COURT OF APPEAL (CIVIL DIVISION)
ON APPEAL FROM THE HIGH COURT OF JUSTICE
CHANCERY DIVISION (PATENTS COURT)
Mr Roger Wyand QC
Strand, London, WC2A 2LL
B e f o r e :
THE RT HON LORD JUSTICE JACOB
THE RT HON LORD JUSTICE HOOPER
| Mayne Pharma Pty Ltd
Mayne Pharma plc
|- and -
|Pharmacia Italia SPA
Colin Birss (instructed by Taylor Wessing) for the Defendant
Hearing date : 9 February 2005
Crown Copyright ©
Lord Justice Jacob:
What the dispute is about
"An injectable, ready-to-use, sterile, pyrogen-free, anthracycline glycoside solution which consists essentially of a physiologically acceptable salt of an anthracycline glycoside dissolved in a physiologically acceptable aqueous solvent therefor at an anthracycline glycoside concentration of from 0.1 to 50 mg/ml, which has not been reconstituted from a lyophilizate and the pH of which has been adjusted to from 2.5 to 5.0 solely with a physiologically acceptable acid, the said acid being selected from hydrochloric, sulfuric, phosphoric, acetic, succinic, tartaric, ascorbic, citric, glutamic, methanesulphonic or ethanesulphonic acid."
"Mayne purchase epirubicin hydrochloride which has been subjected to a bulk lyophilization process. Mayne takes this lyophilizate, dissolve it in water, add […]. The resulting solution is […] and is then filled into vials […]."
The Principles of Construction
"(a) The first, overarching principle, is that contained in Art 69 itself.
(b) Art 69 says that the extent of protection is determined by the terms of the claims. It goes on to say that the description and drawings shall be used to interpret the claims. In short the claims are to be construed in context.
(c) It follows that the claims are to be construed purposively – the inventor's purpose being ascertained from the description and drawings.
(d) It further follows that the claims must not be construed as if they stood alone – the drawings and description only being used to resolve any ambiguity. Purpose is vital to the construction of claims.
(f) Nonetheless purpose is not the be-all and end-all. One is still at the end of the day concerned with the meaning of the language used. Hence the other extreme of the Protocol – a mere guideline – is also ruled out by Art 69 itself. It is the terms of the claims which delineate the patentee's territory.
(g) It follows that if the patentee has included what is obviously a deliberate limitation in his claims, it must have a meaning. One cannot disregard obviously intentional elements.
(h) It also follows that where a patentee has used a word or phrase which, acontextually, might have a particular meaning (narrow or wide) it does not necessarily have that meaning in context.
(i) It further follows that there is no general "doctrine of equivalents".
(j) On the other hand purposive construction can lead to the conclusion that a technically trivial or minor difference between an element of a claim and the corresponding element of the alleged infringement nonetheless falls within the meaning of the element when read purposively. This is not because there is a doctrine of equivalents: it is because that is the fair way to read the claim in context.
(k) Finally purposive construction leads one to eschew what Lord Diplock in Catnic called (at p.243):
"the kind of meticulous verbal analysis which lawyers are too often tempted by their training to indulge.""
The Skilled Man and Common General Knowledge
i) The active ingredient to be used for the invention (anthracycline glycosides) were anti-tumour agents having widespread actual use;
ii) The agents were very toxic so that any risk of medical staff or manufacturing staff coming into accidental contact with them was serious;
iii) The existing products on the market were vials containing a "cake" consisting of a mixture of the active ingredient with an excipient such as lactose;
iv) The vials were used by injecting solvent through the rubber stopper to dissolve the cake. Shaking was necessary. Once the solid material had been dissolved there could be a bit of adjustment to get the solution toward isotonicity;
v) The cake within the vials consisted of a lyophilized product. They were made this way: the appropriate amount of a solution containing the active ingredient and the excipient or bulking agent was placed in the open vials. These were placed in lyophilizing conditions. Broadly (the details do not matter) this consisted of freezing followed by low pressure to evaporate the ice;
vi) The resulting product was, to use Mr Birss's word, "fluffy" – it had a low-bulk density. So there is more risk involved in handling this than handling crystalline material. The latter, being denser, is less apt to fly about;
vii) The reason for using the solid product in the vials, rather than simply having a solution was because solutions did not have very good stability – the product would deteriorate.
The specification of the patent
"The present invention relates to a stable intravenously injectable ready-to-use solution of an antitumor anthracycline glycoside, e.g. doxorubicin, to a process for preparing such a solution, and provide the same in a sealed container, and to a method for treating tumors by the use of the said ready-to-use solution."
"At present, anthracycline glycoside antitumor drugs, in particular, e.g., doxorubicon, are solely available in the form of lyophilized preparations, which need to be reconstituted before administration."
"To administer a lyophilized preparation, double handling of the drug is required, the lyophilized cake having to be first reconstituted and then administered and, moreover, in some cases, the complete dissolution of the powder may require prolonged shaking because of solubilization problems."
"As the risks connected with the manufacturing and the reconstitution of a lyophilized preparate would be highly reduced if a ready-to-use solution of the drug were available, we have developed a stable, therapeutically acceptable intravenously injectable solution of an anthracycline glycoside drug, e.g. doxorubicin, whose preparation and administration does not require either lyophilization or reconstitution."
"A process for producing a solution according to any one of the preceding claims; which process comprises dissolving the physiologically acceptable salt of the anthracycline glycoside, which salt is not in the form of a lyophilizate, in the physiologically acceptable aqueous solvent therefor; adding solely the physiologically acceptable acid to adjust the pH within the said range as desired; optionally, adding an additional component selected from a co-solublizing agent, a tonicity adjustment agent and a preservative to the solution; and then passing the resulting solution through a sterilising filter."
"With the solutions of the invention it is possible to obtain compositions having a very high concentration of the anthracycline glycoside active substance even at 50 mg/ml. This constitutes a great advantage over the presently available lyophilized preparates wherein high concentrations of anthracycline glycoside can only be obtained with difficulty because of solubilization problems encountered in reconstitution, mainly with saline. The presence of the excipient, e.g. lactose, in the lyophilized cake, and its generally high proportion in respect of the active substance, even up to 5 parts of excipient per part of active substance, has a negative effect on solubilization so that difficulties may arise in obtaining dissolution of the lyophilized cake, especially for concentrations of anthracycline glycoside higher than 2 mg/ml."
The detailed arguments on construction
i) The heart of the invention was, as its title said, an injectable ready-to-use solution.
ii) The passage about "the manufacturing and the reconstitution" is of "such preparations", i.e. the vials on the market. It is saying that the making and use of these each involves exposing people to risk. The workers at risk are those who operate the lyophilizing machines containing the vials. The medical workers at risk are those who have to inject solution into the vials to reconstitute (dissolve) the solid material within them.
iii) The passage about administration ("To administer a lyophilized preparation ..") is clearly only about the formulated product. The "lyophilized preparation" is that contained in such a product.
iv) The passage about "The risks connected with the manufacturing and the reconstitution of a lyophilized preparate …" is likewise about the final product. What it is saying is that if final product were a ready-to-use stable solution the risks would be reduced. The risks being talked about are those concerned with the manufacture of the vials containing lyophilized preparations and their use.
v) The passage on p. 9 about the great advantage of the invention is by comparison with the "presently available lyophilized preparates" i.e. those on the market now. It is saying you can get high concentration of the active ingredient and avoid the solubilisation problems of the prior art. That has nothing to do with the nature of the original raw material active ingredient.
vi) So the essential teaching of the patent is not concerned with the nature of that basic raw material. It is about how you make a stable, ready-to-use solution from such a material.
vii) The fact that claim 31 is more limited than claim 1 (as it is) makes no difference. Claim 31 is, Mr Miller accepts, not infringed. This is because it is specifically limited to a process which starts with a raw material ("salt") which "is not in the form of a lyophilizate". Mr Miller says that by contrast in claim 1 it is "the solution which has not been reconstituted from a lyophilizate". There is a shift from the unlyophilized starting material of claim 31 to the unlyophilized material used to make the ready-to-use solution.
"36. On a fair reading of the claims and in the context of the specification and such evidence of common general knowledge as is before me I find that the skilled addressee would form the view that the patentee regarded lyophilization as not just an unnecessary but as an undesirable process step in the production of the injectable solution and intended to exclude a solution made by the use of such a step, even if it were to be followed by other steps, such as the adjustment of pH and sterilising by filtration."
The Deputy Judge's conclusions
"28. Pharmacia counters by saying that claim 31 is effectively dependent on claim 1 and is therefore narrower than claim 1 and should be construed in such a way. This is not strictly correct. Claim 31 is a process claim whereas claim 1 is a product claim. Whilst it is correct that the process of claim 31 may not be the only process that will produce a product within claim 1 this does not mean that it must necessarily be construed as a subset of the processes that can produce such a product. There may be other processes: there may not. It is neutral."
"27. Mayne submit that their product is made by the process of claim 31 except that the salt of the anthracycline glycoside which they dissolve is in the form of a lyophilizate. Thus, they do not infringe claim 31, as is acknowledged by Pharmacia. They point out that the examples being silent as to how the API is produced, it must be assumed that the API is not a lyophilizate otherwise there is no example of the process claimed. Thus, they say, the skilled addressee would understand the phrase in claim 1 "which has not been reconstituted from a lyophilizate" as excluding a solution which has been made by the process of claim 31 but with the starting material, the API, being a lyophilizate."
"I have two problems with Pharmacia's approach to construction of the disputed phrase. The first is that even if the patent does not teach achieving stability by adjusting the pH the claim also refers to an anthracycline glycoside concentration of from 0.1 to 50 mg/ml. The passage set out above from page 9 line 11 of the patent explains that this is an advantage over "the presently available lyophilized preparates". I have heard no evidence as to how the skilled addressee would regard this passage but on its face it seems to be teaching away from the use of lyophilizates.
The second problem is more fundamental. If one concludes that the skilled addressee does not regard the disputed phrase as necessarily excluding any lyophilization/reconstitution step, where does he/she draw the line? The suggestion by Pharmacia is that the skilled addressee would understand the phrase to mean that lyophilization was not used on the final product but could have been used on a precursor. This, says Pharmacia, would only exclude precisely what was done before in the hospital pharmacy."
Lord Justice Hooper:
Dame Elizabeth Butler-Sloss P: