T 2248/12 - Unity

Key points

• The Board notes, following established case law that " The assessment of unity of invention requires as a precondition the analysis of the technical problem or problems underlying the respective groups of inventions, because only then is it possible to decide whether or not the same or corresponding special technical features exist for the different embodiments under consideration" 
• In this examination appeal, the Board finds that: " The "special technical features" [] common to the three variants S96C, R170C and K179C are that (i) the residues present at the three positions in the native protein are substituted by a cysteine, (ii) the three positions lie outside of the receptor contact region [] and (iii) these positions display a high solvent accessibility. The technical effects resulting from these features are that the three variants are readily PEGylated, and yet substantially retain their biological activity []. Consequently, the board considers that the technical problem underlying the three variants (see point 4 above) is the provision of Apo2L variants which are readily PEGylated and biologically active.
• As a note, this decision shows that, a rejection for lack of unity of invention requires an in-depth analysis of the patent application, not an analysis of the claims only.

EPO T 2248/12 -  link

Reasons for the Decision

Unity of invention (Article 82 EPC)

1. In the European grant procedure, the ultimate responsibility for establishing whether an application complies with the requirements of Article 82 EPC rests with the examining division, which has the duty to review the unity assessment made by the search division. The fact that the appellant has not paid further search fees does not prohibit this review (see e.g. decision T 631/97, headnote and points 3.6 to 3.8 and 3.9.2 of the Reasons).

2. Article 82 EPC states that "The European patent application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept".

The case law has established in this context that a "single general inventive concept" is present only when the concept underlying the invention is new and inventive (see Case Law of the Boards of Appeal, 7th edition 2013, II.B.4.2, page 291, third paragraph).

3. Rule 44(1) EPC further interprets the concept of unity of invention where a group of inventions is claimed. In such cases "the requirement of unity of invention under Article 82 EPC shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression "special technical features" shall mean those features which define a contribution which each of the claimed inventions as a whole makes over the prior art".

4. The assessment of unity of invention requires as a precondition the analysis of the technical problem or problems underlying the respective groups of inventions, because only then is it possible to decide whether or not the same or corresponding special technical features exist for the different embodiments under consideration (see Case Law of the Boards of Appeal, 7th Edition, II.B.4.1).

In the decision under appeal, the examining division concluded that the two claimed Apo2L variants R170C and K179C which were not covered by the Supplementary European Search Report (SESR) lacked unity of invention a posteriori in view of the disclosure of the closest prior art document D1 in combination with that of document D4 with regard to the variant S96C covered by the search report (see section IV above), because the concept, i.e. the "special technical features" linking the three variants, was not inventive. (Note added by the board: In the designation of the Apo2L variants, the number indicates the position of the amino acid in the Apo2L protein, the first letter indicates the amino acid at that position in the native protein and the last letter that in the variant. Moreover, in the standard one-letter abbreviation for amino acids, "C" stands for cysteine, "K" for lysine and "R" for arginine).

6. Document D1 discloses that the native cytokine Apo2L interacts with the two death receptors 4 (DR4) and 5 (DR5), thereby causing apoptosis of target cells, which recommends its use as a pharmaceutical compound (see page 4, lines 12 to 24). The document also reports on Apo2L variants with improved biological activity, including two having mutations in the positions cited in claim 1, i.e. 170 and 179 (see Table I).

7. The board notes that the claimed variants R170C and K179C differ from those disclosed in document D1 in that the native amino acid residue at each position is substituted by cysteine. The searched, but no longer claimed variant, S96C is not disclosed in this document.

The "special technical features" (see point 3 above) vis-à-vis the disclosure in document D1 common to the three variants S96C, R170C and K179C are that (i) the residues present at the three positions in the native protein are substituted by a cysteine, (ii) the three positions lie outside of the receptor contact region of Apo2L in a binding complex with DR5 and (iii) these positions display a high solvent accessibility. The technical effects resulting from these features are that the three variants are readily PEGylated, and yet substantially retain their biological activity, i.e. they bind to their receptors and induce apoptosis (see Table 1 on page 47 and page 50, third paragraph of the application as filed). Consequently, the board considers that the technical problem underlying the three variants (see point 4 above) is the provision of Apo2L variants which are readily PEGylated and biologically active.

9. Document D1 is not concerned with revealing positions in Apo2L characterised by a high solvent accessibility allowing a PEGylation which does not significantly interfere with the biological activity of the protein but rather with the identification of positions affecting trimer formation and stability of Apo2L. Consequently, a potential substitution of the native residues at these positions with cysteine is not derivable from the document.

10. Document D4 discloses the advantages of PEGylation for therapeutic proteins in general and also that the amino acid cysteine is one of the possible linking partners. The document further draws the skilled person's attention to the potential risk of loosing the biological activity of a protein when trying to improve its pharmacokinetics by conjugation to PEG and reports in this context that "[t]he same mechanism that prevents the approach of proteolytic enzymes or antibodies to PEGylated protein can also reject a substrate from the protein active site" (see page 411, left-hand column). However, suggestions as to how the skilled person could avoid or minimise such a risk for therapeutic proteins known to be involved in protein-protein interactions, let alone for Apo2L in particular, are not derivable from the document.

Therefore, neither the teaching of document D1 alone nor that of a combination of documents D1 and D4 discloses or suggests the common concept underlying the three variants under consideration, i.e. having modified cysteine residues at positions lying outside of the receptor contact region of Apo2L which concomitantly display high solvent accessibility and thereby allowing a ready conjugation to PEG without significantly reducing the biological activity of the proteins.

12. Thus, contrary to the examining division, the board arrives at the conclusion that the concept by which the three variants S96C, R170C and K179C are linked is new and inventive and is therefore to be considered as a "single general inventive concept" in accordance with Article 82 EPC. Hence, the three variants fulfil the requirements of unity of invention.

13. Accordingly, the subject-matter of claim 1 of the main request relating to the variants based on R170C and K179C fulfils the requirements of Article 82 EPC.

14. Moreover, although both claimed variants relate to unsearched subject-matter, both combine with the searched variant S96C to form a "single general inventive concept". Therefore, the requirements of

Rule 164(2) EPC and Rule 137(4) EPC 2000 are also met. (Note added by the board: The examining division erroneously referred to Rule 137(5) EPC 2010 in the decision under appeal. However, since the SESR had been drawn up in 2005, it is in fact Rule 137(4) EPC 2000 that applies).

15. The appeal is thus allowable.

Remittal (Article 111(1) EPC)

16. The board considers that in a case such as the present one, where the decision under appeal has dealt with

Article 82 EPC only, remittal to the first instance is the appropriate option. The board has therefore decided to exercise its discretion under Article 111(1) EPC and to remit the case to the examining division for further prosecution.

Order

For these reasons it is decided that:

The decision under appeal is set aside.

The case is remitted to the examining division for further prosecution.