Regeneron Pharmaceuticals Inc v Kymab Ltd & Anor

In patent sufficiency, the specification must enable the skilled person to perform the invention across the whole scope claimed, without undue burden or inventive skill. Ordinary trial and error is permissible, particularly in a technically complex field, but the skilled person cannot be required to devise a new or inventive method when the disclosed methods fail.

A claim for in situ replacement may cover insertion at the original genomic position even where the displaced endogenous sequence is retained in an inactive form. A product-by-process claim extends to products having the characteristic inevitably resulting from the process, even if the process has been repeated. Claims exceeding the technical contribution are insufficient.

Regeneron claimed infringement of European Patent (UK) Nos 1 360 287 and 2 264 163 concerning transgenic mice with human variable immunoglobulin gene segments and endogenous mouse constant regions. Kymab denied infringement and counterclaimed for revocation. Novo maintained validity challenges after the infringement claim against it was abandoned.

The issues included construction of in situ replacement, infringement, product-by-process claims, insufficiency, anticipation, obviousness and added matter. The court also considered whether the disclosed techniques enabled large-scale genetic replacements across the breadth of the claims.

1. Construction. In situ replacement meant replacement in the original position. It included both deletion of the relevant mouse sequences and their displacement to another genomic location followed by functional inactivation. The claims were not limited to physical deletion.
2. Product-by-process claims. Claims 5 and 6 of the 287 Patent were directed to products possessing the characteristic resulting from the claimed process, namely a modified immunoglobulin locus in the endogenous position. They were not restricted to products made in one step or using a single BAC. Repeated insertions could produce a product within the claims.
3. Sufficiency. The applicable question was whether the skilled person could perform the invention over the whole area claimed without undue burden and without inventive skill. Ordinary trial and error was permissible, but the skilled team lacked inventive capacity. The central disclosed replacements, involving approximately 100–150 kb of mouse sequence and 75–300 kb of human sequence, were unprecedented and could not be achieved by the disclosed methods without undue burden.
4. The alternative approaches in Example 3, including large homologous-recombination replacements and RMCE, did not enable the full scope of claim 1. The sequential approach ultimately developed by Regeneron was inventive and was not disclosed. The claims therefore exceeded the technical contribution.
5. The claims were not anticipated or rendered obvious by Kucherlapati or Brüggemann 1997. Those materials were directed to fully human antibodies and did not disclose or motivate the claimed reverse chimeric locus, LTVECs or the MOA assay.
6. The added-matter objections failed. The court distinguished the scope of a claim from what the patent disclosed: displacement and inactivation fell within the scope of claim 1 but were not thereby treated as disclosed subject matter.
7. All claims considered from both patents were invalid for insufficiency. Regeneron’s infringement claim was dismissed and Kymab’s and Novo’s counterclaims for revocation were allowed.