Mayne Pharma PTY Ltd & Anor v Pharmacia Italia SPA

This is a patentee’s appeal in a case rightly subjected to the streamlined procedure. The litigation began on 17^th May 2004 when the respondents (“Mayne”) commenced proceedings for a declaration of non-infringement of Pharmacia’s UK patent No. 2,178,311. A counterclaim for infringement followed. The only issue was whether Mayne’s product falls within claim 1 of the Patent. The case was heard before Mr Roger Wyand QC, sitting as a Deputy Judge. He gave judgment, holding non-infringement, on 1^st November 2004 and granted permission to appeal. So the case has gone from start to determination on appeal in less than 9 months.

Mayne wish to sell an injectable solution of an anti-cancer drug called epirubicin (an anthracycline glycoside) hydrochloride. They say it does not fall within any of the claims of the patent. Pharmacia say it does. It is agreed that the whole question turns on claim 1. This reads:

“Lyophilization” (US spelling) means freeze-drying. What Mayne do is described, it is agreed accurately, by the Deputy Judge as follows:

So lyophilization of the epirubicin hydrochloride forms part of the history of Mayne’s product, but it is not the immediate precursor to its production – it is an “upstream” process. Is the final product nonetheless covered by the claim? This turns on its meaning, particularly the words solution … which has not been reconstituted from a lyophilizate. It is conceded that the Mayne process fulfils the remainder of the claim, pH adjustment with appropriate acid.

To decide upon that meaning one must construe the claim in context. I summarised the principles in paragraph 41 of my judgment in Technip SA’s Patent [2004] RPC 919. The House of Lords in Kirin-Amgen [2004] UKHL 46, through Lord Hoffmann’s speech, has approved those principles (save for one minor matter) and provided a much fuller justification for them than did I. As a practical working guide, it will generally be sufficient to use my summary as approved. I repeat it here, but stripped down to bare essentials:

In this case it is agreed that the “Protocol questions” do not assist. What matters is the meaning of the claim read in context. Since the claim is assumed to be read by the person skilled in the art, it is sensible to begin by summarising his relevant background knowledge - the common general knowledge. I accept here, as Mr Birss, for Mayne, contended, that the relevant notional skilled man would be a pharmaceutical manufacturer, not merely a hospital pharmacist. Such a man (or team) would have knowledge not only of how the end product was to be used but also how to make it.

In particular he would know that:

The active ingredient to be used for the invention (anthracycline glycosides) were anti-tumour agents having widespread actual use;

The agents were very toxic so that any risk of medical staff or manufacturing staff coming into accidental contact with them was serious;

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;

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;

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;

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;

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.

With that, I can turn to the specification. Its title is “Injectable ready-to-use solutions containing an antitumor anthracycline glycoside.” The opening general words say this:

Next it acknowledges that the anthracycline glycoside compounds are well known and used as anti-tumor agents. It then sets out the nature of the existing products on the market:

After summarising two references which discuss the dangers to medical personnel from this type of agent in general, the patent says this:

It then states the problem to be solved by the invention:

Next it sets out what the invention is in the so-called consistory clause. It is repeated in claim 1 so I need not set it out again. There then follows a second consistory clause, which corresponds to independent claim 31:

There then follows detail about how the solution is made. None of the detail matters for present purposes save this: that the description of the detailed variants of the process at no point mentions the use of lyophilized product. All the 12 examples start with the words “Doxorubicin.HCl was dissolved …” without explicitly saying whether it was lyophilized or not.

The last passage I need mention is a general statement on p. 9 about an advantage of the invention:

Mr Richard Miller QC for the patentees contended that the patent was essentially about formulation of the ready-to-use solution. It was this formulation step which had not to involve lyophilization and its reconstitution on the ward. The starting materials for the formulation were not part of the invention. He submitted in detail that:

The heart of the invention was, as its title said, an injectable ready-to-use solution.

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.

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.

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.

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.

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.

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.

Mr Birss submits that his case is crucially dependent upon whether the Deputy Judge was right in his paragraph 36:

Putting it another way, he submitted that the whole teaching of the patent is about the complete avoidance of lyophilization. You do not need lyophilization at any stage. And it is that which is to be avoided if you are to avoid danger to workers during any part of the manufacture. As he put it “you can throw away the lyophilizing machine.”

He drew a homely analogy – with instant coffee. If you want a cup of real coffee (i.e. coffee which has not been reconstituted from a lyophilizate) containing milk and sugar you will not be satisfied with a cup of instant coffee where the milk and sugar has been added after the reconstitution.

Mr Birss further relied upon the process aspect of the invention – claim 31. First he pointed out that if the examples were truly indifferent as to whether the starting material was lyophilized or not, then none of them would be examples of the process of the invention. So it was implicit that the starting material was not lyophilized. Second he submitted that claim 31 tracks claim 1 and in particular both claims use the word “lyophilizate”. If Mr Miller were right then the word would have a different meaning in each claim which was improbable.

I have already quoted the most crucial paragraph of his judgment. But I should mention some other points too. First there is the way he dealt with claim 31. He said this:

I think that is right. In general in a patent with product and process claims one may perhaps expect the process to produce the product, but there is no necessary corollary that the product must be made only by the process. All depends on the language used in context.

In the preceding paragraph the Judge said this:

Mr Birss submitted that the Judge’s comment about the claim 31 argument being “neutral” did not apply to this paragraph. I think he is right. On the other hand the Judge here does no more than record Mr Birss’ argument about the examples. He never found it necessary to take the argument specifically into account, though he may have done in his crucial paragraph 36.

Next I should mention the Judge’s paragraphs 33 and 34:

I do not agree with either of these points. As Mr Miller pointed out the passage on p.9 is by way of contrast with the existing product – “the teaching away from lyophilizates” relates only to lyophilizates in the final product.

Nor do I see any real problem about where the line is drawn. Mr Miller put it this way: “only if the step of reconstitution produces a ready-to-use solution is there no infringement.” Mr Birss suggested there was a problem here: suppose you reconstituted and then diluted the solution or added saline for isotonicity – as you sometimes did with the prior art. Would that mean no infringement? I see no problem. The product is either ready-to-use or it is not. If it is, then if the immediately prior step was reconstitution, there is no infringement – otherwise there is.

Finally the Judge thought there was support from a linguistic analysis of the claim. I do not go into the detail of this – Mr Birss did not seek to support it as such. His support for the Judge, as I have already said, rested essentially on paragraph 36.

I have come to the conclusion that Mr Miller is right, essentially for the reasons he advanced. I need elaborate only a little. I think the skilled man would see the real point of the teaching in the description as being the provision of a stable, ready-to-use solution. Such a desirable substance was not previously available. The patent teaches him how to make it. He can make it without having to lyophilize the material in the vials. He knows he will have to start his formulation with active ingredient raw material. But he would not regard the nature of that as part of the formulation process. The patent teaches him how to do away with a previously essential lyophilization.

When he comes to read claim 1, knowing that its purpose in law is to set out the monopoly, he sees that it is the “ready-to-use solution” which must not “have been reconstituted from a lyophilizate.” With the understanding of the purpose and teaching of the description he would read it as meaning that the solution itself has not been made by reconstitution – it is avoidance of that which fulfils the purpose of doing away with the previously essential step. If he considered the nature of the starting raw material, lyophilized or not, he would see it made no real difference – just that starting with lyophilizate would introduce an unnecessary complication.

I think this construction is that which is consistent with the inventor’s purpose as disclosed in his specification – the manufacture of a ready-to-use solution which does not involve the previously essential lyophilization stage.

As to Mr Birss’s coffee example, like many analogies it is beguilingly misleading – there is no true analogy because coffee in its raw material form can never be lyophilized. Nor do I think it matters whether the examples are read as starting with unlyophilized material – whether they do or not is not what matters because they are essentially about producing the stable solution.

Accordingly I would allow the appeal. I would not want to part from this case without paying tribute to the high quality of the argument on both sides. Sadly, however, I must also record the fact that I was most disappointed to see the quite extraordinary number of files of paper produced, quite unnecessarily, for this appeal. We were only referred to two pages not included in the one main file. They were obviously not wanted on voyage or to put it more formally not “relevant to proceedings in the Court of Appeal” within the meaning of para. 15.1(1) of the Practice Direction to Part 52 of the CPR. No doubt this will be taken into account on assessment of costs.

I agree.

I also agree.