Vilanterol & Umeclidinium - UK

On Dec 13, 2018, UK high court found Vectura’s patents invalid, not infringed by Glaxo & thus granted Arrow declaration.

Background:

Vectura (Defendant) alleged that the  GSK (Claimant) have infringed the patents by the manufacture and sale of dry powder inhalers (“DPIs”) containing the active ingredients vilanterol trifenatate (“vilanterol”) and/or umeclidinium bromide (“umeclidinium”) which are used to treat asthma and chronic obstructive pulmonary disease (“COPD”) and which GSK market under the trade mark Ellipta.

Vectura is the proprietor of European Patents (UK) Nos. 1337240 (“240”), 2283817 (“817”), 2283818 (“818”), 1337241 (“241”) and 1920763 (“763”). The patents all have the same earliest claimed priority date of 30 November 2000. Patents claim “composite active particles” & methods of making same. The composite active particles are very fine particles of active material which have upon their surfaces an amount of the additive material. The additive material is preferably in the form of a coating on the surfaces of the particles of active material. Vectura only rely upon claims which require the Magnesium sterate (additive material) to form a coating on the surface of the active. Certain claims require that “the particles of additive material become fused to the surface of the particles of active material”.  It is common ground that these phrases are all ways of describing the same concept, namely that the structure of the additive particles is altered in the milling process so that they become structurally combined with the surface of the active particles. The additive particles no longer keep their original particulate shape and instead deform over the surface of the active particles (i.e. so as to form a coating, which may be discontinuous). 

On 5 August 2010 Vectura granted GSK a licence in respect of Staniforth and any patents deriving from it (“the Staniforth Patents”). GSK exploited the Staniforth Patents and paid Vectura substantial royalties pursuant to this agreement. The agreement identified an additional class of patent applications (referred to as “the Non-Assert Patents”) in respect of which GSK had the option to take a licence. The Staniforth Patents expired on 31 January 2016. On 8 February 2016 GSK informed Vectura that it did not require a licence under of the Non-Assert Patents. GSK’s position was that it uses an obvious development of the process disclosed in Staniforth and not the processes claimed in the patents. Vectura commenced proceedings against GSK for Non-Assert Patents & in response GSK commenced these proceedings. GSK deny infringement and claim revocation of the patents on the grounds of obviousness over three prior arts and insufficiency. GSK also contended that they have a Gillette defence because their process is objectively obvious in the light of the prior art & seeks Arrow declaration. In a nutshell, GSK say that, although their process uses MgSt, this is disclosed by each of the three items of prior art.

Infringement:

GSK disputed the infringement for five main reasons. First, GSK deny that their process includes a milling step where this is required. Secondly, GSK rely on the fact that, if they mill, they do so in the absence of the lactose. Thirdly, GSK dispute that the MgSt particles become structurally combined with the active particles to form composite active particles. Fourthly, GSK dispute that the MgSt is fused to/smeared over the surfaces of the active particles so as to form a coating. Fifthly, GSK dispute that the MgSt is evenly distributed over the active material as required by claim. Vectura relies upon the results of the SEM and EDX experiments carried out by the parties to establish that these integers of the claims are satisfied by GSK’s process and products. GSK challenge the suitability of these techniques for this purpose.

Court said that GSK do not dispute that the experiments show the presence of magnesium, and hence MgSt, in the samples examined. Nor do GSK dispute that it may be concluded that MgSt was closely associated with particles of the active ingredients. But the crucial question is whether Vectura’s experiments demonstrate the presence of composite active particles with MgSt structurally combined with and fused to/smeared over the surfaces of active particles so as to form a coating. On this question there was little disagreement between the experts. Having considered the evidence as a whole, court held that the limitations of EDX experiment, together with the absence of validation, mean that one can have no confidence that the MgSt is on the surface of the active particles, let alone structurally combined with and fused to/smeared over them. It may be, but equally it may not. Therefore, Vectura has not established that GSK have infringed the patents.

Insufficiency:

GSK contend that the specifications of the patents do not disclose the invention clearly and completely enough for it to be performed by a person skilled in the art. Specifically, GSK contend that the patents are insufficient because they do not enable the skilled person to determine whether a process or product falls within the claims since they do not enable the skilled person to determine whether or not there are composite active particles with additive particles fused to/smeared over active particles so as to form a coating, and certainly do not enable the skilled person to do so without undue burden. GSK accept that the skilled person would consider it plausible that, if the process described in Example 4 is followed, the MgSt would deform and spread over the surfaces of the active particles, but point out that the Example does not demonstrate that the MgSt particles are structurally combined with the active particles or fused to/smeared over them to form a coating. Even assuming that the skilled person took on trust the assertion that Example 4 did produce composite active particles as claimed, GSK contend that the skilled person would not know how to determine whether any other process did so. Court agreed with GSK & held that the limitations of EDX mean that it is not a suitable technique for this purpose, at least in the absence of validation, as is demonstrated by Vectura’s failure to establish infringement. This is not because of any peculiarity in GSK’s process, but due to the nature of the technique and Vectura’s failure to validate its use for this purpose. Accordingly, court concluded that the patents are insufficient because they do not enable the skilled person to determine whether or not a process or product is within the claims. Certainly, the patents do not enable the skilled person to do so across the breadth of the claims without undue effort.

Obviousness:

The prior arts disclose blending of MgSt with lactose so as to coat the lactose with the MgSt, followed by blending the mixture with API. Court in conclusion said that there is no evidence, however, that following the teaching of prior arts using a high-shear blender would produce composite active particles with MgSt fused to/smeared over the active particles to form a coating as claimed in the patents. Therefore, GSK have not established that any of the Patents are obvious over prior arts.

Arrow declaration:

An Arrow declaration is, in effect, a declaration that, as of a particular date, a party as Gillette defence against claims of infringement of later patents. In response to GSK’s application to strike out the claim for Arrow relief, Vectura gave an undertaking that it will not assert in any patent applications from within the Non-Assert Patent families. GSK say that Vectura has shown a propensity over many years to describe what is essentially a single inventive concept in a variety of ways. Vectura has the potential to continue to reformulate the inventive concept using applications which are still on file, even if GSK were successful in revoking each of the patents. Vectura contends that its undertaking gives GSK all the protection they require assuming that Vectura is unsuccessful in its claim for infringement of the patents, and according the declarations sought by GSK will not serve a useful purpose. Court said that the GSK’s process and the products obtained thereby, were obvious over prior arts as at 30 November 2000. That is a necessary foundation along with the other evidences for the relief sought by GSK.

Summary of principal conclusions:

i)  Vectura has not established that GSK’s process or products infringe any of the patents;

ii)  all of the patents are invalid on the ground of insufficiency;

iii)  GSK have not established that any of the patents were obvious over any of the cited prior art;

iv)   GSK’s process, and products obtained directly from it, were obvious over prior arts; and

v)   it is appropriate to grant GSK an Arrow declaration in the form of Declaration B, but not Declaration A.