness.

In these circumstances, it is not necessary to consider Mr Hacon’s separate argument that, because of delay, my discretion should be exercised against permitting amendment. I reject Vericore’s application.