Smithkline Beecham Plc v Apotex Europe Ltd (No. 3)
| Jurisdiction | England & Wales |
| Judge | Lord Justice Jacob,Lady Justice Arden,Lord Justice Ward |
| Judgment Date | 29 November 2004 |
| Neutral Citation | [2004] EWCA Civ 1568 |
| Date | 29 November 2004 |
| Docket Number | Case No: A3/2003/2722 |
| Court | Court of Appeal (Civil Division) |
[2004] EWCA Civ 1568
Lord Justice Ward
Lady Justice Arden and
Lord Justice Jacob
Case No: A3/2003/2722
HC 02 C03101/HC 02 C02937
IN THE SUPREME COURT OF JUDICATURE
COURT OF APPEAL (CIVIL DIVISION)
ON APPEAL FROM THE HIGH COURT OF JUSTICE
CHANCERY DIVISION (PATENTS COURT)
The Hon Mr Justice Pumfrey
Royal Courts of Justice
Strand, London, WC2A 2LL
Andrew Waugh QC, Justin Turner and Geoffrey Pritchard (instructed by Simmons & Simmons) for the Appellants
Antony Watson QC, Colin Birss and Thomas Mitcheson (instructed by Taylor Wessing) for the Respondents
Lord Justice Jacob:
The claimant/patentee parties ("SKB") appeal from a judgment of Pumfrey J of 5 th December 2003 whereby he rejected their claim that the defendant parties ("Apotex") infringed patent No. 2,297,550, held the patent invalid and ordered its revocation. Mr Waugh QC argued the case for SKB; Mr Watson QC that for Apotex.
In previous litigation, a claim by BASF for revocation of the patent resulted in a finding that most claims of the patent were invalid, but that two claims (10(i) and 11) were valid. These proceedings were before Pumfrey J whose decision [2002] EWHC 1373 (Ch) was upheld by the Court of Appeal [2004] IP&T 846, [2003] EWCA Civ 87As a consequence of these findings SKB successfully applied to amend the patent to restrict the monopoly to that claimed in those two claims, now renumbered as claims 1 and We are concerned with the validity of these and whether or not they cover the process used by Apotex.
The primary attacks on validity were based on two prior published documents. The more important of these is UK patent application 85–26407 ('407), which was published in 1987 as part of the file for what became EP 223,403 ("the hemihydrate patent"). The other is US patent No. 2,864,817 ("the erythromycin patent") published in 1958. Other attacks on validity are also advanced in the nature of a squeeze – it is said that if the claims are wide enough to cover what Apotex do, they also cover that which obvious or are so wide or ambiguous as to be insufficient. It is also contended that the claims are so ambiguous that one is unable to say what their scope is and hence one is unable to say whether the Apotex process falls within them.
The BASF proceedings were more limited in scope than these. Only validity was in issue and only upon the basis of the '407 prior art. Neither the erythromycin patent nor the various invalidity arguments based on a "squeeze" were raised. Moreover the evidence was, of course different. It is not suggested that Pumfrey J in this action was, or this court is, any way bound by the previous decision so far as it turned on evidence. This case has to be decided on its own evidence though some of that has been imported via hearsay notices from the earlier case.
Background
The case is concerned with forms of the pharmaceutical paroxetine – it is far from the first (or last) of such cases in this jurisdiction alone. From that one can infer that a great deal of money is involved. A company called Ferrosan found the paroxetine molecule in about 1980 and that it had potential therapeutic effect. SKB (strictly its predecessors) bought up the rights and did all the very great risky work to test it and bring it to market. By the mid-90's SKB's paroxetine product, under the trade mark Seroxat, was their biggest selling pharmaceutical drug.
The salt of paroxetine on which SKB did most work was the hydrochloride. This, it is now known, can exist in a number of crystalline forms:
i) The hemihydrate: a form which consists of a regular lattice made up of one water molecule to two of paroxetine hydrochloride. SKB's Seroxat is in this form. It is protected by the hemihydrate patent, which has not expired;
ii) The anhydrate: a crystalline form with no water bound into the crystal – no "water of crystallisation." There is no patent protection for the anhydrate as such. It itself comes in several forms, but nothing turns on that.
iii) A solvate. This is a looser expression. Broadly it means a kind of crystal which contains within its structure some of the solvent from which the product was crystallised out. The hemihydrate is a class of solvate where the molecules of solvent (water) are in a defined ratio to those of paroxetine hydrochloride, but a defined ratio is not necessary for a product to be a solvate because solvent can be retained in other ways than as part of a regular crystal lattice, within interstices for instance. Having said that the word may take its detailed meaning from context which may present real problems – see below.
Depending on the particular solvate, the solvent within it may be removed more or less readily. In the case of some solvates it is sufficient to treat them with known drying techniques to remove virtually all the solvent. In the case of others the solvent is more difficult to remove – some at least will not come out even with stringent drying. Because the term "solvate" encompasses a range of possibilities, it is generally necessary to consider its use in context to ascertain the precise meaning intended.
In which crystalline form a drug is actually marketed is of considerable significance. Although at a crude level one might think it does not matter (once it is dissolved in the stomach, it can hardly matter what form the original crystal was) in practice it does. Regulatory authorities are concerned with which form for reasons of bioavailability (some forms dissolve more readily than others), stability and the like. Also, and for more obvious reasons, the authorities are concerned with amounts of impurity. So solvates with large amount of unremoved solvent are (at least where the solvent is one not found in the body naturally) unlikely to get marketing authorisation. We were told that an impurity level of more than 0.5% of any compound is not permitted. Curiously two impurities, each less than 0.5% are permitted. Apotex's product has about 0.4% of each of IPA (see below) and acetone – so it is permitted.
When SKB first started investigating paroxetine hydrochloride in the early 1980's they made the anhydrate at pilot scale at their Harlow plant. Their process involved the use of water. At some point, although ostensibly nothing had changed, they discovered that the process was making hemihydrate instead of anhydrate – they could no longer make the anhydrate. This is a known type of phenomenon. It is attributed to the fact that once a particular environment is "seeded" with a particular type of crystal, the seeds will encourage the formation of that type rather than any other type. It is not necessary to go further into this at this stage, though it necessary to discuss it a little more when I come to Mr Watson's "Bodmin" point.
In 1985 SKB applied for patent '407 which, in its broadest aim "provides crystalline paroxetine hydrochloride as a novel material, in particular in pharmaceutically acceptable form."
'407 goes on to state that SKB have discovered that paroxetine hydrochloride can exist in at least the hemihydrate and anhydrate forms and that it "can form crystalline solvate with certain solvents …. in particular isopropyl alcohol." (I shall call this IPA. It has other names, e.g. propan-2-ol, but I shall change all quotations to just IPA for consistency and brevity). Example 1 (of which lots more anon) purports to describe the preparation of the anhydrate. Examples 2–4 purport (and indeed, it is common ground do) describe the production of hemihydrate. Example 5 describes the production of the IPA solvate. Because, say SKB, example 1 in fact produced the hemihydrate and not the anhydrate, '407 was used to obtain patent priority only for the hemihydrate. At that point (in the late 1980's and early 1990's) therefore, SKB did not have any protection for the anhydrate, nor, self-evidently, for any process for making it.
The Patent in Suit
This was applied for in 1996. Its title is "Paroxetine hydrochloride anhydrate substantially free of bound organic solvent." In its broadest form it was an attempt to gain patent protection for the anhydrate sufficiently pure to pass regulatory approval. As I have said, following the BASF litigation it was considerably amended – broadly down to particular processes for making the anhydrate free of solvent.
Claims 1 and 2 (as amended) read:
1. A process for the preparation of paroxetine hydrochloride anhydrate substantially free of IPA which comprises crystallising paroxetine hydrochloride in an organic solvent or mixture of organic solvents which form a solvate with the paroxetine hydrochloride and which are not removable by conventional drying techniques thereafter displacing the solvated solvent or solvents using a displacing agent.
2. A process for the preparation of paroxetine hydrochloride anhydrate substantially free of bound organic solvent which comprises displacing the solvated solvent or solvents from a paroxetine hydrochloride solvate using a displacing agent."
Notwithstanding their brevity, they present formidable problems of construction. At this stage it is merely necessary to quote bits of the specification left following the amendment. The patent begins by referring to Ex.8 of EP '403 (the hemihydrate patent) which is the same as ex.1 of 407. It...
To continue reading
Request your trial
-
Actavis Group PTC EHF (a company incorporated under the laws of the state of Iceland) v ICOS Corporation (a company incorporated under the laws of the state of Washington, USA); Actelion Pharmaceuticals Ltd (a company incorporated under the laws of the st
...and therefore insufficient. That makes sense. However, while the principle cannot be limited just to technical tests, after all SmithKline Beecham v Apotex [2004] EWCA Civ 1568 was not that sort of case, nevertheless it does not apply simply because one can imagine difficult cases to judge ......
-
Sandvik Intellectual Property AB v Kennametal UK Ltd
...will not. It makes it impossible to work the invention at all until one has found out what ingredient is needed." 120 In SmithKline Beecham plc v Apotex Europe Ltd [2004] EWCA Civ 1568, [2005] FSR 23 at [115] Jacob LJ recorded the following argument of Apotex as having "considerable force" ......
-
Arrow Generics Ltd v Akzo NV
...Pam SA v Fusion Provida LtdUNK [2005] EWCA Civ 117; (2005) 28 (6) IPD 28043 SmithKline Beecham plc v Apotex Europe LtdUNKUNK [2004] EWCA Civ 1568; [2005] FSR 524; (2005) 28 (2) IPD 28003 Socit Technique de Pulverisation STEP v Emson Europe LtdUNK [1993] RPC 513 Synthon BV v SmithKline Beech......
-
Unwired Planet International Ltd v Huawei Technologies Company, Ltd and Others Unwired Planet, Inc. and Others (Tenth Party) Telefonaktiebolaget LM Ericsson (Eleventh Party)
...bring an aspect of Art 84 EPC into the test for sufficiency. 160 A month after Kirin-Amgen the Court of Appeal gave judgment in SmithKline Beecham v Apotex [2004] EWCA Civ 1568. The claim was held not to be infringed but Jacob LJ (with whom Arden and Ward LJJ agreed) went on and considered ......
-
Actavis v Eli Lilly: The Impact On Patent Infringement Law In The UK Two Years On
...example, such an approach was successful for the party alleged to infringe in Chiron v Evans [1997] EWHC 359 (Pat) and SKB v Apotex [2004] EWCA Civ 1568. Similarly, a squeeze between infringement and anticipation could be employed, invoking the principle illustrated by the House of Lords' j......