Synthon BV v Teva Pharmaceutical Industries Ltd

In patent validity proceedings, obviousness depends on what the skilled person would have reason to investigate or change. A general preference for purity, or evidence that a reagent is corrosive or coloured, does not establish that claimed impurity limits were obvious where the relevant problem was not suspected. A manufacturing control step may be inventive where it addresses an unsuspected impurity. For added matter, the claimed subject matter must be disclosed directly and unambiguously in the application. Implicit disclosure is possible, but the inquiry is not one of obviousness. Disclosure of low impurity in an intermediate or reagent does not, without more, disclose the same concentration in the finished product, particularly where later steps may introduce impurities. Both appeals were dismissed.

Synthon sought revocation of Teva’s patent concerning glatiramer acetate. Birss J dismissed Synthon’s attacks based on novelty, obviousness and insufficiency, but held claim 20 and claims dependent on it invalid for added matter: [2015] EWHC 1395 (Pat). Synthon appealed on obviousness, arguing that the claimed limits on free bromine, metal ion impurities and brominated tyrosine were obvious. Teva appealed the added-matter ruling, contending that the application implicitly disclosed a finished glatiramer acetate product containing less than 1000 ppm metal ion impurities. The central questions were whether the relevant process and product limitations were obvious and whether the final-product disclosure was directly and unambiguously derivable from the application.

Both appeals dismissed.

1. Synthon had not established that claim 3 was obvious. Keeping HBr/AcOH away from metal surfaces was not the same as proving that the solution would contain less than 500 ppm metal ion impurities. The evidence showed that ions could arise from many sources, including other reagents and process water. The claimed purity level therefore could not be inferred merely from use of glass vessels or non-metal apparatus.

2. The free-bromine claims were not shown to be obvious. Colour provided only a qualitative indication and could not quantify the bromine concentration. Evidence that freshly prepared HBr/AcOH might be colourless did not establish that it necessarily contained less than 0.1% free bromine. Nor did the pharmaceutical context supply the missing motivation: the skilled person had no reason to expect free bromine to cause a significant side reaction with tyrosine.

3. Claim 29 was also not obvious. Brominated tyrosine was an unsuspected impurity. Requiring its measurement and excluding batches at or above the specified threshold was a useful control step, even though prior-art data showed that some batches would already meet the threshold.

4. On added matter, the applicable test was direct and unambiguous disclosure, including implicit disclosure but not an obviousness inquiry. The principle was stated with reference to European Central Bank v Document Security Systems Inc [2007] EWHC 600 (Pat), approved in Vector Corporation v Glatt Air Techniques Ltd [2007] EWCA Civ 805. The application disclosed low metal-ion levels in TFA-polypeptides and HBr/AcOH, but did not disclose, expressly or implicitly, a corresponding level in the finished glatiramer acetate. Downstream steps could introduce further impurities, and the appropriate final-product limit was not disclosed.

5. Lord Justice Briggs and Lord Justice Kitchin agreed with Lord Justice Floyd’s judgment. The claim 20 added-matter finding, and the dismissal of Synthon’s obviousness appeal, were upheld.

• Court of Appeal (Civil Division): Both Synthon’s appeal on obviousness and Teva’s appeal on added matter were dismissed under [2017] EWCA Civ 148.
• High Court of Justice, Chancery Division, Patents Court: Birss J dismissed Synthon’s revocation action, rejecting the validity attacks relied upon by Synthon, but held claim 20 and claims dependent on it invalid for added matter under [2015] EWHC 1395 (Pat).