T 0414/07 (Diseases of the breast/ABBOTT) 03-06-2008

Main request

Requirements of Article 123(2) EPC

1.1 The amendments contained in the main request are allowable under Article 123(2) EPC. In particular, the replacement of the term "complements" by the expression "full-length complementary sequences" (see claims 1, 3, 7, 16, 18 and 21) is supported by the sentence on page 22, lines 15 to 16 of WO 98/07857 (the published form of the application as filed). The expression "one epitope from an amino sequence selected from the group" which no longer includes the term "derived" before "from" as used in claim 6 still has support in the sentence bridging pages 6 and 7 in WO 98/07857, in the light of the passages from lines 22 to 26 on page 10 and from lines 18 to 22 on page 16. Specifying in the claims directed to a method of detecting (see claims 16, 18, 21, 25 and 26) that it is intended to detect breast cancer in an individual is reflected by the passage from line 18 to line 22 on page 11 of WO 98/07857. It is also agreed that, as argued by the appellant, the reference to oligonucleotides which "have at least 90% identity to a sequence selected from the group consisting of SEQUENCE ID NOS 1-4" in claim 21 and to an amino acid sequence "having at least 90% identity to an amino acid sequence selected from the group consisting of SEQUENCE ID NOS 15-23" in claim 26 have a counterpart in WO 98/07857 in the passage from line 26 to line 28 on page 23 and in the passage from line 12 to line 15 on page 13, respectively. Thus the main request complies with Article 123(2) EPC.

Clarity requirement of Article 84 EPC

2. The board is satisfied that, in view of the newly filed amendments, in particular the removal of the indefinite term "BU101" throughout the claims and the deletion of the unambiguous term "derived" formerly used in the expression "one epitope derived from an amino acid sequence" in the claim directed to an antibody (see claim 6), the main request meets the clarity requirement of Article 84 EPC. The explanations provided by the appellant in its letter of 2 May 2008 with respect to the term "amplicon" as used in claim 18 are accepted. They convincingly show that it was commonly used in the field of biotechnology at the relevant filing date to refer to a piece of DNA that has been synthesised using amplification techniques. As argued by the appellant, the expression "having at least 90% identity to" is clear in view of the unambiguous definition given to the term "identity" on page 11, lines 7 to 17, of the application, namely "identity" meaning in the context of the claims exact nucleotide to nucleotide or amino acid to amino acid correspondence.

Novelty (Article 54(3) EPC 1973)

3. At the oral proceedings the board exercising its discretionary power (see decision G 10/93 (OJ EPO, 1995, 172; see the Order) has on its own motion questioned whether an antibody according to claim 6 may be regarded as new over document D3.

4. Document D3 is a Euro-PCT application published as WO 97/34997. It was filed on 21 March 1996, i.e. before the earliest priority date of the application in issue, which is 19 August 1966, and published, after this latter date, on 27 September 1997. WO 97/34997 entered the European regional phase on 21 October 1998. The designation and filing fees provided for in the EPC were duly paid. Ten of the Contracting States, namely AT, BE, CH, DE, ES, FR, GB, IT, LI, NL, designated in respect of the European application were the same as those designated in respect of the application in issue. Therefore, WO 97/34997 has to be considered as comprised in the state of the art under Article 54(3) EPC 1973 for the novelty assessment of the application in issue.

5. Document D3 describes inter alia three polypeptides, referred to therein as hESF I, II and III, hESF II having a 90 amino acid sequence named SEQ ID NO:4 which is represented in Figure 2 (Drawing 2/10). That sequence corresponds exactly with the sequence of the "BU101" polypeptide of the application in issue (see the sequence SEQ ID NO: 15).

6. Document D3 contains two sections entitled "Polypeptide assays" and "Antibodies", respectively, in which antibodies in relation with the hESF polypeptides are referred to (see pages 40 to 42).

7. The question to be answered is whether the subject-matter of claim 6 (see Section VII, supra) is disclosed in pages 40 to 42 of document D3.

8. The "Antibodies" Section provides a very general disclosure. Antibodies specifically directed to hESF II are not mentioned. A skilled person cannot derive therefrom any relevant information as to the characterising features of those antibodies. The "Polypeptide assays" Section reports on diagnostic assays in which antibodies specific to any of hESF I, hESF II and hESF III may be used. Antibodies specifically directed to hESF II are not described.

9. The skilled person having read document D3 is left with a lack of crucial information especially as regards the localisation of the relevant epitopes. He/she is not in a position to derive therefrom that epitopes - conformational or not, and generally consisting from 3 to 10 amino acids (see page 16, lines 18 to 22 in the application in issue) to which antibodies can specifically bind - are to be found in the partial sequences of the polypeptide referred to in the application in issue as SEQ ID NO:16 (amino acids 22 to 36), SEQ ID NO:17 (amino acids 37 to 51), SEQ ID NO:18 (amino acids 45 to 59), SEQ ID NO:19 (amino acids 54 to 68), SEQ ID NO:20 (amino acids 69 to 83), SEQ ID NO:21 (amino acids 69 to 90) and SEQ ID NO:22 (amino acid 46 to 90). Individual antibodies, whether polyclonal or monoclonal, capable of specifically binding to those epitopes as such are not described in document D3. In contrast, such antibodies have been prepared and tested in the experiments reported in the application in issue (see Examples 14 to 17, including Table 2 on page 83).

10. In view of the above remarks, the board considers that, in agreement with the submissions by the appellant, antibodies according to claim 6 represent groups of antibodies selected within a larger population of antibodies known from document D3.

11. Thus, claim 6 is novel. The board is satisfied that the rest of the claims are also new over the relevant state of the art and concludes that the main request as a whole meets the requirements of Article 54 EPC.

Inventive step (Article 56 EPC)

12. Claim 5 which is directed to a number of selected polypeptides or peptides (see Section VII, supra) is chosen as the starting point for the assessment of inventive step.

13. Document D2, which is considered to represent the closest state of the art, describes inter alia a protein, designated mammaglobin, a mammary-specific member of the uteroglobin gene family, which is overexpressed in human breast cancer and believed to be a clinically useful marker for managing patients with breast cancer (see the "Discussion" on pages 864 to 865).

14. In view of that closest state of the art, the technical problem is regarded as the provision of a further marker for the management of human breast cancer, the solution thereto being the polypeptides according to claim 5, as well as methods and means for using or making them.

15. The question to be answered is whether at the relevant filing date the skilled person would have found in the state of the art all the necessary guidance to discover without undue burden a polypeptide according to claim 5 and characterise it as a putative marker for the management of human breast cancer.

16. The only other prior art document on file, as identified by the examining division, is document D1 which reports on the isolation of cDNA clones specific for each of the mRNAs which code for a rat protein, referred to as prostatic steroid binding protein, and for which no application is foreseen in the document as a marker for cancer, let alone as a marker for breast cancer. Thus, it is obvious that document D1 which deals with a totally unrelated subject-matter (even if an hindsight analysis may reveal that the rat protein and the BU101 polypeptide with the sequence SEQ ID NO:15 are partially homologous in terms of their amino acid sequences; see page 53, lines 25 to 28, in the application in issue) would have been ignored by the skilled person facing the aforementioned objective technical problem. In the absence of any other prior art document, the only possible conclusion is that the skilled person would simply not have arrived at the said polypeptides without the exercise of inventive skill.

17. Similarly, at the relevant filing date, the skilled person would not have predicted that a polynucleotide according to claim 1 coding for the BU101 polypeptide with the sequence SEQ ID NO:15 or parts thereof, such as the polypeptides according to claim 5, might exist. Therefore, the polynucleotides of claim 1 also involve an inventive step.

18. The conclusive remarks made with respect to both claims 1 and 5 apply de facto also to the rest of claims as they are directly or indirectly dependent thereupon or their subject-matter is defined with a reference to polynucleotides having a sequence represented by SEQ ID NO:1 to 4 (see claims 2 to 4, 7, 8 and 16 to 24) or polypeptides encoded by those polynucleotides or portions thereof (see claims 6, 9 to 15 and 25 to 27). This leads to the conclusion that the claimed invention as a whole involves an inventive step. Thus, the main request meets the requirements of Article 56 EPC.

19. As the board is satisfied that the other requirements of the EPC are also meet, the main request may form a basis for the grant of a patent.