T 1153/23 (Stable Heparinoid Lidocaine Compositions / URIGEN) 04-04-2025

Reasons for the Decision

1. Main request

1.1 Article 123(2) EPC

1.1.1 Claim 1 of the main request differs from the combination of claims 38 and 50 as filed as follows (amendments emphasised by the Board):

- the quantity of heparinoid in step (a) is "[deleted: about 100] 10,000 units to [deleted: about] 250,000 units per unit dose or, alternatively, from [deleted: about 0.5] 50 mg to [deleted: about] 1250 mg per unit dose"; and

- the quantity of the acute-acting anesthetic lidocaine in step (c) is "from [deleted: about 5] 50 mg to [deleted: about] 1000 mg per unit dose".

1.1.2 The appellant indicates paragraph [0041] as basis for the amended amounts of heparinoid. However, this paragraph only discloses the amounts 10,000 units and 50 mg among several alternative intermediate quantities, and only in respect of heparin (and not more generally any heparinoid). As indicated at the end of the same paragraph, determining suitable quantities of heparinoids other than heparin would require a calculation based on the molecular weight of the heparinoid to be used. The values given in this paragraph for heparin can accordingly not be generalised as such to any heparinoid. This generalisation in claim 1 of the main request thus introduces added subject-matter.

1.1.3 In addition, paragraph [0045] discloses the amount of 50 mg also as one of many alternative intermediate quantities of lidocaine, and in the context of lidocaine amounts of at most 400 mg. The subject-matter of claim 1 of the main request thus results from the combination of a range (50-1000 mg) created by selecting one quantity of lidocaine as the lower limit, with a range (either 10,000-250,000 units or 50-1250 mg) which also involves a selection from the various heparin(oid) amounts. In the absence of a pointer to this combination of selections, the amendment introduces added subject-matter.

The criteria of Article 123(2) EPC are thus not met.

1.2 Novelty - product-by-process claim

1.2.1 Claim 13 of the main request relates to:

- a stable composition

- produced by the method of claim 1 or 7,

- wherein the stability of the heparinoid and the lidocaine is at least 90% after one year, up to 18 months.

1.2.2 The composition of claim 13 is thus firstly defined in terms of the process for its manufacture, i.e. by the method of claim 1 or 7. Claim 13 is nonetheless directed to the composition per se. Claims for products defined in terms of a process of manufacture are allowable only if the products as such fulfil the requirements for patentability, i.e. inter alia that they are new and inventive. A product is not rendered novel merely by the fact that it is produced by means of a new process. Furthermore, in proceedings before the examining division, the burden of proof for an allegedly distinguishing "product-by-process" feature lies with the applicant (see T 713/01, point 2.5.8 of the reasons, and Case Law of the Boards of Appeal of the European Patent Office, 10th edition ("CLB"), III.G.5.1.2 a)).

D1 discloses (see page 25, solution 2) a stable composition produced by a method comprising dissolving heparin (50,000 units) and lidocaine (200 mg) in water and then adding sodium bicarbonate, yielding a final pH of 7.4.

Even if the particular sequence of steps of the processes of claims 1 and 7 are not shown in D1, there is no evidence that the claimed processes impart to the resulting products any property differentiating them from those of the prior art.

1.2.3 The only property on which the appellant relies is the claimed stability of the heparinoid and lidocaine of "at least 90% after one year, up to 18 months", which is specified in claim 13.

It is however not shown either that the product of D1, solution 2, fails to achieve this property. Considering that D1 describes the resulting solutions as stable for three months or more with no precipitation (see paragraph [0031]), and that similar process features are employed in D1 and in the application to avoid precipitation and decomposition of lidocaine (i.e. the presence of the heparinoid when buffering lidocaine, see paragraph [0031] of the application and [0030] of D1), the silence of D1 as to the particular parameter of stability after one year cannot be equated with a proof that this claimed parameter is not fulfilled in D1.

On the contrary, as noted by the examining division, the process of D1 (solution 2) is very similar to the process of example 1 of the application, which is stated to lead to a stability over 95% after both 12 and 18 months. Both processes use the same amounts of heparin and lidocaine, the same buffer (sodium bicarbonate), and lead to the same volume (15 mL) with essentially the same pH (7.4 vs 7.5). This similarity of the process of D1 with a process which the application states to lead to the claimed stability supports the view that the stability parameter is implicitly met in D1.

Under these circumstances, the onus of proof remains with the applicant to show a distinction with D1. No benefit of the doubt can be accorded. The appellant chose to use this unusual parameter to define the claimed composition, but did not provide evidence that this parameter feature as such represents a difference over D1.

1.2.4 Accordingly, the subject-matter of claim 13 of the main request lacks novelty.

1.3 Inventive step - claims 1 and 7

1.3.1 The closest prior art D1 discloses a process for preparing a stable composition comprising dissolving heparin (50,000 units) and lidocaine (200 mg) in water and then adding sodium bicarbonate, yielding a final pH of 7.4 (see page 25, solution 2).

1.3.2 The process of claim 1 differs by step (b) of buffering the heparinoid to a pH value of greater than 6.8 to 8.3.

The appellant contends that the stability of the heparinoid and lidocaine of at least 90% after one year, up to 18 months, constitutes a technical difference to D1. The Board does not share this view. For the reasons given above (see 1.2.3), the silence of D1 as to this precise parameter cannot be regarded as evidence that this parameter is not met by solution 2.

1.3.3 The appellant further argues that, by controlling the pH of the heparinoid solution to 6.8-8.3 prior to adding the lidocaine, the method of claim 1 allows to achieve a superior stability of at least 90% for one year, up to 18 months. There is however no evidence supporting this assertion in the application, considering that it does not contain any example of the claimed processes. In particular, the process of paragraph [0078] (example 1) does not comprise the step of claim 1 of buffering the heparinoid before adding lidocaine, nor the steps of claim 7 of buffering to pH 7.0 followed by raising the pH using sodium hydroxide.

1.3.4 Lastly, the appellant submits that the fact that solution 2 in D1 requires a sterile filtration step is a clear pointer that a precipitation is expected or already occurred in D1 for solution 2. The Board does not consider this sterile filtration to be indicative of any stability issue. Such a filtration step is also considered in the application, and the stability period is anyway defined to start after the preparation of the final vial (see paragraph [0068] of the application).

1.3.5 The appellant defines the technical problem as the provision of an increased stability and avoidance of precipitation of lidocaine such that a stable solution containing lidocaine and heparin can be generated suitable for storage prior to administration to a patient.

However, no evidence or comparison was adduced to show that the claimed process achieves any improvement over the process of D1. In fact, the product resulting from the claimed process is not shown to differ from that of D1, for the reasons set out above (see 1.2). There is also no evidence that the pH adjustment would be relevant to immediate versus long term stabilization of lidocaine.

Accordingly, the objective technical problem may be seen in the provision of an alternative method for preparing compositions comprising heparin, lidocaine and a buffer for use in the treatment of a lower urinary tract disease.

The Board shares the conclusion of the examining division that the solution proposed in claim 1 does not involve an inventive step. D1 suggests in one embodiment to buffer the heparinoid before the addition of lidocaine (see paragraph [0055]). In the absence of an associated technical effect, the skilled person would consider this measure in order to solve the problem of providing an alternative.

1.3.6 As to claim 7, starting from D1 (solution 2), the differentiating features are

- step (b) of adding the buffer to produce a pH of 7.0 in the heparinoid+lidocaine solution of (a), and

- the fact that, in step (c) of raising the pH to a value in the range of from 7.1 to 8.3, sodium hydroxide is used. In D1, the adjustment to pH 7.4 is done using sodium bicarbonate.

The vague feature that the solution of step (a) is "slightly" more concentrated than the final product merely represents a consequence of the additions in steps (b) and (c).

In the case of claim 7 also, no evidence of any improvement over the process of D1 was adduced. The objective technical problem is to provide an alternative method for preparing compositions comprising heparin, lidocaine and a buffer for use in the treatment of a lower urinary tract disease.

The Board shares the examining division's view that the claimed solution is obvious in light of paragraphs [0057]-[0058] of D1, which suggest the addition of a buffer to the heparinoid + lidocaine solution and the subsequent pH adjustment. The particular pH values defined in claim 1 for each of steps (b) and (c), and the use of sodium hydroxide, are also not associated with any particular effect and remain within the ambit of what the skilled person would select based on the disclosure of D1.

1.3.7 Accordingly, the subject-matter of the main request does not involve an inventive step.

2. Auxiliary requests

2.1 Each of auxiliary requests 1-4 comprises a claim (respectively, claims 12, 5, 12 and 5) directed at a composition defined in terms of the process for its preparation and by a stability of at least 90% after one year, up to 18 months. For the same reasons as for claim 13 of the main request (see 1.2 above), none of auxiliary requests 1-4 meet the criteria of novelty.

2.2 In addition, in auxiliary requests 1 and 2, step (a) of claim 1, the same intermediate quantities (10,000 units and 50 mg) are extracted from their disclosure in the context of heparin in paragraph [0041] and generalised without basis to all heparinoids (see 1.1.2 above). Auxiliary requests 1 and 2 thus infringe Article 123(2) EPC.

2.3 None of the amendments introduced in auxiliary requests 1-8 overcome the objection of inventive step either.

In claim 1 of auxiliary request 1, the addition of sodium hydroxide or potassium hydroxide is optional ("possible addition") and has no impact on the assessment of inventive step.

There is furthermore no evidence for the appellant's allegation, or statement on page 12 (paragraph [0031]) of the application, that a pH of 7.2 to 7.6 (as specified in auxiliary requests 1 and 2), or even of 7.5 (as required in auxiliary requests 3, 4 and 8), leads to the best lidocaine stability. The Board recalls that alleged advantages to which the appellant merely refers, without offering sufficient evidence to support the comparison with the closest prior art, cannot be taken into consideration in determining the problem underlying the invention and therefore in assessing inventive step.

The amendments to the ranges defining the amount of heparinoid and lidocaine (100-250,000 units or 0.5-1250 mg heparinoid and 5-1000 mg lidocaine per unit dose, see claim 5 of auxiliary request 3 and claim 1 of auxiliary request 4), and the limitation of the heparinoid to heparin (see claim 1 of auxiliary request 7), do not define any additional differentiating feature over D1. Lastly, claim 6 of auxiliary request 5, and claim 1 of auxiliary request 6 are both identical to claim 7 of the main request (see 1.3.6 above). The same conclusion as for the main request therefore applies.

Accordingly, none of auxiliary requests 1-8 meet the criteria of inventive step.