T 2321/13 - Pathway associated disease unclear

Key points

• In this opposition appeal, claim 1 of the Main Request is amended by taking features from the description. These features are examined for clarity. Claim 1 is a second medical use claim for an anti HER3 antibody or use in the treatment of a hyperproliferative disease (e.g. cancer). The disease is further specified in the claim as being "MAP kinase pathway associated" The Board finds this feature (and also another feature taken from the description) to be unclear.
• The Board, on the principle: "Article 84, second sentence, EPC requires the claims to be clear, which serves the purpose of ensuring that the public is not left in any doubt as to the subject-matter covered by a claim. From this principle of legal certainty, it follows that there is a lack of clarity if a claim does not allow this distinction to be made. [The Board finds] that the definition of the "forbidden area" of a claim should be considered in relation to Article 84 EPC, and not to Article 54 EPC or Article 56 EPC as suggested by the [patentee]."
•  " [T]he board notes that the [patentee] does not dispute that the MAP kinase pathway is one of many possible pathways which may cause a hyperproliferative disease. Therefore, in order to determine whether or not a hyperproliferative disease is such a disease as cited in the claim the skilled person needs to know or be taught under what circumstances the hyperproliferative disease is to be considered "associated" with the MAP kinase pathway or not. []"
• "  The board notes that the term "associated" itself provides no guidance in this respect. Also the specification of the patent does not provide any instructions regarding circumstances in which a particular hyperproliferative disease is to be considered "associated" with the MAP kinase pathway. " " a diagnostic assay which would allow a skilled person to discriminate hyperproliferative diseases that are "associated" with the MAP kinase pathway from those that are not is not disclosed in the patent either."
• Also the [patentee]'s further argument that the term "MAP kinase pathway associated hyperproliferative disease" has a clear meaning in that it indicates that "the therapy includes the inhibition of the MAP kinase pathway", fails in the opinion of the board as it amounts to an attempt to define the hyperproliferative diseases in terms of the means by which they can be treated, i.e. uses a circular definition.
• Hence, the feature is unclear.
• I believe the features of the kind at issue (pathway associated disease) are not uncommon in the medical field. Perhaps their clarity will be examined more in-depth in the future. 

EPO T 2321/13 -  link

Claim 1 of the main request reads as follows:

"1. Use of an inhibitor of HER3 kinase activity for the manufacture of a medicament for the diagnosis, prevention or treatment of a MAP kinase pathway associated hyperproliferative disease associated with HER3 kinase activity directly phosphorylating PYK2, wherein the inhibitor is an anti HER3 antibody or a fragment thereof, said anti HER3 antibody or a fragment thereof being capable of inhibiting HER3 kinase activity."

Reasons for the Decision

Clarity (Article 84 EPC) - claim 1

5. The claim has been amended vis-à-vis claim 1 as granted and it is not disputed that the features "a MAP kinase pathway associated" and "kinase activity directly phosphorylating PYK2" derive from the description of the application as filed and may thus be examined for compliance with the requirements of Article 84 EPC (see also decision G 3/14, OJ EPO 2015, 102, Reasons, point 87).

6. Article 84, second sentence, EPC requires the claims to be clear, which serves the purpose of ensuring that the public is not left in any doubt as to the subject-matter covered by a claim. From this principle of legal certainty, it follows that there is a lack of clarity if a claim does not allow this distinction to be made. In this respect the board thus agrees with the finding of decision T 1811/13 of 8 November 2016 (see Reasons, point 5.1) that the definition of the "forbidden area" of a claim should be considered in relation to Article 84 EPC, and not to Article 54 EPC or Article 56 EPC as suggested by the appellant.

7. The claim is a second medical use claim which defines the condition to be treated as "a MAP kinase pathway associated hyperproliferative disease associated with HER3 kinase activity directly phosphorylating PYK2" (see section IV). Thus, the condition to be treated is not defined in terms of a specifically defined disease, but in functional terms with two requirements, namely that the hyperproliferative disorder is associated with (i) the MAP kinase [mitogen-activated protein kinase] pathway and (ii) HER3 kinase activity directly phosphorylating PYK2 [Protein-tyrosine kinase 2-beta]. The question is thus whether or not the skilled person would be in a position to determine without any doubt which disease or group of diseases falls within this functional definition and which do not.

8. As regards requirement (i), the board notes that the appellant does not dispute that the MAP kinase pathway is one of many possible pathways which may cause a hyperproliferative disease. Therefore, in order to determine whether or not a hyperproliferative disease is such a disease as cited in the claim the skilled person needs to know or be taught under what circumstances the hyperproliferative disease is to be considered "associated" with the MAP kinase pathway or not.

9. The board notes that the term "associated" itself provides no guidance in this respect. Also the specification of the patent does not provide any instructions regarding circumstances in which a particular hyperproliferative disease is to be considered "associated" with the MAP kinase pathway or how the skilled person can determine whether or not a particular hyperproliferative disease is "associated" with the MAP kinase pathway. It is thus uncertain whether, for example, a hyperproliferative disease in which the MAP kinase pathway was active but where the hyperproliferative disease is then driven by processes outside the MAP kinase pathway, is to be considered "associated" with the MAP kinase pathway or not.

10. Furthermore, a diagnostic assay which would allow a skilled person to discriminate hyperproliferative diseases that are "associated" with the MAP kinase pathway from those that are not is not disclosed in the patent either.

11. In this context, the appellant's argument that the skilled person would have a detailed knowledge of the well-characterised MAP kinase pathway is not persuasive. It ignores in fact that this knowledge does not help the skilled person to understand which hyperproliferative diseases are to be considered "associated" with the MAP kinase signalling pathway, and which are not.

12. Also the appellant's further argument that the term "MAP kinase pathway associated hyperproliferative disease" has a clear meaning in that it indicates that "the therapy includes the inhibition of the MAP kinase pathway", fails in the opinion of the board as it amounts to an attempt to define the hyperproliferative diseases in terms of the means by which they can be treated, i.e. uses a circular definition.

13. Regarding requirement (ii) (see point 7), and similar to the situation for the first requirement, neither the claim nor the specification of the patent provide any guidance for the skilled person as to which assay can be used to determine whether any given MAP kinase pathway associated hyperproliferative disease is also associated with HER3 "kinase activity directly phosphorylating PYK2".

14. The board has furthermore not seen any evidence that the skilled person, as a matter of common general knowledge, would know which hyperproliferative diseases are "associated" with the MAP kinase pathway and associated with HER3 "kinase activity directly phosphorylating PYK2" or any assays that could be used to verify this. Indeed, the signaling pathway leading from HER3 kinase activity to the MAP kinase pathway was not known in the prior art and it would appear that it is in fact the patent which is the first disclosure of HER3 showing kinase activity and that native HER3 protein is capable of directly phosphorylating PYK2 and thereby stimulating the mitogenic activity mediated by the MAP kinase pathway (see paragraph [0024] of the patent).

15. The board notes that in the relevant example of the patent, HER2 and HER3 were over-expressed in HEK293 fibroblasts and stimulated with heregulin. Receptor-immunocomplexes were then subjected to in vitro kinase assays using a GST-fusion protein of the C-terminal region of PYK2 (GST-PYK2-CT) as substrate (see paragraph [0052], Figure 4c). However, in the board's opinion, the biochemical in vitro kinase assays used in the patent for determining that HER3 directly phosphorylates PYK2 are manifestly unsuitable for use as diagnostic assays for measuring HER3 kinase activity directly phosphorylating PYK2, in e.g. a tissue sample where PYK2 is subject to phosphorylation by several kinases - not only HER3. The appellant has also not argued otherwise. Moreover, the patent also fails to provide instructions on how to design an assay that would allow the skilled person to discriminate, in such a tissue sample, between HER3 directly phosphorylating PYK2 from HER3 indirectly phosphorylating PYK2 and any other kinase phosphorylating PYK2, e.g. HER2 phosphorylating PYK2.

16. Therefore, as the patent provides no guidance to the skilled person to specifically assay for HER3 directly phosphorylating PYK2, the appellant's arguments, which rely on "HER3-PYK2 signalling" as the diagnostic criterion to be applied by the skilled person for determining whether or not a hyperproliferative disease was a MAP kinase pathway associated hyperproliferative disease, must also fail.

17. The board concludes from the above that the use of the term "associated" in the functional definition of the hyperproliferative diseases in relation to the MAP kinase pathway and the lack of any guidance in the form of experimental tests or any testable criteria, in the patent documents and the common general knowledge, which would allow the skilled person to recognise which conditions fall within the functional definition and accordingly within the scope of the claim, leads to a lack of clarity of the claim. The board notes that this finding is in line with the established jurisprudence of the Boards of Appeal (see decision T 241/95, OJ EPO 2001, 103, Reasons, point 3.1.1).

18. The board also notes that the board's finding that the lack of clarity of the claim arises from the use of the term "associated" and the lack of guidance regarding an assay which makes it possible to determine unambiguously whether or not a hyperproliferative disease falls within the functional definition of the claim or not, would also apply when taking into account the appellant's argument that the terms "MAP kinase pathway", "HER3" and "PYK2" had a clearly defined meaning for the skilled person.

19. Consequently, the amendments in claim 1 of the main request result in a lack of clarity (Article 84 EPC).