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Thursday, 21 May 2015

Colourless Copaxone in the clear: Teva's synthesis patents held to be (mostly) valid

Glatiramer acetate in action
In the patent world, there are some cases that just keep on giving.  One such is the continuing litigation between Synthon and Teva over Copaxone (glatiramer acetate), which is a treatment for multiple sclerosis, and which is responsible for $4.2 billion worth of annual sales for Teva worldwide.  This has already given us interesting and striking decisions from the Patents Court  (also here) and the Court of Appeal in England, and also the US Supreme Court.  These cases concerned EP 07862888 and its equivalents.  The parties have been back in court to fight over other patents, resulting in the decision Synthon B.V. v Teva Pharmaceutical Industries Ltd [2015] EWHC 1395 (Pat), which came out this morning.

The patents concerned are EP (UK) 2 177 528 and EP (UK) 2 361 924, both divisionals of EP (UK) 1 799 703, which was revoked by the EPO in opposition proceedings pursuant to Teva's withdrawal of it after a negative preliminary opinion.  Both patents relate to reduction of metal ion impurities and/or free bromine in glatiramer acetate and the processes leading to it.  Free bromine was found to result in brominated side-products, while metal ion impurities were found to cause the glatiramer acetate to turn red on storage.  Synthon was seeking revocation of the patents.

A few claims fell because of added matter problems, but otherwise both patents were maintained as valid.  Mr Justice Birss decided in a compact and very readable judgment that both aspects of the invention were novel and not obvious:
  • Synthon had not established that the skilled person would necessarily note the brominated side-products in routine analysis of the product. Even though, once the issue was identified, it was obvious to remove any free bromine from the HBr reagent that was used, in order to prevent formation of the brominated side-products, it was not obvious to do that if the problem had not been identified.
  • It was not obvious that the red colour was caused by metal ion impurities.  The judge accepted the opinion of Teva's expert Prof Ben Davis that the standard practice of a skilled person faced with a problem of colouration would be to identify the cause of the colouration and then, having identified the cause, employ a solution based on that knowledge.  However, it was entirely clear on the evidence that identifying the cause of the red colour is challenging, so the presence of metal ions would not have obviously been identified as the cause.  Therefore, there would have been no reason to reduce the metal ion content.
In relation to the metal impurity aspect, Synthon also mounted an insufficiency squeeze argument that, if the patent was novel and inventive over the prior art, then the patent did not disclose sufficiently how to ensure the absence of metal ions.  This was pretty much doomed from the start, since it relied on equating the position of the skilled person following the prior art with the position of the skilled person after reading the patent.  There was no evidence adduced that the skilled person could not make glatiramer acetate with less than 100 ppm metal ion impurities without undue burden.  This illustrates that even in a squeeze argument, a pleading of insufficiency needs to be backed up with evidence.

These are the main substantive findings in the judgment.  There are however a number of other points of interest.

1) Synthon's expert, Professor Alethea Tabor, got into hot water because some inaccuracies in her initial expert report, pointed out by Prof Ben Davis in his reply report, were not corrected in a further reply report, but rather left to be dealt with in cross-examination. This was apparently on the advice of Synthon's legal team.  Although she was criticised by the judge for this, he also paid tribute to her oral evidence, and considered that the fact that this was her first time acting as expert witness contributed to the error.

2) The judge noted (at [115]) that there is no requirement for a patent specification to indicate that any particular element of the invention is surprising or difficult. While such language appears sometimes in patents, Birss J pointed out that it can be a hostage to fortune when it turns out that prior art, which perhaps was unknown to the inventors, shows that something was not so surprising after all.  He concluded "The primary task of the specification is to explain the invention so that the claims are supported and can be understood and so that the skilled person can perform the invention to the standard required by the law. That is quite enough."

3) Synthon tried to advance a case of lack of inventive step due to no technical advance, or lack of plausibility that the invention works (based on EPO caselaw of Agrevo/Triazoles [T939/92] ).  Birss J held that such a point has to be expressly pleaded, and it cannot be argued on the basis of a general pleading of lack of inventive step.  Because it was not specifically pleaded, he considered that Synthon could not advance it.  He doubted it on the merits in any event.

4) Synthon argued that the EPO decision  Novartis/Erythro-compounds T990/96, which states that "a document disclosing a low molecular chemical compound and its manufacture makes normally available this compound to the public ... in all desired grades of purity" created a general legal principle that purity is not patentable.  Birss J rejected this submission, partly distinguishing the decision because it related to small molecules, whereas glatiramer acetate is a larger biological molecule, and partly because  T990/96 itself accepts the possibility of exceptions.

5) Both patents had in the meantime been revoked on 22nd April 2015 by the Hague District Court, but Birss J considered that the evidence before the Dutch court was different in key respects.  He therefore had no compunction about reaching an opposite conclusion.

Merpel was very happy that the judgment came out just in time to note the election of Prof Davies as a Fellow of the Royal Society.  This Kat in the meantime is left wondering whether, when a point seems hopeless in the final judgment, did the team advancing it not notice, or did they have nothing better to put forward?


Sandeep said...

Any news of this going into appeal?

Darren Smyth said...

Dear Sandeep
I believe that leave to appeal has been requested, but that is all the information that I have. Perhaps other readers have further news.

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