Les Laboratoires Servier Servier Laboratories Ltd v Apotex Inc & Ors

A patent claim defined by an experimental powder X-ray diffraction pattern must be construed uniformly, allowing for the intrinsic experimental error in the stated measurements. For anticipation, the prior disclosure must enable something that inevitably falls within the claim; a process need not produce the claimed result at every possible scale if the skilled person would inevitably carry out an enabled implementation that does so. Evidence of an absence of plausible alternative polymorphs may be probative of identity. The analysis differs from sufficiency: the skilled person may use uninventive preliminary work and refinements to implement a method for sufficiency, but such refinements cannot be used to create the necessary result for anticipation. A process and product lacking novelty or inventive step cannot be saved by an amendment introducing arbitrary process conditions.

Servier, the patent proprietor and exclusive licensee, sued Apotex for infringement of a patent concerning the α crystalline form of perindopril tert-butylamine salt. Apotex challenged validity on grounds including anticipation by EP 0 308 341, insufficiency and obviousness. Servier sought to amend the process claims by adding specified cooling conditions.

The dispute centred on the interpretation and reproducibility of the claimed powder X-ray diffraction pattern, whether reasonable laboratory and pilot-scale implementations of the earlier industrial synthesis inevitably produced the claimed form, and whether the proposed amended process claim involved an inventive step.

1. Construction of the claim. The diffraction figures in the claim were most naturally read as experimental results. Experimental error had to be allowed for uniformly. On that basis, a result within approximately ±0.3° of a stated value was treated as the same where both results were experimental measurements; if the claimed figures were absolute values, approximately ±0.2° would be appropriate.
2. Anticipation. A skilled person faced with the industrial synthesis disclosed in EP 0 308 341 would inevitably begin with a reasonable laboratory-scale implementation. The laboratory experiment and its repeat produced the claimed α form. The evidence established no plausible alternative polymorph and did not show that a fair repetition of the earlier process would avoid producing that form. The claim was therefore anticipated.
3. Difference between anticipation and sufficiency. For anticipation, the prior art had to enable something which inevitably fell within the claim. It was impermissible to use a refinement of technique to cause that result. For sufficiency, however, the skilled person could undertake preliminary work and uninventive refinements, without undue effort, to produce a product within the claim.
4. Obviousness. Even if the pilot-scale process did not inevitably produce the claimed form, the process and the claimed product were obvious in the light of EP 0 308 341. The process claims merely recited typical conditions and lacked an inventive step.
5. Amendment and disposition. The proposed amendment, which added specified cooling rates and temperatures, covered the relevant crystallisation experiment but the significance of those conditions was obscure. They were arbitrary and lacked inventive step. The amendment failed, the patent was revoked in its entirety, and the infringement claim, which would otherwise have succeeded, could not stand.