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26 June 2020
The patents in question were European Patent (UK) No 1 360 287 (see here) and European Patent (UK) No 2 264 163 (see here) to Regeneron Pharmaceuticals Inc (“Regeneron”). These patents are directed towards transgenic mice capable of producing humanised antibodies. Regeneron alleged infringement by Kymab Ltd, and Kymab counterclaimed that the patents were invalid through insufficiency.
At the High Court, the patents were held infringed but invalid. The Court of Appeal overturned the decision on validity, to find the patents were valid and infringed. Kymab appealed to the Supreme Court.
At the priority date (16 February 2001), it was known that antibodies (or immunoglobulins) could be used to treat disease in humans. Mice were identified as suitable platforms for production of these antibodies. However, there were two problems associated with this approach: i) rejection of mouse (murine) antibodies by the host; and ii) an impaired immunological response in mice transplanted with human antibody genes.
Antibodies are produced by B cells and, in mice and humans, comprise light and heavy chains. Gene segments for variable regions of antibodies comprise variable (V) and joining (J) segments in the light chain locus, and variable (V), diversity (D), and joining (J) segments in the heavy chain locus. Natural recombination of somatic genes encoding polypeptide chains means that a huge variety of antibodies are produced with different amino acid sequences in the antigen-binding regions, providing a huge repertoire of antibodies.
The solution to the problems associated with production of antibodies in mice was to create a hybrid (chimeric) antibody gene structure, called a “Reverse Chimeric Locus” comprising the murine constant region and the human variable region. These structures are integrated into the mouse genome for the production of hybrid antibodies, and murine constant regions removed from isolated B cells prior to mass production.
This enables the production of human antibodies that respond naturally to antigenic challenge and therefore mimic natural immunity. On encountering antigens, B cells divide and differentiate, enabling the production of a diverse spectrum of antibodies against a single target.
In accordance with both UK law and that of the European Patent Convention (EPC), a set of claims to a single product or a range of products is required to be “enabled”, which means that the skilled person must be able to put the invention into effect, with no more than common general knowledge at the priority date, and without “undue experimental burden”. This is termed the sufficiency requirement of a patent and ensures that the extent of the monopoly granted corresponds to (and does not exceed) the contribution to the art.
In the High Court, Judge Henry Carr found infringement proved through Kymab’s use of transgenic mice, but held the claims invalid for insufficiency. The Court held that the example provided in the patent to produce the claimed mouse would not have worked because the method to insert and delete large sections of DNA was not known at the priority date.
The Court of Appeal took a different view in 2018 and found the claims both valid and infringed. Lord Justice Kitchin agreed that the example of the patent would not have worked, but that common general knowledge could be used to make obvious changes. Importantly, Lord Justice Kitchin reasoned that this would enable the skilled person to make one type of transgenic mouse within the scope of the claims, and that this was sufficient for disclosure, despite the skilled person being unable to make all types of mouse within the scope of the claims from the teaching of the patent and in the light of the common general knowledge.
The Court of Appeal reasoned that the broad general contribution provided by the patent should be rewarded, and not limited to a monopoly over products that could be immediately made.
By majority (Lady Black dissenting), the UK Supreme Court found that the “disclosure in the patent should enable substantially all products within the scope of a product claim to be made by the skilled person at the priority date”.
The reasoning of the Supreme Court’s decision relies on the analysis that at the priority date, the disclosure of the two patents, in the light of common general knowledge, enabled “making” transgenic mice with a Reverse Chimeric Locus containing only a small portion of the human variable region.
The extent to which the human antibody variable region could be incorporated was understood to be a crucial factor in determining the repertoire of antibodies that could be produced. The claims conferred a monopoly over mice incorporating any or all of the human variable region when a hybrid gene structure comprising the whole variable region was achieved only with further inventive processes.
As summarised by Lord Briggs, an invention cannot be considered enabled if it does not permit the skilled person to make it. The invention was held not enabled over “substantially the whole range of products” claimed.
Kymab’s appeal was upheld, and the claims concerned held invalid for insufficiency.
This case marks the return to a more traditional approach to insufficiency and has particular implications with regard to the patentability of claims to a range of products.
Dr. Abbie Fisher
Life Sciences & Chemistry group
If you require further information on anything covered in this briefing, please contact Abbie Fisher; or your usual contact at the firm. This publication is a general summary of the law. It should not replace legal advice tailored to your specific circumstances.
© Withers & Rogers LLP May 2020