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England and Wales High Court (Chancery Division) Decisions |
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You are here: BAILII >> Databases >> England and Wales High Court (Chancery Division) Decisions >> Vericore Ltd v Vetrepharm Ltd & Anor [2003] EWHC 111 (Ch) (06 February 2003) URL: http://www.bailii.org/ew/cases/EWHC/Ch/2003/111.html Cite as: [2003] EWHC 111 (Ch) |
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CHANCERY DIVISION
PATENTS COURT
ON APPEAL FROM THE PATENT OFFICE
Strand, London, WC2A 2LL |
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B e f o r e :
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VERICORE LIMITED |
Appellant |
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- and - |
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(1) VETREPHARM LIMITED (2) ALPHARMA |
Respondent |
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Mr Richard Hacon (instructed by Bristows for the Respondent)
Hearing dates: 14 & 15 January, 2002
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Crown Copyright ©
Mr Justice Laddie:
"11. Before turning to the subject matter of the patent, it may be helpful briefly to outline the technical field of these proceedings. It relates to salmon and other sea fish, and more especially to infestation with sea lice to which they are susceptible. Sea lice are ectoparasitic marine crustacea which eat the membrane, skin and blood of their host. There are two main types of louse relevant here: Lepeophtheirus salmonis and Caligulus elongates. Treatments for sea lice infestation do not differentiate between the two. On wild salmon only small numbers of sea lice are normally found, but in farming conditions where fish density is very high, infestation is a major problem. Heavy infestations cause stress amongst the fish, reduced feeding activity, and low weight gains. The consequences for the fish are highly unpleasant and may result in high mortality rates. Over the years, different treatments for sea lice infestation had been used, in particular the organophosphate dichlorvos. For various reasons which I shall come too, dichlorvos was not regarded as the last word, and alternative treatments were being sought.
"12. Pyrethrum is an extract from Chrysanthemum flowers which contains a mixture of natural compounds including pyrethrins. Pyrethrum powder has been used for many years as an insecticide in domestic situations. Compounds having similar structures and properties to pyrethrins have been developed as insecticides. The use of pyrethrum and related synthetic compounds in treating sea lice infestation on salmon and other seawater fish goes to the heart of the present dispute."
"It is known commercially to treat salmon suffering from infestation with sea lice by the use of the insecticide dichlorvos. However dichlorvos is generally only effective against mature lice and is considered not to affect juvenile sea lice. Furthermore great care has to be taken with the dichlorvos dosage as the insecticide is fatal to fish at only 8 times the recommended dose for sea lice treatment. Further there are indications that resistance to dichlorvos is developing in sea lice. It is therefore desirable to find alternative agents for treating sea lice on salmon and other fish especially materials for which the dose recommended can be very much less than the fatal (LD50) dose."
"It is known to use the pyrethroid pesticides cypermethrin and iTs related compound alphacypermethrin for both the control of pests in crops and against ectoparasites in cattle and sheep including scab, lice and ked in sheep (see The Pesticide Manual, 7th Edition, page 3690 ed CR Worthing, The British Crop Protection Council). Cypermethrin and alphacypermethrin are thus used in crop sprays or cattle and sheep dips or sprays. However they and other pyrethroids had not been proposed for use in treating fish. Although it is stated in the Pesticide Manual that the LD50 (96 hours) for brown trout is 2.0 2.8 microgram per litre (mcg/l), such tests are only to check that fish are not at risk from normal agricultural usage. Further data on the toxicity of cypermethrin to fish is to be found in "Environmental Health Criteria 82: Cypermethrin", published by World Health Organisation, Geneva in 1989 as part of IPCS International Programme on Chemical Safety. This summarises work on the toxicity of cypermethrin and reports in Table 8 that for technical cypermethrin, dispensed in ethanol, at 10oC the LD50 (96 hours) for an atlantic salmon having a weight of 5.3g is 2-2.4 microgram active ingredient/litre. Because of these figures it has been considered that cypermethrin is toO toxic for use on fish.
However, we have found that pyrethroids, particularly cypermethrin and alphacypermethrin, can be administered to salmon and other seawater fish in a manner which is highly effective in the control of sea lice in the salmon and other fish while being much less toxic to the fish themselves than dichlorvos."
"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."
"It is not fully understood why cypermethrin is not toxic to the salmon or other seawater fish in the circumstances in which it is used in this invention. This greater tolerance may be due to the presence of seawater rather than fresh water. The use of alphacypermethrin as a component of fish food for oral administration may also be an important factor. Certainly, it is particularly surprising that alphacypermethrin is highly effective when administered orally. Good results at dosage rates equivalent to 0.005mg/litre in water have been found whereas the dosage rate for dichlorvos to give equivalent results is of the order of 1mg/litre."
"A number of other pyrethroid pesticides have been tested in accordance with the invention and the following table gives the percentage mortality in sea lice following 1 hour bath treatments in-vitro with 6 different pyrethroid compounds each administered at 2 different concentrations.
Hours past treatment | Hours past treatment | |
Compound | 1 | 6 |
Negative control | 0 | 0 |
Solvent (ABS) control | 10 | 10 |
Cypermethrin 0.1 ppm | 0 | 70 |
Cypermethrin 0.01 ppm | 10 | 40 |
Deltamethrin 0.1 ppm | 20 | 90 |
Deltamethrin 0.01 ppm | 20 | 70 |
Resmethrin 0.6 ppm | 50 | 70 |
Resmethrin 0.06 ppm | 50 | 15 |
Permethrin 0.5 ppm | 0 | 30 |
Permethrin 0.05 ppm | 0 | 10 |
Cyhalothrin 0.2 ppm | 60 | 40 |
Cyhalothrin 0.02 ppm | 0 | 10 |
Tetramethrin 0.8 ppm | 10 | 100 |
Tetramethrin 0.08 ppm | 0 | 70" |
"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.
"8. Use according to claims 6 or 7 wherein the pyrethroid pesticide is administered in the range between 0.001 and 0.5 ppm by weight of pyrethroid pesticide to water.
"9. A composition when used for controlling sea lice infestation in salmon which comprises a pyrethroid pesticide suspended in water."
Anticipation
"Like the natural pyrethrums, the pyrethroids are contact poisons which have a rapid paralytic action on insects, preceded by muscular excitation and convulsions."
Obviousness
(i) D2 "New Pesticide for Salmon Lice promising trial using pyrethrum"
"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 emusified (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. We added an anti-oxidant (piperonyl-butoxide) to retard the photo-chemical destruction of the pyrethrum.
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."
" parasites present in Norwegian salmon fish farming can be eradicated with a natural substance extracted from flowers " (emphasis added)
(ii) D9 "Alternative Chemical Treatments to Sea Lice"
"The first administration principle is to surround the cage with a plastic canvas collar, and add the pyrethrum mixture to the water surface within the cage. The salmon leaping activity will provide self-delousing with a minimum of stress. The leaping activity is higher in infested compared to non-infested fish, and is decreasing with size. However, the method have some negatives at present. Degradation of the pyrethrum (by light), as well as the removal of oil after the treatment are topics for further project activity. This method will be a effective for small fish when light intensity is medium or low. The other principle is to submerge the fish in a small reservoir of pyrethrum mixture. This seems to be more reliable and controlled, but will induce more stress. The method can be combined with grading or change of nets."
"... Pyrethrum is readily broken down by sunlight into harmless metabolites so for outdoor use an antioxidant is needed.
In 1987 the testing of new delousing agent was started at Austevoll Aquaculture Research Station. One of the first experiments used a Pyrethrum emulsion. Then we rediscovered that emulsified in water Pyrethrum is poisonous to fish and acts very much like Rotenone (used in watercourses to remove fish populations). In the autumn of 1989 a new administration principle was used for the first time. This method make use of the fact that Pyrethrum is oil soluble. Pyrethrum and antioxidant were mixed with an oil and poured on top of the fish cage. The oil solution was prevented to float away by a plastic collar. The idea was to let the salmon jump through the layer and delouse themselves. A significant treatment effect was observed. The high water content of the salmon mucus leaves the fish unharmed. The salmon lice however has a lipid membrane in the exoskeleton that makes oil solubles able to selectively penetrate the lice and not the fish."
"Pyrethrum has shown itself to the effective as a delousing agent but the method of applying the Pyrethrum is not optimal at the moment.
So far the best achieved result is a total delousing of 89%. This was in the bath experiment. The issue must be to find a way to apply the right amount of Pyrethrum in the easiest way for the farmer."
(iii) D1 "Chemotherapy of Sea Lice Infestations in Salmonids: Pharmacological, Toxicological and Thereapeutic Properties of Established and Potent Agents"
"5.2.5 Pyrethroids
Among the substances currently being studied for their potential as delousing agents in salmon are the pyrethroid insecticides. In Norway, interest has so far been concentrated on pyrethrum, an extract of the plant Chrysantehmum cinerariaefolium containing various pyrethrins with insecticidal properties. Preliminary clinical trials with pyrethrum administered on the water surface using an oil as the vehicle, have demonstrated a certain chemical effect on sea lice (Jakobsen & Holm, 1990).
Pyrethrum is, however, a mixture of insecticidal agents which are extremely toxic to fish. The LC50 (96 h) of a 20% pyrethrum extract is 24.6(g/l for rainbow trout (Mauk & al., 1976). Being highly toxic does not necessarily exclude a substance from therapeutic use, since it is the margin between the toxic dose for the parasite and the toxic dose for the fish that is important. This margin remains, however, to be determined for pyrethrum. The extremely high toxicity towards several non-target aquatic organisms also raises the question of possible adverse impact of any solution released into the environment."
"Due to the instability of the natural pyrethrins and the need for the addition of several chemicals to overcome this, synthetic derivatives are used as insecticidal agents. These include compounds such as deltamethrin, permethrin, cypermethrin and fenvalerate, and more recent products such as flucythrinate, fluvalinate etc. The synthetic pyrethroids are more stable than the pyrethrins, and are equally or more potent pesticides. It seems probable that in the future, synthetic pyrethroids will be of more interest than pyrethrum as possible delousing agents."
"On 27 February 1991, I also supplied copies of the thesis to people who requested a copy of it. Consequently, various employees of the NVH, including my supervisor and other scientific and technical personnel, received copies of the thesis from me at that time. No expressed or implied restrictions were placed by me on the use of the thesis by the recipients of it. No copyright was declared in the thesis. The recipients would have been free to use the thesis however they saw fit. Likewise I would not consider as confidential, copies of theses I received from colleagues and students. The nature of a doctoral thesis is that it is a public document, intended for publication."
"The Study Section is open to the public during office hours and to my knowledge, once the thesis was delivered to the Study Section, anyone could have seen it."