Regeneron Pharmaceuticals, Inc v Kymab Ltd & Anor

In patent law, a broad claim is not insufficient merely because the specification does not enable every possible embodiment. The claim may extend to variants and improvements where the skilled team can reasonably expect the invention to work across its scope without undue burden or inventive skill, and the monopoly corresponds to the technical contribution.

Common general knowledge and obvious modifications may be used to perform the invention. “In situ replacement” requires positional replacement only. It does not necessarily require deletion or inactivation of displaced genetic material. A product-by-process claim covers the product with the characteristics conferred by the process, regardless of the process actually used.

Regeneron appealed from Henry Carr J’s decision ([2016] EWHC 87 (Pat)) holding European Patent (UK) No 1 360 287 and its divisional patent No 2 264 163 invalid for insufficiency. Kymab cross-appealed against the finding that its transgenic mice would infringe specified claims if the patents were valid.

The issues concerned the construction of “in situ replacement”, infringement, and whether the specifications enabled the claimed reverse chimeric immunoglobulin loci and associated methods across the scope of the claims.

1. Disposition. Kymab’s appeal was dismissed and Regeneron’s appeal was allowed. The patents were not invalid for insufficiency. The Kymab mice infringed on the proper construction of the claims.
2. Construction and infringement. “In situ replacement” meant positional replacement. The claims required insertion of human variable sequences into the position formerly occupied by the murine sequences, but did not require their physical deletion or inactivation. The phrase was not a term of art and had to be construed in the context of the specification. Kymab’s mice therefore infringed even though the murine sequences had been inverted and displaced. The court applied the first stage of the approach described in Actavis UK Limited and others v Eli Lilly and Company ([2017] UKSC 48): infringement followed on normal interpretation, so the second-stage equivalents question did not arise.
3. Scope of the claims. Claim 1 of the 287 patent required at least one V, D and J segment, but did not require all human D or J segments. The method could be performed in several steps. Claims 5 and 6 were product-by-process claims. They covered products having the characteristics conferred by the claimed process, irrespective of the process actually used.
4. Sufficiency. Under section 72(1)(c) of the Patents Act 1977, the specification had to enable the skilled team to perform the invention without undue burden, assessed in light of the specification, the common general knowledge, the nature of the invention and the technical contribution. The law did not require enablement of every embodiment. A claim could cover future variants or inventive improvements where they embodied the same technical contribution and the skilled team could reasonably expect the invention to work across the relevant general term.
5. The reverse chimeric locus was a principle of general application. The skilled team could use minigene constructs, LTVECs, MOA assays and separate deletion steps to make products and perform methods within the claims without undue effort. The claims were therefore adequately enabled and commensurate with the contribution disclosed.
6. The court declined to interfere with factual findings concerning the feasibility of particular large insertions and deletions, applying the appellate caution stated in Fage UK Ltd v Chobani UK Ltd ([2014] EWCA Civ 5). Regeneron’s failure to draw the minigene issue to the trial judge’s attention after receiving the draft judgment was unsatisfactory, but did not preclude reliance on the evidence on appeal.

• Court of Appeal (Civil Division): In [2018] EWCA Civ 671, Kymab’s appeal against the infringement finding was dismissed and Regeneron’s appeal against invalidity for insufficiency was allowed.
• High Court, Chancery Division, Patents Court: Henry Carr J held in [2016] EWHC 87 (Pat) that the patents were invalid for insufficiency, but that Kymab’s mice would infringe specified claims if the patents were valid.