Yesterday and today the Supreme Court has been hearing an appeal concerning Regeneron’s patent relating to improved transgenic mice for antibody generation. Although concerned with a complex gene technology, the outcome of this appeal will have substantial impact on the validity of patents generally where doubts are raised as to the level of disclosure provided in a patent to support its claims.
The appellant, Kymab, is seeking to overturn the Court of Appeal’s decision which – contrary to the first instance judge of the Patents Court – upheld that patent’s validity. Kymab’s case is built upon a particular point related to the requirement for sufficient disclosure in a patent under the European Patent Convention and corresponding UK law, i.e. that a patent must contain enough information for the invention the subject of the patent to be reproduced by others without undue burden. The specific point concerns patents with broad claims which purport to cover products or methods seemingly beyond the level of teaching details expressly provided in the description. The question that arises in such cases is: should patentees be granted a monopoly broader than the specific information they provide in their patents? In earlier cases, the English Courts, influenced by case law from the European Patent Office, has upheld patents with broad claims of this kind in certain circumstances – if the products or methodologies are an invention that is based on a principle that is of general application, this may justify a broad claim.
Here, Regeneron’s patents covered transgenic mice that were better for producing antibodies than the pre-existing transgenic mice (as well as how to produce the transgenic mice). Research in this area had previously pursued antibody production by introducing complete human gene sequences of the desired antibodies into the mice in order to produce purely human antibodies. This was seen to be advantageous over antibodies produced partly from human and partly from murine (mouse) genes which could cause immunological reactions in human patients, known as the human anti-mouse antibody response or HAMA response. Unfortunately, mice producing fully human antibodies had their own disadvantages; the mice had reduced immune responses (they were “immunologically sick”) and produced sub-optimal antibodies with reduced affinity compared to unmodified “wild type” mice. Regeneron’s scientists instead conceived the idea of producing antibodies from mixed human-murine gene sequences that could be modified later to replace the murine portions and avoid HAMA response. To do this, they created transgenic mice with only part of the gene (the “mouse variable sequence”) substituted for the human part (the “human variable sequence”) – hence mice with DNA containing a “reverse chimeric locus”. This approach produced mice which were not “immunologically sick” and the HAMA response could be avoided by subsequently replacing the murine region (the “mouse constant region”) in the resulting antibodies with a corresponding human constant region. However, Kymab contended that the introduction of the reverse chimeric locus into the mouse DNA, which required a targeted approach to introducing all the relevant material at the right location in the genome, presented a challenge to the skilled person, a challenge which Regeneron’s patents left too much to the reader to solve, in particular that they would not know how to introduce DNA in a targeted way across the whole range of the sequence lengths covered by the claim. Much of the evidence in the lower courts centred on one of the examples in the method patent (Example 3) and whether this could have been put into effect at the priority date without undue burden.
At first instance the Patents Court found Example 3 could not be put into effect without undue burden and without invention. It found that the reverse chimeric locus was not a principle of general application that could be followed but rather a result achieved when a targeted method could be made to work. The Court of Appeal disagreed. The Court of Appeal considered the reverse chimeric locus described by the patent was a unifying principle of general application that was a major scientific contribution and would justify a broad claim. The principle of general application could be followed and the patents broad monopolies were justified, notwithstanding the difficulties with Example 3. While there were problems with the information provided, e.g. in Example 3, this was not fatal to the claim because the Court of appeal held that there was an obvious way in which the skilled person could have overcome the inadequacies of Example 3 and other deficiencies in the specification.
In the Supreme Court yesterday, Kymab’s counsel Mr Ian Purvis QC told the court that “in a nutshell the law of sufficiency requires that to justify a patent monopoly the patent must provide enough information to ensure the skilled reader at the priority date can, without the need to make further inventions and using only the information provided and his common general knowledge, fully implement the invention across the full scope of the monopoly”. In this case, he argued, even on the Court of Appeal’s findings, “only a small subset of the claimed range was actually made available [i.e. by the information given in the patent] without making inventions or with undue effort”. Mr Purvis referred to the fact that Regeneron’s publication of their successful real-world production of transgenic mice had followed around ten years after the priority date, coming after Kymab’s high-profile publication in Nature which had set out Kymab’s successful technique (which differed in some respects from that of Regeneron).
Mr Purvis acknowledged that in the early years of the EPC, both the EPO and English Courts had not required patents to provide information to reproduce the invention across the entire claim scope but rather required only that information be provided to produce one thing covered by the claim. As he pointed out, however, this approach had been rejected in both jurisdictions around 25 years ago.
As Mr Purvis began to explore the legal history of this, the Supreme Court judges sought a cogent explanation of what was meant by a “principle of general application” referred to in much of the case law. Mr Purvis referred to an element of the claim which is expressed in general terms and is enabled. He gave the example of a “connecting means” in a mechanical patent – something that any skilled reader would understand and be able to choose for himself which particular connecting means to use.
As applied to this case, Mr Purvis contrasted the position of a patentee who provided sufficient information to work the invention across the scope of the claim even if, later, some further inventions made would be covered by the claim with a patentee who provides limited information and leaves a substantial portion of the claim’s scope to be filled in by others making their own inventions later. He also emphasised that the “invention” the focus of this inquiry was that defined by the claim, not some general idea derivable from the patent. Here, he said, it was accepted that at the priority date it would not have been possible for the skilled person to introduce reverse chimeric loci into the mouse DNA other than for short sequence lengths.
In response, Regeneron’s counsel Lord Pannick QC identified eight propositions underlying their case:
- Claims’ scope must correspond with and be justified by the technical contribution;
- Satisfying test of sufficiency depends on the invention and whether the content of the claim has been sufficiently disclosed;
- In this case, Regeneron invented what the Court of Appeal recognised as a “striking, radical and highly original departure” from what came before it. This invention was the transgenic mice with the reverse chimeric locus, causing the mice to avoid the immunological sickness of the prior art mice;
- The claim the parties focused on was a product claim (to a transgenic mouse with certain features). The technical contribution is the reverse chimeric locus. It is not a claim to a product produced by a process of a specific DNA insertion of the right quantity of DNA;
- The claims breadths are commensurate with the technical contribution. It is no broader than the contribution to the art;
- The requirement of sufficiency does not require that the patent must disclose information to enable the skilled person to make every product across the scope of the claim. Where the claim is to a principle of general application, the requirement of sufficiency is satisfied by the disclosure of sufficient information to enable the making of at least one embodiment of the claimed invention and also sufficient information that the skilled person can reasonably expect that the invention will work across the scope of the claim. The Court of Appeal found both of these here. The question is not whether the patentee must enable, but what must be enabled. Here, the general principle was the inclusion of the reverse chimeric locus in the mouse;
- The approach of Kymab, requiring greater disclosure, would frustrate the purpose of patent law. He quoted again the positive terms in which the Court of Appeal had characterised the invention of the patents; and
- Unsurprisingly, given the policy consideration of (7), the case law supports the validity of patent claims that are not enabled for all embodiments covered provided that the claim is to a principle of general application that will work across the scope of the claim. i.e. that any mouse with the reverse chimeric locus would realise the technical contribution and avoid immunological sickness, not necessarily that all mice with the reverse chimeric locus could necessarily be made at the priority date.
He emphasised that the patent law represents a balance between the monopoly claimed and the disclosure given. He highlighted the Court of Appeal’s desire to see that the balance in this case fell such as to reward Regeneron for their invention, rightly so he argued.
A further aspect of these eight propositions that Lord Pannick emphasised was that the invention works across the scope of the claim, i.e. any mouse with the reverse chimeric locus will avoid immunological sickness. Thus the benefit of the invention was established as realised across the whole scope of the claim. The effect achieved was not dependent on the length of the sequence inserted. Therefore even if the patent enabled the production of mice with reverse chimeric loci only of short sequence length, this was sufficient. Lord Pannick said that the length of the sequence was no more relevant than the colour of the mouse. If the law required that claims of this kind had to be limited to the sequence lengths that could actually be inserted at the priority date, as soon as the technology moved forward such that slightly longer sequences could be inserted, patent protection would be lost for the principle of the reverse chimeric locus that Regeneron had invented because competitors would merely use longer sequences while taking the benefit of the invention.
After Lord Pannick, Regeneron’s counsel Mr Adrian Speck QC made further submissions about the principle of general application as an idea, and about the invention in this case. He provided examples of a fixed wing shape to provide lift, and the cathode ray tube used, among other things, in old-style televisions. He suggested that the effect of these need not necessarily be reflected in the claim for patent law, although in this case there were elements of the claim that related to the technical effect. He characterised the invention here as the mouse with the reverse chimeric locus which, in producing antibodies, avoid the “immunological sickness”.
He argued that the nature of the technical effect underlying the invention was crucial in establishing what level of information was required. In a case like this, he said, a new inventive product was different from a case where a new way was found of achieving a known or obvious goal. If all new products possess the new technical effect, they all embody the principle of general application which enables the scope of the claim. By disclosing this principle, the inventor does enable the invention to be performed across its full width. The fact that some products that could have used the principle are not able to be made for other reasons, is not relevant to sufficiency of disclosure. He gave the example of the jet engine not being available at the invention of powered flight by the Wright brothers – the principle of the fixed wing shape could still be put into effect at the point in time it was invented notwithstanding that later, better implementations were available later the specific details of which were not enabled by the original invention but which used the principle of the general application of the original invention.
The dispute here goes to the heart of the ‘patent bargain’, the justification for patent monopolies being provided at all. While the specific facts of the case as always flavour the arguments, the Supreme Court must now consider the fundamental requirement of the level of information that must be provided in patents with claims with broad claims.
The submissions of the parties called to mind, among other things, the doctrine of equivalents recently introduced into the UK law by the Supreme Court in 2017. Regeneron’s submissions as to the narrower scope of the claim that they could have been driven to by Kymab’s interpretation of the law were reminiscent of the same issues addressed by the doctrine of equivalents, i.e. the ability of a competitor to take the benefit of the invention while avoiding the scope of the claim as written.
The decision in Regeneron v Kymab is expected later this year.