T 0149/15 (Testosterone gel/UNIMED) 08-05-2018

I. European patent No. 1 937 276 was granted with the following independent claims 1, 7 and 8:

"1. A hydroalcoholic gel pharmaceutical composition comprising:

i. from 1.50 % to 1.70 % (w/w) testosterone;

ii. from 0.6 % to 1.2 % (w/w) isopropyl myristate;

iii. from 60 % to 80 % (w/w) of an alcohol selected from the group consisting of ethanol and isopropanol;

iv. a sufficient amount of a thickening agent to give the composition a viscosity in excess of 9000 cps; and

v. water.

7. The composition according to any of claims 1 to 6, for use in the treatment of hypogonadism in a male subject.

8. Use of testosterone for the manufacture of a composition according to any of claims 1 to 6 for treating hypogonadism in a male subject."

In addition, granted claim 9 reads as follows:

"9. The composition for use according to claim 7 or the use of claim 8, wherein the subject has a pretreatment serum testosterone concentration less than 300 ng/dl."

II. The following documents are referred to in the present decision:

(1) Operating instructions of the programmable rheometer Brookfield DV-II+ Pro EXTRA. Manual No. M/09-166, Brookfield Engineering Laboratories, Inc., pages 1-79

(2) WO 2007/044976

(3) US 6,503,894

(4) WO 2006/027278

(5) WO 02/17926

(12) Declaration of Ramana Malladi dated 26 March 2014

(15a) C. Wang et al., J. Clin. Endocrinol. Metab., 2000, 85(8), 2839-2853

(15b) R.S. Swerdloff et al., J. Clin. Endocrinol. Metab., 2000, 85(12), 4500-4510

III. The patent was opposed on the grounds of Article 100(c), 100(b) and 100(a) EPC, for lack of novelty and inventive step.

IV. The appeal by the patent proprietors (appellants) lies from the decision of the opposition division revoking the patent. The decision was based on the patent as granted (main request) and five auxiliary requests.

In the decision, the division concluded that the patent as granted did not add subject-matter and that the underlying invention was sufficiently disclosed. However, the composition in granted claim 1 was not novel over some of the formulations disclosed in tables 3, 11 and 22 of document (2), a divisional application of the patent. The formulations in document (2) belonged to the prior art because they enjoyed the priority date of 12 October 2005 while granted claim 1 had no priority right and its effective date was 12 October 2006. For the same reason, the subject-matter in claim 1 of auxiliary requests 3 and 5 was not novel either. In addition, auxiliary requests 1 and 2 added subject-matter and auxiliary request 4 was not admitted into the opposition proceedings.

V. With their statement of grounds of appeal dated 5 June 2015, the appellants filed seven claim sets as auxiliary requests 1 to 7.

VI. The opponent (respondent) replied to the statement of grounds of appeal by letter of 21 October 2015.

VII. In its preliminary opinion, annexed to a summons to oral proceedings, the board concurred with the opposition division that the patent as granted did not add subject-matter and that the underlying invention was sufficiently disclosed. However, on the issue of novelty vis-à-vis document (2), the board considered that, in accordance with G 1/15, granted claim 1 enjoyed the priority of 12 October 2005 for the formulations disclosed in tables 3, 11 and 22 of document (2). Therefore, those formulations did not belong to the claim's prior art and could not anticipate its subject-matter.

VIII. The appellants' arguments, where relevant to the present decision, may be summarised as follows:

Amendments

The appellants maintained that the composition in granted claim 1 did not add subject-matter because it was supported by the combination of paragraphs [043] and [045] of the application as filed. Additional support could be found in the experimental part of the application, in paragraphs [010] and [023], and in claims 1 and 7 as filed.

Paragraph [043] disclosed a composition comprising 1.15% to 1.8% (w/w) testosterone and the components ii. to v. in granted claim 1. This generic composition was a hydroalcoholic gel, since it contained water and alcohol and had a viscosity of above 9000 cps. In addition, the composition could be combined with the testosterone ranges defined in paragraph [045], which were generally applicable to the invention. One of those ranges was the one in granted claim 1, 1.50% to 1.70% (w/w). An additional basis could be found in the composition used in the method of claims 1 and 7 as filed because, contrary to the respondent's opinion, the application made a direct link between the formulations and the methods according to the invention, for instance in paragraphs [010] and [023], which stated that the invention related to both testosterone gel formulations and methods of use.

With respect to the objection of added subject-matter in relation to granted claim 6 raised in appeal, the appellants objected to its admission because it was different from the objection raised in opposition and created a fresh case. Thus, even though the two objections were based on an alleged lack of support for granted claim 6 in table 22 of the application as filed, while the objection in opposition had focused on the nature of the alcohol, in appeal it was directed to the expression "obtainable by".

Regarding the substance of the objection, table 22 provided full support for the composition in granted claim 6, which was limited by a list of specific components and their corresponding amounts, leaving no room for variability. Furthermore, table 22 defined not only a composition but also its method of preparation. Therefore, the definition of the composition as obtainable by combining the ingredients in table 22 had to be allowable. In this context, the expression "obtainable by" was equivalent to "obtained by", in accordance with the principles established in T 20/94.

Sufficiency of disclosure

In the appellants' view, the patent contained sufficient information for the skilled person to measure the viscosity of the hydroalcoholic gels according to granted claim 1 and to prepare them. In addition, he could select male subjects with the serum testosterone concentration required in granted claim 9 without undue burden.

On the aspect of viscosity, the appellants stressed that the patent taught in paragraph [035] that the viscosity of the claimed compositions was measured using a Brookfield RV DVII+ viscosimeter with an RV6 spindle, a rotation speed of 10 rpm and a temperature of 20°C. This information was sufficient to obtain a reliable measure of viscosity, as had been explained in the expert declaration, document (12), and was apparent from the general measuring procedure disclosed on page 20 of document (1) for Brookfield DVII+ viscosimeters. According to that procedure, a 600 ml beaker was filled with the fluid up to the immersion groove on the spindle's shaft. Once the sample had been loaded, the motor was turned on and a time was allowed for stabilisation before reading the viscosity value. In addition, the use of a guard leg was optional and did not affect the correctness of the result obtained, as taught in document (1), page 63, paragraph 4. In conclusion, the essential parameters for measuring viscosity listed in document (1), page 55, that had not been mentioned in the patent in paragraph [035] were clear to the skilled person from the general procedure disclosed in document (1), page 63. So, the skilled person could carry out a reliable measurement with the information provided in the patent. In this context, the appellants noted that the fact that granted claim 1 did not define an upper viscosity limit was not an obstacle to carrying out the invention because the viscosity was limited in practice, as in the case underlying the decision T 2213/08. This lack of upper viscosity limit would not require a change of spindle type since the RV6 spindle was suitable for measuring viscosities within the range 1000 to 2000000 cps, which was appropriate for the gels of the invention, which in the examples in the patent had viscosities of around 25000 cps (see table 4).

Regarding the preparation of the claimed gels, the appellants argued that the amount and type of thickeners that could be used for achieving the viscosities in claim 1 belonged to the skilled person's general knowledge: thickeners were generally used to increase viscosity and the fact that the range in granted claim 1 was broad made it even easier to prepare a composition fulfilling this condition. Furthermore, the respondent had not provided any proof of the contrary.

Turning to the issue of the selection of male subjects with a pretreatment serum testosterone concentration of less than 300 ng/dl (see granted claim 9), the appellants argued that the patent taught in paragraph [005] that maximum testosterone levels occurred at approximately 6:00 to 8:00 a.m. Thus, the skilled person simply needed to measure the testosterone level within that time period and check whether it was below 300 ng/dl. If that was the case, then the subject belonged to the patient group of granted claim 9. This assessment was normal practice in the identification of hypogonadal men, as shown in documents (15a) and (15b).

Partial priority - novelty over document (2)

Document (2) was a divisional of the application underlying the patent. Therefore, in accordance with the decision G 1/15, if document (2) benefited from priority for certain subject-matter, the patent did so too. Conversely, if the patent did not benefit from priority for certain subject-matter, document (2) could not do so either. Accordingly, the formulations disclosed in document (2) could not belong to the patent's prior art.

In addition, the respondent's argument that granted claim 1 could not benefit from partial priority because the priority application and the patent related to different inventions was wrong; the objective as stated in paragraph [0009] of the priority application and in paragraph [0011] of the patent was literally the same.

IX. The respondent's arguments, where relevant to the present decision, may be summarised as follows:

Amendments

The respondent argued that granted claim 1 added subject-matter because it did not find a proper basis in paragraphs [043] and [045] of the application as filed. Paragraph [043] disclosed a range of compositions which were not specified as being hydroalcoholic gels and which comprised a broader testosterone concentration range than the one in granted claim 1, namely 1.15% to 1.8% (w/w). The compositions in paragraph [043] had been disclosed as stand-alone embodiments and could not be combined with the testosterone ranges disclosed in paragraph [045], especially taking into account that the ranges in paragraph [045] had not been disclosed as preferred but merely as an anticipation of the ranges provided in the subsequent embodiments in paragraphs [047] to [049].

The method in claims 1 and 7 as filed was not a valid basis either because, in the application, methods and compositions were intended for different purposes. This was apparent from claims 1 to 35 (methods) and 36 to 44 (compositions) as filed. Thus, while the methods aimed to treat hypogonadism, the compositions were intended for transdermal delivery. Hence, a composition disclosed in a method claim could not constitute a basis for a composition claim, in spite of the references to methods and compositions in paragraphs [010] and [023] of the application as filed.

Regarding the objection of added subject-matter in relation to claim 6 raised in appeal, the respondent was of the view that it should be admitted because it was not a new objection but a further elaboration of the arguments already raised in opposition. The argument in both proceedings had been that table 22 in the application as filed was not a valid support for the composition in granted claim 6.

Turning to the substance of the objection, the respondent argued that granted claim 6 added subject-matter due to its dependency upon claim 1 in combination with its expression "obtainable by", which opened the composition in granted claim 6 to the addition of components not specified in table 22 of the application as filed, such as further thickeners or ingredients that assist in reaching the viscosity required in claim 1. In addition, while the alcohol in table 22 as filed was limited to ethanol, the dependency of granted claim 6 upon claim 1 extended the alcohol to ethanol and/or isopropanol. Lastly, the new claim dependency provided the information that the viscosity of the composition in table 22 as filed was higher than 9000 cps, information that had not been made available in the application as filed.

Sufficiency of disclosure

With regard to the viscosity range defined in granted claim 1, the respondent maintained that the patent lacked sufficiency of disclosure in two respects: it did not contain enough information to reliably measure the viscosity of the claimed compositions and it was missing information regarding the type and amount of thickeners that could be used to reach those viscosities.

Thus, paragraph [035] indicated the viscosimeter, spindle, test speed and temperature that should be used for measuring viscosity. However, the paragraph failed to specify five parameters that, according to document (1), page 55, were essential for measuring viscosities. Those parameters were the sample container size, the sample volume, whether or not to attach the guard leg, the length of time or the number of spindle revolutions to record viscosity, and how the sample was prepared and/or loaded into the container. In the absence of indications regarding these parameters, the skilled person was not able to carry out a reliable measurement of viscosity, as confirmed by decision T 808/09. This was even more true considering that the viscosity range in granted claim 1 had no upper limit, since such a broad viscosity range could not be accurately measured without adjusting the spindle speed or the type of spindle (see document (1), passage bridging pages 72 and 73), operations on which the patent did not provide any information.

On the issue of the amount and type of thickening agents that could give the claimed composition with the required viscosity, the respondent argued that the patent illustrated only formulations containing a combination of 1.0% (w/w) Carbopol 980 with 7.00% (w/w) 0.1N sodium hydroxide (see tables 2, 3, 11 and 22). The skilled person was therefore missing the necessary information to prepare compositions with the required viscosity using thickeners and amounts other than those in the formulation examples.

As a result of this impossibility of reliably measuring viscosities and the lack of information on the amount and type of suitable thickening agents to achieve the required viscosity, the skilled person could not prepare the composition of granted claim 1 without undue burden.

With regard to the selection of male subjects having the pretreatment serum testosterone concentration defined in granted claim 9, the respondent questioned the skilled person's ability to unambiguously determine whether or not a subject belonged to the required group of patients since, as noted in paragraph [005] of the application, the serum testosterone concentration fluctuated during the day. In this respect, the teaching in documents (15a) and (15b) did not help because it did not represent common general knowledge and because it confirmed the problem of measuring serum testosterone levels due to their diurnal variations.

Partial priority - novelty over document (2)

According to the respondent, the case in hand was an exception to which the principle of partial priorities established in G 1/15 could not be applied. This arose from the fact that the assessment of priority and novelty were not governed by the same rules. Thus, while the assessment of priority required an analysis of the teaching in the application (same invention), that of novelty was an analysis of the facts disclosed, and required no consideration of priority.

In that context, the respondent noted that the appellants had not disputed the facts that document (2) disclosed formulations which fell under the scope of granted claim 1 (formulations 41, 48, 51, 53 and 55 in table 3, formulation 59 in table 11, and the formulation in table 22) and that granted claim 1 as a whole did not benefit from priority. Moreover, the respondent added that granted claim 1 did not benefit from partial priority for the relevant formulations in document (2) either, for the following reasons:

Although the formulations in document (2) had also been disclosed in both the patent and its priority application, the patent and the priority application did not relate to the same invention, as required by Article 87(1) EPC for the acknowledgement of priority. Thus, while the problem in the priority application had been defined as the provision of an improved transdermal hydroalcoholic testosterone gel, especially in terms of viscosity compared with a marketed 1% testosterone gel (see paragraphs [0009], [0045], [0047] and [0048]), the patent did not relate to any improvement. This was apparent from a comparison of the viscosity values in table 4 of the patent for formulation 51 (according to granted claim 1, 20700 cps) with formulation 56 (control, 22033 cps). Hence, as the patent and its priority application did not relate to the same invention, the patent could not benefit from partial priority in the sense of G 1/15.

Thus, taking into consideration that, contrary to the assessment of priority, the examination of novelty did not require a consideration of the invention but merely an analysis of the facts disclosed, the respondent concluded that formulations 41, 48, 51, 53 and 55 in table 3, formulation 59 in table 11, and the formulation in table 22 of document (2) anticipated the subject-matter of granted claim 1.

X. The final requests of the parties were as follows:

- The appellants requested that the decision under appeal be set aside and that the case be remitted to the opposition division for further prosecution on the basis of the patent as granted or, alternatively, on the basis of any of the auxiliary requests 1 to 7 filed with the statement of grounds of appeal. The appellants also requested that the objection of added subject-matter raised by the respondent with respect to granted claim 6 not be admitted into the appeal proceedings.

- The respondent requested that the appeal be dismissed or, alternatively, that the case be remitted to the opposition division for further prosecution.

XI. At the end of the oral proceedings, the board's decision was announced.