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UK – Regeneron Pharmaceuticals v. Kymab / Supreme Court

29 Jun 2020

Regeneron Pharmaceuticals Inc (Respondent) v Kymab Ltd (Appellant) [2020] UKSC 27

The Supreme Court has handed down its first patents judgment of 2020 in the case of Regeneron Pharmaceuticals vs Kymab. The judgment (by a four to one majority) overturns the previous decision of the Court of Appeal to find two of Regeneron’s patents covering transgenic antibody-producing mice invalid for insufficiency.

Technical Background

Mice were already being used for production of antibodies for the treatment of human diseases by the priority date of Regeneron’s patents in 2001. The problem with genetically engineering mice to express fully human antibodies (i.e. those suitable for use in humans without themselves causing an immune response) was that those mice could not mount successful immune responses themselves (rendering them “immunologically sick”). The innovative solution at the heart of the dispute was the use of a hybrid (chimeric) antibody gene structure consisting of both murine elements (the “constant” region of the antibody) and human elements (the patents teaching this to be the whole of the “variable” region, which is made up of large number of different gene segments responsible for the huge diversity of antibodies that can be generated). This structure is referred to as the “Reverse Chimeric Locus”.

The Decisions of the Lower Courts

The trial judge (the late Henry Carr J) had found that the patents, coupled with the available common general knowledge at the priority date, did not enable any type of mouse that fell within the claims to be made. In other words, he decided that none of the methods disclosed in the patents would have worked and the task could only have been achieved by means of further inventive processes (as in fact carried out by both parties several years later).

The Court of Appeal’s decision that the patents did meet the sufficiency requirement was based on their acceptance of a new argument run by Regeneron, namely that it was in fact possible for the skilled team to implement the Reverse Chimeric Locus by using “minigenes” (use of which formed part of the common general knowledge), although such a method would only have been suitable for incorporating a subset of the human variable region and not the whole human variable region as taught by the patents and also covered by the claims. Although this method did not enable all embodiments within the relevant claim, in their judgment the sufficiency hurdle was still met in a case where the invention (namely the Reverse Chimeric Locus) amounted to a principle of general application of use in all embodiments of the claim, even if only a few such embodiments could in fact be made at the priority date.

This finding of a principle of general application was based on their conclusion that “the character of this invention is therefore such that any transgenic mouse which falls within the scope of the claim and so produces hybrid antibodies containing the human variable regions and mouse constant regions will benefit from the technical contribution the disclosure of the 163 patent has made to the art, and will do so irrespective of the antigen which is used to challenge the mouse.

The Supreme Court’s decision

Lord Briggs, giving the leading judgment with which three of the other Lords agreed, focussed his judgment squarely on the fact that the claim in question is a product claim covering the mice themselves and the UK case law requiring such an invention to be enabled over the whole of the range of products covered by the claim.

Reviewing the principles from the EPO case law requiring product claims to be enabled across their breadth, he noted that a “substantially” qualification is often used to soften the strictness of the requirement but took this as meaning that there “may be a tiny or inconsequential number of embodiments which are not enabled” rather than extending to the shortfall in the present case.

In his judgment the cases finding that disclosure of a principle of general application can enable a product claim across its scope still dictate that the general principle must actually make the embodiments within the claim available and it cannot be “enough for the general principle to make all those variants, if and when they become available, fit or better than their predecessors for beneficial or efficient use”.

Further, he sought to draw a distinction between those EPO cases concerning claims defined by reference to function for which a principle of general application had to found to justify claim breath (such as Genentech I/Polypeptide expression) and those that did not (such as Exxon and Unilever/Detergents).

In his judgment the present case fell with the latter cases, which concerned patents that failed to disclose any general technical principle by which the skilled person could achieve the desired result across the whole range of claimed embodiments. In Regeneron’s case “the inventive shortfall at the priority date lay not in the range of possible inputs to which the invention could be applied, but in the inability to create a Reverse Chimeric Locus involving the whole (or anything more than a very small part of) the human variable region. It was truly a shortcoming in the invention itself, which, as at the priority date, limited its use to only a small part of the relevant range within the scope of Claim 1”.

The distinction from the Polypeptide line of cases was their disclosure of “a sufficient general principle which, without any further inventive step, would enable the skilled person to work the relevant invention by using, as input elements, examples of those components described generally in the claims, which were unavailable as at the priority date, in order to make products across the scope of the claim.

He distilled his analysis of the EPO and UK case law into the following list of principles:

i) The requirement of sufficiency imposed by article 83 of the EPC exists to ensure that the extent of the monopoly conferred by the patent corresponds with the extent of the contribution which it makes to the art.

ii) In the case of a product claim, the contribution to the art is the ability of the skilled person to make the product itself, rather than (if different) the invention.

iii) Patentees are free to choose how widely to frame the range of products for which they claim protection. But they need to ensure that they make no broader claim than is enabled by their disclosure.

iv) The disclosure required of the patentee is such as will, coupled with the common general knowledge existing as at the priority date, be sufficient to enable the skilled person to make substantially all the types or embodiments of products within the scope of the claim. That is what, in the context of a product claim, enablement means.

v) A claim which seeks to protect products which cannot be made by the skilled person using the disclosure in the patent will, subject to de minimis or wholly irrelevant exceptions, be bound to exceed the contribution to the art made by the patent, measured as it must be at the priority date.

vi) This does not mean that the patentee has to demonstrate in the disclosure that every embodiment within the scope of the claim has been tried, tested and proved to have been enabled to be made. Patentees may rely, if they can, upon a principle of general application if it would appear reasonably likely to enable the whole range of products within the scope of the claim to be made. But they take the risk, if challenged, that the supposed general principle will be proved at trial not in fact to enable a significant, relevant, part of the claimed range to be made, as at the priority date.

vii) Nor will a claim which in substance passes the sufficiency test be defeated by dividing the product claim into a range denominated by some wholly irrelevant factor, such as the length of a mouse’s tail. The requirement to show enablement across the whole scope of the claim applies only across a relevant range. Put broadly, the range will be relevant if it is denominated by reference to a variable which significantly affects the value or utility of the product in achieving the purpose for which it is to be made.

viii) Enablement across the scope of a product claim is not established merely by showing that all products within the relevant range will, if and when they can be made, deliver the same general benefit intended to be generated by the invention, regardless how valuable and ground-breaking that invention may prove to be.

In Lord Briggs’ judgment, applying these principles to the present case clearly resulted in a finding of insufficiency. The patents did not enable transgenic mice with a Reverse Chimeric Locus containing more than a very small part of the human variable region gene locus and the extent to which the variable region could be included was understood to be a very important factor affecting the diversity of the antibodies produced. As such this range was a relevant range for sufficiency purposes, even though it did not affect the immunological health of the mice. For this reason he concluded that “the claim to a monopoly over the whole of that range went far beyond the contribution which the product made to the art at the priority date, precisely because mice at the more valuable end of the range could not be made, using the disclosure in the patents”.

Lord Briggs continued by explaining that the Court of Appeal did not correctly apply the law as it stands, having failed to recognise that “the contribution to the art is the product which is enabled to be made by the disclosure, not the invention itself”, and having erroneously concluded that it was enough that the benefits unlocked by the invention would in due course be realised over the whole range if and when all embodiments could be made.

Whilst going on to acknowledge at the end of his judgment that this decision would result in patentees with ground-breaking inventions only being able to obtain short-lived reward, ultimately this point gained little traction with Lord Briggs stating that this was outweighed by the need to apply the settled law that sufficiency of product claims must be measured by the products which could be made at the priority date.

Lady Black’s dissenting judgment

In the only other judgment, Lady Black voiced strong views in favour of sufficiency of the patents.

She highlighted that Regeneron did not run their “minigene” enablement argument at first instance and, as a result, the Court of Appeal inevitably had a different starting point for its consideration of the central legal issue of whether the claim was enabled across its whole scope. Whilst this finding had not been challenged and the Supreme Court had therefore adopted the same starting point as the Court of Appeal, she seemingly raised it to caution against reliance Lord Briggs had placed on statements made by Henry Carr J at first instance.

In her view, Lord Briggs’ judgment provides “little, if any, real disagreement with the Court of Appeal’s statement of the legal principles” and it is only in the application of them that the paths diverge. However, she stressed the importance of the Court of Appeal’s characterisation of the claim having been informed by the principle that “the protection covered by a patent should correspond to the technical contribution to the art made by the disclosure of the invention described therein” and the fact that the authorities made it clear that assessing sufficiency depends on the nature of the invention and the facts of the particular case.

Lord Briggs’ judgment focussed on the quantum of replaced material in the Reverse Chimeric Locus, rather than on the Reverse Chimeric Locus as a general principle, and it is that alternative focus that ultimately leads to the different conclusion from that of the Court of Appeal. Lady Black did not agree with this alternative focus concluded that she would not have interfered with the Court of Appeal’s conclusion that the claim here relates to a principle of general application. In her view, the claim would still be enabled across the scope in that sense; the Reverse Chimeric Locus being deployed in each mouse across the range, irrespective of the quantum of human material incorporated and/or in curing all mice across the scope of “immunological sickness”.

The full judgment can be accessed here.

Summary: Amy Crouch, Simmons & Simmons LLP