T 0020/12 (Antibodies specific for beta-amyloid ends/INTELLECT NEUROSCIENCES) 15-04-2016

1. The appeal is admissible.

Main request - Article 100(c) EPC

2. The subject-matter of a European patent must not extend beyond the content of the application as filed. It is the established case law of the boards of appeal that amendments are permitted only within the limits of what the skilled person would derive directly and unambiguously, using common general knowledge, from the the application as filed.

3. Claim 1 relates to a recombinant antibody which is end-specific for the free N-terminus of an amyloid-beta peptide or the free C-terminus of an amyloid-beta peptide Abeta1-40, wherein the antibody does not bind to the amyloid-beta precursor protein (APP) from which said amyloid-beta peptide may be proteolytically derived.

xThe free N-terminus and the free C-terminus of the amyloid-beta peptide differ from the termini of the much longer amyloid-beta precursor protein (APP) (see paragraph [0002] and Figure 1 of the patent in suit).

4. It is undisputed that the feature that "the antibody does not bind to the amyloid-beta precursor protein from which said amyloid-beta peptide may be proteolytically derived" is not explicitly disclosed in the application as filed.

The appellant argued that this feature was directly and unambiguously derivable from features that were explicitly disclosed in the application as filed and that were synonymous and thus interchangeable with it.

4.1 The application as filed refers to DNA molecules containing a gene encoding a recombinant antibody molecule which "discriminates between an Abeta peptide and the beta-amyloid protein precursor from which it is proteolytically derived" (page 10, lines 8-10).

The board considers that said passage does not provide a basis for the feature in claim 1 that "the antibody does not bind to the amyloid-beta precursor protein from which said amyloid-beta peptide may be proteolytically derived". An antibody may discriminate between two different antigens by binding to one more strongly than to the other. This does not allow the conclusion that such an antibody does not bind to one of the antigens. Whilst the group of antibodies that discriminate between an Abeta peptide and APP may encompass a subgroup of antibodies which do not bind to APP, the specific reference to this subgroup of antibodies represents new technical information which is not directly and unambiguously derivable from said passage of the application as filed.

4.2 The application as filed further refers to DNA molecules containing a gene encoding a recombinant antibody molecule which is "end-specific for the N-terminus or the C-terminus of an Abeta peptide" (page 10, lines 5-8) and which "binds specifically to a terminus/end of an Abeta peptide" (page 10, lines 12-13).

As stated in decision T 189/01 of 15 June 2004, "specificity (...) is an expression of the high affinity of a given antibody for the antigen against which it has been raised". However, the term does not exclude the possibility that an antibody binds to peptides other than that against which it has been raised. Consequently, it cannot be directly and unambiguously derived from said passages on page 10 of the application as filed that the antibody does not bind to the APP.

In this context, the appellant has referred to documents D13 and D14, which are extracts from textbooks. Document D14 was published in 2006, well after the filing date of the patent in suit, and for document D13 the appellant has not provided evidence that it was available to the public before the filing date of the patent in suit. These documents are therefore not relevant with respect to the question of what was directly and unambiguously derivable from the application as filed at the filing date. In any case, the board's understanding of the term "specific" does not contradict the contents of these documents. Document D13 states that the "specificity determines the ability of the antibody to distinguish the immunogen from other antigens", and document D14 states that the "specificity of an antibody or antiserum is defined by the ability to discriminate between the antigen against which it was made (...) and any other antigen one might test". The ability to distinguish or discriminate between two different antigens does not however imply that the antibody "does not bind" to one of the antigens (see point 4.1 above).

4.3 Similarly, the term "selectivity" referred to in the application as filed (see page 13, lines 9-17; page 14, lines 29-37; page 15, lines 9-12) is a relative term which provides no basis for the feature that the antibody "does not bind" to the APP.

4.4 The application as filed further states that "an end-specific antibody is defined as an antibody which uniquely recognizes the free N-terminus or the free C-terminus of a peptide and which can further discriminate between the peptide and the precursor from which it is proteolytically derived" (page 12, lines 26-33).

The board takes the position that, in the context of said passage of the application as filed, the skilled person would understand the words "uniquely recognizes" as expressing that an end-specific antibody recognises the free N-terminus or the free C-terminus in a unique way, but not that the antibody "does not bind" to the APP.

Said passage refers to two features of the end-specific antibody, namely (i) that it uniquely recognises the free N-terminus or the free C-terminus, and (ii) that it can further discriminate between the peptide and the precursor from which it is proteolytically derived. If feature (i) meant that the antibody only recognised Abeta peptides with a free N- or C-terminus and did not bind to anything else, then feature (ii) would not provide any additional information on the antibody and would be superfluous. The board considers that such a reading of said passage would not make sense to the skilled person and would moreover be at odds with the remaining teaching of the application as filed.

Consequently, the feature that the antibody does not bind to the APP is not directly and unambiguously derivable from page 12, lines 26-33 of the application as filed.

4.5 Furthermore, the application as filed describes in its "prophetic" example at page 25, line 24 to page 26, line 13, that "high affinity polyclonal antibodies specific for the free N-terminus of Abeta peptides were made where the antibodies were raised using the restricted peptide: H2N-SEQ ID NO:6-aminohexanoate-C-amide" (page 25, lines 24-29), whereby SEQ ID NO:6 consists of six amino acids. Following immunization of rabbits, a peptide "that spans the 0 to 1 splice site that yields the free N-terminus", acetal-SEQ ID NO:7-Ahx-C-amide, whereby SEQ ID NO:7 consists of 13 amino acids, was "used to preabsorb away all antibodies which do not depend upon the free amine-Asp being present. The antibodies were then purified and collected using the N-terminal peptide. Whereas the crude serum shows substantial activity towards the spanning peptide, once affinity purified, there is no reactivity of the resulting antibody with the spanning peptide, only with the N-terminal peptide" (page 26, lines 2-14).

The appellant submitted that the lack of reactivity of the antibodies with the peptide of SEQ ID NO: 7 meant that the antibodies would not bind to APP.

The board cannot follow the appellant's line of argumentation, because - irrespective of the question whether the terms "has no reactivity" and "does not bind" have the same meaning - an antibody which has no reactivity with the 13 amino acids long peptide of SEQ ID NO: 7 may still bind to the much longer APP.

Therefore, said disclosure on pages 25 and 26 of the application as filed does not provide a basis for the feature that the antibody "does not bind" to the APP.

4.6 It follows that the feature that "the antibody does not bind to the amyloid-beta precursor protein from which said amyloid-beta peptide may be proteolytically derived" in claim 1 of the main request is not directly and unambiguously derivable from the application as filed.

5. To support its argument that the feature "does not bind" was synonymous with the terms and expressions used in the application as filed, the appellant referred to additional documents, in particular documents D22, D23 and D19, but also documents D4, D7, D8, D11, D20 and D21.

To decide whether or not a claim contains added subject-matter, it is necessary to establish what a skilled person would derive, on the date of filing, from the application as filed. Documents other than the description, claims and drawings of the application as filed may be used insofar as they prove the common general knowledge on the date of filing.

Of the documents referred to by the appellant in the context of the feature "does not bind", document D4 - a European patent application - is the only document that was published before the filing date of the patent in suit. The document describes an antibody "specifically reactive to a partial peptide on the C-terminal side of a beta-amyloid", which antibody "does not recognize" certain other, defined peptides (see page 5, line 31 to page 6, line 46; page 10, lines 25-48). The document neither constitutes common general knowledge, nor does it in any way suggest that "specifically reactive" and "does not recognize" are synonymous.

The remaining documents referred to by the appellant in this context became available to the public only after the filing date of the patent in suit. These documents thus likewise do not prove that, according to the skilled person's common general knowledge at the filing date of the patent in suit, the feature "does not bind" was synonymous with any of the features explicitly disclosed in the application as filed.

6. Consequently, the main request does not meet the requirements of Article 123(2) EPC.

Auxiliary requests 2 to 7 - Article 123(2) EPC

7. Claims 1 of each of auxiliary requests 2 to 7 include the feature that "the antibody does not bind to the amyloid-beta precursor protein from which said amyloid-beta peptide may be proteolytically derived."

For the reasons set out in points 2 to 6 above for the main request, this feature is not directly and unambiguously derivable from the application as filed.

Therefore, auxiliary requests 2 to 7 do not meet the requirements of Article 123(2) EPC.

Auxiliary request 1 - Article 123(3) EPC

8. Article 123(3) EPC stipulates that the claims of a patent as granted may not be amended in such a way as to extend the protection conferred. To decide whether or not an amendment of the patent in suit satisfies that requirement, it is necessary to compare the protection conferred by the claims before amendment, i.e. as granted, with that of the claims after amendment.

9. Claim 1 of auxiliary request 1 is directed to "a recombinant antibody which is end-specific for the free N-terminus of an amyloid-beta peptide or the free C-terminus of an amyloid-beta peptide Abeta1-40".

The feature of granted claim 1 that the claimed antibody "does not bind to the amyloid-beta precursor protein from which said amyloid-beta peptide may be proteolytically derived" has been omitted from claim 1 of auxiliary request 1.

10. For the reasons set out in points 4.1 and 4.2 above, the board cannot follow the appellant's argument that any recombinant antibody which is end-specific for the free N-terminus of an amyloid-beta peptide or the free C-terminus of an amyloid-beta peptide Abeta1-40 would not bind to the amyloid-beta precursor protein from which said amyloid-beta peptide may be proteolytically derived. Therefore, amended claim 1 does not have the same meaning as granted claim 1.

By no longer excluding antibodies which do not bind to the amyloid-beta precursor protein, the scope of claim 1 has thus been extended to encompass antibodies which bind to said precursor protein.

11. It follows that auxiliary request 1 does not comply with Article 123(3) EPC.

Auxiliary request 8 - Admission

12. Claim 1 of auxiliary request 8 is substantially the same as claim 1 of auxiliary request 2 submitted to the opposition division with letter of 29 April 2011; it differs therefrom only slightly in wording by referring to "the antibody having no reactivity" instead of "the antibody has no reactivity". The board regards both claims as identical in terms of their technical features.

According to the minutes of the oral proceedings before the opposition division, the proprietor (appellant) replaced auxiliary requests 1-5 filed with letter of 29 April 2011 by new auxiliary requests 1-5 (see point 7 of the minutes), and later on withdrew auxiliary requests 2-5 (see point 13 of the minutes).

13. Although auxiliary request 8 was presented with the statement of grounds of appeal, the board has the power to hold inadmissible requests which could have been presented in the first instance proceedings (Article 12(4) RPBA). This includes requests which were filed but then withdrawn or abandoned.

One criterion for exercising that discretion is whether the withdrawal of a request prevented the department of first instance from giving a reasoned decision on the critical issues, thereby compelling the board of appeal either to give a first ruling on those issues or to remit the case to the department of first instance (see point 2.1.2 of decision T 495/10 of 3 July 2012, and point 12 of decision T 679/09 of 13 November 2012).

The withdrawal of said auxiliary request 2 in opposition proceedings had exactly this effect. While the appellant may not have intended to avoid a decision of the opposition division on the allowability of auxiliary request 2, this was the inevitable result of withdrawing it (cf. point 2.1.7 of decision T 495/10).

14. Furthermore, in its communication accompanying the summons to oral proceedings, the board drew the parties' attention to Article 12(4) RPBA and pointed out that auxiliary request 8 was rather similar to auxiliary request 2 filed during the first instance proceedings and then withdrawn before the opposition division could take a decision on it.

Nevertheless, the appellant chose not to attend the oral proceedings before the board and also submitted no written arguments as to why auxiliary request 8 should be admitted into the proceedings before the board.

15. For these reasons, the board, in exercising its discretion under Article 12(4) RPBA, decided not to admit auxiliary request 8 into the proceedings.

"Amended" main request and "amended" auxiliary requests 1 to 8

Claim 1 of each of the "amended" claim requests is identical to claim 1 of the corresponding "unamended" claim requests (see section VI above). As set out in points 2 to 11 above, claims 1 of the main request and of auxiliary requests 2-7 do not meet the requirements of Article 123(2) EPC and claim 1 of auxiliary request 1 does not meet the requirements of Article 123(3) EPC. These findings equally apply to claims 1 of the corresponding "amended" main and auxiliary requests.

Furthermore, the reasons for the board's decision not to admit auxiliary request 8 into the proceedings (see points 12 to 15 above) equally apply to "amended" auxiliary request 8.

17. It follows from the above that none of the claim requests is both admissible and allowable.