On 7 October 2024, Mr Justice Mellor handed down his decision in Pfizer v. GSK [2024] EWHC 2523 (Pat)
GSK were the proprietors of the patents in suit : EP (UK) 3 109 258 (EP 258) and EP (UK) 2 222 710 (EP 710) (together “the Patents”) both of which described a strategy for vaccinating against respiratory syncytial virus (RSV) using a form of the “F” antigen of RSV which had been modified to stabilise it in its “pre-fusion” form.
In his judgment, Mr Justice Mellor reached several key conclusions:
· Both EP258 and EP710 patents were found to be invalid for obviousness over all the prior art relied upon by Pfizer;
· Even if valid, the Court determined that Pfizer’s RSV vaccine product would not infringe either patent; and
· An Arrow declaration, as sought by Pfizer, was granted.
Skilled team and CGK
Although the parties agreed that the skilled team would be led by a vaccinologist and the team would have expertise in immunology, virology and structural/molecular biology, they disagreed on whether the vaccinologist would have sufficient knowledge of molecular biology to avoid consulting an expert in that field. Pfizer contended that the vaccinologist would consult a structural/molecular biologist who would be part of the skilled team when issues arose relating to protein structure. The Judge held that Pfizer’s submission was borne out on the evidence of how real-life research groups had operated at the priority date, and that the prior art and the Patents both suggested that the skilled team should comprise a structural/molecular biologist. The Judge also criticised GSK’s approach whereby experts were “siloed” from each other and had not been able to share their views as a real skilled team would, leading to an “unduly narrow” approach to the CGK and the prior art.
Infringement
As a preliminary issue in the infringement analysis, the Judge had to rule on the definition of “polypeptide”. Although GSK provided several examples of “polypeptide” being used interchangeably with “protein” and thereby encompassing structures containing more than one chain of amino acids linked by peptide bonds, the Judge held that these examples were irrelevant as they did not address the term as used in the claims of the Patents. The Judge therefore preferred Pfizer’s construction, whereby “polypeptide” referred to a single chain of amino acids linked by amide bonds.
In light of his finding as to the meaning of “polypeptide” the Judge held that since Pfizer’s product comprised two polypeptides linked by disulfide bonds (rather than amide bonds), it did not fall within the scope of the claim wording (present in both EP 258 and EP 710) of “a soluble F protein polypeptide comprising an F2 domain and an F1 domain” on a normal construction.
In considering infringement of by equivalence, the Judge preferred the evidence of Pfizer’s expert – by relying on a disulfide linkage between two polypeptides rather than a single polypeptide, the goal of stabilisation had been achieved in a substantially different way in Pfizer’s product over the method claimed in the Patents. Also, in relation to the third Actavis question, the Patents had described additional methods of stabilisation over those claimed – leading the Judge to find that the patentee had probably intended strict compliance with the claimed method.
Obviousness
One of Pfizer’s challenges to validity was lack of inventive step. In this regard, Pfizer relied on prior art including the abstract published at an RSV symposium by Professor Ted Jardetzky (who also appeared as a fact witness in the case), together with the slides and the public oral disclosure made at that symposium by Professor Jardetzky (the Jardetzky Materials). Pfizer also relied on a Nature paper by Professor Jardetzky’s group on the structure of the F protein (Yin) and an abstract from the American Society for Virology (the ASV Abstract).
GSK sought to argue that the approach of the Patents was just one of many open to the skilled vaccinologist at the priority date. However, the Judge found that GSK’s contentions seemed to be directed to an unpleaded case of obviousness over the common general knowledge and did not address the prior art.
Applying the Pozzoli test which is commonly used to evaluate obviousness in the UK, the Judge found that the difference between the Jardetzky Materials and the Patents was the virus whose F protein was stabilised – PIV (parainfluenza, like RSV a member of the Paramyxovirus family) rather than RSV. The Judge held that the skilled team would have been aware of the analogy between the two viruses and would have considered it obvious that they could make a stabilised form of the pre-fusion conformation of the F protein of RSV as claimed by the Patents.
Although the Judge considered the Jardetzky Materials the closest prior art, he also found the Patents obvious over Yin and the ASV Abstract.
Secondary Evidence
In their closing skeleton argument, GSK introduced a case based on secondary evidence. GSK cited a large number of pre- and post- priority publications and sought to argue that, since none of those documents suggested that the pre-fusion form of the F protein in RSV should be stabilised in an effective vaccine, the invention must not have been obvious.
The Judge was unconvinced – the published literature cannot reflect everything that is going on in a particular field. Although there might not have been data produced on the approach of the Patents for some years after the publication of the prior art, this was not sufficiently strong to rebut the Judge’s conclusion on obviousness. Additionally, Pfizer were able to provide certain Novartis patent applications filed during the period addressed by GSK which took a similar approach to that of the Patents.
The Judge was also critical of GSK’s decision not to plead their case on secondary evidence before closing, as it had deprived Pfizer of a chance to properly address and respond to it with their own evidence. GSK had also failed to provide oral evidence from real-world workers whose words it had relied on, meaning that the secondary evidence was not, in the Judge’s view, sufficiently complete and testable to be of value to him.
Plausibility
A further challenge based on alleged lack of plausibility was rejected using the FibroGen approach. Pfizer argued that the examples of the Patents had only made it plausible that the claimed modified antigens could be used for vaccinating against RSV in the presence of adjuvants. However, the Judge held that the demonstration of an immune response in the absence of adjuvants, even a reduced one, in some of the examples, was sufficient to render it plausible that the invention worked both with and without adjuvants and was therefore plausible across the scope of the claims.
Arrow declaration
Finally, Pfizer applied for an Arrow declaration on the grounds that at the priority date it was obvious to make an RSV antigen which resembled the pre-fusion state and to use that antigen in the treatment or prevention of RSV-associated diseases. The Judge referred to his findings on obviousness and granted the declaration, noting that making the declaration would serve a useful purpose. The Judge agreed with Pfizer that the Arrow declaration would be useful as it would provide commercial certainty to Pfizer in light of GSK’s unclear strategy in relation to its other divisionals. There was also a public health interest in having Pfizer’s vaccine made available in the UK.
The decision is of particular interest because it demonstrates a rather sceptical approach to so-called secondary indicia of obviousness – e.g. contemporaneous reactions of people working in the relevant field at the time. It also provides a further example of the English Patents Court being wiling to grant Arrow relief where the interests of justice would be served.
A copy of the judgment can be read here.
