T 2455/18 (Controlled release formulations/ALPHAPHARM) 18-05-2021

1. Reimbursement of the appeal fees

1.1 According to appellant-opponent 02, the decision under appeal was insufficiently reasoned in the sense of Rule 111(2) EPC and was based on grounds on which the appellant-opponent 02 had no opportunity to present its comments. This failure amounted to a substantial procedural violation.

The points raised by appellant-opponent 02 are the following:

(a) The opposition division did not provide an adequate reasoning of its interpretation of claim 1 of all requests under point 33.2 of the decision. In the absence of any support of its claim interpretation, the opposition division's assessment under Article 123(2) EPC must be regarded as arbitrary.

(b) There was an inconsistency in the decision of the opposition division between the decision taken under Article 123(2) EPC with regard to the interpretation of the feature "comprising" in claim 1 as granted, and the requirement to reconsider example 4 of the contested patent as a reference example. This constituted a surprise to appellant-opponent 02 which had an incidence on its argumentation, in particular regarding inventive step, during the oral proceedings before the opposition division.

(c) It was furthermore unclear from the decision why the opposition division changed the formulation of the problem from "the provision of an improved controlled release formulation for...galantamine..., with a simplified manufacturing process" to "the provision of an improved controlled release formulation of...galantamine..., mimicking the biphasic release of D27 while providing a simplified manufacturing process". The opposition division was under the obligation to explain to the opponent why the formulation of the objective technical problem was changed during the oral proceedings. The decision under appeal was based on a ground on which the opponent had no opportunity to present its comments.

1.2 The Board cannot follow the appellant-opponent 02 on any of the raised points.

1.2.1 With regard to point (a), the decision of the opposition division states in point 33.2 that "the opposition division is of the opinion that the term "an uncoated pellet or mini-tablet" allows only one interpretation. By using just one indefinite article, the adjective "uncoated" clearly relates to both subjects, to "pellet" and to "mini-tablet"".

Hence, the opposition division gives a clear interpretation of the term "an uncoated pellet or mini-tablet" in paragraph 33.2, i.e that the adjective "uncoated" applies to both "pellet" and "mini-tablet" present in claim 1 of all requests as specified under point 33.1, hence applying to all requests.

The opposition division also gives a concrete reason under point 33.2 why they interpretated the term in this way and specified explicitly that it could not follow the argument of opponent 02 that the adjective "uncoated" applied only to the "pellet", which proves explicitly that the arguments of opponent 02 on this point were considered.

Moreover, the opposition division gives a complete reasoning as to Article 123(2) EPC in paragraph 36, which explains and clarifies its decision with regard to the subject-matter of claims 1, 10, 14 and 15. In this paragraph, the opposition division also provides its interpretation of the feature "an extended-release agent comprising a matrix".

Consequently, the objection of the appellant-opponent 02 on this point is not founded and the opposition division's assessment under Article 123(2) EPC cannot be regarded as arbitrary.

1.2.2 With regard to point (b), the opposition division states in point 36.1 of its decision that it agrees with the position of the patent proprietor that the wording "an extended-release agent comprising a matrix" is the same as the wording "an extended-release agent is a matrix" and that the change from "is" to "comprising" does not add subject-matter to the original disclosure. This point is extensively discussed in point 36.1 of the decision .

The decision of the opposition division cannot constitute a surprise for any party, since the opposition division concurred with the opinion and arguments provided by the patent-proprietor. Whether or not the decision on this point is convincing or justified is a different issue.

The considerations concerning example 4 of the patent, were submitted by appellant-opponent 2 for the first time during the oral proceedings. In the Board's view, the reformulation of example 4 of the patent, which relates to coated mini-tablets, is in line with the explanations and interpretation of the opposition division and does not present any inconsistency with the interpretation made by the opposition division in its decision with regard to the term "an extended-release agent comprising a matrix". It is noted in particular that example 4 was recalled as "comparative example", although this was contested by the patent-proprietor, and was not objected by any opponent (see the minutes of the oral proceedings before the opposition division ).

Consequently, the objection of the appellant-opponent 02 on this point is also not founded.

1.2.3 As regards point (c) the problem as defined by the opposition division in its decision on auxiliary request 14 is "the provision of an improved controlled-release formulation of zopiclone, galantamine, rosiglitazone or eszopiclone mimicking the biphasic release of D27, while providing a simplified manufacturing process".

The problem as defined by the patent-proprietor in its reply to the notices of opposition on claim 1 as granted was "the provision of an improved dosage form, where the improvement is simplified manufacture and ease of providing multiple doses" (see letter of 12 July 2017, point 7.3). Furthermore, in its letter of 13 June 2018 the patent-proprietor explains that the approach followed by the inventors allows the skilled person to "mimic the release profile of existing formulation approaches" (point 36). Indeed in point 31.6 of its decision the opposition division states the the patent proprietor formulated the technical problem as the provision of an improved dosage form mimicking the biphasic release of the dosage form of D27 while providing a simplified manufacturing process.

Hence, in formulating the technical problem the opposition division essentially endorsed the arguments of the patent proprietor which were known to the opponents.

The Board notes furthermore that appellant opponent-02 considered D27, corresponding to the commercial product Reminyl® as closest prior art, in particular example 5 of D27 which discloses capsules comprising a mixture of controlled release pellets and immediate release pellets of galantamine, i.e. providing a biphasic release of galantamine. The appellant-opponent 02 defined in its notice of opposition the problem over D27 as "providing an alternative controlled release formulation for galantamine that is suitable for Reminyl® titration regimen".

Hence, the problem as defined by the opposition division in its decision is based on the problem as it was posed by the patent-proprietor, with the specification of the active ingredients claimed in auxiliary request 14, and this formulation cannot constitute a surprise to any party.

Moreover, apart from the recognition of the existence of an improved controlled release formulation, the problem as defined by the opposition division is also essentially based on the problem as it was also defined by opponent 02 in the written opposition proceedings, in view of the disclosure of D27 or the product Reminyl®.

The formulation of the objective technical problem was therefore not changed by the opposition division during the oral proceedings and cannot constitute a surprise to appellant-opponent 02. Moreover, the decision under appeal is based on a ground on which the opponent had an opportunity to present its comments, as highlighted by the minutes of the oral proceedings before the opposition division.

Consequently, this point is also not founded.

1.3 Consequently, the objections raised by appellant-opponent 02 appear to represent a criticism of the decision of the opposition division. They neither substantiate a violation of the right to be heard nor a fundamental deficiency in the decision of the opposition division, which is sufficiently reasoned within the meaning of Rule 111(2) EPC.

Consequently, there is no substantial procedural violation which would justify a reimbursement of the appeal fee under Rule 103(1)(a) EPC.

2. Admission of auxiliary requests 6, 7, 9-11 and main request a, auxiliary requests 1a, 2a, 4a, 5a, 6a, 7a, 8a, 9a and 10a, 12-17 and 12a-17a into the proceedings.

2.1 According to appellant-opponent 01, auxiliary requests 6, 7, 9-11 and main request a, auxiliary requests 1a, 2a, 4a-10a should not be admitted into the appeal proceedings since they could have been filed earlier during the opposition proceedings.

2.1.1 These requests were filed at the earliest stage of the appeal proceedings, i.e. with the statement of grounds of appeal of the appellant-proprietor. In said sets of claims, auxiliary request 8 corresponds to auxiliary request 14 maintained by the opposition division.

2.1.2 Article 12(4) RPBA 2007 gives the Board a discretion not to admit requests which could have been presented before the first instance. The purpose of this provision is to avoid that fresh cases be made on appeal and to underline the review character of the appeal procedure. However, also in this context procedural economy and efficiency is a criterion which needs to be considered. In the present case many requests were filed with the statement of grounds of appeal. As pointed out in the Board's communication, some of them can be seen as a reasonable reply to the first instance decision and therefore were to be admitted, while with some others this seemed questionable. In such a case it is sometimes easier to admit all of them, instead of giving reasons for each individual request why it was or was not to be admitted. This applies specifically when the Board can easily deal with these requests and the substantive examination poses no additional problems. In such a situation procedural economy prevails. Hence these requests are admitted.

2.1.3 The same conclusions apply to auxiliary requests 12-17 and 12a-17a,which had been filed with the reply to the appellant-opponents grounds of appeal.

3. Main request

3.1 Amendments

3.1.1 Claim 1

Claim 1 of the patent application as originally filed reads:

"1. A controlled-release formulation comprising one or more distinct and discrete units located in physical juxtaposition to enable administration to a patient in need of treatment in a single dose, characterised in that the or each unit comprise (s) :

(i) a unit dose of an active pharmaceutical ingredient or pharmaceutically acceptable salt thereof;

(ii) one or more extended-release agent(s); and, optionally,

(iii) one or more pharmaceutically acceptable excipients, wherein the sum of the unit dose(s) constitutes a pharmaceutically effective amount of the active pharmaceutical ingredient."

Claim 1 as granted reads as follows with the main amendments shown in bold:

"1. A controlled-release formulation comprising 1 to 20 distinct and discrete units located in physical juxtaposition within a capsule to enable administration to a patient in need of treatment in a single dose, wherein each unit comprises:

(i) a unit dose of an active pharmaceutical ingredient or pharmaceutically acceptable salt thereof;

(ii) an extended-release agent comprising a matrix of one or more polymers; and, optionally,

(iii) one or more pharmaceutically acceptable excipients,

each unit being in the form of an uncoated pellet or mini-tablet, wherein the sum of the unit doses constitutes a pharmaceutically effective amount of the active pharmaceutical ingredient."

The features "1 to 20" and "within a capsule" find a direct disclosure on page 11, line 20 and page 14, lines 14-15 and original claims 7 and 10 of the application as filed. The feature "each unit being in the form of an uncoated pellet or mini-tablet" finds a direct basis on page 11, lines 1-2 of the application as filed.

The feature "comprising a matrix of one or more polymers" originates from original dependent claim 12 which reads "A formulation as claimed in any one of claims 1 to 11 wherein the extended release agent is a matrix comprising one or more polymers". The reformulation of the wording of claim 12 from "is" to "comprising" has been questioned by appellant-opponents 01 and 02.

In the Board's view, both terms do not have the same meaning, since the term "comprising" does not exclude the presence of a further additional component as part of the extended release agent, which is not disclosed in the original application, while the originally used term "is" limits the extended release agent solely to a matrix. Consequently, the term "comprising a matrix of one or more polymers" does not find a basis in the application as filed. The subject-matter of claim 1 does not meet the requirements of Article 123(2) EPC for this reason.

3.1.2 Dependent claim 10

Dependent claim 10 reads:

"10. A formulation as claimed in any one of claims 1 to 9 which is a tablet formulation comprising a matrix of one or more pharmaceutically acceptable excipients and a plurality of units comprising a predetermined amount of an active pharmaceutical ingredient and one or more extended release agents, the plurality of units dispersed within said matrix."

Having regard to the reference to claim 1, claim 10 appears to relate to a tablet comprising a capsule.

The subject-matter of this claim originates from original claim 26, which relates to a tablet formulation and not to a capsule formulation as claimed in claim 1 of the main request. A tablet form was presented in the original application as an alternative formulation to a capsule form, and not as a tablet comprising a capsule, for which there is no basis (see original application, page 14, lines 17-21).

The Board also agrees with the conclusion of the opposition division, in that original claim 26 was an independent claim which does not comprise the technical features of claims 1-9 as granted, and that it cannot serve as valid basis for dependent claim 10 being dependent from claims 1-9 as granted.

The subject-matter of claim 10 of the main request does not meet the requirements of Article 123(2) EPC.

3.1.3 Dependent claim 14

Dependent claim 14 reads:

"14. The formulation as claimed in claim 13 wherein the unit dose of galantamine is 8 mg."

A basis for "the unit dose of galantamine is 8 mg" can be found on page 11, lines 4-17 of the original description which mentions also the size of the corresponding units having this specific dose. The Board agrees with the opposition division that the claimed dose is linked with the pellet diameter given in the same passage and the feature "the unit dose of galantamine is 8 mg" cannot be taken in isolation from said passage.

Consequently, the subject-matter of claim 14 does not meet the requirements of Article 123(2) EPC.

3.1.4 Dependent claim 15

Dependent claim 15 reads:

"15. The formulation of claim 14 consisting of 1, 2 or 3 units, wherein each unit comprises:

(i) a unit dose of 8 mg of galantamine;

(ii) a polymer matrix which is a mixture of polyvinylpyrrolidone and polyvinylacetate;

(iii) hydrogenated vegetable oil;

(iv) povidone; and

(v) magnesium stearate."

The subject-matter of claim 15 is based on example 2 and represents an unallowable generalisation of said example, as it was also decided by the opposition division. Said example comprises numerous features which were omitted in dependent claim 15, such as inter alia the amounts of excipients or the size of the mini-tablets.

Consequently, the subject-matter of claim 14 does not meet the requirements of Article 123(2) EPC.

3.1.5 Accordingly, the main request does not meet the requirements of Article 123(2) EPC in view of the deficiencies illustrated above in claims 1, 10, 14 and 15.

3.2 Novelty over D19

Example 1 of document D19 discloses a capsule with two uncoated pellets made from metformin HCl in a polymeric matrix of Polyox which provides a controlled release of metformin. Consequently, the subject-matter of at least claim 1 of the main request lacks novelty over D19, and the main request does not meet the requirements of Article 54 EPC.

4. Main request a, auxiliary requests 1, 1a 2, 2a

Claim 1 of the main request a and of auxiliary requests 1, 1a 2, 2a is identical to claim 1 of the main request and therefore lacks novelty over D19, and does not find a basis in the original application.

Moreover dependent claims 10 and 11 of the main request a, and dependent claims 13, 14 of auxiliary requests 1 and 1a correspond to dependent claims 14 and 15 of the main request and do neither find a basis in the application as filed.

Consequently, the main request a, auxiliary requests 1-2 and 1a-2a do not meet the requirements of Article 54 EPC and Article 123(2) EPC.

5. Auxiliary requests 3-5 and 3a-5a

Claim 1 of these requests has been amended by the feature:

"(ii) an extended-release agent which is a matrix of one or more polymers;".

This amendment has no incidence on the assessment of lack of novelty over D19, since the extended release agent in example 1 of D19 is limited to a matrix polymer. Consequently, none of these requests meet the requirements of Article 54 EPC.

Moreover, claims 10, 14 and 15 of auxiliary request 3 correspond to claims 10, 14 and 15 of the main request and claims 10 and 11 of auxiliary request 3a, claims 13, 14 of auxiliary request 4 and claims 9, 10 of auxiliary request 4a correspond to claims 14 and 15 of the main request, and therefore have no basis in the application as filed. Consequently, these requests do also not meet the requirements of Article 123(2) EPC.

6. Auxiliary requests 6-8 and 6a-8a

These requests still comprise in claim 1 the feature "(ii) an extended-release agent comprising a matrix of one or more polymers;" which is also present in the main request.

Auxiliary requests 6, 6a, 7, 7a also comprise dependent claims corresponding to dependent claims 14 and 15 of the main request, namely claims 13 and 14 of auxiliary request 6, claims 9 and 10 of auxiliary requests 6a, claims 12 and 13 of auxiliary requests 7, claims 8 and 9 of auxiliary requests 7a.

Consequently, auxiliary requests 6-8 and 6a-8a do not meet the requirements of Article 123(2) EPC for the same reasons as the main request.

7. Auxiliary requests 9-10 and 9a-10a

Dependent claims 9, 13, 14 of auxiliary request 9 correspond to claims 10, 14 and 15 of the main request; dependent claims 9 and 10 of auxiliary request 9a, dependent claims 12 and 13 of auxiliary request 10, and dependent claims 8 and 9 of auxiliary request 10a correspond to dependent claims 14 and 15 of the main request.

These claims have no basis in the application as filed for the same reasons as the main request.

Consequently, these requests do not meet the requirements of Article 123(2) EPC.

8. Auxiliary request 11 and 11a - Inventive step

8.1 Claim 1 of auxiliary request 11 and 11a are identical and have been amended by the introduction of the feature "(ii) an extended-release agent which is a matrix of one or more polymers" and by the restriction to some specific active ingredients, namely "wherein the active pharmaceutical ingredient is selected from zopiclone, zolpidem, galantamine, rosiglitazone and eszopiclone, or pharmaceutically acceptable salts thereof".

8.2 The invention relates to modified release pharmaceutical compositions.

8.3 The opposition division considered D27 (corresponding also to D3) to be the closest prior art since inter alia this document was the only document which related specifically to galantamine, which is one of the claimed active ingredient. D27 is also the choice of the appellant-proprietor and the Board agrees that this is a reasonable starting point.

D27 discloses capsules comprising sugar spheres coated with an active agent such as galantamine and over-coated with an extended release polymer. Example 4 discloses furthermore the presence of immediate release mini-tablets in the capsule, namely 75% of controlled release pellets and 25% immediate release tablet in the capsule. Said formulation is prepared through a multi-step manufacturing process. This document does not disclose an extended release agent which is a matrix of one or more polymers and shows on the contrary coated particles.

8.4 According to the appellant-proprietor, the problem can be seen as the provision of an improved dosage form, where the improvement is a simplified manufacture and ease of providing multiple doses with an appropriate pharmacokinetic profile.

8.5 The problem as defined by the appellant-proprietor is solved in a credible manner. Table 1 of the contested patent shows that formulations according to the claimed invention, here the capsules filled with mini-tablets as disclosed in examples 1-3, provide an extended release of galantamine. Moreover, the process of preparing the formulations of examples 1-3 is a simple mixing and compression step of the active ingredient and excipients in mini-tablets and their filling in capsules.

8.6 The solution to the problem is the use of an extended release agent which is a matrix of one or more polymers, each unit being in the form of an uncoated pellet or mini-tablet.

8.7 The question remaining is whether the skilled person, starting from the teaching of D27, in particular example 4, would arrive at the subject-matter of claim 1 of auxiliary request 11 in an obvious manner in order to solve the problem posed.

Documents D31-D33, D35 and D41 have been cited by the appellant-opponents to show that the claimed solution is obvious.

D31 is a common general knowledge document relating to capsules. It discloses capsules filled by mini-tablets on page 326 in Figure 14.41. On pages 357 and 358, D31 discusses the preparation of capsules filled with multiple units in the form of tablets or pellets (see page 357, par. 6.2.1) and specifies that said pellets or tablets may be in a coated form or in a matrix form embedding the active ingredient (see page 358).

D32 discloses the filling of solid dosage forms, such as tablets into hard gelatin capsules (see pages 170 and 171, Figure 12 on age 171).

D33 discloses also the filling of capsules with mini-tablets (see page 21).

D35 discloses the preparation of encapsulated mini-tablets providing a controlled release. D35 particularly points out that such systems are easier to manufacture compared to coated multi-particulate systems (see D35, page 12).

D41 discloses mini-tablets based on a matrix of wax and starch incorporated in a gelatin capsule (see pages 195-197). This document emphasizes the ease of manufacture of such mini-tablets (see page 195, right-hand column).

It emerges from these documents and their teachings that formulations comprising discrete units based on a matrix system and located within a capsule were well-known before the priority date. Thus, the claimed solution was not only known, but common. Equally known were the advantages linked to the solution, i.e. a simplified manufacture and the ease of providing multiple doses with an appropriate pharmacokinetic profile.

Therefore, the claimed solution is not inventive and auxiliary requests 11 and 11a do not meet the requirements of Article 56 EPC.

9. Auxiliary request 12-14, 12a-14a - Inventive step

In comparison to claim 1 of auxiliary requests 11 and 11a, the subject-matrix of claim 1 of these requests has been amended by the introduction of the term "comprising" in "(ii) an extended-release agent comprising a matrix of one or more polymers" and it has been restricted to a specific active ingredient, namely "and wherein the active pharmaceutical ingredient is galantamine or a pharmaceutically acceptable salt thereof".

These features do not constitute a further technical difference over the closest prior art D27, and the conclusion reached for auxiliary requests 11 and 11a applies mutatis mutandis to these requests.

Consequently, auxiliary requests 12-14 and 12a-14a do not meet the requirements of Article 56 EPC.

Furthermore, the feature "(ii) an extended-release agent comprising a matrix of one or more polymers" does not comply with the requirements of Article 123(2) EPC for the reasons discussed in point 3.1.1 above.

10. Auxiliary requests 15-17, 15a-17a

In comparison to claim 1 of auxiliary requests 11 and 11a, the subject-matrix of claim 1 of these requests has been restricted to a specific active ingredient, namely "and wherein the active pharmaceutical ingredient is galantamine or a pharmaceutically acceptable salt thereof".

This feature does not constitute a further technical difference over the closest prior art D27, and the conclusion reached for auxiliary requests 11 and 11a applies mutatis mutandis to these requests.

Consequently, auxiliary requests 15-17 and 15a-17a do not meet the requirements of Article 56 EPC.