Commissioner’s Decision # 1371
The Commissioner refused to grant GlaxoSmithKline’s Patent Application No. 2,438,942 (“the Application”) for an “influenza vaccine formulation for intradermal delivery” due to obviousness. The Application proposed the use of a short needle device for the intradermal (ID) delivery of a trivalent split flu vaccine as opposed to the standard intramuscular (IM) route of administration. [6] To make its case for inventiveness, GlaxoSmithKline argued that there had previously been no motivation to use the ID route over the conventional IM route and that the prior art actually teaches against using the ID route. The Patent Appeal Board determined, however, that there was always a motivation to use the ID route, but it had always been impractical until the advent of a short needle device. Once a short needle device entered into the state of the art, the obstacle against administering vaccines through the ID route was removed, and making use of it became obvious. [76]
The Application contains four independent claims. Claims 1 and 20 are independent use claims, for which claim 1 is representative:
1. The use of a trivalent, split influenza virus antigen preparation in the manufacture of a one-dose intradermal influenza vaccine, said vaccine provided in a short needle intradermal delivery device. [51]
The Board looked past the “artificial nature” of this claim in its Swiss format to construe the claim as the “[u]se of a trivalent, split one-dose influenza vaccine provided in a short needle intradermal delivery device for the prevention of influenza.” [53]
Claims 12 and 15 are independent kit claims, for which claim 15 is representative:
15. A pharmaceutical kit comprising:
(i) a short needle intradermal delivery device adapted to a location between 1.0 mm and 2.0 mm below the surface of the skin; and
(ii) a trivalent split influenza vaccine. [49]
The “1.0mm and 2.0mm below the skin” distance would have been understood to correspond to ID delivery. [50]
Obviousness Analysis
1) The Skilled Person and their Common General Knowledge
Not in dispute in the case, the person skilled in the art was taken to be a “person or group of people working in the fields of immunology and vaccinology, including medical professionals.” [12]
Also not in dispute was that it was common general knowledge (CGK) that it was conventional to vaccinate with trivalent split virus vaccines delivered by the IM route. [15] It was also CGK that ID administration had certain advantages, such as that it can help conserve vaccine in certain circumstances. [35, 76] Most critically, it was CGK that there was difficulty associated with the standard “Mantoux” technique for ID delivery (not using a short needle) that previously made ID delivery impractical for mass vaccinations. [15, 29]
In dispute was whether or not it was CGK that the ID route was a “suitable route of administration” [31] and whether or not the skilled person would have expected immunogenicity of the known trivalent split vaccine to diminish if the route were changed from IM to ID. [36]
GlaxoSmithKline contended that two pieces of prior art in particular “teach away” from using ID instead of IM, but the Board was unconvinced. The first document showed better results in primed subjects vaccinated by the IM route as compared to the ID route, but the Board found that other prior art treated this finding as an “outlier” and dismissed it as such. [46] A second document described an instance where a vaccination campaign by the ID route was abandoned, but the Board found the abandonment was due to a side effect of the vaccine and not a downside of using the ID route itself. [47]
Overall, it was CGK that the preferred method of vaccine delivery was IM and there was a lack of interest in developing a use of ID for vaccinations, but the prior art did not go as far as to teach away from using ID. [48]
2) The Inventive Concept
The inventive concept for the independent use claims was not in dispute and was found to be equivalent to all the elements of claim 1: “Use of a trivalent, split one-dose influenza vaccine provided in a short needle intradermal delivery device for the prevention of influenza.” [60] The inventive concept for the independent kit claims was more limited: “A pharmaceutical kit comprising (i) a short needle intradermal device, and (ii)a trivalent split flu vaccine.” [61]
3) Differences between the State of the Art and the Inventive Concept
The only difference between the relevant prior art and the inventive concept of the use claims is that the prior art makes no mention of combining the short needle device with a flu vaccine that is protective after a single dose. [69] The difference for the kit claims is similarly that the prior art makes no mention of combining the short needle device with a flu vaccine. [70]
4) Were the Differences Obvious?
None of the independent claims were found to require any degree of invention. [80] Before the advent of the short needle device in the prior art, the difficulty associated with the ID technique that made it impractical for use in mass vaccinations was well known. [76] However, the development of the short needle device removed this obstacle, and the skilled person would have then realized that there was a practical means to deliver split trivalent vaccines by the ID route. [76]
The kit claims did not add any degree of invention. [74] Neither did any of the dependent claims, which generally claimed variations of the proposed invention that would have been expected given the CGK. [82-84] GlaxoSmithKline argued that some of its dependent claims pointed to never-before identified better immunogenicity outcomes, [85] but these benefits could not be attributed to the ID delivery method that was being claimed in the Application. [86]
Commentary
This case turned considerably on the Board’s interpretation of prior art that made up the common general knowledge of the skilled person. GlaxoSmithKline’s principal argument for inventiveness was that using ID delivery for vaccinations ran contrary to conventional knowledge, and supported this position with a number of studies showing problems where ID delivery was used for vaccinations in the past. The Board’s handling of the disputes about the meaning of these studies was lengthy and appears to have been thorough, [31-48] perhaps with the somewhat unsatisfying exception where it dismissed a critical piece of prior art (which favoured GlaxoSmithKline) as an outlier. [46] Once GlaxoSmithKline lost on these arguments, hurdle of inventiveness was seemingly removed, and the conclusion that using a short needle device for intradermal delivery would have been obvious was likely inevitable.