Pfizer infringed haemophilia B gene therapy patent

The High Court has held that a patent owned by uniQure for the treatment of haemophilia B is valid and was infringed by Pfizer.

The case, brought by Pfizer, is one of the first gene therapy patent disputes to be ruled on by a UK court. The High Court dismissed Pfizer's argument that uniQure's patent was invalid as the new gene therapy for treating haemophilia B disclosed in the patent was obvious, based on what is already known (wherein an invention must be non-obvious to be patentable). Pfizer admitted infringement if the patent was held to be valid, as the company had developed a similar gene therapy with identical modifications made to the Factor IX (FIX) gene essential to uniQure's invention.

In his judgment, His Honour Judge Hacon, who presided over the case, concluded that 'the patent is valid and in consequence it is infringed'.

Haemophilia B is caused by a defective FIX gene on the X chromosome which fails to produce normal levels of the FIX enzyme needed for blood clotting. UniQure's patented invention discloses a gain-of-function mutation in the FIX gene, wherein the arginine at position 338 of the amino acid sequence of the protein is replaced by leucine to produce a mutant FIX enzyme with increased activity compared to wild-type FIX. This variant is referred to as the 'Padua variant' or R338L-FIX.

Pfizer argued that uniQure's patent was invalid, as substituting arginine for leucine for gene therapy would be obvious to a skilled team (consisting of a gene therapist and a structural biologist in this case) based on the teachings of another patent application referred to as Stafford, after the name of the first stated inventor, published in 1999.

However, though Stafford indicated that various substitutions could be made at position 338 of the sequence, Judge Hacon dismissed Pfizer's claim on the basis that no rationale was indicated for why such substitutions - including a leucine substitution - were suitable for gene therapy, and that such substitutions could instead be detrimental to the function of the enzyme.

'In my view, the skilled team would have attached no scientific significance to the notion of substituting leucine at position 338. There were no data at all in relation to R338L-FIX in Stafford... the inventive concept of [uniQure’s] patent is that DNA encoding the R338L-FIX... is suitable for use in a gene therapy treatment of haemophilia B. Stafford does not say that it would be suitable...' said Judge Hacon.

Crucially, the judge went beyond 'primary' evidence, for example considering whether the approach would be obvious to a hypothetical skilled team, to also consider 'secondary' evidence, considering the current approaches of research teams in the field. Judge Hacon found it 'compelling' that no other team had tried the leucine solution, following Stafford.

Krishna Kakkaiyadi, a senior associate at Pinsent Masons, not directly involved in the case, said: 'The judge was strongly influenced by ... "secondary" evidence ... which is not often relied upon in patent cases… In other patent cases concerning ATMPs [advanced therapy medicinal products], secondary evidence as to why actual teams were or were not working on particular options could become relevant to their inventiveness, especially in the early years as these products come on the market,'.