Regeneron v Kymab – important findings on enablement across the whole of the claim from the UK Supreme Court
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After 7 years of litigation in the long running Regeneron v Kymab transgenic mouse case, the UK Supreme Court has now issued its judgement and in a surprising 4:1 favour to Kymab, declaring Regeneron’s patents invalid for lack of sufficiency.
The UK Supreme Court overturned the Court of Appeal’s decision, and decided that where the skilled person could not make all of the embodiments covered by the claim scope at the priority date, in this case mice with a whole or large part of the human variable gene locus inserted, the claims lack sufficiency because the patentee is claiming a monopoly which is wider than its contribution to the art.
This was a significant blow to Regeneron whose transgenic mice have been commercially successful over the past few decades. It also signals a tightening up of the law on sufficiency, with an emphasis from the Court on drilling down to the technical contribution of the invention at the time of the priority filing and ensuring the claim scope is commensurate with that technical contribution.
Regeneron’s transgenic mice Patents
The case centres around two of Regeneron’s patents, European Patent (UK) No 1360287 and its divisional European Patent (UK) No 2264163, which cover transgenic mice created by inserting parts of the human variable regions into a mouse. These transgenic mice can be used to produce antibodies for human use.
Prior to Regeneron’s discovery, scientists inserted the entire human immunoglobulin gene of the desired antibodies into mice in order to produce purely human antibodies. Although the immune response in these mice was poor, this approach was seen to be advantageous over antibodies produced partly from human and partly from murine (mouse) genes because a human patient would react to the mouse antibodies themselves as foreign proteins, resulting in a response known as the human anti-mouse antibody (HAMA) response.
To avoid this problem, Regeneron created transgenic mouse, in which all of the mouse immunoglobulin variable (V), domain (D) and constant (C) regions are replaced with human counterparts. A mouse having this new hybrid human/mouse genetic structure (so-called “reverse chimeric locus”) avoids the problem of the mice becoming immunologically sick whilst producing antibodies that can be administered to a human without inducing a HAMA response.
Regeneron’s transgenic mice have proven to be extraordinarily efficient and commercially valuable over the past few decades, generating antibodies that can help tackle some of the world’s most challenging diseases. In recent times, the transgenic mouse platform technology is being used to help find immunisation against COVID-19.
Background of the case
In 2013, Regeneron sued Kymab, alleging that the latter’s transgenic mouse platform infringed these patents. Kymab’s defence was to argue that the Regeneron patents were invalid on the grounds of lack of sufficiency.
At first instance, The High Court found in favour of Kymab, and held that the two Regeneron patents were insufficient. They also held that, if valid, Kymab’s transgenic mice would have infringed both patents.
Both Regeneron and Kymab appealed against the High Court’s ruling, with Regeneron appealing the finding of insufficiency and Kymab appealing the finding of infringement.
In contrast, the Court of Appeal overturned the original decision and found the patents valid as well as well as dismissing Kymab’s cross appeal, finding that the patents were also infringed.
Regeneron’s product claims cover all mice containing a reverse chimeric locus. The claim covered mice with only a few human segments introduced into the mouse genome. The claim was also broad enough to cover mice with the entire human variable gene introduced into the mouse genome. However, at the time of the priority filing, only a very small range of the mice claimed could be made and none at all containing the entire human variable region.
The Court of Appeal extensively reviewed the previous UK and EPO case law, and held that the technical contribution of the patents was the use of a reverse chimeric locus, and that this was a principle of general application and was a feature of all embodiments. Therefore, the Court of Appeal found the claims were sufficient and to restrict the scope of the Regeneron patents would be unfair given their “contribution to the art”. The Court of Appeal argued that such a major scientific contribution, namely the inventive concept that using a reverse chimeric locus prevents mice being immunologically sick, would apply to all mice that could be made under the claim and thus justified the broad claim.
There was a non-working example in the application (Example 3). However, the Court of Appeal, following the guidance in previous case law, held that the skilled person could adapt the example without undue effort to produce a transgenic mouse falling with the scope of the claim. Therefore, this did not deprive the claim of sufficiency.
The point of contention
Kymab subsequently appealed the decision to the Supreme Court, arguing that the range of the human genes incorporated into the chimeric mouse was of key importance and part of the technical contribution. Kymab argued that the full range was not sufficiently disclosed at the priority date. Regeneron counter argued, stating that all of the transgenic mice containing the reverse chimeric locus had the unique advantage of reduced immunological sickness, regardless of the amount of human variable region DNA inserted into the mouse genome.
The question before the Supreme Court was whether the patents were insufficient because the disclosure did not enable the skilled person to work the claimed invention across the whole scope of the claims, or whether the scope of the claims was justified on the basis that the use of a reverse chimeric locus was a disclosure of a principle of general application?
The Supreme Court decision
The Supreme Court allowed Kymab’s appeal by a majority of four to one, holding that the patents are invalid for lack of sufficiency.
The Supreme Court re-iterated that the requirement of sufficiency 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. Given that the skilled person could not make all of the reverse chimeric mice covered within claim 1 at the priority date, namely mice with a whole or large part of the human variable gene locus inserted, the Supreme Court found that Regeneron was claiming a monopoly which was far wider than its contribution to the art.
The Supreme Court further found the legal concept of a “principle of general application” to be limited in scope. The Court decided that to allow Regeneron protection over embodiments that could not be made at the priority date would “tilt the careful balance thereby established in favour of patentees and against the public in a way which is not warranted by the EPC , and which would exceed by a wide margin the scope for the development of the law by judicial decision-making in a particular Convention state” .
The Supreme Court held that in terms of limiting patent protection to the contribution it makes, Regeneron did not meet their side of the patent bargain. The Court considered the breadth of the claims to be wider than justified by the contribution to the art, because only a small area of the invention could actually be put into practice at the priority date.
The Supreme Court referred to the EPO Board of Appeal decision T409/91 (Exxon/Fuel Oils). In that case, claim 1 claimed fuel oils containing wax crystals having an average particle size of less than 4,000 nm, with no lower limit, and smaller particle sizes were preferred. However the application did not contain any information about how to produce wax crystals having a size of less than 1,000 nm and the applicant admitted that this was not common general knowledge for a skilled person. Therefore, the Board decided that claim 1 was not sufficiently disclosed across its entire scope.
The Court, despite the very different subject matter, concluded that there was an obvious similarity between the claimed range in the Exxon case (wax crystals from 3,999 nm down to 1 nm) and the claimed range in the Regeneron patents (from all the segments in the human variable region locus down to just one V, D and J segment in the heavy chain locus and one V and J segment in the light chain locus). Mice having only a small amount of the V, J and D segments replaced with their human counterparts are limited in the diversity of antibodies they can produce. In contrast, mice having of the V, D and J segments replaced are significantly more useful. Although the lower the better in Exxon contrasts with the higher the better in the Regeneron case, the Court’s view was that it is a feature of both cases that the invention was not enabled by the disclosure in the patent at the more beneficial end of the range.
Therefore, following this reasoning, the Supreme Court agreed with Kymab that the amount of human DNA incorporated into the chimeric mouse is crucial in determining the diversity of useful antibodies which the mice would produce and was relevant to the technical contribution of the patent.
The Supreme Court concluded that the Regeneron patents were unduly broad and lacked sufficiency because the most valuable end of the range, namely a mouse having all of the human immunoglobulin DNA, was not enabled at the priority date of the patents.
What does this mean in practice?
With ever more focus on the technical contribution of the invention and framing the claim scope accordingly, this most recent judgement from the Supreme Court is a clear reminder to patentees to be cautious about including broad essential claim features without a detailed disclosure of representative embodiments in the application. Of importance is the Supreme Court’s reference to the priority date as being the determinative date. Often a patentee will make an initial priority filing with some experimental data and use the priority year to include additional data. A careful balance needs to be struck between obtaining an early priority date and ensuring a sufficient disclosure. It is crucial to ensure that the initial priority filing has enough representative examples for a broad claim and sufficient fall back options, with any later experimental data simply serving as a confirmation of the principle of general application.
This article is for informational purposes only and does not constitute legal advice. Please, therefore, get in touch with your usual Forresters Attorney if you need further advice.
