T 0831/94 (Anthracycline/VESTAR) 13-11-1998

1. The appeal is admissible.

Main request

2. The Appellant made no objection under Article 100(c) EPC and the Board considers that the requirements of Article 123(2) and (3) EPC are satisfied.

3. Having regard to the Opposition Division's decision, the point at issue is the novelty of the subject-matter of claim 1 as granted corresponding to claim 1 of the present main request.

3.1. Comparing the general procedure for preparing liposomes described in document (8) on page 80 under the heading "Methods and Materials", with the subject-matter of claim 1, the Board sees no reason to doubt the Opposition Division's analysis that, except for the feature that the phospholipid micellular particles are suspended in a low ionic strength aqueous phase containing sugar, this document discloses a composition falling within the scope of claim 1 as granted.

3.2. It is particularly to be noted that the Appellant contested neither that phosphatidylserine and phosphatidylcholine are respectively an anionic phospholipid and a neutral phospholipid, nor that Adriablastine produced by Farmitalia contains doxorubicin and lactose in a ratio of 1:5 and that according to the preparation method at least a part of the lactose will be present in the final composition of (8). The Appellant's statement that the sugar (lactose) in document (8) was present accidentally in that it happened to be present in the commercially available source of doxorubicin is tantamount to admitting the presence of sugar. Where a product claim is to be examined, this statement clearly cannot have any influence on the decision concerning novelty but rather on the question whether or not the claimed subject-matter would involve an inventive step in the light of the prior art disclosure. It was furthermore not disputed between the parties that the presence of 0.8% NaCl in the composition according to document (8) provides an ionic strength of about 150 mM.

3.3. Accordingly, in the absence of any reference to the ratios of the components in the claimed composition, it only remains to be considered whether the relative term low ionic strength can be regarded clearly and unequivocally as a characterising feature distinguishing the claimed composition from the composition of document (8) which also comprises phospholipid micellular particles suspended in an aqueous phase with an ionic strength of 150 mM, or whether on the contrary in the field of phospholipid micellular particles a value of the ionic strength of 150 mM clearly and unequivocally does not fall within the technical meaning of low ionic strength.

3.4. Relative terms such as "low" are not necessarily excluded when defining the subject-matter of a product claim. Although in the present case the term low ionic strength finds support in the description of the patent in suit as originally filed on page 8, second paragraph in the reference to "low-ionic media, such as sugar solutions or de-ionized distilled water", the description neither contains numerical values exemplifying low ionic strength aqueous phases, nor does it contain a concrete value delimiting the relative term "low" vis-à-vis other possible relative terms such as "medium" or "high". In this context it is to be noted that ionic strength in accordance with the common general knowledge of those skilled in the field of physical chemistry is defined as the half of the algebraic sum of the concentration values of each type of ion - cationic and anionic ions being taken separately - present in a liquid phase with each of the concentration values multiplied by the square of the corresponding ionic valence status. Therefore, it would be not possible to exemplify the ionic strength of an aqueous phase only by reference to the concentration of one ionic species out of a group of different species having different ionic valence status present in the aqueous phase. Accordingly, in the circumstances of the present case, the term low ionic strength in claim 1 has to be understood in its broadest sense and not therefore as an absolute numerical feature when comparing the claimed subject-matter with ionic strength values disclosed in the known prior art.

3.5. As regards the relevant prior art for a comparison of so-called "high" and "low" ionic strength values, the Appellant cited document (14), which was deemed by the Opposition Division to support the conclusion that the 150 mM NaCl solution of document (8) represents a low ionic strength aqueous phase. By reference to calculations on the basis of concentration values disclosed in column 5, lines 22 to 33 and column 11, Table 1, of this document, and in contrast to the Opposition Division's conclusions, the Appellant has sought to demonstrate that this prior art does not disclose a buffer solution with a low ionic strength of 0.3. M or 300 mM but 0.3 mM.

The Board, however, cannot follow the Appellant's way of reading or interpreting the disclosure in document (14). The above-mentioned passages indicate as a general rule that "the ionic strength of the aqueous phase has a bearing on the encapsulating efficiency obtained in the methods of the invention". Reference is made to sodium chloride concentrations of 15 mM in line 27. and 500 mM in line 29 in connection with attainable percentage values of encapsulated aqueous phases. In the same context and immediately following in the subsequent sentence starting in line 30, it is more generally stated that

"to maximize the encapsulation of macromolecules, a buffer of low ionic strength (less than 0.3) is preferably employed" and that "the encapsulation efficiency is also dependent on the concentration of lipid or phospholipid present in the 2-phase system".

This is, however, not the only disclosure in document (14) relating to a relationship between varying sodium chloride concentrations and the encapsulation efficiency obtainable under conditions described in this document. Table 1 in column 11, belonging to Example 5, which table has also been considered by the Appellant, shows values of percentage encapsulation depending on 0.5; 0.15; 0.1; 0.04; 0.02 and 0.00 moles of NaCl. This table clearly shows a step of 47.5% to 62.3% encapsulation between 0.04 moles and 0.02 moles of NaCl content and a trend to about the same values for 0.02 moles and below, down to 0.00 moles NaCl in the phase system forming the basis for Example 5. The said step and trend is confirmed by Figure 2 on page 4196 of document (17). Said Figure 2 of document (17) is a graphical representation of the same experimental data as Table 1 of document (14). Accordingly, there is no basis for the Appellant's assumption that the low ionic strength of 0,3 mentioned in document (14) without a reference to M or mM relates clearly and exclusively to 0.3 mM and that a value of 150 mM is clearly and unequivocally outside the scope of claim 1 of the main request containing the mere reference to the low ionic strength of an aqueous phase.

3.6. Since document (14) clearly indicates that the encapsulating efficiency not only depends on the ionic strength of the liquid phases, but also on other parameters such as the phospholipid content, there is no reason to follow the Appellant's argument that the absolute maximum of encapsulation occurs only at "0.00 M NaCl". Moreover, the wording of the passages in document (14) relevant to this matter can only be understood to mean that the reference to a "low ionic strength (less than 0.3)" is intended to show under what experimental conditions it is possible to maximize one of the parameters influencing the encapsulating efficiency.

3.7. This situation is not changed by taking into account the disclosures in further documents on file exemplifying ionic strength values, eg document (18). This document contains on page 306, the front page of this publication, a reference to an ionic strength of 0.01. M being "relatively low" and then goes on to describe conditions "at higher ionic strength" of 0.15 M. In these circumstances, each of the ionic strength values referred to subsequently in this prior art, for example the so-called high and low ionic strength buffers of 0.15 M and 0.01 M respectively, mentioned on page 307, as well as the low ionic strength of 0.01 M and the high ionic strength of 0.15 M according to Table 1 on page 309, must be understood in the same way as being "relatively low" and "higher", but cannot be understood as representing absolute values for high and low ionic strength conditions in aqueous phases.

The Board agrees with the Appellant's analysis that document (21) does not refer in relative terms to a high ionic strength in respect of a value of 150 mM NaCl. However, taking into account the fact that the disclosure in document (14) does not exclude a value of 150 mM being of low ionic strength, document (21) could be regarded as being contradictory to the disclosure in document (14).

3.8. As regards the prior art disclosure, it is to be noted that none of the documents contradict the interpretation of Table 1 in document (14) and Figure 1 in document (17) as given in points 3.5 above, but that at least the disclosures in two documents on file, namely (14) and (21), contradict each other. Taking into account the circumstances of the present case, it can therefore only be concluded that the Appellant failed to show clearly and unequivocally the novelty of the composition of claim 1 of the main request compared with compositions described in document (8), and that having regard to the facts on file, the Opposition Division's arguments cannot be disregarded.

Claim 1 of the main request does not meet the requirements of Article 54(1) EPC.

Auxiliary requests

4. Each of the auxiliary requests 1 to 6 on file can be regarded either as a fair response by the Appellant to overcome the grounds of revocation as set out in the Opposition Division's decision or as constituting a bona fide attempt to overcome objections raised by the Respondent during the appeal proceedings. Since the auxiliary requests also appear to limit the scope of the main request, the Board sees no grounds to exclude these claims from the further procedure.

4.1. Auxiliary requests 1 to 4, however, do not meet the requirements of Article 123(2) EPC.

Each claim 1 of these requests comprises the feature "...phospholipid micellular particles... exhibiting a greater than 90% trapping efficiency...". According to the description as originally filed, page 6, second full paragraph, such a trapping efficiency is only disclosed for micellular particles in the form of unilamellar phospholipid vesicles 45-55 nanometres in diameter.

Accordingly auxiliary requests 1 to 4 must be rejected.

4.2. Having regard to the aforementioned passage on page 6 of the description as originally filed, claim 1 of auxiliary request 5 fulfils the requirements of Article 123(2) and (3) EPC.

It is to be noted, however, that the combination of features newly introduced into claim 1 of auxiliary request 5 relating to unilamellar vesicles 45-55 nanometres in diameter and exhibiting a greater than 90% trapping efficiency, has not been discussed in the light of the disclosures in the prior art documents on file, nor did the Respondent have the opportunity to comment in detail on this request. Moreover, the question whether or not the subject-matter of the patent in suit involves an inventive step was not considered in the decision of the Opposition Division.

4.3. Accordingly, it does not seem appropriate at the present stage of the procedure for the Board to carry out an investigation in the state of the art on file on the basis of auxiliary request 5 and possibly auxiliary request 6, both requests not having formed the basis for the decision of the Opposition Division. Apart from the fact that the parties would be deprived of an instance of jurisdiction for this matter, in the circumstances of the present case the Board wishes to point out that the essential function of the appeal proceedings is to determine whether the decision of the first instance was correct (T 47/90, OJ EPO 1991, 486).

4.4. Since it is well known to the parties that the normal purpose of oral proceedings is to bring the case to a conclusion (Article 11(3) RPBA), the parties' failure to attend the oral proceedings, together with the request to continue the proceedings in writing, can be regarded as further support for the decision to remit the case to the first instance. As a consequence it is also meaningful to continue the proceedings in writing before the first instance.

Accordingly, the Board has decided to invoke its powers under Article 111(1) EPC and to remit the case to the Opposition Division with the order to prosecute the proceedings further.