Ranbaxy (Uk) Ltd v Astrazeneca Ab
| Jurisdiction | England & Wales |
| Judgment Date | 15 July 2011 |
| Neutral Citation | [2011] EWHC 1831 (Pat) |
| Docket Number | Case No: HC10 CO3103 |
| Court | Chancery Division (Patents Court) |
| Date | 15 July 2011 |
[2011] EWHC 1831 (Pat)
IN THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
PATENTS COURT
Royal Courts of Justice
Strand, London, WC2A 2LL
The Hon Mr Justice Kitchin
Case No: HC10 CO3103
John Baldwin QC and Mark Chacksfield (instructed by Messrs S J Berwin LLP) for the Claimant
Henry Carr QC and Miles Copeland (instructed by Messrs Bristows) for the Defendant
Hearing dates: 9–10 June 2011
MR. JUSTICE KITCHIN:
Introduction
In this action Ranbaxy, an importer of generic pharmaceuticals, seeks a declaration of non infringement and revocation of EP 1 020 461 ("the Patent") which is owned by AstraZeneca. AstraZeneca has counterclaimed for infringement.
The Patent covers one of AstraZeneca's drugs called Nexium which is used to treat gastric acid related disease. The active ingredient of Nexium is magnesium esomeprazole, the magnesium salt of the S enantiomer (the (-) enantiomer) of the racemic mixture known as omeprazole which was itself introduced onto the market under the brand name Losec in 1988.
The Patent was granted on 22 July 2009 upon a divisional application which was published on 19 July 2000 and has a filing date of 27 May 1994. As will be seen, it describes the use of magnesium esomeprazole with a high optical purity such that the ratio of the S enantiomer to the R enantiomer (the (+) enantiomer) must be >= 99.9/0.1. This optical purity is expressed in terms of enantiomeric excess (e.e.), that is to say the fraction of the compound present as the major enantiomer less the fraction of the compound present as the minor enantiomer. Hence the Patent explains the magnesium esomeprazole must have an optical purity of >= 99.8 % e.e. This, it is to be noted, is a bulk characteristic of the compound.
The parent application was published on 17 May 1995 and granted as EP 0 652 872 on 8 November 2000. This described and claimed the use of magnesium esomeprazole which was "essentially free" of the magnesium salt of the R enantiomer. On 9 December 2006, the Board of Appeal of the EPO held this patent invalid for lack of inventive step.
The matter is of some urgency because at present AstraZeneca is the only supplier of esomeprazole in the United Kingdom. Ranbaxy wishes to import a product which it believes does not infringe the Patent and for which it now expects to secure regulatory approval in the course of July 2011. If it is successful in this claim it will be free to sell that product without competition from other generic suppliers. Accordingly, on 25 October 2010, it issued an application for a speedy trial. That application was heard by Mann J who, on 12 November 2010, directed that the infringement issues in the action should be tried as preliminary issues.
I am therefore concerned only with the claim by Ranbaxy for a declaration of non infringement and the counterclaim by AstraZeneca for infringement. The parties are agreed these may be determined by reference to claim 1 of the Patent. This is in "Swiss form" and is directed to the use of magnesium esomeprazole with an optical purity of >= 99.8 % e.e. for the manufacture of a medicament for the inhibition of gastric acid secretion.
The product which Ranbaxy wishes to import is made in India. For the purposes of these proceedings there is no dispute that the process of manufacture begins with magnesium esomeprazole with an optical purity of >= 99.8 % e.e. There is also no dispute that the process involves the addition of a quantity of omeprazole racemate such that the finished product no longer contains magnesium esomeprazole of that optical purity.
In these circumstances AstraZeneca contends that claim 1 is infringed. It argues that the product which Ranbaxy wishes to import is the direct product of a process in which magnesium esomeprazole with an optical purity of >= 99.8 % e.e. is used to make a medicament for the inhibition of gastric acid secretion.
Ranbaxy, on the other hand, contends that claim 1 is not infringed. It says that the product which it wishes to import was not formulated using, and does not contain, magnesium esomeprazole with an optical purity of >= 99.8 % e.e.
The claim and counterclaim therefore depend upon the proper interpretation of claim 1.
I heard evidence from only one witness, Dr Roland Collicott, the expert called on behalf of Ranbaxy. He is an analytical chemist with experience of the pharmaceutical industry extending over forty years. He was a careful witness and, so far as it went, I found his evidence of assistance.
The Patent
The Patent is entitled "Magnesium salt of the (-) enantiomer of omeprazole and its use". The description begins with an identification of the field of the invention. Paragraph [0001] explains that the invention is directed to new compounds with high optical purity, their use in medicine and their use in the manufacture of pharmaceutical preparations.
Paragraphs [0002] to [0005] set out the background of the invention. Paragraph [0002] explains that omeprazole and its alkaline salts were known to be effective gastric acid secretion inhibitors and useful as anti-ulcer agents. Further, the compounds, being sulfoxides, have an asymmetric centre in the sulfur atom and so exist as two optical isomers.
The problem addressed by the Patent is then identified. It is said to have been desirable to obtain compounds with improved pharmacokinetic and metabolic properties which would give an improved therapeutic profile such as a lower degree of inter-individual variation. The invention is said to provide such compounds, these being novel salts of single enantiomers of omeprazole.
Paragraph [0003] explains that the separation of the enantiomers of omeprazole on an analytical scale has been described in a paper by Erlandsson published in the Journal of Chromatography in 1990 and on a preparative scale in German patent DE 4 035 455. The latter discloses the use of diastereomeric ether which is separated and thereafter hydrolysed in an acidic solution. The specification continues that omeprazole is quite sensitive under acidic conditions and so the acid has to be neutralised quickly with a base to avoid degradation of the compound. This is said to be disadvantageous. Accordingly, paragraph [0004] explains that a further aspect of the invention provides a new method for preparing the novel compounds of the invention on a large scale. However, the Patent does not contain a claim to any such new method.
These paragraphs suggest that the inventors did not consider the single enantiomers of omeprazole to be new in themselves. However, paragraph [0005] continues that there is no description in the prior art of any isolated or characterised salt of any of the single enantiomers of omeprazole, or of any optically pure omeprazole analogue. Dr Collicott said, and I agree, that the Patent therefore appears to draw a distinction between the isolated enantiomers of omeprazole and the isolated salts of those enantiomers.
There then follows a detailed description of the invention. Paragraph [0006] says that the invention refers to new optically pure magnesium salts of omeprazole having a particular formula which is depicted, this being the formula for magnesium esomeprazole.
Paragraph [0007] describes the first aspect of the invention as being the provision of the magnesium salt of (-) omeprazole with an optical purity of at least 99.8% e.e. It continues that the invention also provides the use of this salt for the manufacture of a medicament for the inhibition of gastric acid secretion.
Paragraph [0008] describes the advantages of the invention. It says that single enantiomers of omeprazole had previously only been obtained as syrups and not as crystalline products. It continues that by means of the method of one aspect of the invention the salts of the invention are now easy to obtain. Further, their crystalline form means they can now be obtained in very high optical purity. Moreover, the salts have a high stability towards racemization which makes it possible to use a single enantiomer salt of the invention in therapy. This important aspect of the invention is repeated in paragraph [0036].
The various uses of the compounds of the invention are described in paragraph [0010]. They include the inhibition of gastric acid secretion; the treatment of gastric acid related diseases and gastrointestinal inflammatory diseases such as gastric ulcers, duodenal ulcers, reflux esophagitis and gastritis; the treatment of patients on NSAID therapy, patients with gastrinomas, and patients with acute upper gastrointestinal bleeding; the treatment of patients in intensive care or pre- and post-operatively to prevent acid aspiration and stress ulceration; and the treatment of Helicobacter infections.
Paragraphs [0012] to [0017] describe a method of manufacturing the single enantiomers and their salts but, as I have mentioned, this is not the subject of any claim.
Paragraphs [0018] to [0025] deal with formulation. They are, I think, important because they provide the basis for claim 1. Paragraph [0018] reads:
"For clinical use the single enantiomers, i.e. the optically pure compounds, of the invention are formulated into pharmaceutical formulations for oral, rectal, parenteral or other modes of administration. The pharmaceutical formulations contain the single enantiomers of the invention normally in combination with a pharmaceutically acceptable carrier. The carrier may be in form of a solid, semisolid or liquid diluent, or capsule. These pharmaceutical preparations are a further object of the invention. Usually the amount of active compound is between 0.1–95% by weight of the preparation, between 0.2–20% by weight in preparations for parenteral use and between 1–50% by weight in preparations...
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