T 1139/06 (Preparation of Microcapsules/QUADRANT DRUG DELIVERY LTD.) 19-02-2009

1. The appeal is admissible.

2. Admissibility of the new requests:

2.1 Main request and auxiliary requests I, II and III:

These requests were filed only at an advanced stage of the oral proceedings before the board. However, the amendments made do not introduce any new features as compared to auxiliary requests II and III, filed with letter dated 4 October 2006. Furthermore, the various deletions simplify the procedure and can essentially be seen as a reaction to the board's communication of 12 February 2009. As a consequence, the main request as well as auxiliary requests I, II and III are admissible.

2.2 Auxiliary request IV:

Auxiliary request IV was filed at a very advanced stage of the oral proceedings before the board, i.e. at 18.00 hrs. In this request, a new element was introduced into claim 1 that had hitherto played no role at all in the proceedings, namely that the microcapsules are a dry powder. Taking into consideration that this request was filed very late, after numerous auxiliary requests had already been submitted, and that the other parties were taken by surprise by this amendment so that they were not in a position to appropriately react at this late stage, the board decided not to admit auxiliary request IV into the proceedings.

2.3 Auxiliary request V:

In auxiliary request V, the claimed subject-matter was restricted to a single claim, which is identical to claim 1 of auxiliary request I, which had already been found to meet the requirements of Articles 123(2) and (3), 84 and 54 EPC (see paragraph 4 below). As a consequence, although filed at a very advanced stage of the oral proceedings before the board, the board decided to admit auxiliary request V into the proceedings.

3. Main request - Article 123(2) EPC:

In claim 1, the range of the diameter of at least 90% of the hollow microcapsules was changed from 10.1 to 19.9 mym to 12 to 19.9 mym.

For the "large" microcapsules, the following diameter ranges are disclosed in the original application: 10.1 to 19.9 mym (claim 1), 12 to 25 mym (page 10, lines 23-24 and page 11, line 9), 15 to 20 mym (page 2, line 20) and 13 to 18 mym (page 15, line 8). Although there may be cases where it is possible to define a new range Z with a lower endpoint taken from an original range X and an upper endpoint taken from a different original range Y, the board came to the conclusion that such a rearrangement was not possible in the present case for the following reasons:

Claim 1 relates to hollow microcapsules having a specific particle size distribution which is defined by a combination of interdependent inseparable features, i.e. by the features that more than 30% of the microcapsules have a diameter within a 2 mym range and at least 90% have a diameter within the range 10.1 to 19.9 mym. The fact that a first population A of microcapsules is characterised by more than 90% of the microcapsules having a diameter within the range of 10.1 to 19.9 mym and a second population B of microcapsules by more than 90% of the microcapsules having a diameter within the range of 12 to 25 mym does not automatically imply that more than 90% of a new population C have a diameter within the range of 12 to 19.9 mym. Thus, the population A mentioned above includes compositions in which a high proportion of microcapsules is within the range of 10.1 to less than 12 mym and a proportion of close to 10% has a diameter of above 19.9 mym. Cutting off the range from 10.1 to < 12 mym results in a population of microcapsules in which less than 90% of the microcapsules are within the claimed range of 12 to 19.9 mym.

Likewise, the second population B mentioned above includes compositions in which a high proportion of microcapsules is within the range of > 19.9 mym to 25 mym and a proportion of close to 10% has a diameter of < 10.1 mym. Again, by discarding the range from > 19.9 mym to 25 mym, a new population of microcapsules is obtained, wherein less than 90% of the microcapsules are within the claimed range of 12 to 19.9 mym.

It follows therefrom that, in order to arrive at the population of hollow microcapsules as claimed in claim 1 of the main request, selections have to be made from the entirety of the original populations A and B, for which there is no basis in the original application.

The appellant-patentee additionally referred to the disclosure on page 15, lines 6-8 of the original application, where at least 90% of the microcapsules have a diameter within the range of 13 to 18 mym, and argued that in such a composition the concentration of microcapsules having a diameter in the range of 12 to 19.9 mym must also be at least 90%. However, by extending the range from originally 13 to 18 mym to 12 to 19.9 mym, the concentration of 90% is also shifted to a higher value of e.g. 92 or 93% in consequence of this extension. In other words, a composition in which at least 90% of the microcapsules have a diameter within the range of 13 to 18 mym does not specifically disclose a composition, in which the percentage of microcapsules having a diameter within the range of 12 to 19.9 mym is exactly 90%.

Further selections which have no basis in the original application must be made when a further limitation of claim 1 is taken into consideration, namely that more than 30% of the microcapsules have a diameter within a 2 mym range. As there are no further indications about the exact position of this 2 mym range within the wider range of 10.1 to 19.9 mym, the population A mentioned above includes compositions in which the more than 30% of the microcapsules having a diameter within a 2 mym range are predominately in the range of 10.1 to < 12 mym. Likewise, population B comprises compositions in which the more than 30% of the microcapsules having a diameter within a 2 mym range are in the range of > 19.9 to 25 mym.

In both cases, the new population C would be characterised by less than 30% of the microcapsules having a diameter within a 2 mym range.

For all these reasons, the subject-matter of claim 1 of the main request does not meet the requirements of Article 123(2) EPC.

4. Auxiliary request I:

4.1 Amendments - Article 123(2) EPC:

4.1.1 Claim 1:

The use of the block copolymers of the poloxamer series as claimed in claim 1 is based on the passages on page 20, lines 17-21 and the paragraph bridging pages 20 and 21 of the original application. In this context, it is noted that the passage on page 20, lines 17-18 does not specifically relate to the human circulation time, but to the circulation time in the body in general. However, the fact that the coated or "long life" microcapsules have a prolonged human circulation time is derivable from the disclosure of the original application in its entirety (see e.g. page 2, lines 18-23).

The three distinct types of microcapsules which are defined in the latter part of claim 1 correspond to the microcapsules of original claims 3, 5 and 7, except for the replacement of the terms "hollow microsphere" and "in vivo t½" (original claims) by "hollow microcapsule" and "human circulation t½" (present claim 1). As for the former amendment, it is noted that the terms "hollow microsphere" and "hollow microcapsule" were used synonymously and interchangeably in the original application. As a consequence, this replacement does not change the subject-matter as claimed at all. As for the second replacement, reference is again made to page 20, lines 17-21 and the paragraph bridging pages 20 and 21 of the original application, where the (human) circulation t½ is disclosed for the coated long life microcapsules.

In the light of this disclosure in the original application, the board cannot follow the argumentation of the respondent, according to which claim 1 must comprise the feature that the microcapsules are injected into the blood circulatory system in order to be allowable under Article 123(2) EPC. As a consequence, the subject-matter of claim 1 meets the requirements of Article 123(2) EPC.

4.1.2 Claim 2:

The inclusion of a material that changes the charge of microcapsules to selectively target the microcapsules to an area of the human or animal body in or on the wall of the microcapsules is disclosed on page 17, line 30 to page 18, line 6 of the original application. As regards the original disclosure of the three distinct types of microcapsules, see paragraph 4.1.1 above, which applies mutatis mutandis to the subject-matter of claim 2. As a consequence, the requirements of Article 123(2) EPC are met.

4.2 Clarity:

4.2.1 Claim 1:

4.2.1.1. Human circulation time:

Parameters such as the human circulation t½ are allowable under Article 84 EPC only if they can be clearly and reliably determined either by indications in the description or by objective procedures which are usual in the art.

In the present case, the description does not contain any indications as to how the human circulation t½ was determined. While it does not appear necessary to describe how to measure the human circulation t½, as the person skilled in the art would know how to draw a blood sample and subsequently determine the concentration of microcapsules in that sample, the board had concerns that the human circulation t½ might be highly dependent on the exact site where the microcapsules are introduced into the body. Thus, microcapsules injected close to the heart might have a human circulation t½ which is quite different from that of the same microcapsules when introduced e.g. into the lower limbs.

However, the appellant-patentee argued that substances circulate very quickly in the bloodstream, so that differences in the human circulation t½ caused by different sites of application are negligible compared to the time span of at least 5 minutes as claimed. In the absence of any counter-arguments from appellant-opponent II and the respondent, the board sees no reason to contest this reasoning. As a consequence, the parameter "human circulation t½" is allowable under Article 84 EPC.

4.2.1.2. Definition of the term "percent":

As was correctly pointed out by appellant-opponent II, there is no information in the original application as to whether the percentages used in claim 1 relate to percent by weight, percent by volume or to any other calculation base. The absence of such information does not, however, result in any ambiguity; it simply means that the claimed percentages must be fulfilled for any calculation base.

As a consequence, the subject-matter of claim 1 meets the requirements of Article 84 EPC.

4.2.2 Claims 2 and 6:

The reasoning of paragraph 4.2.1.2 above applies mutatis mutandis to the subject-matter of claims 2 and 6. As a consequence, the requirements of Article 84 EPC are met.

4.3 Sufficiency of disclosure:

In the light of the finding in paragraph 4.2.1.1 above, the absence of a method for determining the human circulation t½, which had been objected to by appellant-opponent II under Article 83 EPC, does not lead to any problems concerning sufficiency of disclosure either. As a consequence, the requirements of Article 83 EPC are also met.

4.4 Extension of the protection conferred - Article 123(3) EPC:

4.4.1 Claim 1:

Before a conclusion can be drawn as to whether the subject-matter of claim 1 is allowable under Article 123(3) EPC, it has first to be decided which category of use this claim pertains to: whether it exclusively relates to the use of a compound for obtaining a certain effect, i.e. to the use of a block copolymer of the poloxamer series for providing microcapsules with a human circulation t½ of at least 5 minutes, or whether it concerns a process for preparing the microcapsules. In the former case, claim 1 would not be allowable under Article 123(3) EPC, as the totality of the subject-matter of the claims as granted does not encompass the use of a block copolymer of the poloxamer series for obtaining such an effect.

However, the wording of claim 1 reads "Use of a block copolymer of the poloxamer series to coat microcapsules in order to provide them with a human circulation t½ of at least 5 minutes...". As coating constitutes an activity associated with the preparation of microcapsules, the board came to the conclusion that the subject-matter of claim 1 is directed to a method of preparing microcapsules, as was asserted by the appellant-patentee. The various microcapsules prepared by the method according to present claim 1 are included in claims 5, 6 and 7 as granted except for the replacement of "in vivo t½" by "human circulation t½" (see paragraph 4.1.1 above). As already pointed out by the opposition division (see paragraph B.1 of the contested decision), the "in vivo t½" encompasses e.g. "tissue t½" and is therefore broader than the term "human circulation t½". It follows therefrom that the subject-matter of present claim 1 concerns a method for preparing microcapsules which are encompassed by the microcapsules as defined in claims 5, 6 and 7 as granted. As a product claim covers all methods for making the same, the board sees no problem under Article 123(3) EPC with regard to the change of claim category from a product to a process for its preparation.

4.4.2 Claim 2:

Again, it has to be established in a first step whether the subject-matter of present claim 2 is exclusively directed to the use of a compound for obtaining a certain effect, i.e. to the use of a material that changes the charge of microcapsules for selectively targeting the microcapsules to an area of the human or animal body, or whether it concerns a process for preparing microcapsules. Again, the board came to the conclusion that the claimed subject-matter defines a process for preparing hollow microcapsules which are encompassed by the microcapsules as defined in claims 5, 6 and 7 as granted. As a consequence, the reasoning of paragraph 4.4.1 above applies mutatis mutandis to the subject-matter of claim 2, which therefore also meets the requirements of Article 123(3) EPC.

4.4.3 Claim 6:

Claim 6 corresponds to claim 19 as granted. The requirements of Article 123(3) EPC are therefore met.

4.5 Novelty:

4.5.1 Claim 1:

Reference is made to paragraph 4.4.1 where it was reasoned that the subject-matter of claim 1 is directed to a process for preparing microcapsules.

Example 1 of document (1) describes a method for preparing hollow microcapsules by atomising a 20% solution of rHA. The intermediate microcapsules thus obtained then undergo heat fixation. In a further step, they are milled in a mixture with lactose. This mixture is then resuspended in water containing 1 mg/ml Pluronic F68 (block copolymer of the poloxamer series). It follows therefrom that example 1 of document (1) describes the use of a block copolymer of the poloxamer series to coat microcapsules. However, neither example 1 nor the subsequent examples based on example 1 specifically disclose microcapsules comprising all the features of the three types of microcapsules defined in present claim 1.

4.5.1.1. As regards the first type of microcapsules of present claim 1, there is no specific disclosure in document (1) that the microcapsules of example 1 or of the subsequent examples are capable of surviving a 0.25 s application of a pressure of 2.66 x 10**(4) Pa without bursting, collapsing or filling with water. Hollow microcapsules predominantly of 1.0-10 mym in diameter comprising this resistance to outside pressure are disclosed on page 15, lines 9-14 and in claim 17 of document (1), but not in context with block copolymers of the poloxamer series. Therefore, document (1) is not detrimental to the novelty of claim 1 as far as the preparation of the first type of microcapsules is concerned.

4.5.1.2. In connection with the second and third types of microcapsules of present claim 1 it is noted that the examples of document (1) do not specifically disclose the preparation of hollow microcapsules in which more than 30% of the microcapsules have a diameter within a 2 mym range (second type) or in which the interquartile range of diameters is 2 mym or less (third type).

As a consequence, the subject-matter of claim 1 of auxiliary request I is novel over document (1).

4.5.2 Claim 2:

Document (1) discloses a process for preparing hollow microcapsules by atomising a solution of a microcapsule-forming agent, preferably a proteinaceous material such as human serum albumin, and then insolubilising the microcapsules (see page 2, lines 6-9, 15-16; page 6, lines 9-16). The preparation to be sprayed may contain additional substances which are listed on page 7, line 25 to page 8, line 27. This list of compounds includes substances such as polyglutamic acid (page 8, line 3), which, being ionic, changes the charge of microcapsules. This general disclosure of preparing hollow microcapsules is applicable to all types of microcapsules subsequently described, including the microcapsules defined on page 15, lines 9-14 (which correspond to the first type of microcapsules of present claim 2), the microcapsules defined in the paragraph bridging pages 13 and 14 (which correspond to the second type of microcapsules of present claim 2) and the microcapsules defined on page 14, lines 3-4 (which correspond to the third type of microcapsules of present claim 2). It follows therefrom that document (1) discloses the inclusion of a material that changes the charge of microcapsules into or onto the wall of microcapsules as defined in present claim 2. It therefore has to be evaluated whether or not the feature "use of a material that changes the charge of microcapsules to selectively target the microcapsules to an area of the human or animal body", which constitutes the only potentially distinguishing feature of the claim, can establish novelty.

As was pointed out in paragraph 4.4.2 above, the subject-matter of claim 2 concerns a process for preparing hollow microcapsules. A process for preparing a composition is defined by the various process steps which are necessary in order to obtain the desired composition. The above feature, however, defines an effect of a compound used in the preparation of microcapsules, which has no influence whatsoever in their preparation: in both document (1) and the patent under appeal, the charged compound is preferably added to the wall-forming material before spray-drying (see page 7, lines 25-27 of document (1) and page 18, lines 25-29 of the original application). As a consequence, the above feature has merely an explanatory function and cannot therefore render novel the process for preparing hollow microcapsules as claimed in claim 2 of auxiliary request I. In this context, it is noted that, in view of the fact that the subject-matter of claim 2 concerns a process for preparation rather than a use of a compound for obtaining an effect, decision G 002/88 (OJ 1990, 093) does not apply in the present case. The requirements of Article 54 EPC are therefore not met.

4.5.3 In the light of the above finding, an evaluation of the novelty of independent claim 6 is not necessary.

5. Auxiliary request II:

Claim 2 of auxiliary request II is identical to claim 2 of auxiliary request I. As a consequence, the requirements of Article 54 EPC are not met for the same reasons as outlined in paragraph 4.5.2 above.

6. Auxiliary request III:

Claim 2 of auxiliary request III is identical to claim 2 of auxiliary request I, except that the material that changes the charge of microcapsules is now limited to a negatively charged polyamino acid, a phospholipid, hyaluronic acid and polygluconic acid. In view of the fact that in document (1) the list of compounds that may be added to the wall-forming material includes substances such as polyglutamic acid (negatively charged polyamino acid), the reasoning of paragraph 4.5.2 applies mutatis mutandis to claim 2 of auxiliary request III. As a consequence, the requirements of Article 54 EPC are not met.

7. Auxiliary request V:

7.1 Novelty:

Claim 1 of auxiliary request V is identical to claim 1 of auxiliary request I. As a consequence, the subject-matter as claimed therein is novel over document (1) for the same reasons as outlined in paragraph 4.5.1 above.

As none of the other documents cited in the course of the proceedings relates to the use of block copolymers of the poloxamer series for preparing hollow microcapsules, the subject-matter of claim 1 of auxiliary request V meets the requirements of Article 54 EPC.

7.2 Validity of the priority:

As the fact that the subject-matter of auxiliary request V is disclosed in the priority document was not contested by appellant-opponent II and the respondent, the only question to decide is whether the priority document constitutes the first application of the invention as required by Article 87 EPC or whether the appellant-patentee had already disclosed this invention in document (1). In this context, reference is made to paragraph 4.5.1, where the board came to the conclusion that the subject-matter of claim 1 was novel over document (1). It follows therefrom that the priority document constitutes the first application in the sense of Article 87 EPC. As a consequence, the priority is valid for the subject-matter as claimed in auxiliary request V.

7.3 Inventive step:

In view of the fact that the priority date of 10 October 1992 is the effective filing date for the subject-matter of auxiliary request V, document (1), which was published on 29 October 1992, does not constitute prior art applicable for inventive step.

Although the appellant-opponent II and the respondent were repeatedly informed by the board that post-published document (1) did not constitute state of the art for inventive step, they nevertheless based their reasoning exclusively on document (1) and did not cite any other evidence. Therefore, the board concluded that the argumentation with regard to lack of inventive step was not well founded. As a consequence, the board, being satisfied that the subject-matter of auxiliary request V is not obvious in the light of the common knowledge of the person skilled in the art, decides that the requirements of Article 56 EPC are met.