Posted: June 10th, 2015
Synthon v Teva, London, UK, 21 May 2015,  EWCH 1395 (Pat) Birss J
In his judgment of 21 May 2015, Birss J upheld the validity a number of claims of EP’528 and EP’924, both owned by Teva and relating to glatiramer acetate (“GA”). This was so notwithstanding that the Dutch designations of the same patents had previously been revoked (albeit with some differences in the evidence taken into account). Three of the claims of EP’924 were, however, found to be invalid for added matter.
GA is a mixture of synthetic polypeptides made of four amino acids, a low molecular weight fraction of which is sold by Teva (brand name Copaxone) for the treatment of relapsing remitting multiple sclerosis.
EP’528 and EP’924, both being divisionals and differing of note only in relation to their claims, relate to improvements in the process for making GA, namely those resulting in low levels of free bromine and metal ion impurities. The claims in issue were mostly process claims for making GA or its intermediate (TFA-GA) and claims to the GA product itself (claims 22-26 of EP’924).
The main dispute in relation to CGK related to “free” bromine in HBr/AcOH, one of the reagents used in the process of making GA. Birss J favoured the view of Teva’s expert that HBr/AcOH was a robust unproblematic reagent and found that the skilled person, agreed to be a synthetic chemist with practical experience of peptide synthesis, would not be concerned about a risk of a side reaction between free bromine and tyrosine residues. The skilled person would therefore not consider there to be a need to use a scavenger to remove free bromine.
Prior sales of Copaxone before the priority date were admitted but were not novelty destroying because Synthon failed to establish that any of the products had a metal ion impurity level within the claims (from less than 100ppm in claim 22 to “free” in claim 26).
An earlier patent application (“Lemmon”) did not destroy the novelty of any of the claims of either patent. Claim 1 of EP’528 differed from Lemmon in that it included requirements that the HBr/AcOH has a metal ion concentration of less than 1000ppm and a free bromine concentration of less than 0.5%. Claim 1 of EP’924 differed from Lemmon in that the level of free bromine in the HBr/AcOH must be below 0.1%. It was found that there was no evidence that the HBr/AcOH that the skilled person would produce following Lemmon would necessarily have these properties because there were a number of choices that the skilled person could have made, for example, whether or not to use entirely non-metal apparatus for the production process. In any event, other potential sources of metal ions would still be present in the process, such as in the piperidine and process water used in various steps.
Birss J chose to deal with the claim features in two groups: (i) the levels of bromine and the use of a bromine scavenger and (ii) the levels of metal ions, and APHA colour of the HBr/AcOH.
It would not have been obvious to the skilled person that there was a risk of free bromine in HBr/AcOH reacting with tyrosine, either from their CGK (as dealt with above) or from any teaching in Lemmon. Synthon’s argument that the skilled person would routinely perform an amino acid analysis to characterise their product having followed Lemmon and, that that analysis would reveal the presence of bromotyrosine, was also rejected because it was not established that bromotyrosine would emerge “unlooked for”.
The skilled person had an open ended range of conditions for HPLC analysis and the correct conditions would only be chosen if the skilled person knew that they were looking to isolate bromotyrosine. Further, focusing on amino acid analysis involved an element of hindsight as three other analytical techniques were available, which would not have highlighted the presence of bromotyrosine in a way which would allow the skilled person to “stumble across it”.
In relation to the metal ion purities, Synthon submitted that these features were obvious because if the material produced following Lemmon had turned red in colour the skilled person would have considered metal ion impurities to be a possible cause and proceeded to use non-metal apparatus to produce the HBr/AcOH. This argument was found to fail on the evidence of both experts, which made clear that identifying the cause of the red colour is challenging. Metal ions would be one possible cause among a number of others and the skilled person would not proceed to eliminate metal ions without having identified the cause of the colour. The level of uncertainty as to what they would do next was not indicative of obviousness. Further, as with novelty, even if the skilled person had decided to use entirely non-metal apparatus, it is not certain that this would inevitably solve the problem due to the other potential sources of metal ions.
Synthon submitted that both patents were insufficient on the basis of a squeeze with novelty/inventive step, namely that since the patents taught that the only source of metal ion contamination was the apparatus, a finding of novelty/inventiveness over Lemmon because the GA produced using HBr/AcOH made using non-metallic apparatus may still contain metal ion impurities must necessarily demonstrate a lack of sufficient disclosure in the patents.
Birss J rejected this argument, finding that the correct question should be what would the skilled person do, if following the express teaching of the patent, they found that they had coloured GA or metal ions above 100ppm. This was unlikely be a difficult task, although a finding on this point was unnecessary as Synthon had not submitted evidence on this point. The patent did contain an important teaching over the prior art, so the patent could only be found to be insufficient if there had been evidence that the skilled person could not in fact have made GA with less than 100ppm ion impurities without undue burden.
There were a number of added matter challenges to certain claims of EP’924 based on three attacks. The first was unsuccessful as there was found to be no added matter in the difference between “desired molecular weight” and “desired average molecular weight”. The second and third attacks were successful as there was found to be no clear and unambiguous disclosure in the application either (i) that the level of metal ions in the final GA product is necessarily the same as the level of metal ions in the TFA-GA intermediate or (ii) of the APHA scale being used to measure the colour of the GA. Accordingly, the claims that contained this new information, claims 20, 27 and 28 of EP’924, were invalid for added matter.
Read the entire decision here.
Head note: Amy Crouch and Scott Parker, Simmons & Simmons