Regeneron Pharmaceuticals Inc v Kymab Ltd [2020] UKSC 27

Regeneron's patents claimed transgenic mice with a hybrid antibody gene structure (Reverse Chimeric Locus) spanning a wide range. The Supreme Court held the patents invalid for insufficiency because the disclosure enabled only mice at the least valuable end of the range, not across the whole claimed scope.

Facts

Regeneron Pharmaceuticals Inc held two European patents (the 287 Patent and the 163 Patent, a divisional of the 287 Patent), each with a priority date of 16 February 2001, relating to genetically engineered transgenic mice used as platforms for the development of human therapeutic antibodies. The key innovation was the ‘Reverse Chimeric Locus’, a hybrid antibody gene structure combining the murine constant region with the human variable region, which solved the problem of ‘immunological sickness’ previously suffered by mice carrying wholly human antibody gene structures.

A typical human heavy chain gene locus contains around 125 V segments, 27 D segments and nine J segments. Claim 1 of the 163 Patent covered a transgenic mouse producing hybrid antibodies with human variable regions and mouse constant regions, achieved by in situ replacement. The courts below construed this as covering a range, from mice with only a single human V, D and J segment up to mice with the entire human variable region inserted.

Regeneron alleged infringement by Kymab Ltd’s ‘Kymouse’. Kymab challenged validity for insufficiency. Henry Carr J held the patents invalid because no mouse within the claim could be made using the teaching. The Court of Appeal disagreed on feasibility, finding that mice with a small subset (between two and six human V segments) could be made, but mice with the whole human variable region could not have been made at the priority date without further inventive steps made years later.

Issues

The sole legal issue (as formulated by Lord Briggs at para 5) was whether a product patent, the teaching of which enables the skilled person to make only some, but not all, of the types of product within the scope of the claim, passes the sufficiency test where the invention would contribute to the utility of all products in the range, if and when they could be made.

Arguments

Appellant (Kymab)

Kymab submitted that the range denominated by the amount of human variable region DNA inserted was highly relevant because it directly affected the diversity of B cells and the usefulness of the mouse as a platform for antibody discovery. A mouse with only four V segments would produce a fraction of the antibody variety compared to one with all 125. Sufficiency required enablement across substantially the whole of the relevant range, and the teaching failed to enable mice at the most valuable end of the range.

Respondent (Regeneron)

Regeneron argued that the range was irrelevant because the unique advantage of the Reverse Chimeric Locus — curing murine immunological sickness — applied across the whole range regardless of the amount of human variable DNA inserted. The invention was a principle of general application, and the patent monopoly should correspond to the contribution made by that principle. Denying protection would give only short-lived, illusory reward.

Judgment

The Supreme Court (Lord Briggs, with Lord Reed, Lord Hodge and Lord Sales agreeing; Lady Black dissenting) allowed the appeal and held the claims invalid for insufficiency.

The sufficiency principle

Lord Briggs reaffirmed that the essence of the patent bargain is that the patentee dedicates the invention to the public by full disclosure, in return for a time-limited monopoly. In a product claim, ‘working the invention’ means making the product. If the patentee could obtain a product monopoly without disclosing how to make the product, the public would get nothing of substance.

Enablement across the range

The court undertook a chronological review of EPO jurisprudence, including Unilever/Stable Bleaches (T 226/85), Exxon/Fuel Oils (T 409/91), Unilever/Detergents (T 435/91), Genentech I/Polypeptide expression (T 292/85), Nabisco/Micro-organisms (T 361/87), and Novartis II/Transgenic plant (G 1/98), and UK authorities including Biogen v Medeva, Kirin-Amgen v Hoechst Marion Roussel, and Generics v Lundbeck.

The court held that the Polypeptide line of cases represents a limited exception: where a claim is framed functionally and the invention discloses a general principle which enables the invention to be worked with variants unavailable at the priority date, sufficiency may be satisfied. That exception did not apply here. The shortfall in this case lay not in the range of possible inputs but in the inability to create a Reverse Chimeric Locus incorporating anything more than a very small part of the human variable region — a shortcoming in the invention itself.

The court approved Henry Carr J’s observation that the Reverse Chimeric Locus was not a principle enabling the products to be made, but rather the result of successfully making them.

Principles distilled

Lord Briggs set out eight principles at para 56, including: (i) sufficiency ensures monopoly corresponds to contribution; (ii) in a product claim the contribution is the ability to make the product; (iv) disclosure must enable the skilled person to make substantially all embodiments within the claim’s scope; (vii) the range must be ‘relevant’, denominated by a variable significantly affecting the value or utility of the product; (viii) enablement is not established merely by showing all products would deliver the same general benefit if and when made.

Application

The range denominated by the amount of human variable region segments was relevant because it significantly affected the diversity of useful antibodies produced. As the disclosure enabled only mice at the least valuable end of the range, the claim far exceeded the contribution to the art and failed for insufficiency. The Court of Appeal had erred by treating enablement as satisfied merely because the benefit (curing immunological sickness) would be realised across the range if and when the mice could be made.

Dissent

Lady Black dissented. She would have upheld the Court of Appeal’s characterisation of the claim as a principle of general application — the reverse chimeric locus — which was deployed in each mouse across the range irrespective of the quantum of human material incorporated. In her view, the claim was sufficiently enabled across its scope and the protection corresponded to the technical contribution of solving immunological sickness.

Implications

The decision reinforces the orthodox position that, for a product claim, the disclosure must enable the skilled person to make substantially all products within the scope of the claim at the priority date. A patentee cannot obtain a monopoly extending to products that cannot be made at the priority date merely by showing that the invention would benefit such products once they become available through later, separate inventive effort.

The judgment clarifies the limited nature of the ‘principle of general application’ exception derived from the Polypeptide line of EPO authority: the principle must actually make the embodiments available, not merely confer a shared benefit on them once they are independently made.

The court identified a qualification: the requirement to enable across the whole scope applies only to a ‘relevant’ range — one denominated by a variable that significantly affects the value or utility of the product for its intended purpose. Irrelevant features (such as mouse tail length in the example given) do not trigger the requirement.

The decision is significant for patentees operating in rapidly developing fields such as biotechnology and genetic engineering. It limits the ability to claim broad, forward-looking monopolies over products that cannot yet be made, even where a ground-breaking concept has been disclosed. Lord Briggs acknowledged at para 60 that this may give inventors ‘scant and short-lived reward’ in fast-moving fields, but held that the settled law reflects a careful balance between patentee and public that could not be altered by judicial decision-making in a single Convention state. The judgment thus emphasises the primacy of actual, immediate enablement over the potential future utility of an inventive concept.

Verdict: Appeal allowed. The Supreme Court held that claim 1 of the 163 Patent (and consequently claims 5 and 6 of the 287 Patent) was invalid for insufficiency, restoring the outcome at first instance, with Lady Black dissenting.

Source: Regeneron Pharmaceuticals Inc v Kymab Ltd [2020] UKSC 27