Regeneron v. Kymab – “Sufficiency” and Enablement in the U.K.
Guest post from Paul Cole.
Regeneron Pharmaceuticals Inc v Kymab Ltd. [2020] UKSC 27 related to infringement of EP-B-1,360,287 and its divisional EP-B-2264123. The 287 parent related to a method of modifying an endogenous immunoglobulin variable region gene locus in an isolated mouse embryonic stem (ES) cell by an in situ replacement of V, D and J gene segments of the endogenous locus with orthologous human V and J, or V, D and J gene segments to create a modified immunoglobulin locus that produces hybrid antibodies containing human variable regions and mouse constant regions. It was opposed by Kymab and others, but the opposition was dismissed following amendment, see T 2220/14 REGENERON/VelocImmune mouse. The appeal centred on the 123 patent which was not opposed and of which claim 1 read:
“A transgenic mouse that produces hybrid antibodies containing human variable regions and mouse constant regions, wherein said mouse comprises an in situ replacement of mouse VDJ regions with human VDJ regions at a murine chromosomal immunoglobulin heavy chain locus and an in situ replacement of mouse VJ regions with human VJ regions at a murine chromosomal immunoglobulin light chain locus.”
The courts below held that the italicised phrases covered a mouse with e.g. any number of V segments between 1 and 125.
Regeneron submitted that the existence of this range was irrelevant because the invention involved a ground-breaking general principle such that every type of mouse with the specified characteristics (so-called reverse chimeric locus) would display the benefits which the invention was designed to achieve. The invention provided a cure for the immunological sickness of the recipient mouse and worked regardless of the amount of the human variable region DNA inserted into the murine genome because the reverse chimeric locus was the product of the retention in the hybrid gene structure of the murine constant region genes. The case for Kymab was that the problem facing those skilled in the art at the priority date was that there was no known way, even using the teaching in the patents, to combine more than a very small part of the human variable region gene locus with the endogenous murine constant region gene locus in the same hybrid gene structure. It took several years and significant further inventive steps before methods were developed sophisticated enough to accommodate the whole of the human variable and murine constant region genes in a single hybrid gene structure.
The question before the court was therefore whether a product patent, the teaching of which enabled the skilled person only to make some, but not all, of the types of product within the scope of the claim, passed the sufficiency test where the invention amounted to a principle of general application and would contribute to the utility of all the products in the range, if and when they could be made. The court’s preliminary view was as follows:
“This analysis may be tested by a simple example. Suppose that five types of product (types A to E) were all claimed to be more efficient or useful than their predecessors by the application to their manufacture of the same new invention. The patentee made separate claims in relation to each type, all supported by the same disclosure. Each claim would be subjected to the sufficiency test: could a product of that type be made by use of the teaching in the patent, coupled with the existing common general knowledge? Suppose that types A and B could but C, D and E could not. Then claims A and B would be valid, and the remainder invalid. But now suppose that all five types were covered by the more compendious wording of a single claim. Would this enable the patentee also to obtain a monopoly for the making of types C, D and E? Surely not.”
For a fuller answer to this question, and for furthering the interpretive objective [30] of consistency between European and UK patent law, a detailed analysis of a number of UK and EPO Appeal Board decisions followed. Relevant UK decisions were May & Baker Ltd v Boots Pure Drug Co Ltd (1950) 67 RPC 23; Chiron Corpn v Organon Teknika Ltd (No 3) [1994] FSR 202; Biogen Inc v Medeva plc [1995] RPC 25 and [1997] RPC 1; Rockwater Ltd v Technip France SA [2004] RPC 46 at [7] and [10]; Kirin-Amgen Inc v Hoechst Marion Roussel Ltd [2005] RPC 9; Generics (UK) Ltd v H Lundbeck A/S [2008] EWCA Civ. 311, [2008] RPC 19 at [30] and [2009] RPC at [86]; and Actavis Group PTC EHF v ICOS Corpn [2019] UKSC 15; [2019] Bus LR 1318 at [57]. Relevant EPO Appeal Board decisions were T 226/85 UNILEVER/Stable bleaches; T 292/85 GENENTECH/Polypeptide expression; T 361/87 NABISCO/Microorganisms; T 409/91 EXXON/Fuel Oils; T 435/91 UNILEVER/Detergents; T 694/92 MYCOGEN/Modifying plant cells; and D 1/98 NOVARTIS II/Transgenic plant.
Lord Briggs (joined by Lords Hodge, Briggs and Sales) derived the following principles from these earlier cases which are likely to be influential in many subsequent UK decisions:
- “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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 the outcome, it was held that in relation to the essential patent bargain, in the case of a product claim the contribution to the art was the product which was enabled to be made by the disclosure, not the invention itself. Patents were about products and processes, not pure ideas.
The disclosure of the two patents, coupled with the common general knowledge, did not enable transgenic mice to be “made” with a reverse chimeric locus containing more than a very small part of the human variable region gene locus. The extent to which that variable region of the human antibody gene structure could be included in the hybrid antibody gene structure was, at that date, understood to be a very important factor affecting the diversity of useful antibodies capable of being “discovered” by the use of transgenic mice, so that the range thus denominated was a relevant range for sufficiency purposes, even though it did not affect the immunological health of the transgenic mouse. Thus 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. In conclusion:
“What matters is that it is settled law, in relation to a product claim, that sufficiency requires substantially the whole of the range of products within the scope of the claim to be enabled to be made by means of the disclosure in the patent, and this both reflects and applies the principle that the contribution to the art is to be measured by the products which can thereby be made as at the priority date, not by the contribution which the invention may make to the value and utility of products, the ability to make which, if at all, lies in the future.”
The sole dissenting opinion was that of Lady Black who agreed that the outcome turned on how this particular claim should be characterised and how the law should be applied to the particular facts of this case, holding that undue emphasis was placed by the majority on the quantum of replaced material in the reverse chimeric locus, rather than on the reverse chimeric locus as a general principle.
As explained in my inaugural lecture at Bournemouth University[2], many inventions arise in empirical research fields at least partly from Edisonian trial and error. Feynman[3] emphasizes the importance of fully understanding the conditions under which an experiment is carried out so that the results obtained are under the control of the experimenter. Inventors have a long history of exaggerating what they have under their control, while not always clearly defining what they have brought into the realm of predictability. Thus, in relation to T 435/91 UNILEVER/Detergents, the relevant “Richard Feynman” question that the inventors should have asked themselves when instructing their patent attorney was:
“What materials have we got under our control that force the detergent into a hexagonal phase?”
The Regeneron inventors might well respond that the principle that they had allegedly devised rendered their research systematic, or not less than semi-empirical and that the claim scope for which they sought was reasonable in the circumstances. However, that position is difficult to maintain in the face of the finding of Carr J at first instance [2016] EWHC 87 (Pat) at [257]:
“The difficulty does not relate to some hypothetical puzzle at the edge of the claim, but rather to the central disclosure of the specification, and the amounts of genetic sequence of which it contemplates the deletion and insertion. None of the methods of the 287 Patent for achieving this, as disclosed in Example 3 would have worked. 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. I do not accept that all embodiments within the claim are unified by a single principle of a reverse chimeric locus. This is not a principle that enables the method to be performed, rather it is the result of successfully carrying out the method. Accordingly, the insufficiency objection succeeds in respect of claim 1 of the 287 Patent” (emphasis added)
Example 3 appears to be a predictive example and little actual experimental work appears, at least on cursory examination, to be reported. The proposition that a skilled reader confronted with an unworkable predictive example would necessarily seek a remedy from the common general knowledge rather than simply dismissing it is not to be taken for granted. The Feynman address is something that all concerned with the drafting of patent applications would benefit from reading at regular intervals.
[1] https://www.bailii.org/cgi-bin/format.cgi?doc=/uk/cases/UKSC/2020/27.html&query=(Regeneron)
[2] Paul Cole, Patents and Scientific integrity, The CIPA Journal, May 2008, 2-10
[3] Richard Feynman, Cargo-Cult Science, Some remarks on science, pseudoscience, and learning how to not fool yourself, Caltech’s 1974 commencement address, http://calteches.library.caltech.edu/51/2/CargoCult.htm