T 0583/09 (Novel genes/MILLENNIUM) 13-12-2011

Reasons for the decision

1. According to the Order of the decision G 10/93 of the Enlarged Board of Appeal (OJ EPO, 1995, page 172) "in an appeal from a decision of an examining division in which a European patent application was refused, the board of appeal has the power to examine whether the application or the invention to which it relates meets the requirements of the EPC. The same is true for requirements which the examining division did not take into consideration in the examination proceedings or which it regarded as having been met. If there is reason to believe that such requirement has not been met, the board shall include this ground in the proceedings". Thus, the board is not limited to the examination of the objections raised in the decision under appeal but has to examine whether the appellant's requests fulfil all the requirements of the EPC.

In a first step, the board is therefore examining whether the requests before it meet the requirements of Article 123(2) EPC.

Article 123(2) EPC

2. In order to determine whether or not the subject-matter of an amended claim extends beyond the content of the application as filed, it has to be examined whether that claim comprises technical information which a skilled person would not have clearly and unambiguously derived from the original application. The disclosure of such technical information can be explicit or implicit. The term "implicit disclosure" should not be construed to mean matter that does not belong to the content of the technical information provided by a document but may be rendered obvious on the basis of that content. The term "implicit disclosure" relates solely to matter which is not explicitly mentioned, but is a clear and unambiguous consequence of what is explicitly mentioned (decision T 823/96 of 28 January 1997; point 4.5).

Main request

3. The subject matter defined by SEQ ID NOs 59 to 61, and 63 is labelled "Tango 332" and discussed briefly in a paragraph bridging pages 9 and 10, and in more detail on pages 90 to 99 of the published international patent application.

The present application discloses not only Tango 332 but also several other unrelated molecules. Pertinent sections of the application relating to additional features of "Tango 332" and these other molecules can be found on pages 11 to 14, and 100 to 127.

4. Claims 1(a) and 2(a), (b), and (c), respectively, refer to nucleic acid molecules comprising nucleotide sequences with respectively 80, 90, 95, and 98% of identity with SEQ ID NOs 59 or 60.

A paragraph of the description discussing related sequences can be found on page 2, lines 24 to 30, where the following is explicitly stated: "The invention also features nucleic acid molecules which are at least 40%(or, 50%, 60%, 70%, 80%, 90%, 95%, or 98%) identical to the nucleotide sequence of any of SEQ ID NOs: 1, 2, 9, 10, 33, 34, 38, 39, 46, 47, 54, 55, 59, 60, 81, 82, and 92". In the board's view, this paragraph presents two lists of properties or features of the claimed subject matter, a first list of sequence identities and a second list of sequence numbers.

According to decision T 727/00 of 22 June 2001 (reasons, pt 1.1.4), the specific combination of one item from each of two lists of features results in subject matter which, although conceptually comprised in the application as filed, is not disclosed in the particular individual form. This decision is in line with established case law, and the board is convinced that this rationale equally applies to the case at issue.

Conceptually, any of the degrees of identity of the first list can be combined with any of the sequences of the second list. The board does however not regard this as a direct and unambiguous disclosure of the nucleic acid molecules of claim 1(a), i.e. of those molecules comprising a nucleotide sequence which is "at least 80% identical to the nucleotide sequence as shown in SEQ ID IN: 59 or 60". The same applies to the specific combinations of features of claims 2(a), (b), and (c).

5. Similarly, the board cannot find basis for claims 9(a) and 19(b). The paragraphs of the description relating to polypeptide fragments (e.g. page 3, lines 20 to 24) present a first list of possible fragment lengths ("at least 8(10, 15, 20, 25, 30, 40, 50, 75, 100, 125, 150, or 200)") and a second list of polypeptides defined by SEQ ID numbers ("SEQ ID NOs: 3-8, 11-32, 35-37, 40-45, 48-53, 56-58, 61-63, 83-88, and 93-98"). This can however not be regarded as a direct and unambiguous disclosure of polypeptide fragments of SEQ ID NOs 61 or 63 of at least 200 amino acids in length.

Moreover, there is no disclosure of fragments of SEQ ID NOs 61 or 63 of at least 200 amino acids binding to hyaluronic acid or extracellular matrix. The sections of the description relating specifically to Tango 332 describe the presence of a domain binding to hyaluronan (p. 94, lines 8-9). There is however no mention of fragments of Tango 332 specifically binding to hyaluronan, let alone of fragments comprising at least 200 contiguous amino acids.

6. Regarding claims 9(c), 10(a), (b), and (c), and 19(c), respectively, directed to isolated polypeptides and a method for producing such, the board cannot find direct and unambiguous disclosure of polypeptides which are respectively and specifically at least 80% or 90% or 95% or 98% identical with SEQ ID NOs 61 or 63. The respective paragraph on page 4 (lines 3 to 6), and the last paragraph on page 111 each present a first list of sequence identities and a second list of sequence numbers.

7. As a consequence of the lack of a proper basis for the polypeptides of claims 9 and 10, there is also no proper basis for claims 13, 16, and 17 directed to antibodies specifically binding to the polypeptides of these claims.

Moreover, there is no basis for claims 16 and 17, directed to such antibodies conjugated to a cytotoxic agent and an antimitotic agent, respectively (claims 16 and 17). Paragraphs of the description relating to antibodies conjugated to therapeutic substances contain lists of several therapeutic substances (cf. page 122, lines 17-18, "an antibody substance can be conjugated with a therapeutic moiety such as a cytotoxin, a therapeutic agent, or a radioactive metal ion"; cf. also page 122, line 25 to page 26, line 2, "Therapeutic agents include, antimetabolites (e.g. ...), alkylating agents (e.g. ...), anthracyclines (e.g. ...), antibiotics (e.g. ...), and anti-mitotic agents (e.g. ...).")(emphasis added). There is however no direct and unambiguous disclosure of the conjugation of specific antibodies selected from the many lists of antibodies (cf. pages 123 to 125) to specifically a cytotoxin or an antimitotic agent, both selected from lists of possible therapeutic substances.

8. Basis for claims 25 and 26, directed to methods for modulating the ability of any of the polypeptides with the features of claims 9 to 12 to bind to hyaluronic acid or extracellular matrix, is also not apparent from the application as filed. Original claims 21 and 22 provide basis for methods for identifying a compound which modulates the activity of a claimed polypeptide. The part of the description relating to Tango 332 provides numerous activities such as "establishment and maintenance of neural connections, cell-to-cell adhesion, tissue and extracellular matrix invasivity, and the like" (page 9, line 32 to page 10, line 1), cartilage organization, extracellular matrix organization, neural growth and branching, cell-to-cell and cell-to-matrix interactions (page 94, lines 13 to 16). It is also mentioned that the protein contains a pair of extracellular link domains indicating that this protein is also involved in HA binding. But there is no direct and unambiguous disclosure of methods in which modulation of the binding of any of the proteins of claims 9 to 12 to hyaluronic acid or extracellular matrix is assayed.

9. In view of the above mentioned deficiencies, the main request does not meet the requirements of Article 123(2) EPC.

Auxiliary request I

10. The claims of auxiliary request I differ from those of the main request by the fact that the claimed nucleic acid and polypeptide sequences are defined as consisting of, instead of comprising, the recited sequences (cf. section VIII). This has however no influence on the conclusions drawn by the board in relation to the objections under Article 123(2) EPC (cf. points 4 to 9 above). The objections raised in the preceding paragraphs against the claims of the main request equally apply to the corresponding claims of auxiliary request I.

Auxiliary requests II and III.

11. Claims 11 to 13 of auxiliary requests II and III (cf. section IX above), refer to antibodies according to preceding claim 8, which are conjugated to a therapeutic substance and specifically bind to the polypeptides of claim 7, i.e. to the polypeptides consisting of the amino acid sequences of SEQ ID NO: 61 and 63. Basis for the antibodies of claim 8 can be derived from the paragraph beginning at page 123, line 28 and ending at page 124, line 2, in combination with paragraph 2 on page 126 stating that any of the antibody substances of the invention can be combined with a therapeutic moiety.

For the reasons already given in point 7, 2nd paragraph, above, there is no direct and unambiguous disclosure of antibodies binding to the polypeptides consisting of SEQ ID NOs 61 and 63, which are conjugated to a cytotoxic agent (claims 11 and 13) or an antimitotic agent (claim 12). The paragraph bridging pages 123 and 124 provides a first list of antibodies specifically binding to many different peptides and the second paragraph on page 122 provides a second list of possible therapeutic substances.

12. Regarding claims 20 and 21 (cf. section 9 above), the reasoning given under point 8 for claims 25 and 26 of the main request equally applies.

13. In view of these deficiencies, auxiliary requests II and III do not meet the requirements of Article 123(2) EPC.

Auxiliary request IV

14. Since claims 11 to 13 of auxiliary request IV are identical with claims 11 to 13 of auxiliary requests II and III, the above said (cf. point 11) equally applies, and auxiliary request IV does not meet the requirements of Article 123(2) EPC.

15. In conclusion, none of the requests on file complies with the requirements of Article 123(2) EPC.