This article was first published in Lexis®PSL IP & IT analysis on 11 February 2016.

What does this case tell us about insufficiency? Dr Beatriz San Martin, partner at Fieldfisher, draws out key points and lessons from Regeneron Pharmaceuticals Inc v Kymab.

Regeneron Pharmaceuticals Inc v Kymab Ltd and another [2016] EWHC 87 (Pat) [2016] EWHC 87 (Pat)

The Patents Court made rulings in a claim concerning transgenic mice that could be used as platforms for therapeutic antibody discovery. In dismissing the claim of Regeneron Pharmaceuticals, the court held that the defendants’ counterclaim for insufficiency of the patent succeeded.

What is the commercial and legal background to this judgment?

The claimant, Regeneron, brought a claim for infringement of two of its European patents (UK) — EP(UK)1,360,287 (the 287 Patent) and EP(UK)2,264,163 (the 163 Patent) — with priority dates of 16 February 2001 (the priority date), which relate to transgenic mice that can be used as platforms for therapeutic antibody discovery. Kymab, the defendant, offered various strains of transgenic mice that were alleged, either per se or through the process by which they are produced, to infringe claims 5 and 6 of the 287 Patent and claim 1 of the 163 Patent (the Claims).

Kymab denied infringement and, as is usual in these cases, counter-claimed for revocation of the patents on the basis of insufficiency, ‘cross anticipation’, lack of novelty, obviousness and added matter. There was a second defendant, Novo Nordisk, although the claim against it was abandoned shortly before trial. For the purposes of this article, the reference to Kymab is to both defendants.

Claim 1 of the 287 Patent was also considered in detail as being relevant to the construction of claims 5 and 6 and issues of validity.

What were the legal aspects of the insufficiency attack?

Henry Carr J provided a summary of the law on both ‘classical insufficiency’ and ‘excessive claim breadth’ insufficiency before concluding that claim 1 of the 287 Patent was invalid for insufficiency on the basis that the whole of the subject matter of claim 1 was not capable of being performed at the priority date without undue burden and without invention. According to Henry Carr J: ‘the task contemplated was unprecedented and could not have been achieved, if at all, without a great deal of creative thinking at the priority date.

As Henry Carr J had concluded that claims 5 and 6 of the 287 Patent were of considerably wider scope than claim 1 of the 287 Patent, it followed that these two other claims were also invalid for insufficiency, as well as claim 1 of the 163 Patent.

What was said about product-by-process ‘obtainable by’ claims?

Claims 5 and 6 of the 287 Patent were product-by-process claims which used the phrase ‘obtainable by’. The products in the case of claim 5 were a genetically modified eukaryotic cells or a mouse and, in the case of claim 6, a mouse embryonic stem cell containing a genetically modified immunoglobulin heavy chain variable region gene locus.

Henry Carr J gave a helpful summary of the principles derived from Hospira UK Ltd v Genentech Inc [2014] EWHC 3857 (Pat), in respect of ‘obtainable claims’:

  1. their purpose is to claim a product irrespective of how it was made but with a shared characteristic which results from using a given process;
  2. the claim has to specify the characteristics being referred to;
  3. ‘obtainable by’ claims present clarity problems and should only be permitted if there is no alternative way of defining the product in question; and
  4. for a product to be ‘obtainable by’ a process it must have every characteristic which is the inevitable consequence of that process.

What was the finding on infringement?

A feature of all of the claims of the 287 Patent was ‘in situ replacement’ of mouse variable region immunoglobulin (Ig) genes with human variable region Ig gene segments. The judge rejected Kymab’s primary submission in support of non-infringement of all claims based on its construction of ‘in situ replacement’ and the submission that there was no infringement because the Ig sequence in Kymab’s strains of mice had not been deleted. In Henry Carr J’s judgment, ‘in situ replacement’ meant replacing ‘in the position of’ and was apt to describe a positional replacement and this included both replacement through deletion and by displacement/inactivation.

He also rejected Kymab’s argument that it did not infringe because the inversion and displacement of the mouse V genes did not cause them to be substantially inactivated. Kymab had failed to point him to any evidence supporting this and Kymab’s own publication and a witness under cross-examination indicated otherwise. Finally, he rejected the contention that the product was not ‘obtainable by’ the method of claim 1 because Kymab’s mice carried more orthologous sequence (300kb) than could have been carried on a single bacterial artificial chromosome (BAC). There was no evidence that each insertion by Kymab was of an orthologous sequence greater than 300kb.

Overall, Henry Carr J held that all strains of the Kymab mouse (so-called Kymouse) were or would be generated from a product within the scope of claims 5 and 6 of the 287 Patent and that Kymouse strains having both modified IgH and IgK loci were mice within the scope of claim 1 of the 163 Patent.

What was the nature and outcome of the cross-anticipation attack involving priority?

Kymab claimed ‘cross-anticipation’ based on alleged loss of priority, ie that the patents were anticipated by matter that retained priority in the application for the other patent. This was, in Henry Carr J’s own words, a complex argument which depended on:

  1. the proposition that the patents were insufficient at the priority date, and
  2. the results of a reference to the Enlarged Board of Appeal in T 557/13, which is not yet available

Henry Carr J did not consider it necessary to decide this issue, given that he had decided that the Claims were invalid for insufficiency. He did not think this argument advanced Kymab’s case any further.

Are there any points for lawyers and their clients to take away?

Technical Primers

The judge admitted at para 6 that both the subject matter of the patents and the prior art were of great technical complexity. He found the agreed technical primer very helpful as an introduction to the technology and included parts of it in his judgment. He also encouraged lawyers to cooperate on this type of approach in other complex patent cases and congratulated the lawyers in this case for achieving an agreed document.

Submission on draft judgments

In the UK, draft judgments are circulated confidentially to legal counsel for suggested corrections of obvious errors. In this case, the judge received a further written submission on behalf of Regeneron alleging that there were certain material omissions in the draft judgment which should be considered before handing down the judgment.

While Henry Carr J made it clear that he did not criticise Regeneron’s counsel for raising post-judgment submissions and he emphasised that lawyers should draw the court’s attention to any material omissions in a judgment rather than saving up such points for the Court of Appeal, he also warned against this becoming a frequent occurrence. He noted that post-judgment submissions should be rarely necessary and that the temptation to raise just one more point in complex high value cases should be resisted. He reiterated that the primary purpose of circulating a draft judgment was to correct typographical or other obvious errors rather than to provide an opportunity to re-argue the case.

Criticism of experts

The judge noted that professor Francis Stewart appeared to have been unduly influenced by accounts from Kymab’s legal team of the problems that Regeneron experienced in its research and development. This affected the weight that the judge attached to particular aspects of his evidence, although not his evidence in general. It was also noted that professor Howard’s expert evidence was based on hindsight reasoning rather than his own involvement in the relevant field at the priority date and this was taken into account when considering the issue of inventive step.

This emphasises the need to choose experts carefully such that they have the relevant expertise at the priority date. It also highlights the care that should be taken to avoid providing personal opinions or anecdotes to experts when preparing expert reports.