Patent News London September 2011

Pharma Focus How to Infringe Swiss Form Claims Mr Justice Kitchin recently considered the scope of Swiss form claims in the context of the proton pump inhibitor esomeprazole. The patent in suit (EP1,020,461), held by AstraZeneca, seeks to protect the magnesium salt of the S enantiomer of omeprazole (magnesium esomeprazole) with an optical purity of 99.8% enantiomeric excess1 and the use of that salt for the manufacture of a medicament for inhibition of gastric acid secretion. The patent comprises claims in various forms, including product per se claims and “Swiss form” claims. For the purposes of the English action the case turned on the construction of claim 1 only. Before the English High Court2 Ranbaxy sought a declaration of non-infringement to enable it to import product into the UK which had been manufactured in India. AstraZeneca counterclaimed for infringement. There was no dispute between the parties that the manufacturing process utilised by Ranbaxy started with magnesium esomeprazole with an optical purity of 99.8% e.e. During the manufacturing process a quantity of omeprazole racemate is added; thus the finished product does not have the same optical purity. According to AstraZeneca this was irrelevant, as the product to be imported by Ranbaxy was a direct product of a process in which magnesium esomeprazole with the requisite optical purity was used to manufacture a medicament. The use of the claimed compound to make any product, regardless of its final optical purity, was protected. Ranbaxy on the other hand argued that their product did not infringe the claim as the medicament was not formulated using, and did not contain, magnesium esomeprazole with the required optical purity. Ranbaxy contended that the claim required the final medicament also to contain magnesium esomeprazole with an optical purity of 99.8% e.e. Kitchin J. was persuaded by the arguments of Ranbaxy, finding that the skilled man would believe the patent to be directed to the production of optically pure magnesium esomeprazole and its use in particular therapies. Recognising that magnesium esomeprazole with an optical purity of 99.8% e.e. was new, he would understand the teaching of the claim to be towards the use of this new compound for manufacture of a medicament containing that compound. This, he said, would be reinforced by the skilled man’s understanding of patent claims and in particular claim 9 of the patent which claimed the compound itself and was thus not asserted against Ranbaxy (as it was not importing a product containing the esomeprazole salt of sufficient purity). Thus in the Judge’s view the Swiss form claim 1 was directed to a medicament which contained magnesium esomeprazole with an optical purity of 99.8% e.e. Such a construction of the claim does appear to read a limitation into the claim, which is not otherwise present on a strict literal interpretation. After all, the claim specifies only the use of the esomeprazole salt for the manufacture of a medicament for a specific purpose, there is no limitation in the claim regarding the composition of the final medicament. Conversely Astra– Zeneca accepted there was no infringement of the product claim, and logically there should be no broadening of the claimed invention simply because the claim is framed in a Swiss form as opposed to direct form. This is not the last we will hear of this patent. It is likely this decision will be appealed; the outcome of that appeal will no doubt affect whether the validity side of the case is put before a judge at the trial scheduled for early 20123. In the meantime the KRKA action concerning infringement and validity comes before the High Court later this year. In a further twist the Opposition Division at the EPO earlier this summer held the patent to be invalid for lack of inventive step. AstraZeneca have already lodged an appeal against this decision. Furthermore in July the District Court of the Hague in the Netherlands gave its judgment on the validity of the ‘461 patent, finding the patent to be valid. This decision was given after the OD had made its pronouncement, though the OD decision was not brought to the Court’s attention as the case had been heard and closed prior to the OD hearing. We are thus left with a complex picture throughout Europe. Given the value of the product, it is certain that there will be many more chapters in the coming months and even years.

Catherine Drew +44 (0)20 7011 8727 [email protected]

1 Enantiomeric excess refers to the ratio of the most prominent enantiomer in a mixture to the least prominent enantiomer. In this case to fall within the scope of the claim there must be in excess of 99.9% of the S enantiomer and less than 0.1% of the R enantiomer, giving an enantiomeric excess of at least 99.8% i.e. the compound has an optical purity of at least 99.8% e.e. 2 Ranbaxy (UK) Limited v AstraZeneca AB [2011] EWCA 1831(Pat). 3 Interestingly this is one of the rare occasions on which a patent trial has been bifurcated before the English courts. Winston & Strawn London Patent News | 2

Further Highlights from the Pharma World Below we run through some other recent significant patent/SPC and regulatory developments relating to pharmaceutical products.

There has been much activity in the European courts concerning supplementary protection certificates (SPCs) in the last few years. Two new developments came in the shape of the Advocate-General’s opinion in the Medeva4 case and the ruling of the Court of Justice in the Synthon and Generics [UK] cases. The first of these related to when SPCs could be granted on combination products if the basic patent on which the applicant was founding the claim to an SPC did not have a specific claim to a combination product. The solution suggested by the Advocate-General is complex. She has suggested abandoning a literal interpretation of the SPC Regulation and instead creating a new definition of the term “product” within the Regulation, in order better to reflect the purpose of the legislation. Unfortunately, the change to the definition runs through the Regulation, and has the, possibly unintended, consequence of restricting the number of SPCs likely to be granted from each basic patent. If the Court of Justice follows this opinion it could lead to numerous revocation actions being brought on current combination product SPCs and also encourage patentees to file additional, divisional patents to circumvent the suggested restrictions on the number of SPCs that can be granted from one basic patent.

The Synthon and Generics [UK] cases5 focussed on whether or not products authorised in the EU before the implementation of the EU medicines legislation (in the shape of Directive 65/65/EEC) could fall within the SPC regime and/or whether the duration of the SPC certificates of such products should be set from the date of the first marketing authorisation in the EU, whether this was an authorisation compliant with Directive 65/65/EEC or not. The Court of Justice followed the opinion of the Advocate-General in this case in stating that such products should not be considered for SPCs in any event. Their status as “older” products meant that they fell outside the scope of legislation that was designed to encourage innovation in bringing “new” products to the market. After deciding the Synthon case on this point, the Court of Justice stated it did not need to consider the questions on duration (on which the legal argument in the Generics [UK] case turned) as they were irrelevant if these “old” products did not qualify for SPCs in any event.

In the biotechnology field a lengthy judgment was handed down in the case of Novartis v Medimmune6. This case concerned Medimmune attempts to claim that Novartis had infringed its early phage display technology patents by employing this technique in the production of an antibody that became the marketed product Lucentis. Many invalidity arguments were ranged against the Medimmune patents but one that stuck was that, in so far as the patents related in general to a method of displaying antibody fragments on the surface of phage, the patents were obvious over a lecture given at a conference in Banbury in 1990. This was ironic since it was a conference co-organised by Professor Greg Winter, one of the key inventors working in the field of antibody gene library and phage display at the time with the MRC and Cambridge Antibody Technology (which became Medimmune). The judge also found the patents not infringed, largely because Novartis persuaded him that its construction of the relevant technical terms found in the patents’ claims was correct.

Other points to note from the decision were that the judge thought that, if the claims had been infringed, then the antibody within the Lucentis product would have been a product “directly obtained” from the patented process, and that an interesting non-infringement argument based on Article 8(2) Biotechnology Directive7 was not engaged because the antibodies produced were not “biological material” within the definitions found in the Biotechnology Directive and so this legislation did not apply. The case is also noteworthy for the extensive review of the technical specialisms and language skills of the expert witnesses chosen (see earlier article on this topic).

We are also anticipating soon a first patents judgment from the newly formed Supreme Court (it replaced the House of Lords last year). In the case of Eli Lilly v Human Genome Sciences, the parties are battling it out over the validity of a patent directed at neutrokine-a. This molecule is now known to be important in the immune system and both GSK (working with Human Genome Sciences) and Eli Lilly have products either approved or about to be approved that target this molecule. Eli Lilly’s main invalidity arguments centred around the lack of information in the Human Genome Sciences patent relating to the function of the neutrokine-a protein. This, say Eli Lilly, means that the invention either lacks industrial applicability as required under the section 1(1)(c) Patents Act 1977 or renders the invention obvious contrary to sections 1(1)(b) and 3 of this Act because the patent, in effect, only discloses a gene of no known function hence makes no contribution to the art. The case was heard in mid-July with the judgment expected in the next month or so.

4 Case C-322/10 This publication has been prepared for general guidance only and does not constitute 5 Cases C-195/09 and C-427/09 professional advice or a comprehensive review of the law. No representation or warranty 6 [2001] EWHC 1669 (Pat) (express or implied) is given to the accuracy or completeness of the information contained 7 Directive 98/44/EC in this publication. You should seek specific legal advice before acting on the information contained herein. No reproduction or redistribution is permitted without the written Gareth Morgan permission of Winston & Strawn LLP. +44 (0)20 7011 8726 [email protected] © 2011 Winston & Strawn LLP