T 0851/19 (Tablets comprising Sorafenib Tosylate / BAYER HEALTHCARE LLC) 17-02-2022

1. Transfer of the appellant's representation

Dr Andreas Altmann filed an opposition against the patent in suit. Dr Altmann is both the opponent and a professional representative. In a letter dated 12 August 2019, signed by Dr Altmann, the following was stated: "The representation in the above-mentioned appeal procedure by our law firm has been finished. All further correspondence shall be sent [...] to Elkington and Fife LLP [...]". On the day of the oral proceedings Dr Mullen, a European patent attorney with Elkington and Fife LLP, who had also signed the appellant's submissions of 28 November 2019 and had been announced to attend the oral proceedings, appeared as representative for the appellant.

The respondent questioned that Dr Mullen was duly authorised to undertake the representation for the appellant. The wording of the letter dated 12 August 2019 where it was stated that "The representation in the above-mentioned appeal procedure by our law firm has been finished" was in the respondent's view not unambiguous and might imply a withdrawal of the opposition or the appeal.

The Board cannot follow this argument. An opposition or an appeal can only be withdrawn if such a request is expressed by the opponent or appellant in unambiguous terms. The above-mentioned letter clearly does not lend itself to such an interpretation. Furthermore, one of the usual ways of transferring representation from one attorney or law firm to another is precisely what has happened in this case: that one attorney or firm indicates that they lay down representation and give the details of the new representatives to the EPO. Dr Mullen confirmed during the oral proceedings that he was duly authorised to represent the appellant. The Board has no reason to doubt that.

2. Admittance of documents D13, D15 and D17-D21

2.1 The appellant objected to the admittance of D17-D19 into the appeal proceedings. The respondent submitted that D13, D15, D20 and D21 should not be admitted into the proceedings either.

For the following reasons, the Board takes the view that all of these documents are part of the appeal proceedings.

2.2 D17-D21 were all presented during the first instance proceedings and admitted by the opposition division (see the decision under appeal, points 3.3.1-3.5 of the reasons). The opposition division referred explicitly to D20 and D17 in its reasoning on the issues of sufficiency of disclosure and inventive step (see points 5 and 6.4 of the reasons). The appellant and respondent refer to D20-D21 and D17-D19 respectively in their grounds of appeal (see e.g. page 6 and 16) and reply thereto (see pages 8-10).

Consequently, since D17-D21 are neither evidence which could have been presented in the first instance proceedings (i.e. but was not), nor evidence which was not admitted, the discretionary power to hold such evidence inadmissible under Article 12(4) RPBA 2007 does not apply to these documents. Accordingly, these documents are to be taken into account in the appeal proceedings.

2.3 D13 and D15 were filed during the earlier appeal proceedings leading to decision T 489/13. Both decision T 489/13 (see point 5 of the reasons) and the appealed decision (see point 3.2.1 of the reasons) leave their admittance undecided. Hence there is no decision not to admit D13 or D15 in the proceedings.

Consequently, as for documents D17-D21, the discretionary power to hold such evidence inadmissible under Article 12(4) RPBA 2007 does not apply to D13 and D15. The Board considers that D13 and D15 are to be taken into account in the appeal proceedings.

3. Auxiliary request 1, inventive step

3.1 Auxiliary request 1 is the appellant's highest ranking request.

3.2 Claim 1 of auxiliary request 1 pertains to immediate release tablets comprising at least 55 wt% sorafenib tosylate. The objective of the invention is to provide a pharmaceutical sorafenib composition which should be applied no more than three times a day in order to achieve an effective plasma level of sorafenib. The tablet should not be too large, to provide good swallowing, and no more than two should have to be taken at the same time (see paragraph [0005] of the patent).

3.3 Both parties consider D1 to be a suitable starting point for the assessment of inventive step.

D1 discloses aryl ureas with angiogenesis inhibiting activity, in particular sorafenib tosylate (see claim 22 of D1). D1 further mentions that the compounds shown therein may be administered orally (see page 25, bottom paragraph) and that compositions intended for oral use may be in the form of tablets (see page 26, first full paragraph). As established in T 489/13 (see points 1.1 and 2.5-2.8), sorafenib tosylate is individualized in claim 22 of D1, such that its combination with the general disclosure relating to tablets only requires one selection among the dosage forms mentioned in D1. Thus, D1 discloses tablet forms of sorafenib tosylate.

However, the Board does not share the appellant's opinion that D1 discloses, in combination, the features pertaining to immediate release tablets comprising sorafenib tosylate. The first full paragraph on page 26 of D1 generally discusses compositions intended for oral use. This paragraph mentions in particular tablets, including coated tablets with delayed disintegration and adsorption (see lines 15-19). This passage is followed by the statement "These compounds may also be prepared in solid, rapidly released form". This statement logically pertains to alternatives to the delayed release tablet mentioned earlier. However, D1 does not clearly and unambiguously disclose that this alternative is a rapid release tablet, but only that it is, more generally, a solid, rapidly released form.

3.4 Thus, the subject-matter of claim 1 differs from the disclosure of D1 by the drug load of at least 55% by weight and in that the tablet is an immediate release tablet.

3.5 Turning to the technical effect associated with these differences, the respondent contends that the highly loaded tablet formulation of the invention allows for the preparation of small, easy to swallow dosage forms resulting in a high patient compliance. In addition, the tablets show immediate release characteristics associated with good bioavailability, high stability and sufficient hardness.

3.5.1 The Board accepts, and the appellant does not contest, that formulating the tablets with a high drug load of at least 55 wt % sorafenib facilitates administration and, consequently, patient compliance, since smaller and/or fewer tablets will then be needed for administering a given dose of the drug (see T 489/13, point 2.10 of the reasons).

The claimed tablets necessarily exhibit an immediate release since this is a feature of claim 1.

3.5.2 The Board however does not consider that the above differentiating features credibly lead to any improvements with respect to the further characteristics alleged by the respondent (namely bioavailability, stability or hardness).

In order to demonstrate that these effects are achieved by the claimed invention, the respondent relies on D12a, D12b and D17-D19. D12a and D12b show the dissolution behavior of highly loaded tablets comprising sorafenib free base and sorafenib tosylate, and differing additionally by the amount of microcrystalline cellulose. D17-D19 report the drug release properties, hardness and disintegration time of tablets comprising different sorafenib forms/salts.

However, the comparisons made in D12a, D12b and D17-D19 relate to the effect of choosing sorafenib tosylate over other forms of sorafenib. The closest prior art D1 already discloses sorafenib tosylate. Thus, D12a, D12b and D17-D19 do not suitably show any technical effect associated with the distinguishing features over the closest prior art, namely the drug load and the immediate release.

3.6 Accordingly, the technical problem starting from D1 is the provision of tablets of sorafenib tosylate leading to improved patient compliance.

3.7 Obviousness

3.7.1 The skilled person starting from the sorafenib tosylate tablets of D1 and seeking ways to improve patient compliance would turn to higher drug loads as a straightforward solution to the problem, since this would allow the administration of the required dose either with smaller tablets or with fewer tablets. A drug load of at least 55 wt% would be considered by the skilled person as a matter of routine considering the common general knowledge reflected in D4, a textbook on tablet development (see page 64, last complete paragraph; page 65, table 2/1). Following D4, in the case of tablets which are to be swallowed, it will generally be the aim of the formulator to achieve small tablet sizes. D4 further mentions that for active agent contents of 350-550 mg (which encompasses the recommended oral daily dose of sorafenib of around 400 mg, see D6, page 1144, column 2; page 1145, column 1; and D7, abstract), typical drug loadings extend well above 55 wt%.

3.7.2 Furthermore, immediate release tablets and how to formulate them are part of the common general knowledge. Immediate release is the most common form of tablet, and it is well-known that such a formulation allows release of the active agent in a rapid manner. The closest prior art D1 (see page 26, lines 19-20) suggests solid, rapidly released forms, which corresponds to the definition of "immediate release" in the patent (see paragraph [0027]) as a delivery of the compound in a rapid manner. In this respect, the much narrower parametric feature appearing later in the same paragraph of the patent ("forms having a Q-value (30 minutes) of 75% due to USP-release method with device 2 (paddle, 75 rpm, in 0.1M HCl + 1% sodium dodecylsulfate)") is neither the commonly accepted definition of an immediate release form nor is it a feature of claim 1. The respondent's contention that "immediate release" should be so narrowly interpreted in light of the description amounts to an attempt to read into claim 1 features which it does not comprise.

3.7.3 The Board cannot share the respondent's position that there is any prejudice against, or any technical difficulty in, formulating the tablet with both a high drug load and as an immediate release form. On the contrary, immediate release tablets use fewer excipients relative to other tablet forms because they do not require anything to retard the release of the drug. Thus the skilled person would all the more consider immediate release forms in the case of high drug loads since these allow for lower amounts of excipients. Furthermore, the general teaching of D4 regarding high drug loads is not limited to any particular tablet type, and there is no reason to assume that this teaching should not be applicable to immediate release tablets.

3.7.4 Lastly, the respondent's position is that the prior art does not give the skilled person any motivation to choose the tosylate salt of sorafenib to provide immediate release tablets having the claimed high drug load. An inventive step over D1 can however not be based on the choice of sorafenib tosylate, or on any technical effect associated with the choice of this salt, since sorafenib tosylate is already disclosed in the closest prior art D1, and is even the sole specific salt of sorafenib shown therein.

3.8 Accordingly, the subject-matter of auxiliary request 1 does not meet the requirements of inventive step.

4. Auxiliary requests 1A and 6A, admittance

The respondent filed auxiliary requests 1A and 6A by letter dated 11 January 2022, thus after notification of the summons to oral proceedings dated 3 May 2021. Auxiliary requests 1A and 6A correspond respectively to auxiliary requests 1 and 6 with an additional limitation to compositions with a hardness of more than 80 N.

Under Article 13(2) RPBA 2020, any amendment to a party's appeal case made after notification of a summons to oral proceedings shall, in principle, not be taken into account unless there are exceptional circumstances, which have been justified with cogent reasons by the party concerned.

The filing of auxiliary requests 1A and 6A represents a change in the respondent's case. The respondent argues that these new requests result from combinations of claims of the granted patent or of auxiliary requests 1 or 6, and thus were under investigation from the beginning of the opposition proceedings. However, the respondent does not contest that the limitation of the claimed subject-matter to a hardness of more that 80 N represents a change of case. Indeed, the respondent did not, at any earlier point in the appeal proceedings, discuss the relevance of this particular feature to inventive step.

Furthermore, the respondent did not justify the late filing of auxiliary requests 1A and 6A. The respondent submitted that this late filing was in direct reaction to the Board's preliminary opinion, in particular the considerations pertaining to D13 (see the communication under Article 15(1) RPBA, paragraph 2.3). However, this communication did not contain any argument or objection which had not been raised by the parties before. Hence, the Board can identify no exceptional circumstances in the present case to justify the late filing of auxiliary requests 1A and 6A.

Accordingly, auxiliary requests 1A and 6A were not admitted into the appeal proceedings.

5. Auxiliary requests 3, 4, 6 and 8, inventive step

5.1 Claim 1 of auxiliary request 3 differs from claim 1 of auxiliary request 1 by the presence of 3-20% filler, 5-12% disintegrant, 0.5-8% binder, 0.2-0.8% lubricant and 0.1-2% surfactant. In claim 1 of auxiliary request 4, these excipients are limited respectively to microcrystalline cellulose, croscarmellose sodium, hypromellose (i.e. hydroxypropylmethylcellulose), magnesium stearate and SDS.

D1 mentions all of the above specific excipients (see page 26, first full paragraph), albeit not in combination together with the features of a sorafenib tosylate tablet. D1 is silent about the amounts of these excipients.

The respondent did not demonstrate that these further limitations result in any additional technical effect over the sorafenib tosylate tablets known from D1. Accordingly, the technical problem is still the provision of tablets of sorafenib tosylate leading to improved patient compliance.

Neither the selection of these well-known excipients which are already shown in D1, nor the arbitrary choice of the amounts specified in claim 1 without any associated effect, involves any inventive step. The respondent argued, during the oral proceedings, that the skilled person would not consider the low amounts of disintegrant specified in claim 1, namely 5-12 wt%. However, the respondent did not show that this amount of disintegrant, or any of the amounts specified in claim 1 either, depart from the usual amounts which the skilled person would consider in the course of routine work. On the contrary, the range for the amount of disintegrant is subsumed by the range shown in e.g. D5 (see bottom of page 3, 5-40 wt%). In addition, the choice of tablets with a high load in active ingredient would necessarily entail the choice of low amounts of excipients.

Accordingly, the subject-matter of claim 1 of auxiliary requests 3 and 4 does not involve an inventive step.

5.2 Auxiliary requests 6 and 8 correspond to auxiliary requests 1 and 4, wherein the drug load is amended to at least 75% by weight.

This limitation does not modify the assessment of inventive step. The drug loads considered in D4 (see page 65, table 2/1, 350-550 mg active ingredient for a tablet weight of 400-650 mg) extend well above the value of 75 wt% of claim 1. The fact that particular examples of D13 use a much lower amounts of active ingredient does not modify this assessment based on D1 and D4. Accordingly, the subject-matter of claim 1 of auxiliary requests 6 and 8 lacks an inventive step for the same reasons as auxiliary requests 1 and 4.