Wednesday, 6 January 2010

T 18/09 – Skilful Cherry-Picking

The present decision also dwells on an EPC requirement that is not discussed very often: industrial applicability. Whereas this requirement is almost always fulfilled in the field of mechanics, things are less clear-cut in biotechnology.

[...] Both parties agreed, as does the board, that on the basis of its structural properties, Neutrokine-α has been correctly identified in the patent-in-suit as a new member of the TNF ligand superfamily. No reasons have been put forward to dispute this conclusion. A large body of post-published evidence on file supports this finding. The question arises under A 57 whether this in itself suffices to suggest a practical way to exploit the claimed invention which is centred on Neutrokine-α, thereby providing an “immediate concrete benefit” (cf. T 898/05). [21]

As pointed out in T 870/04 [5-6], 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. [22]

As known in the art and acknowledged in the patent-in-suit, all members of the TNF ligand superfamily are known to participate in the regulation of (immune) cell proliferation, activation, and differentiation, and are involved in various medical conditions. […] In view of the assignment of Neutrokine-α to the family, the skilled person expects it to display this common feature, the relevant question here being whether anything in the patent specification contradicts this expectation. [23]

The patent specification, besides providing the undisputed structural identification of Neutrokine-α as a member of the TNF ligand superfamily, also provides some further relevant technical data which are fully in line with the expected properties of a member of that superfamily. […] In the light of the common general knowledge of the TNF ligand superfamily and its properties, no serious doubts can be cast on this explicit additional information. Nor can this information be taken as a mere theoretical or purely hypothetical assumption. First of all, it is plausible and, secondly, there is ample post-published evidence on file confirming both the presence of Neutrokine-α on activated T-cells and its ability to co-stimulate T-cell proliferation. [24]

The [opponent] has nevertheless argued that, in view of the numerous contradictory statements and of the broad range of conditions and diseases referred to in the patent-in-suit, the skilled person would have disregarded such information as constituting only hypothetical assumptions, or speculations with no actual significant relevance. [25]

The board cannot agree with this view. When reading the patent specification, a skilled person would distinguish the positive technical information such as that mentioned above from other allegedly contradictory and broad statements found in the patent-in-suit, such as - in the [opponent’s] view - the wide range of activities and conditions for which Neutrokine-α could be useful. This is because the skilled person realises that the description of the structure of Neutrokine-α, its structural assignment to the family of TNF ligands, and the reports about its tissue distribution and activity on leukocytes, 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. At any rate, none of these specific conditions and/or activities is actually claimed and the language used in the specification is in many instances quite prudent. [26]

Filing patents with such long lists of conditions and activities and subsequently relying on the few which have been confirmed or demonstrated is what the [opponent] criticised as a “boiler-plate” and “cherry-picking” practice. It can certainly be argued whether or not such a practice is proper but it is significant that the [opponent] acknowledged, albeit in the form of criticism of the [patentee], that it is a practice used by patentees, and the [patentee] pointed to document D150 (the [opponent’s] own US patent). Thus, the skilled person is acquainted with this practice and able to differentiate mere “boiler-plate” from positive technical information. In the present case, the description of the patent delivers sufficient technical information, namely the effect of Neutrokine-α on T-cells and the tissue distribution of Neutrokine-α mRNA, to satisfy the requirement of disclosing the nature and purpose of the invention and how it can be used in industrial practice. [27]

As regards the effect on T-cells, the [opponent] argued that, in view of the technical difficulties involved in measuring the co-stimulation of T-cells by Neutrokine-α and in the absence of any detailed experimental information on the activities of Neutrokine-α listed in the patent-in-suit, the skilled person would not have been able to reproduce them without the undue burden of undertaking a research programme. Moreover, in its view, no industrial application can be directly derived from a mere co-stimulation of T-cells. [28]

The board cannot accept this line of argument. Firstly, in the light of the great number of documents concerned with known members of the TNF ligand superfamily which – as explicitly acknowledged in the patent-in-suit – disclose standard assays for measuring their activities and effects on (immune) cells, no particular effort would be required to verify the co-stimulation of T-cells by Neutrokine-α. Even though a few contradictory results are reported in post-published documents on file, there is also a convincing body of post-published evidence showing that, using standard assays, Neutrokine-α activity is indeed present on T-cells, in particular on mature T-cells at all stages of differentiation.

Secondly, the reference in the patent-in-suit to the presence of Neutrokine-α activity in lymphocytes would inevitably prompt the skilled person to look for that activity in all types of lymphocytes, not only in T-lymphocytes but also in B-lymphocytes. There is post-published evidence on file showing that Neutrokine-α activity in B-lymphocytes could be easily measured with standard assays.

Thirdly, and contrary to the [opponent’s] view, these activities of Neutrokine-α may represent a valid basis for a possible industrial application. In particular, the inhibition of co-stimulation and/or proliferation of lymphocytes might be prima facie of relevance for certain immune diseases. [29]

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, 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, may be used to develop appropriate means and methods for their diagnosis and treatment based on the disclosure of the patent-in-suit. [30]

The [opponent], relying on alleged technical problems, argued that no industrial application could be derived from that information. In particular, reference was made to the absence of any quantitative information on the level of Neutrokine-α mRNA expression, the absence of any evidence showing the presence of Neutrokine-α on the surface of lymphoma cells, a lack of specificity arising from high levels of Neutrokine-α expression and presence in other non-cancerous tissues and the associated side-effects, the difficulties in producing therapeutic and neutralizing antibodies as well as the presence of several biologically relevant products derived from Neutrokine-α which are different from the claimed full-length Neutrokine-α and its extracellular domain [31]

Most of these allegations are more related to A 83 than to A 57 […]. In respect of A 83, established case law states that a patent may only be objected to for lack of sufficiency of disclosure if there are serious doubts, substantiated by verifiable facts (cf. T 19/90). It would not be justified and unfair to set a different standard of proof in respect of A 57. [32]

None of the [opponent’s] allegations has been substantiated by verifiable facts and thus, in the board’s view, they must be seen as unsupported assumptions. All the more so since the claims are commensurate with the level of the disclosure and are not directed to specific optimised (antibodies) products or related to specific optimised (diagnostic or therapeutic) assay conditions. Moreover, post-published evidence on file shows the production of anti-Neutrokine-α antibodies and their possible application for therapy and diagnosis purposes, confirming the plausibility of the disclosure of the patent-in-suit. [33]

Thus, in line with the principles developed in the case law of the Boards of Appeal, the board finds the patent-in-suit provides a concrete technical basis for the skilled person to recognise a practical exploitation of the claimed invention in industry. Thus, the requirements of A 57 are fulfilled. [34]

Whew! I'm almost finished with T 18/09!

To read the whole decision, click here.