T 1869/19 (Ocular implant obtained by double extrusion process/Allergan Inc.) 07-06-2022

Reasons for the Decision

1. Main request - Novelty

1.1 Claim 1 has been drafted in the form of a mix of "product features" and "product-by-process features".

Hence, claim 1 of the main request comprises as essential "product features" a bioerodible implant comprising PLGA and from 40 to 80 wt% dexamethasone as active agent dispersed within a biodegradable PLGA matrix, wherein at least 75% of the particles of the active agent have a diameter of less than 10 mym.

The claimed bioerodible implant is further characterized by "product-by-process features", comprising the essential following preparation steps:

- (a) milling the PLGA;

- (b) blending the milled PLGA and the particles of the active agent,

-(c) carrying out a first extrusion of the blended mixture

- (d) pelletizing the first extrusion product,

- (e) carrying out a second extrusion of the pelletized first extrusion product.

1.2 D1 discloses in example 4 the preparation of a 50/50 Dexamethasone/PLGA ocular implant:

- 2.5 g of PLGA of particle size approximately 9-12 mym in diameter were placed in a mixing vessel. The vessel was placed in the oven at 130°C for ten minutes.

- 2.5 g of dexamethasone of particle sizes less than approximately 10 mym in diameter, were added to the vessel, and the vessel was returned to the oven for 10 minutes.

- The PLGA/dexamethasone mixture was mixed well, the blend loaded into a barrel, and 650-790 mym diameter filaments were extruded. The resulting filaments were cut into lengths of approximately 0.94 and 1.87 mm for 500 myg and 1000 myg formulations, respectively.

D1 mentions that the extrusion temperature is comprised between 60 and 130°C (see D1 par. [00054] and [00055]).

Since D5 discloses exactly the same experiments in example 6, only D1 will be considered for the assessment of novelty.

1.3 Accordingly, the document D1 discloses the same "product features" as claim 1 of the main request regarding the type and amounts of active and polymer.

With regard to the "product-by-process features", the biodegradable implant of D1 is prepared by a single extrusion and pelletization step. D1 does not discloses the following steps involved in the preparation of the claimed implant:

- step (a) milling the PLGA,

- step (b) blending the milled PLGA and the particles of the active agent, to thereby obtain a blended mixture of the milled PLGA and the particles of the active agent and

- step (e) carrying out a second extrusion of the pelletized first extrusion product, thereby obtaining the bioerodible implant.

With regard to these product-by-process features, such features can only contribute to the novelty of the claimed implant insofar as they give rise to a distinct and identifiable characteristic of the product. Accordingly, in order to establish novelty, it has to be verified that the process features of the "product-by-process" claim are such that the resulting product is influenced by them in a way that it can be distinguished from the products of the prior art produced by a different process.

Moreover, where a process feature is the only feature allegedly conferring novelty to a product, the burden of proof for showing the fact that the process feature results in a distinct and identifiable characteristic of the product is on the patent proprietor, e.g. by means of a convincing technical argumentation or comparative tests.

1.3.1 In the absence of any limitation in claim 1 as to the conditions of the milling steps (a) and (b), and considering that the size of dexamethasone in D1 is identical to the claimed size, namely a diameter of less than 10 mym, and the size of PLGA in D1 is comprised between 9-12 mym in diameter while undefined in claim 1 of the main request, it must be concluded that the milling steps (a) and (b) cannot impart any identifiable differentiating feature to the implant. This conclusion was not disputed by the appellant.

1.3.2 The implant of claim 1 is defined by the further extrusion step (e), specifically comprised in a sequence of (c) first extrusion, (d) pelletizing the first extrusion product and (e) second extrusion, constituting a double extrusion process, instead of a simple extrusion process in D1. According to the appellant, these steps lead to the preparation of implants having a higher density and less brittleness than a single extruded one.

While the Board has no doubt that a double extrusion process might have an effect on the structure of the obtained implant, in particular its density, this effect on the structure remains linked with the extrusion parameters used in the preparation of the claimed implant. None of the extrusion parameters are however defined in claim 1.

The importance of the extrusion parameter is emphasized in the description of the contested patent which mentions that "extrusion parameters such as temperature, extrusion speed, die geometry, and die surface finish will have an effect on the release profile of the implants produced" (see paragraph [0113]). It appears that in particular the set temperature, the screw speed and the die nozzle diameter (die geometry and die surface finish) are essential extrusion parameters having an incidence on the structure of the extruded implant. D1 also teaches the importance of the extrusion parameters, namely by specifying that "extrusion methods result in implants with a progressive more homogenous dispersion of the drug within the polymer, as the production temperature is increased" (see par. [0054]).

This is also confirmed by the experiments of D7 on which the appellant relied to show that implants obtained by a double extrusion step have a higher density than implants obtained by a single extrusion step. In the experiments of D7, three implants were prepared. Implant 1 was prepared through a double extrusion, i.e. first extrusion at a barrel temperature of 105°C and screw speed of 120 rpm, second extrusion at a barrel temperature of 107°C and screw speed of 100 rpm. Implants 2 and 3 were prepared using a single extrusion step with barrel temperature of 105°C, the latter with a higher screw speed, namely 200 rpm instead of 120 rpm. Implant 1 shows a greater geometric density as illustrated by the following Table:

FORMULA/TABLE/GRAPHIC

Hence, these experiments show that a double extrusion process might be able to produce a product with different characteristics than with a single extrusion, in particular in term of density. The experiments of D7 however cannot reflect the full scope of the claim and are bound to the specific extrusion parameters used therein. Importantly, these experiments show also the weight of the extrusion parameters in the properties and structure of the final extruded product, since it was possible to obtain an implant 3 with a higher geometric density with a single extrusion simply with a higher screw speed, namely 200 rpm, instead of 120 rpm.

The importance of the extrusion parameters is further illustrated by the experiments of example 8 of the contested patent. In this example, it was possible to produce an implant through a first single extrusion step with a final geometric density comprised between 0.85 and 1.14 g/cm3 (see Table D), hence higher than the density obtained for implant 3 of D7 and potentially identical to the density of implant 1 obtained by a double extrusion.

In the present case, the claimed subject-matter includes implants obtained by extrusion processes performed under extreme conditions, such as a cold extrusion at slow screw speed, as well as a melt extrusion at very high speed. Hence, no conclusion can be drawn from the patent on the effect of carrying out the double extrusion, for instance in much less stringent conditions. As a result, claim 1 covers embodiments in which the double extrusion steps is conducted in such mild conditions that the resulting implant cannot differ structurally from those reported in D1. In this respect, the question is not whether the teaching of the prior art is sufficiently complete or can be modified so as to obtain the same properties as obtained in some examples of the patent or in the experiments of D7, but rather whether the claim is so broadly defined, in respect of the process conditions, as to cover implants that are necessarily undistinguishable from that of D1.

In its declaration of 23 October 2018 (document D6), Mr Salameh states that in his opinion a double extrusion method could not be used to achieve a density value which is the same as, or similar to, the density observed in the single extruded sample of the experimental report D7. However, as explained above, in the absence of any limitation as the conditions in which the double extrusion is performed, claim 1 covers implants that could have very different densities.

1.4 Consequently, the Board concurs with the opposition division that a double extrusion as claimed in claim 1 of the main request does not inevitably cause the obtainable product to have distinctive properties and to be distinguishable from a bioerodible PLGA/dexamethasone ocular implant made by single extrusion as disclosed in D1 (see Decision of the opposition division, point 2.5).

1.5 Accordingly, the claimed subject-matter is not novel over D1.

2. Auxiliary request 1 - Admission into the appeal proceedings

2.1 The subject-matter of the sole claim 1 of this request specifies that the extrusion steps are carried out using a single or twin screw extruder.

2.2 This request was late filed by the Patentee on 9 November 2018 namely five years after the notice of opposition. An objection of lack of novelty over D1 was already raised and the opposition division had already summoned the parties on 14 September 2018, with a negative preliminary opinion on novelty of the main request. The opposition division did not admit this request since it was late filed and it did not prima facie overcome the outstanding issues regarding novelty. The opposition division considered that the use of a certain type of extruder could not address the remaining objections, because in the absence of any limitations as to the processing parameters, the use of common extruders could not give rise per se to a distinct and identifiable property of the obtainable implant.

Moreover, the auxiliary request was not a response to new issues raised in, or to a change of the facts of, the present case.

Indeed, as explained in the decision, according to the Patentee's own explanation, the filing of the Auxiliary request was a reaction to the Board's decision T 726/16 of revocation of the earlier (parent) patent EP 1 870 092 (07017089.9). The oral proceedings for the case T 726/16 took place on 30 October 2018.

2.3 The question as to whether this request should be admitted must be decided on the basis of Article 12(4) RPBA 2007 (see Article 25(2) RPBA 2020). Article 12(4) RPBA 2007 gives the Board discretion to hold inadmissible requests which could have been presented or were not admitted in the first instance proceedings.

A Board of appeal should only overrule the way in which a department of first instance has exercised its discretion when deciding on a particular case if it concludes that it has done so according to the wrong principles, or without taking into account the right principles, or in an unreasonable way, and has thus exceeded the proper limits of its discretion (see T 640/91 (point 6.3) and G 7/93 (reasons 2.6)).

In the present case, the Board considers, that the opposition division had the discretion not to admit these requests, which were submitted well after the expiry of the time limit set under Rule 79(1) EPC for replying to the opposition. This all the more since the facts had not changed, because an objection of lack of novelty over D1, in particular in view of the double extrusion step was already present in the opponent's notice of opposition.

The Board agrees furthermore with the opposition division that the amendment introduced in claim 1 only amounts to a recitation of extruder types commonly used in the art. This amendment cannot possibly address the novelty objection in the absence of any limitation as the processing parameters, and the use of common extruders cannot give rise per se to a distinct and identifiable property or structure of the implant. Moreover, as discussed during the oral proceedings before the Board, example 4 of D1 mentions that the PLGA/dexamethasone blend was loaded "into a barrel", which appear to implies that the extruder used in D1 is a single or twin screw extruder.

In view of these facts, the Board concludes that the opposition division exercised its discretion in accordance with the right principles and not in an unreasonable way. Accordingly, the auxiliary request is not admitted into the appeal proceedings (Article 12(4) RPBA 2007).