First published in our Biotech Review of the year – issue 8.

Although this might be understandable in the current climate, the implications of the ruling, which saw Regeneron’s transgenic mice patents ruled as invalid for insufficiency, are of crucial significance for the biotech sector. Indeed, the ruling cut to the core of a number of the key issues at play for many biotech companies, not only reinforcing the established case law of sufficiency, but also confirming that the standard for sufficiency cannot be lowered where a ground-breaking invention provides a ‘principle of general application’.

The background: Mouse-human hybrids

The patents in suit relate to transgenic mice, namely those whose genomes have been genetically engineered to contain DNA fragments encoding functional gene products from other species (in this case humans). The mice are ultimately intended to be used to produce antibodies suitable for eventual use in human therapies.

By 2001, the priority date of the patents in issue, it had been observed that transgenic mice with fully human antibody sequences often displayed a poor immune response; they were ‘immunologically sick’. Regeneron discovered that this was because the human constant region of the antibody interacted poorly with the downstream mouse immune response effector proteins. To overcome this problem Regeneron created antibody sequences in which the mouse constant region was maintained, but the mouse variable region genes were replaced with human counterparts. At the time this was a groundbreaking invention (a fact acknowledged by the Supreme Court). The hybrid gene structure was termed the ‘reverse chimeric locus’ and was the subject of several process and product patents filed by Regeneron.

The general understanding at the priority date was that hybrid genes containing more human variable region genes produced more diverse antibodies and were, therefore, more useful. However, at the time, it was not possible to combine the mouse constant region with the whole human variable region; indeed – far from it.

In 2013 Regeneron brought proceedings alleging infringement of its patents by Kymab’s transgenic mouse, known as Kymouse. Kymab counterclaimed for revocation on the basis of insufficiency (as well as other invalidity attacks).

At first instance Henry Carr J construed the claims as extending to a range of transgenic mice, spanning those with only a few human variable region genes to those with a full human variable region. Carr J held that Kymouse infringed the claims but the claims were invalid for insufficiency because the skilled person would not have been able to make any of the claimed mice at the priority date.

The Court of Appeal agreed with Carr J’s construction of the claims, but overturned his decision, finding the patents valid and infringed. The Court of Appeal held that while only some of the mice within the range could be made (i.e. those with a very small number of human variable region genes), the ‘invention’ for which protection was claimed was a ‘principle of general application’ because mice across the entire range claimed would (when eventually made) benefit from the invention by being cured of their immunological sickness. The Court found that this teaching was properly taught by the patent and therefore the sufficiency requirement was met.

To the Supreme Court

The question to be addressed by the Supreme Court was whether a product patent, the teaching of which enables the skilled person only to make 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 the products in the range, if and when they could be made.

In addressing this question the Supreme Court closely considered the ‘patent bargain’. In return for a time-limited monopoly to work his or her patent, the patentee must disclose the invention to the public in enough detail to enable the skilled person to work that invention. Lord Briggs confirmed that, in the context of a patent claiming a range of products, the patentee is required to disclose enough information that, coupled with the CGK, would be sufficient to enable the skilled person to make substantially all of the embodiments of products within the scope of the claim’s relevant range. It was also confirmed that a patentee may rely on 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.

In light of these principles, the Supreme Court ruled that the Court of Appeal had erred in two respects. First, the Court of Appeal wrongly held that the contribution to the art in this case was the ‘invention’ (namely the ‘reverse chimeric locus’), rather than the ability of the skilled person to make the product claimed. Second, the Court of Appeal had been wrong to say that a patent is sufficient if products within the claim cannot be made, as long as the benefit of the invention would be enjoyed over the whole range of the claim if and when those embodiments could be made in the future.

Lord Briggs characterised the Court of Appeal’s reliance on a ‘principle of general application’ as giving a monopoly for unlocking benefits that would be realised in the future. Lord Briggs made it clear that any such principle must still actually make the embodiments within the claim available to the skilled person at the relevant date. The reverse chimeric locus does not in itself enable the products to be made. Rather, the reverse chimeric locus is the result of successfully making the products, the full range of which could not be done.

Their Lordships ruled 4-1 in Kymab’s favour (Lady Black dissenting), finding Regeneron’s patents to be invalid for insufficiency.

What does the future hold?

The Supreme Court’s decision highlights a strict approach to sufficiency and the importance of fulfilling the ‘patent bargain’. The Supreme Court described the sufficiency requirement as “part of the bedrock of the law”, and noted that to water this requirement down would “tilt the careful balance […] in favour of patentees and against the public in a way which is not warranted by the EPC”.

A key aspect of the disagreement between the Court of Appeal and the Supreme Court seems to come down to a desire to reward a genuinely ground-breaking technology. How could Regeneron have properly claimed its invention in a way that would reward its contribution to such a fast-moving field as genetic engineering, but not be deemed insufficient? Perhaps by framing the claim as “a method of curing immunological sickness in transgenic mice…”, as advocated by Lady Black in her dissenting judgment.

However, framing the claim in this way could have resulted in other insufficiencies such as excessive claim breadth. Lord Briggs acknowledged that the patentee might have had to confine itself to “scant and short lived reward for their efforts and ingenuity”, but that what matters is the settled, strict reading of law that a product claim must properly enable the products to be made.

It is possible that the decision could fuel further insufficiency attacks on claims to broad ranges, not least in the form of ‘Markush’ formulae. Such a development would strike at the heart of the sector whose hallmark is arguably the continued development of ground-breaking technology. Only time will tell whether this is the case, but in the meantime, the Supreme Court ruling provides vital guidance.

In January 2021, Cambridge biotech firm Kymab was acquired by Sanofi for a record-setting $1.1bn, the largest ever deal for a private British biotech company. Kymab is a clinical-stage company developing antibody treatments and immunology therapeutics and was the first company to be was spun out of the Wellcome Trust’s Sanger Institute in 2010.