GENERICS (UK) LIMITED t/a MYLAN v YEDA RESEARCH AND DEVELOPMENT CO. LIMITED

[2014] R.P.C. 4 121 GENERICS (UK) LIMITED t/a MYLAN v YEDA RESEARCH AND DEVELOPMENT CO. LIMITED COURT OF APPEAL Moses, Kitchin and Floyd L.JJ.: 18–20 June 2013 and 29 July 2013 [2013] EWCA Civ 925, [2014] R.P.C. 4 H1 Patent – European patent – Treatment for multiple sclerosis – Revocation – Validity – Construction – Obviousness – Inventive step – Whether post-dated evidence admissible in identifying technical contribution – Whether technical contribution plausible – Whether any technical contribution in fact – Burden of proof – Insufficiency – Meaning of “approximately” – Declaration of non-infringement – Whether allegedly infringement fell within the claimed range – Validity upheld – Declaration of non-infringement refused – Appeal to Court of Appeal H2 European Patent Convention, art.56 This was an appeal from a decision of Arnold J. in proceedings commenced by the appellant (“Mylan”) seeking revocation of European Patent (UK) No. 0,762,888 (“the Patent”) and a declaration of non-infringement with a view to clearing the way for a product which it wished to launch in the UK. The respondents were respectively the registered proprietor of the Patent (“Yeda”) and its exclusive licensee (“Teva”). The Patent related to an improved composition of a synthetic mixture of polypeptides known as copolymer-1. Teva marketed a glatiramer acetate product for the treatment of relapsing–remitting multiple sclerosis (“MS”) under the brand name Copaxone and which it claimed was copolymer-1 and protected by the Patent. The product which Mylan wished to market was its own generic glatiramer acetate product. Mylan attacked the validity of the Patent on grounds which included obviousness (including obviousness for want of technical contribution) and insufficiency. In MS, an inflammatory response led to the removal of the myelin sheath around the nerves. Copolymer-1 had been designed to mimic myelin basic protein (“MBP”). In 1987 the results of a pilot trial of copolymer-1 in the treatment of relapsing–remitting MS had been published and these announced, with a degree of caution, that copolymer-1 might be beneficial. The material tested was identified as being of a molecular weight of 14–23 kDa. A further trial (“the Phase III trial”) then went ahead and, although the full results were not published until after the relevant priority date, May 1995, it was the subject of a paper (“Johnson 1994”) which provided a retrospective of the work on copolymer-1 and recorded that it had a molecular weight of approximately 7 kDa. The headline results were announced at a meeting of the American Neurological Association (“ANA”) in October 1994. Claim 1 of the Patent was to H3 H4 “a copolymer-1 fraction, wherein said fraction contains less than 5% of species of copolymer-1 having a molecular weight over 40 kilodaltons and wherein over 75% of said fraction is within a molecular weight range from 2 kilodaltons to 20 kilodaltons”. [2014] R.P.C., Issue 2 ß Crown Copyright 122 H5 H6 H7 H8 H9 GENERICS (UK) T/A MYLAN V YEDA RESEARCH AND DEVELOPMENT CO. Copolymer-1 was described in [0003] of the specification of the Patent as “a mixture of polypeptides composed of alanine, glutamic acid, lysine and tyrosine in a molar ratio of approximately 6:2:5:1”. At first instance,1 Arnold J. had upheld the validity of the Patent and refused the declaratory relief sought. In particular, he had rejected Mylan’s arguments that the Patent was invalid over Johnson 1994. Although the skilled team would have been motivated to develop the product the subject of the Phase III trial as reported at the ANA meeting, it did not follow that the material it would have developed would have been the 7 kDa material. The clinician would not have concluded that the headline results provided a good basis for developing the 7 kDa copolymer and would have wanted to see a full report to see whether this shed any light on the reasons for and significance of the difference in molecular weight between the material used in 1987 and that used in the Phase III trials. The judge had concluded that Mylan’s case was based on hindsight. Arnold J. had identified the technical contribution claimed in the Patent as being the proposition that copolymer-1 as claimed caused less irritation at the injection site and/or a reduced incidence of systemic side effects and had found both that the specification of the Patent made that technical contribution plausible and that the evidence before him was inconclusive as to whether there had been any lack of technical contribution in fact. The judge had also ruled that if a patent specification made a technical effect “plausible”, a challenge to the existence of that technical effect could not be mounted by the use of post-dated evidence. The respondents had argued that if later evidence could not be adduced to support an effect not made plausible by the specification, it could not be adduced to contradict a plausible effect either. As to construction, Mylan’s primary contention was that the word “approximately” in [0003] covered compositions in which the molar fraction of any single amino acid did not differ from the percentages identified by more than ±10% of their value. However, if this was not correct, Mylan argued that the Patent failed to provide any criterion by which to determine what was covered by the word “approximately", and thus was ambiguous. The respondents’ contended that the word “approximately” reflected the fact that copolymer-1 was a random copolymer whose composition was not precisely defined. Thus the skilled reader would have understood that, in this respect, the claims had a fuzzy boundary. The skilled reader would also have understood that the claims embraced compositions in which the molar ratios of the amino acids (as distinct from the molecular weight distributions) corresponded to those of the prior art copolymer-1 compositions referred to in the Patent. Arnold J. had favoured the respondent’s contention that that the skilled person would have concluded that all the compositions disclosed in the various prior art documents relied upon fell within the definition “approximately 6:2:5:1”. The proposed Mylan product differed from one in which the molar ratios were 6:2:5:1 principally in that the molar fraction of tyrosine was 29.6% greater but Arnold J. had held that that difference was not sufficient to take the proposed Mylan product outside of the claim. On appeal to the Court of Appeal, Mylan contended that Arnold J. had erred in that (i) certain claims of the Patent were obvious over Johnson 1994; (ii) the Patent was also invalid for obviousness on the basis of lack of a technical contribution because the specification did not make it plausible that the technical problem described was solved by products falling within the claims, alternatively, that problem was not in fact solved 1 [2012] EWHC 1848 (Pat). 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