The UK Supreme Court (UKSC) has upheld Kymab’s appeal that two of Regeneron’s patents are invalid for lack of sufficient disclosure. This important decision highlights the potential risks involved in filing patent applications too early and affirms the principle that in order to be valid a patent claim must be enabled across its entire scope.

The UKSC has handed down its much anticipated judgment in Regeneron Pharmaceuticals Inc. v Kymab Ltd. [2020] UKSC 27. The UKSC found that various patents belonging to US biotech company Regeneron, concerning transgenic mice to produce human-mouse chimeric antibodies, were invalid for lack of sufficient disclosure.

The decision was not, however, unanimous with Lady Black dissenting and agreeing with the Court of Appeal’s approach.

The law of sufficiency

As well as being both novel and inventive, to be valid a patent must be sufficiently disclosed to enable the skilled person to perform the invention. Under both the European Patent Convention and the Patents Act 1977, patent claims must be enabled across their full scope. This means the skilled person must be able to make the product using (a) the information disclosed in the patent, with (b) the common general knowledge available at the priority date, without having to undertake further experimentation or make further inventions of their own.

Background to the dispute

This long-running dispute concerned the infringement and validity of two of Regeneron’s patents concerning the creation of types of transgenic mice capable of producing human-murine chimeric antibodies suitable for treating a variety of diseases. The monopoly claimed by Regeneron involved the insertion of human antibody genes into the mouse genome, such that the resulting antibodies do not provoke an adverse immunological response in humans.

Pre-existing transgenic mouse technology had utilised the complete human gene sequence of the antibodies to be produced, but this was known to result in antibodies with reduced affinity in comparison with antibodies produced by unmodified mice.

Regeneron had filed applications for its ‘VelocImmune’ transgenic mice technology in 2001. The 287 and 163 patents (collectively the ‘Murphy Patents’) concerned the use of reverse chimeric locus technology to insert human antibody genes into the mouse genome in order to produce mice possessing chimeric human-murine antibody genes, which could be used to produce human antibodies having fewer adverse immunological side effects.

By the priority date, the potential uses of antibodies made using transgenic mice for treating human disease had been well-recognised, and a number of different antibodies had been developed and approved for such use. However, at the priority date only a small number of human antibody genes had been successfully inserted into a reverse chimeric locus.

Kymab had created its own transgenic ‘Kymouse’ with the entire human antibody variable region as a result of improvements in genetic engineering techniques that post-dated the Murphy Patents. In 2013, Regeneron sued Kymab for infringement of the Murphy Patents.

The decisions of the lower courts

The High Court found the Murphy Patents to be invalid for insufficiency as they did not provide an enabling disclosure across the breadth of the invention claimed. As such, the High Court concluded that Regeneron had sought to protect more than its technical contribution to the field. The High Court held that in light of what was disclosed in the Murphy Patents, it would not have been possible for Kymab to produce its Kymouse at the priority date using only the teaching of the Murphy Patents. However, the High Court also stated that had the Murphy Patents been valid, they would have been infringed by Kymab in making its Kymouse. Both parties appealed the decision.

In 2018, the Court of Appeal overturned the decision of the lower court and found the claims to be sufficiently disclosed. In doing so, the Court of Appeal considered Regeneron’s chimeric locus to be a “principle of general application”, and so infringed by Kymab. In essence, the Court of Appeal gave more weight to the effect and potential of employing a reverse chimeric locus and placed less importance on the ability to produce all of the transgenic mice that would fall within the scope of the claims of the Murphy Patents.

The Court of Appeal granted Kymab permission to appeal its decision on the ground that the Court had not adequately considered Kymab’s submissions on sufficiency. It is noteworthy that the Court of Appeal suspended the pending injunction against Kymab, so as not to disrupt ongoing research pending appeal to the UKSC.

The judgment of the UKSC

Kymab’s appeal was heard by the UKSC in February this year. In essence, the UKSC had to grapple with the question of whether it is necessary for the skilled person to be able to make all the embodiments within the scope of the claim without undue burden.

Regeneron had argued that the invention was sufficiently disclosed, even if it did not enable the skilled team to make all transgenic mice falling within the scope of the claim, on the basis that the skilled team would have a reasonable expectation of success.

Kymab, on the other hand, advanced the argument that the range of human genes able to be inserted using the invention was a key part of the technical contribution and as the Murphy Patents had disclosed only a small number of genes, the Murphy Patents were invalid.

The UKSC ultimately sided with Kymab. In giving the leading judgment, Lord Briggs stated that “the sufficiency requirement is a basic principle of UK and European patent law…..it is too important and too deeply established a principle now to be disregarded or watered down, even in the case of an important scientific invention such as this one.”

Only one of the UKSC Justices (Lady Black) dissented. In her view, the Court of Appeal had been right to find that Regeneron’s transgenic technology related to a broad general principle (i.e. the use of reverse chimeric locus technology to produce antibodies with fewer immunological side effects), which was utilised in all mice across the scope of the claim.

Comment

The UKSC has been clear that claims are not sufficiently enabled if all of the embodiments can only be realised at a date after the priority date. While some may welcome the stance of the UKSC in not granting a monopoly over all transgenic mice not enabled by the patents, others may take the view that denying patent protection to ‘ground-breaking’ inventions at an early stage may actually stifle scientific research and investment.

Given the “first to file” regime for patents, it is inevitable in the race to be first that inventors and their employers are eager to file patent applications at the earliest stages of development, with broad claims attempting to ‘future-proof’ their inventions. None more so than biotech companies and start-ups, which are often under considerable pressure to file early in order to attract potential investors and to secure funding. This important decision serves as a timely reminder of the dilemma faced by patentees and their patent attorneys and the considerable risks in filing too early. Hindsight, as always, is 20/20.

This is one of several recent important decisions of the UKSC affecting the Life Sciences sector, including Actavis UK v Eli Lily & Co [2017] UKSC 48 (which introduced a doctrine of equivalents into English patent law when assessing infringement, but not when considering validity) and Actavis Group v ICOS [2019] UKSC 15 on the test of obviousness. All of these judgments go to the extent of the monopoly that can be claimed by a patentee, and the risks of too soon and too broad.