A principle of general application?

Author: Darren Smyth (EIP, London)

Regeneron Pharmaceuticals Inc v Genentech Inc [2012] EWHC 657 (Pat), Patents Court, England and Wales, 22 March 2012

Journal of Intellectual Property Law & Practice (2012) doi: 10.1093/jiplp/jps087, first published online: June 19, 2012

The Patents Court, England and Wales, has upheld the validity of a claim expressed in broad functional terms and, in relation to sufficiency, has, unusually, considered that the invention relates to a ‘principle of general application’ as set out by the House of Lords in Biogen Inc v Medeva plc [1997] RPC 49.

Legal context

In European patent law, there is no specific prohibition on claiming an invention in broad terms. The closest legal provision, that the claims must be ‘supported by the description’ (Article 84 of the European Patent Convention, EPC) is not a ground of invalidity of a patent. However, a claim that is expressed in broad terms will frequently be found either to lack inventive step (because it encompasses obvious subject matter) or to be insufficient.

The requirement for sufficiency is expressed in Article 83 EPC: ‘The European patent application shall disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.’ Within this broad requirement, UK jurisprudence has established three ways in which insufficiency can arise: classical insufficiency, ‘Biogen insufficiency’ or insufficiency by excessive claim breadth, and insufficiency by ambiguity.

In Biogen the leading judgment stated: ‘If the invention discloses a principle capable of general application, the claims may be in correspondingly general terms’. Therefore, the criterion to be satisfied for a claim which is framed in broad terms to be found sufficient according to Biogen is that it involves ‘a principle capable of general application’.

Accordingly, patentees frequently argue that their invention discloses a principle capable of general application, but cases where this has been accepted are rare. It was recently acknowledged in H. Lundbeck A/S v Norpharma SpA [2011] EWHC 907 (Pat), where the following claim was held not to be insufficient (although the patent was held invalid on other grounds): A process for the synthesis of citalopram, in which a process for the synthesis of [intermediate] according to claim 1 is contained. However, in that case, the part of the claim that was expressed broadly was that part that was peripheral to the actual invention.


The Genentech patent at issue is EP 1238986 and relates to VEGF. VEGF was known at the priority date as one of a number of angiogenic growth factors (others included FGF, PD-ECGF, EGF, TGF-ß, TNF-α, angiogenin and angiotropin). Because angiogenesis (or neo-vascularisation—the process of new blood vessel growth by outgrowth from pre-existing vessels) is implicated in a large number of diseases, including cancer, rheumatoid arthritis, macular degeneration, and atherosclerosis, a growth factor whose activity could be targeted to control angiogenesis would have been therapeutically highly desirable. However, it was not known that VEGF was such a growth factor.

The main claim of the patent was in the following terms:
Use of a hVEGF antagonist in the preparation of a medicament for the treatment of a non-neoplastic disease or disorder characterised by undesirable excessive neovascularisation, wherein the hVEGF antagonist is:

(a) an anti-VEGF antibody or antibody fragment;

(b) an anti-VEGF receptor antibody or antibody fragment; or

(c) an isolated hVEGF receptor.
Regeneron and Bayer sought revocation of the patent, and also a declaration that a product to be marketed by Regeneron under licence from Bayer called VEGF Trap Eye (VTE) did not infringe.

VTE was found to infringe the patent on the basis that it satisfied the definition of (c) in the claim, even though it did not include the whole of the hVEGF receptor sequence.

The claim was found to involve an inventive step over the pleaded closest prior art, a paper entitled ‘The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies’, which disclosed an anti-VEGF antibody (ie an antibody satisfying the definition of (a) of the claim). The judge accepted that, although the paper stated that the antibody ‘may have therapeutic potential’, it did not render it obvious to use anti-VEGF antibodies in therapy, because of ‘the fact that VEGF was only one of many factors and other agents which could be investigated, the commonly accepted view that there was no single factor responsible, the confusing picture presented by the common general knowledge and the view that achieving anti-angiogenesis therapy would be difficult’.

The judge acknowledged secondary indicia of non-obviousness, including a prestigious award given to one of the inventors, and other accolades in the literature.

A number of insufficiency attacks were made on the patent, and the judge rejected them all. On the matter of Biogen insufficiency, the judgment states:
I consider that the patent discloses a principle of general application within the meaning of the authorities insofar as it claims anti-VEGF antagonism as a treatment for all non-neoplastic diseases. The tumour data in the patent establish that VEGF blockade is likely to be a successful strategy for treatment in cancer. The skilled reader would appreciate that the reason it is likely to be successful is because blocking VEGF is a sufficient intervention to prevent angiogenesis, at least in models of cancer. It is common ground that it is possible to extrapolate that reasoning to at least some non-neoplastic diseases.
Thus the judge placed the invention squarely within the situation where, according to Biogen, it can be claimed in broad terms.

The judge rejected sufficiency attacks based on the time and effort that would be necessary to develop treatments according to the claims, in particular the definition in (c) of the claim, not least VTE itself which was accepted to be ‘very clever’. In this regard, the judgment states:
The fact that a claim may extend to further inventions which make use of the principle disclosed in a patent does not necessarily render the patent insufficient. I do not consider that the fact that the claim extends to VTE makes the present patent insufficient, even in the light of the evidence which I have accepted. Finally, therefore, the judge concluded: ‘The patent is not invalid on any ground alleged. The patent is infringed by VEGF Trap Eye.’

Biogen insufficiency in UK jurisprudence relating to broad claims is mirrored by EPO jurisprudence which, however, generally considers the matter as an issue of inventive step. The leading case is AGREVO/T 939/92 according to which, if the technical problem is not solved across the breadth of the claim, the claim lacks inventive step. Lack of inventive step according to AGREVO was separately pleaded, but the judge understandably stated that ‘in the present case this argument traverses the identical ground to that raised by insufficiency’, and so dealt with it accordingly under the insufficiency heading.

Whether expressed as a matter of inventive step or insufficiency, both approaches are intended, in their way, to ensure that the monopoly granted by the patent is commensurate with the contribution to the art. This is still a precept of patent law in Europe.

‘Fair basis’ (that the claims must be fairly based on the description) was a requirement of the Patents Act 1949 in the UK, and is still a requirement in, for example, Australia, but does not survive in that form in current European patent law. Moreover, ‘support’ (that the claims be supported by the description) is not a ground of opposition or revocation. Nevertheless, jurisprudence has been developed in Europe under the current law in relation to inventive step and sufficiency to maintain the balance between contribution to the art and the scope of allowable claim.

In the present case, the claim was unusually broadly defined in that both of the key features were defined in broad functional terms—the medical indication (any disease other than cancer in which undesirable excessive blood vessel growth occurs) and the treatment agent (any antibody or fragment against VEGF or a VEGF receptor, or a VEGF receptor [or, as construed by the judge, part thereof]). Further, VEGF was, as such, already known as an angiogenic growth factor at the priority date of the patent: what was unknown was that VEGF is necessary for pathological angiogenesis, and therefore it was not known what would be the therapeutic effect, if any, of a VEGF antagonist. This might therefore have seemed an unpromising case to successfully argue sufficiency under the Biogen jurisprudence.

The decision rests on a number of findings, key among which are the following: that the patent disclosed a principle of general application; that it was reasonable at the time to predict that anti-VEGF therapy would be effective in relation to non-neoplastic diseases generally; and that allegations of classical insufficiency that specific diseases could not be treated as claimed were not made out. In relation to the ability to make the claimed antagonists, there was no real attack in relation to the antibodies defined in (a) and (b) of the claim, and the objection in relation to the receptor defined in (c) of the claim was only in relation to an antagonist with less than the full extracellular domain of the VEGF receptor. This objection was rejected on the basis that in this industry ‘careful experimentation with a degree of trial and error, sometimes extending over months and years, is entirely normal’, and because:
A patent is not insufficient because it may take much work to develop the most elegant or refined embodiment of its inventive concept. If one were to carry on with the refinement, one would still be making use of the principle disclosed in the patent, working towards an improved embodiment of it.
Practical significance

Because the UK courts since Biogen have so rarely acknowledged that an invention involves a principle of general application, practitioners may have come to believe that such cases would be purely theoretical. This decision should give assurance that in appropriate cases broad protection can be validly obtained.

No comments:

Post a Comment