“30. The Patent is directed to a team of people with about two years of post doctoral experience. It would include a molecular biologist familiar with routine techniques of cloning, expression and sequencing of genes and proteins; a biochemist to make and purify recombinant proteins; and a biologist or immunologist with experience of the TNF superfamily and with the skills necessary to generate and test antibodies. I am also satisfied that any team interested in identifying a new member of the TNF superfamily would carry out a literature search to gather as much knowledge as possible about the existing members. … 32. … [T]he skilled team looking for a new member of the TNF superfamily would have been aware that the science of bioinformatics could provide assistance in the search and, if a bioinformaticist was not already a member of the team, would have considered it worthwhile to consult such a person.”
“i) They were all expressed by activated T-cells and some by other [types of cell]. ii) Their activities were mediated by binding to receptors, of which a number had been identified. iii) They were known to have pleiotropic actions …. Some of those activities were understood to be unique to particular TNF ligands and others were understood to be shared by some or all the other TNF ligands. iv) They all played a role in the regulation of T-cell proliferation and T-cell mediated immune responses [and they all co-stimulated T-cell proliferation –[2008] RPC 29 , para 65]. v) Some of the ligands played a role in the regulation of B-cell proliferation and antibody secretion and some took part in T-celldependent regulation of B-cells. vi) Some of the ligands had an ability to induce cell death by necrosis or apoptosis. vii) TNF-α and TNF-ß were functionally linked as primary mediators of immune regulation and inflammatory response. viii) It had been suggested that various ligands were associated with a very wide range of particular disease states …. But no disease had been identified in which all the ligands were involved. ix) TNF-α was the only ligand shown to have a therapeutic application; that being for the treatment of rheumatoid arthritis through the use of a specific monoclonal antibody. …”
“72. [I]t was appreciated that further studies were both needed and desirable to identify further ligands in the TNF superfamily and, in relation to each ligand, to seek to identify its unique and redundant biological functions. There was undoubtedly an incentive to do so, because of their apparent roles in the regulation of the immune system and inflammatory response, their possible involvement in various different diseases and so also, in due course, their potential as therapeutic agents. The rewards were potentially very great. … 74 … [T]he reality [was] that pharmaceutical companies and academic institutions were indeed looking for further members of the TNF ligand and receptor superfamilies and seeking to elucidate their various biological functions and roles in disease states, ultimately with a view to developing a therapeutic or diagnostic product, if possible.”
“11. … [T]he application does not explicitly disclose the specific nature and the possible significance of [the] suggested roles for BDP1. … [T]he application stops short of suggesting, let alone identifying, an anti-cancer activity for BDP1 or a therapeutic use of BDP1 as a tumour-suppressor agent. There is no evidence as to whether BDP1 plays a passive role … or an active role in cancer. ... 12. Nor can the identification of BDP1 as a PTP-PEST be taken as any clear indication of its function or use, as the prior art does not attribute clear functions to PTP-PESTS as a class. …”
“21. … [A]lthough the present application describes a product (a polypeptide), means and methods for making it, and its prospective use thereof for basic science activities, it identifies no practical way of exploiting it in at least one field of industrial activity. In this respect, it is considered that a vague and speculative indication of possible objectives that might or might not be achievable by carrying out further research with the tool as described is not sufficient for fulfilment of the requirement of industrial applicability. The purpose of granting a patent is not to reserve an unexplored field of research for an applicant. … 22. The present case is already on the [wrong] side of the borderline. … [T]he only practicable use suggested is to use what is claimed to find out more about the natural functions of what is claimed itself. This is not in itself an industrial application, but rather research undertaken either for its own sake or with the mere hope that some useful application will be identified.”
“[A]s a significant structural feature fails to be identical in TGF-9 and the members of the TGF-β superfamily, and no functional characterisation of TGF-9 is forthcoming in the application, it is concluded that the application does not sufficiently identify this factor as a member of this family i.e. that there is not enough evidence in the application to make at least plausible that a solution was found to the problem which was purportedly solved.”
“[T]he technical data provided in respect of the [claimed] polypeptides ... fall somewhat short of fulfilling them insofar as, as already above mentioned, there is no evidence available as to which ligands these polypeptides bind to. Yet, of course, each case has to be considered on its own merit …and it is important here to take into account the common general knowledge at the priority date as well as the then prevalent attitude of the person skilled in the art as it may be inferred from the documents illustrating this common general knowledge.”
“chemokines were already known as mediators of the inflammatory response, a role which most of them were thought to play, in particular, through … a biological interaction of the chemokines with the cells which they attract which involves binding to the receptors present on the cell surface. Thus, the skilled person would understand that any role of a given chemokine was reflected in its receptor.”
“It is clear … that chemokines as a family were considered not only to be interesting in fundamental research but also as important for the pharmaceutical industry irrespective of whether or not their role had been clearly defined. It follows that their receptors must have been considered equally important since the mode of action of chemokines is through their receptors. It is, thus, reasonable to conclude that the [claimed polypeptides] which exhibit the characteristics of receptors of members of the PF4A family of cytokines would have been regarded as important to the pharmaceutical industry, i.e. that industrial applicability may be acknowledged.”
“21. In the present case, based on computer-assisted sequence homology studies and on tissue distribution studies, the Zcytor1 receptor was identified in the application as a putative member of the hematopoietin receptor family and it was assigned a role in proliferation, differentiation and/or activation of immune cells and thus a possible role for its ligands in therapeutic conditions associated with the functioning of the immune system. Admittedly, no experimental evidence for the suggested role of the receptor and/or its ligands is made available in the application. Later evidence, however, confirmed this sort of ‘educated guess’, which the examining division considered to be - in its own words - ‘reasonably credible’. 22. The fact that the putative function of the Zcytor1 receptor was assigned in the examples based on computer-assisted methods, rather than on the basis of traditional wet-lab techniques, does not mean that it has to be automatically disregarded or excluded from a careful and critical examination. … [The] probative value [of such examples] has to be examined on a case-by-case basis regarding the nature of the invention and the prior art relating thereto. Such methods of analysis are increasingly becoming an integral part of scientific investigations and can often allow plausible conclusions to be made regarding the function of a product before it is actually tested.”
“It might well be possible that members of a structurally related family have, notwithstanding their related structure, a different activity and function. However, there is no reference to the prior art in the decision under appeal which supports such a case in the hematopoietin receptor family. In fact, from the prior art cited in the application and concerned with this family of receptors …, it may be derived that, although none of these members are precisely interchangeable in terms of their biological action, there is considerable redundancy of action as well as an ability to elicit, under certain conditions, similar biological responses. Even more important is the fact that this prior art does not cast significant or serious doubts on the suggested role of the Zcytor1 receptor. Thus, the assumption (or ‘educated guess’) made in the patent application is plausible.”
“29. … The function of a protein (and thus of the nucleic acid encoding it) can be seen at different levels. These include: (i) the biochemical activity of the protein …, i.e. its molecular function; (ii) the function of the protein in cellular processes …, i.e. its cellular function; and (iii) the influence of those cellular processes within a multicellular organism, …. this being its biological function in a broad sense. … 30. The elucidation of one of these particular levels of function might result, under certain conditions, in a straightforward industrial application, even though the other levels of activity remain completely unknown or only partially characterized. … For the purpose of Article 57 …, none of these levels is more fundamental … than the other ones … . 31. In the present case, the suggested role of [Zcytor1] corresponds to the level of the biological function and the practical applications or the concrete technical benefits derived therefrom are clearly disclosed in the present application, namely the stimulation of cellmediated immunity and of lymphocyte proliferation by agonist ligands of Zcytor1 and the suppression of the immune system by antagonists of the Zcytor1 receptor … . Although the details of the biochemical activity and the cellular function of the Zcytor1 receptor have not been elucidated in the application, the (therapeutic) treatments directly derivable from the biological function identified by the computer-assisted method cannot be considered to be so ‘vaguely defined’ that they do not suggest any therapeutic or diagnostic use. On the contrary, the treatments referred to in the application are specifically in relation to the function plausibly attributed to the molecule, and are in the areas of rheumatoid arthritis, multiple sclerosis, diabetes mellitus, etc.”
“The sequence information provided in the application with respect to the presence in IL-174 of the characteristic cysteine spacing of the IL-17 cytokine family makes it plausible that [the claimed] polypeptide may belong to this family and have biological activities similar to those of the other family members known at the filing date, in particular CTLA-8. This is confirmed by post-published evidence filed by the appellant.”
“231. In this case I am quite satisfied that the skilled person would consider the Patent does not of itself identify any industrial application other than by way of speculation. ... [I]t contains an astonishing range of diseases and conditions which Neutrokine-α and antibodies to Neutrokine-α may be used to diagnose and treat and there is no data of any kind to support the claims made. The skilled person would consider it totally far-fetched that Neutrokine-α could be used in relation to them all and … would be driven to the conclusion that the authors had no clear idea what the activities of the protein were and so included every possibility. To have included such a range of applications was no better than to have included none at all. 232. But that is not the end of the matter because the disclosure must be considered in the light of the common general knowledge …. The skilled person would have known that TNF was involved as a primary mediator in immune regulation and the inflammatory response and had an involvement in a wide range of diseases as septic shock, rheumatoid arthritis, inflammatory bowel disease, tissue rejection, HIV infection, and some adverse drug reactions. He would have known that all the members of the TNF ligand superfamily identified hitherto were expressed by T-cells and played a role in the regulation of T-cell proliferation and T-cell mediated responses. Further, … the skilled person would anticipate that the activities of Neutrokine-α might relate to T-cells and, in particular, be expressed on T-cells and be a co-stimulant of B-cell production; that it might play a role in the immune response and in the control of tumours and malignant disease; that it might have an effect on B-cell proliferation … . 233. On the other hand, the skilled person would have also known that the members of the family had pleiotropic actions; that some of those activities were unique to particular TNF ligands and others were shared by some or all the other TNF ligands and that no disease had been identified in which they were all involved. Moreover, … the therapeutic application of TNF-α monoclonal antibody for the treatment of rheumatoid arthritis was believed to operate by interrupting the cytokine cascade and by controlling the recruitment and trafficking of blood cells to the joint – a rather specific activity.”
“[T]hey reveal the importance of the identification of the tissues where [it] is expressed, the tissues where it acts, the nature of its biological activity and how that profile varies in any particular disease state. However, no data is provided to support these claims. Further, … the variety of conditions for which the described method is said to be useful [is] puzzlingly wide and … the method itself impossible to operate in the absence of any information as to the standard level of Neutrokine-α expressed in each of these tissues in normal conditions.”
“Neutrokine-α has now been shown to have an important role in the development of autoimmune disease and B-cell cancers; but, at the same time, much of its biology remains unclear and is the subject of continuing study by many different research centres. In my judgment the nature and extent of all this research work, the limited conclusions ultimately drawn and the amount of work that remains to be done point strongly to the conclusion that the therapeutic and diagnostic applications suggested in the Patent were indeed speculative.”
“230. I accept that the contribution made by HGS was to find Neutrokine-α and to identify it as a member of the TNF ligand superfamily. However it is clear from the cases to which I have referred that simply identifying a protein is not necessarily sufficient to confer industrial utility upon it. … It may be sufficient if the identification of the protein will immediately suggest a practical application, such as was the case with insulin, human growth hormone and erythropoietin. But if the function of the protein is not known or is incompletely understood and if no disease has been attributed to a deficiency or excess of it, then the position may well be different. In these cases the industrial utility must be identified in some other way. … 234. Does [the] common general knowledge, taken as a whole, disclose a practical way of exploiting Neutrokine-α? Or does it provide a sound and concrete basis for recognising that Neutrokine-α could lead to practical application in industry? In my judgment it does not. The fact that Neutrokine-α might be expected to play a role in regulating the activities of B-cells and T-cells and play an unspecified role in regulating the immune and inflammatory response did not reveal how it could be used to solve any particular problem. Neither the Patent nor the common general knowledge identified any disease or condition which Neutrokine-α could be used to diagnose or treat. Its functions were, at best, a matter of expectation and then at far too high a level of generality to constitute a sound or concrete basis for anything except a research project. 235. I believe this conclusion is confirmed by the activities of those in the pharmaceutical industry in the years following the filing of the application. HGS, Lilly and Biogen (and possibly others too) carried out research programmes to try and find out where Neutrokine-α was expressed, where its receptors were expressed and what its activities appeared to be. They carried out in vitro assays and animal studies and determined that it appeared to have an activity in relation to B lymphocytes with a particular biological profile. On the basis of this work they recognised that it was an important therapeutic target – some two to three years after the application for the Patent had been filed. It is significant that in so doing they considered that its utility might lie in the treatment of B-cell disorders of particular kinds.”
“22. As pointed out in T 870/04, [paras 5 and 6], in many cases the allocation of a newly found protein to a known protein family with known activities suffices to assign a specific function to the protein because normally the members of the family share a specific function. This may be a well-characterized and perfectly understood function which provides in a straightforward manner enough support for industrial applicability. In such cases, the ‘immediate concrete benefit’ is manifest. In other cases, where the members of a protein family have different, pleiotropic effects which may even be opposite and neither completely characterized nor understood, no effect can be assigned to a new member without relying on some experimental data. Between these two extreme situations, a variety of other situations may arise for which a detailed examination of all the facts may be required. Indeed, this is the case for the TNF ligand superfamily.”
“A European patent takes effect as a bundle of national patents over which the national courts have jurisdiction. It is therefore inevitable that they will occasionally give inconsistent decisions about the same patent. Sometimes this is because the evidence is different. In most continental jurisdictions, including the [EPO], cross-examination is limited or unknown. Sometimes one is dealing with questions of degree over which judges may legitimately differ. Obviousness is often in this category. But when the question is one of principle, it is desirable that so far as possible there should be uniformity in the way the national courts and the EPO interpret the [EPC].”
“European patents shall be granted for any inventions, in all fields of technology, provided that they are new, involve an inventive step and are susceptible of industrial application.”
“An invention shall be considered as susceptible of industrial application if it can be made or used in any kind of industry, including agriculture.”
“Such methods of analysis are increasingly becoming an integral part of scientific investigations and can often allow plausible conclusions to be made regarding the function of a product before it is actually tested.”
“It is clear from these authorities that discovering a nucleotide sequence encoding for a human protein and being able to show that the protein concerned has some common homology with known proteins (ie is a member of a family) may satisfy article 57. But whether it does or not is case dependent and in particular depends upon how well established the functions of the other members of the family are. To say, ‘my new protein is similar to a known family of proteins’ is not all that helpful in indicating a possible use if the function of that family is itself poorly understood at best.”
“It is not good enough to say this protein or any antibody to it probably has a pharmaceutical use. Such a statement is indeed plausible, but is of no real practical use. You are left to find out what that use is.”
“So the Judge addressed the crucial question: is it enough to make the invention ‘susceptible of industrial application’ to tell the skilled reader that Neutrokine-α is ‘structurally similar to TNF and related cytokines and is believed to have similar biological effects and activities’? That depends on what was known about the biological effects and activities of the known members of the superfamily. Each of the postulated uses of Neutrokine-α or its antagonists was possible in the sense that one could not rule that out as a matter of science based on what was known about other superfamily members. So in one sense each was ‘plausible’, even though all of them collectively were not and indeed some contradicted others so both could not be true. But that is miles away from being able to say that any particular use was plausible in the sense of being taken, by the reader, to be reasonably so. In reality one was faced with a research programme to see which, if any, of the possible uses of the Neutrokine-α or its antagonists was real.”
“This is because the skilled person realises that the description of the structure of Neutrokine-α, its structural assignment of the family of TNF ligands, and the reports about its tissue distribution and activity on leucocytes, are the first essential steps at the onset of research work on the newly found TNF ligand superfamily member. In view of the known broad range of possible activities of such a molecule, the skilled person is aware of the fact that the full elucidation of all properties requires further investigations which will gradually reveal them. In this context, the skilled person regards the long listing of possible actions of Neutrokine-α and of medical conditions in which it might take part as the enumeration or generalisation of the properties of the members of the TNF ligand superfamily. This is seen as the frame in which the newly found molecule has to be placed as one could prima facie have a reasonable expectation that most of them could in fact be present.”
“In the board’s judgment, the tissue distribution of Neutrokine-α mRNA disclosed in the patent-in suit, in particular the expression of Neutrokine-α mRNA in B-cell and T-cell lymphomas (cf paragraph [0032]), provides in itself in the context of the disclosure a valid basis for an industrial application. The presence of Neutrokine-α in these lymphomas, which is also confirmed by post-published evidence on file (cf inter alia document D126), may be used to develop appropriate means and methods for their diagnosis and treatment based on the disclosure of the patent-in-suit.”
“Does that common general knowledge, taken as a whole, disclose a practical way of exploiting Neutrokine-α? Or does it provide a sound and concrete basis for recognising that Neutrokine-α could lead to practical application in industry? In my judgment it does not. The fact that Neutrokine-α might be expected to play a role in regulating the activities of B cells and T cells and play an unspecified role in regulating the immune and inflammatory response did not reveal how it could be used to solve any particular problem. Neither the Patent nor the common general knowledge identified any disease or condition which Neutrokine-α could be used to diagnose or treat. Its functions were, at best, a matter of expectation and then at far too high a level of generality to constitute a sound or concrete basis for anything except a research project.”
“The conclusions on obviousness in the proceedings below represented the outcome of a judicial evaluation of a mass of evidence. In the assessment of that evidence, and in the conclusion to be derived from it, the primary judge and the Full Court were better placed to perform the function of fact-finding than this Court is. Unless some error is shown in the application of the relevant law, it would be a rare step for this Court to condescend to re-evaluate such a factual conclusion, reached by concurrent decisions at two levels of the judicial hierarchy.”
“Any exposition of judicial reasons explaining such factual findings is ‘inherently an incomplete statement of the impression which was made upon [the judge] by the primary evidence.’ Judges having replaced juries in such matters in Australia, and having entangled themselves in a web of horrible verbal formulae, must do their best to explain their conclusions where, in the past, juries simply announced their verdicts.”