T 0890/00 (Anti-angiogenic compositions/ANGIOTECH PHARMACEUTICALS) 28-10-2002

1. Admissibility of the appeal

The appellant has confirmed that it no longer pursues the use claims which served as the basis of the Opposition Division decision and that its sole request is the set of claims filed with the grounds of appeal which only contains product claims. The deletion of the use claims took place in response to the contested decision. The appellant's efforts are directed to the product claims which have not been examined by the Opposition Division and which did not form any basis for the decision under appeal. The product claims were however attacked by the opponents during the opposition proceedings and thus fall within the framework of the appeal proceedings. The appeal is admissible.

2. Article 84

The wording of claim 1 may be structured as follows:

a1 a stent (for expanding the lumen of a body passageway)

the stent comprising:

a2 a generally tubular structure

a3 coated with a composition

the coating composition is defined as comprising:

b1 an anti-angiogenic factor and

b2 a polymeric carrier,

the factor is defined as:

c1 being anti-angiogenic by the CAM assay.

The review article D39 (published July 1991), which relates to "Inhibitors of angiogenesis", confirms the existence of the CAM (chick chorioallantoic membrane) assay as a standard in vivo test before the priority date of the patent in suit (cf D39, page 630, right column, line 28 and page 631, left column, second paragraph). Additionally, the statement: "The angiogenesis inhibition was demonstrated in a commonly used assay (emphasis added) using chick chorioallantoic membrane" made in D47, cf column 7, lines 28-30, further confirms this.

The Board is satisfied that the CAM assay, as has been acknowledged by respondent opponent III during the appeal proceedings, belongs to the general knowledge of the skilled person in the pharmacological field and is a standard test to be used in order to avoid tests on animals.

It is clear from the wording of the claim that it is the "anti-angiogenic factor" used as component of the coating composition which is to be tested by the CAM assay. A positive result by the CAM assay is necessary in order that a substance is considered to be an "anti-angiogenic factor" within the meaning of claim 1.

Compared with claim 1 as granted, claim 1 is restricted insofar as it no longer includes as components for the coating composition those substances which do not give positive results by the CAM assay. In other words, there may be substances that give positive results by other tests for anti-angiogenesis (for instance in vitro assays as those listed on page 631 of D39) but negative results by the CAM assay. Such substances are no longer encompassed by amended claim 1 as components for the coating composition. This analysis is confirmed by the statement: "A variety of methods may be readily utilized to determine the anti-angiogenic activity of a given factor, including for example, chick chorioallantoic membrane (CAM) assays" appearing on page 9, lines 34 to 36 of the description as filed.

It is a fact, however, that claim 1 remains silent about the dosage to be tested by the CAM assay. Therefore the choice of the anti-angiogenic factor to be used as component for the coating composition may be made among substances giving positive results by the CAM assay (i.e. tests results showing avascular zones) at a certain (not specified) dosage. Nevertheless, it has to be considered that there are limits, with respect to the dosage, set by the technique itself, e.g. a too low or a too high dosage may lead to negative results (i.e. no effect or death of egg respectively). The wording of the claim only requires a skilled person in the pharmacological field to establish by routine experiments whether a substance gives positive anti-angiogenesis results by the CAM assay or not.

In conclusion, the fact that the dosage is not defined in the claim does not lead to a lack of clarity.

With regard to respondent opponent V's arguments that claim 1 is silent about the amounts of anti-angiogenic factor used for the coating composition (either in relative or in absolute terms with respect to the stent), the Board observes that this was also the case with claim 1 as granted. The absence of amounts in claim 1 means that it encompasses stents comprising a tubular structure coated with a composition in which the anti-angiogenic factor may be present in any conceivable amount suitable for the function stated in the claim and related to the coating of the stent with the further condition that the stent has to be suitable for expanding the lumen of a body passageway. Accordingly, the mention of the CAM assay for assessing the anti-angiogenic activity of one of the components of the coating composition restricts the nature of the substance to be used but does not restrict its amount in the said composition. The fact that the dosage remains undefined in the claim means that the claim encompasses all technically meaningful possibilities. Hence, claim 1 does not lack clarity with respect to the dosage of the anti-angiogenic factor to be used.

As regards the fact that the test results depend on the dosage, this applies to any activity tests in the pharmacological field. However, the consequence is not that claim 1 is obscure, but that claim 1 is broadly defined. Furthermore, the suggestion by respondent opponent V of the possibility of performing a CAM assay when the factor is on the stent appears technically implausible given the nature and form of the assays.

With respect to respondent opponent V's argument relating to the deletion of claim 3 as granted, in which methotrexate was specifically mentioned as an anti-angiogenic factor, the following has to be said. There is no contradiction between the fact that claim 1 has been restricted in respect to the nature of the anti-angiogenic factor and the deletion of claim 3. It has been shown by the appellant (cf test results filed during the appeal procedure) that methotrexate does not give positive results in the CAM assay. Hence, methotrexate is clearly not encompassed by amended claim 1. Whether methotrexate may or may not show anti-angiogenic properties by other tests (for instance in vitro tests) has not been proven by the respondent and is irrelevant for the assessment of amended claim 1. Contrary to respondent opponent V's assertion, it cannot be seen where in the description of the patent in suit colchicine or methotrexate were disclosed as anti-angiogenic factors by the CAM assay. But even if methotrexate were listed as an option for anti-angiogenic factor by the CAM assay, the skilled person would immediately know, after performing routine tests, whether or not that piece of information supposedly appearing in the description was correct. This is no reason for challenging the clarity of the amended claim.

As regards the objection that it is unclear whether heparin is encompassed by the definition "anti-angiogenic factor by the CAM assay" or not, the following has to be said. It has to be tested by the CAM assay. The tests provided by the appellant with its grounds of appeal do not show positive results for heparin by the CAM assay. Respondent opponent V has not provided any technical proof challenging any of the test results.

Claim 1 as amended requires routine tests to assess whether a certain substance falls within the definition given in the claim or not. However, this is usually the case for functional definitions, which are commonly used in claims in the medical field. Moreover, the restriction of the subject-matter claimed is an allowable procedural step which might require subsequent adaptation of the description. The fact that the description has not yet been adapted to the amended claims cannot be used as ground for lack of clarity of the claimed subject-matter.

Finally, many of the arguments put forward by respondent opponent V under the headnote "clarity and sufficiency" (cf. in particular the paragraphs 5.4, 5.6, 5.7, 5.8 of the letter of 14 May 2001) relate to an assessment of the requirements of Articles 83, 54. and/or 56 EPC. These arguments may be advanced before the first instance, as and when appropriate, when the product claims are considered.

In view of the above the Board has come to the conclusion that amended claim 1 meets the requirements of Article 84 EPC.

3. Article 123 EPC

With respect to the requirements of Article 123(2) EPC, the basis for the amendment specificying the CAM assay as the method for assessing the anti-angiogenic activity appears in the original disclosure on pages 9 and 10 of the description as filed.

Amended claim 1 concerns a restriction of the scope of claim 1 as granted in respect to the anti-angiogenic factor to be used as a component of the coating compositions. Furthermore claims 2 and 3 as granted have been deleted, as well as the use claims. Claims 4 to 15 as granted were dependent on claim 1 as granted. Therefore the deletion of claims 2 and 3 and the renumbering of the claims does not cause an extension of the subject-matter claimed in claims 4 to 15 with respect to the granted version. Thus the requirements of Article 123(3) EPC are met.

4. Article 111(1) EPC.

Article 100(b) was stated and substantiated as a ground of opposition. However, no decision was taken by the first instance as to sufficiency of disclosure. Furthermore, the product claims were not examined by the Opposition Division during the opposition proceedings and did not serve as any basis for the decision to revoke the patent. Therefore a remittal to the first instance will ensure two instances for the examination of the essential issues of the product claims (Articles 83, 54 and 56 EPC).

Furthermore respondents, opponents IV and V have requested remittal of the case to the Opposition Division for a first instance decision on the product claims; and the appellant has agreed to such remittal in response to the Board's communication.

In these circumstances the Board makes use of its power under Article 111(1) EPC to remit the case to the Opposition Division for further prosecution.

5. Apportionment of costs

Respondent opponent V's request for an apportionment of costs in the event of such a remittal is based on the allegation that costs (by implication, unnecessary additional costs) have been created by the appellant having filed substantially different requests on appeal and that this is an abuse of procedure. That additional costs are occasioned by a remittal is clear but it would be difficult for the Board to decide now whether the appellant's behaviour was an abuse of procedure or a legitimate reaction to the decision under appeal, and as if not more difficult to decide now whether or not such behaviour has caused respondent opponent V to incur unnecessary costs or not. In all probability, respondent opponent V's costs of this appeal will have been related not only to the limited issues decided in this appeal but also to issues which remain to be decided in the further first instance proceedings - to decide now whether or not those latter costs were incurred unnecessarily would be speculative.

Further, respondent opponent V seeks not just its costs of this appeal but those of the further first instance proceedings. While it may be appropriate for a Board to make such a future costs order when a remittal results from an entirely fresh case on appeal (see for example T 0715/95, unreported in OJ EPO, in which an appellant relied only on new evidence introduced on appeal and the resulting remittal effectively meant the opposition proceedings had to be recommenced), it is far less appropriate when, as here, both the extent to which a remitted case may have to be re-litigated and the extent to which that could have been avoided are unclear. Those matters will be far easier to decide after rather than before the further first instance proceedings.

A further consideration is that the other respondents have not made requests for apportionment of costs but might wish to do so in due course and that the appellant has not answered respondent opponent V's allegations or request. To prolong this appeal by argument over its costs would in itself lead all parties to incur additional but avoidable costs.

Accordingly the Board, while expressing no opinion as to the correctness or otherwise of the appellant's behaviour or respondent opponent V's request, considers the appropriate time for a decision on apportionment of costs to be the end of the further first instance proceedings. This will allow all parties to make such costs requests as they think fit and permit the Opposition Division to consider, when all the issues have been decided, whether there should be an apportionment of costs and, if so, in respect of which part or parts of the proceedings. The Board therefore refuses respondent opponent V's request for apportionment of costs so that all issues of costs can be dealt with at the most appropriate time (with the possibility of subsequent appeal). This is consistent with the Board's earlier decision T 0048/00 (unreported in OJ EPO) in which, in different circumstances but for similar reasons, a request for apportionment of the appeal costs of a remitted case was deferred to the further first instance proceedings.