Posted: May 8th, 2017
The Court of Appeal recently handed down its decision in Synthon BV v Teva Pharmaceutical Industries Limited, upholding Birss J’s decision at first instance that Teva’s patent relating to glatiramer acetate (“GA”) (EP (UK) 2 361 924) was valid but that claim 20 and dependent claims were invalid for added matter.
GA is a mixture of synthetic polypeptides, a low molecular weight fraction of which is sold by Teva under the brand name Copaxone for the treatment of relapsing remitting multiple sclerosis.
At the Court below, Synthon had challenged both EP’924 and a further Teva patent relating to GA, EP 2 177 528, on the grounds of novelty, obviousness and insufficiency. Birss J rejected these arguments, finding that both EP’924 and EP’528 were valid, save for claim 20 (and dependent claims) of EP’924 which were invalid for added matter. A summary of the first instance decision can be found here.
Synthon’s appeal of this decision was limited to obviousness of EP’924. EP’924 concerns the levels of free bromine and metal ion impurities present in the manufacture of GA and in the final GA product. The Court of Appeal also heard an appeal by Teva’s against Birss J’s finding that claim 20 (and dependent claims) of EP’924 were invalid for added matter. The decision of the Court of Appeal, dismissing both appeals, was given by Lord Justice Floyd.
Synthon’s obviousness appeal
The CGK method for preparing GA involved a deprotection step using HBr/AcOH. The claims of the patent are directed to minimising the levels of free bromine or metal ion impurities in the HBr/AcOH solution used to manufacture GA, and also in the final GA product. The broadest claims require less than 0.1% free bromine and less than 500 ppm of metal ion impurities.
Synthon’s appeal comprised four obviousness arguments. The first concerned claims requiring the HBr/AcOH solution to have less than 500 ppm of metal ion impurities. Synthon argued that as HBr/AcOH was known to be highly corrosive to metal, it was obvious to keep HBr/AcOH away from metal during its production and, when preparing GA, to use a solution of HBr/AcOH which had not come into contact with metal. Such a solution of HBr/AcOH, Synthon submitted, would have less than 500 ppm of metal ion impurities. Therefore claims requiring use of a solution of HBr/AcOH with less than 500 ppm of metal ion impurities was obvious.
This was rejected by the Court of Appeal. Floyd LJ noted that keeping HBr/AcOH away from metal surfaces was not the same as creating a solution of HBr/AcOH with less than 500 ppm metal ion impurities. Synthon had not adduced evidence proving that a solution of HBr/AcOH kept away from metal surfaces would result in a solution with less 500 ppm metal ion impurities. This lack of evidence was fatal.
The second obviousness argument concerned the levels of free bromine. Synthon submitted that freshly made, clear HBr/AcOH would have less than 0.1% of free bromine and fall within claim 1. It was obvious to use freshly made HBr/AcOH, and there was evidence that freshly made HBr/AcOH kept away from light and oxygen had less than 0.1% free bromine. Synthon submitted that it was wrong for Birss J to have held that the evidence as to the level of free bromine in freshly prepared HBr/AcOH was not reliable.
Floyd LJ summarised the relevant evidence in paragraphs 60 – 65. He concluded that Birss J was “plainly entitled to reject as unreliable” Synthon’s expert’s evidence on this point. Floyd LJ also noted that Synthon’s failure to establish a quantitative connection between the colour of HBr/AcOH and the bromine content could not be improved by relying on the information in Example 5 of EP’924 (coloured batches of HBr/AcOH which were tested and found to be free of bromine). This ground of appeal failed.
Synthon’s third obviousness argument also concerned the levels of free bromine. Synthon submitted that the judge, when making findings as to the skilled person’s attitude to the presence of free bromine, should have taken account of the fact that the invention concerned the manufacture of a pharmaceutical. In this context, purity was important and there would have been motivation to remove impurities.
Again, Floyd LJ rejected this argument – it was not developed or advanced in the court below; the evidence did not support it and Birss J is an experienced patents judge and would have taken account of the fact that the skilled person would be operating in a pharmaceutical context rather than a research laboratory. In addition, the evidence was that the skilled person would not consider free bromine to be a problem.
Finally, Synthon submitted that claim 29 – involving measurement of bromotyrosine – was obvious as there was no invention in simply performing a measurement on the prior art process. There was no solution to a technical problem.
This argument was also rejected. Floyd LJ held that testing for bromotyrosine in the manufacturing process combined with the requirement to exclude batches above a certain level was not obvious and was a useful advance of the state of the art.
Synthon’s appeal was dismissed.
Teva’s added matter appeal
Teva’s appeal that Birss J was wrong to find added matter in claim 20 when compared with the patent application was succinctly rejected by the Court of Appeal. Floyd LJ noted that a general teaching to minimise impurities is not equivalent to a disclosure of GA with less than 1000 ppm of impurity. Claim 20 (and dependent claims) therefore added matter and Teva’s appeal failed.
A copy of the judgment can be read here.
Headnote: Scott Parker, Simmons & Simmons