W 0006/94 11-04-1995

1. The protest is admissible.

2. According to Rule 13.1 PCT, the international patent application shall relate to one invention only or to a group of inventions so linked as to form a single inventive concept. If the ISA considers that the claims lack this unity, it is empowered, under Article 17(3)(a) PCT, to invite the Applicant to pay additional fees.

3. Lack of unity may be directly evident "a priori", i.e. before considering the claims in relation to any prior art. Alternatively, having regard to decision G 1/89 of the Enlarged Board of Appeal, dated 2 May 1990 (OJ EPO 1991, 155), the ISA is also empowered to raise an objection a posteriori, i.e. after having taken the prior art into consideration. This practice is laid down in the PCT Search Guidelines, Chapter VII-9 (PCT Gazette 30/1992, 10425) which are the basis for a uniform practice of all International Searching Authorities. The Enlarged Board of Appeal indicated that this represented only a provisional opinion on novelty and inventive step which was in no way binding upon the authorities subsequently responsible for the substantive examination of the application (point 8.1 of the Reasons for the decision).

However, the Enlarged Board in point 8.2 of the Reasons mentioned that such invitation to pay additional fees should always be made "with a view to giving the Applicant fair treatment" and should only be made in clear cases.

4. Since the present examination by the Board according to Rule 40.2(c) PCT relates to the protest against the invitation by the ISA to pay additional search fees, said invitation being based on the claims as originally filed, and there is no opportunity for the Applicant to amend the claims in the international phase until he has received the complete international search report [Article 19(1) PCT], there is no room for taking into account any later amendments of these claims (cf., for example, W 3/94 of 15 December 1994, to be published in the OJ EPO, in particular point 3 of the Reasons). Thus, the present decision is based on the claims as originally filed.

5. According to Rule 13.3 PCT, the determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim.

6. The present application relates to methods and means for the activation of receptors with tyrosine kinase activity, cytokine receptors, and members of the nerve growth factor receptor superfamily. For the activation of these three groups of receptors, Claim 1 proposes a method which is essentially based on the recognition that activation can be achieved by mediation of dimer formation through a dimeric ligand. The claimed method consists in contacting receptors selected from the quoted groups with a conjugate that comprises the direct fusion of a first ligand and a second ligand, i.e. a dimeric ligand, said conjugate being capable of binding to first and second receptors which are capable of oligomerisation.

However, the concept underlying the claimed method, namely the activation of certain receptors by mediation of dimer formation through a dimeric ligand, is known from prior art document (1). As correctly observed by the ISA, this document discloses that the activation by oligomerisation of receptors with tyrosine kinase activity, in particular of subclass III receptors, may occur by mediation of dimer formation through a dimeric ligand, in particular through a heterodimeric ligand such as PDGF-AB (see page 203, right-hand column, paragraphs 2 and 3 and Figure 2).

Therefore, Claim 1 which concerns as one alternative receptors with tyrosine kinase activity cannot considered to be novel having regard to document (1). Novelty is lacking also in respect of Claim 13 which concerns only receptors with tyrosine kinase activity. In view of this objection, the question arises whether the subject-matter of the application is based on a single general inventive concept.

7. In support of unity of invention, the Applicant puts forward arguments based essentially on the fact that Claim 1 (and Claim 13) as amended exclude(s) from its (their) ambit the disclosure of document (1). The Applicant maintains that the "single inventive concept" lies in the finding that the dimer-induced activation of receptors is generally applicable to all receptors of the indicated families.

However, as already indicated (see point 4, above), the proposed amendments have to be disregarded.

8. It is general knowledge that a common feature of many receptors is that they need to be oligomerised to become active or that their activity is enhanced by oligomerisation [in this respect, see pages 1 to 5 of the present application and page 203 of document (1)]. It is also known that oligomerisation can be induced by monomeric ligands or by bivalent ligands (ibid.). Document (1), in particular, illustrates this concept in respect of receptors with tyrosine kinase activity (see point 6, second paragraph, above).

In the light of document (1), the technical problem to be solved can be seen in the provision of an alternative method for the activation of receptors selected from the groups of receptors with tyrosine kinase activity, cytokine receptors, and members of the nerve growth factor receptor superfamily.

As a solution thereto, Claim 1 proposes for the groups of receptors in question an activation method which is based on the approach of the dimeric ligand-induced activation. This would constitute a priori the "special technical feature" providing the link between the claimed alternatives in the sense of Rule 13.2 PCT. However, in the present situation, due to the fact that the said feature is known from document (1) in which for the receptors with tyrosine kinase activity an identical activation method is disclosed (cf. novelty objection in point 6, above), the alternatives within Claim 1 are left a posteriori without a common inventive concept.

9. It should, therefore, be investigated whether another "special technical feature" in the sense of Rule 13.2 is available which could link the three alternatives so as to form a single general inventive concept. In this respect it is observed that the finding that a known concept underlying a known method applicable to a given group of receptors (here: receptors with tyrosine kinase activity) can also be applied in an analogous manner to other groups of receptors (here: cytokine receptors and nerve growth factor receptors) per se is not sufficient to achieve unity of invention between the resulting analogous methods, if no further "special technical feature" is available for establishing a technical relationship between them.

The sole feature which defines for each of the separate alternatives within Claim 1 the contribution over the prior art is the reference to the group of receptors to which the approach known from document (1) is applied. This, however, cannot be considered to be a "special technical feature" sufficient to form a single general inventive concept in the sense of Rule 13.2 PCT because of the marked structural and functional differences between the three groups of receptors. Failing such feature, the problem of providing an alternative activation method becomes a distinct - although analogous - problem for each group of receptors which is solved in each case by a separate - although analogous - way. Nor can any of the features referred to in the dependent claims, such as, for example, the fact that the first and second ligands are variants of native ligands (cf. Claim 2) or that the first and second ligands are variants of the same native ligand (cf. Claim 3), be considered as a "special technical feature" sufficient to establish an inventive link between the claimed alternatives in the sense of Rule 13.2 PCT. In fact, being recognised in the prior art [see document (1)] that the activation of receptors by oligomerisation can be achieved by means of binding of a native homo- and heterodimeric ligand, the mere reference to the use of variants of such ligands is not enough to establish a technical relationship between the claimed alternatives so as to reconstitute a single general inventive concept, especially in view of the marked structural and functional differences between the three groups of receptors.

10. For the foregoing reasons, in the Board's judgement, the international application does not comply with the requirement of Rule 13.1 PCT and the invitation to pay the additional fees was justified.