T 1160/18 (Controlled release pharmaceutical compositions comprising a fumaric acid ester/FWP IP APS) 06-09-2021

I. European patent No. 2 801 355 was granted on the basis of a set of 10 claims.

Independent claim 1 as granted read as follows:

"1. A pH controlled release pharmaceutical composition for oral use which consists of dimethylfumarate as the active substance, wherein the composition is provided with an enteric coating wherein the daily dosage is from 480 to 720 mg active substance given in one to three doses for use in the treatment of psoriatic arthritis, neurodermatitis, inflammatory bowel disease, or an autoimmune disease."

II. Eleven oppositions were filed against the patent on the grounds that its subject-matter lacked novelty and inventive step, was not sufficiently disclosed and extended beyond the content of the application as filed.

III. The appeal lies from the decision of the opposition division to revoke the patent. The decision was based on 33 sets of claims, namely the main request as filed with letter of 29 November 2017, auxiliary requests 1-4 filed during the oral proceedings of 29 January 2018, and auxiliary requests 5-32 filed as auxiliary requests 1-28 with letter of 29 November 2017.

IV. According to the decision under appeal, none of the requests met the requirements of Articles 76(1) and 123(2) EPC, in view of the multiple selections necessary to arrive at the claimed subject-matter.

V. The patent proprietor (hereinafter the appellant) filed an appeal against said decision. With the statement setting out the grounds of appeal dated 1st August 2018 the appellant submitted a main request, auxiliary requests 1-28 and 2A, 3A, 4A, 5A, 6A, 9A, 10A, 11A, 12A and the following items of evidence:

Annex - Overview of the examples

HBP 14 - Expert Report of Professor Clive Page

Independent claim 1 of the following requests read as follows, difference(s) compared with claim 1 as granted being shown in bold:

Main request

Independent claim 1 of the main request read as follows, difference(s) compared with claim 1 as granted being shown in bold:

"1. A pH controlled release pharmaceutical composition for oral use which consists of dimethylfumarate as the active substance, wherein the composition is provided with an enteric coating wherein the daily dosage is 480 mg active substance given in one to three doses for use in the treatment of psoriatic arthritis, neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from

i. polyarthritis

ii. multiple sclerosis (MS)

iii. juvenile-onset diabetes mellitus

iv. Hashimoto's thyroiditis

v. Grave's disease

vi. SLE (systemic lupus erythematosus)

vii. Sjögren's syndrome

viii. pernicious anemia

ix. chronic active (lupoid) hepatitis

x. rheumatoid arthritis (RA)

xi. optic neuritis.".

Independent claim 1 of auxiliary requests 13-28 read as follows, difference(s) compared with claim 1 of the main request being shown in bold:

Auxiliary request 13

In comparison to claim 1 of the main request, claim 1 of this request has been further restricted by some limitations in the list of autoimmune disease, namely:

"...an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Grave's disease

v. SLE (systemic lupus erythematosus)

vi. Sjogren's syndrome

vii. pernicious anemia

viii. chronic active (lupoid) hepatitis

[deleted: x.rheumatoid arthritis (RA)]

ix optic neuritis.".

Auxiliary request 14

In comparison to claim 1 of the main request, claim 1 of this request has been further restricted by a limitation in the list of diseases, namely:

"...for use in the treatment of [deleted: psoriatic arthritis,] neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Grave's disease

v. SLE (systemic lupus erythematosus)

vi. Sjögren's syndrome

vii. pernicious anemia

Viii. chronic active (lupoid) hepatitis

[deleted: x. rheumatoid arthritis (RA)]

xi. optic neuritis.".

Auxiliary request 15

In comparison to claim 1 of the main request, claim 1 of this request has been further restricted by a limitation of the autoimmune disease and by a further amendment, namely:

"...an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Grave's disease

v. SLE (systemic lupus erythematosus)

vi. Sjogren's syndrome

vii. pernicious anemia

viii. chronic active (lupoid) hepatitis

[deleted: x.rheumatoid arthritis (RA)]

ix optic neuritis;

wherein the composition includes a diffusion-controlled drug delivery system, an osmotic pressure controlled drug delivery system, or an erodible drug delivery system.".

Auxiliary request 16

In comparison to claim 1 of the main request, claim 1 of this request has been further restricted by a limitation of the autoimmune disease and by the addition of a further feature, namely:

"...an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Grave's disease

v. SLE (systemic lupus erythematosus)

vi. Sjogren's syndrome

vii. pernicious anemia

viii. chronic active (lupoid) hepatitis

[deleted: x.rheumatoid arthritis (RA)]

ix optic neuritis;

wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a rotating basket for a capsule and a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and,

within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released."

Auxiliary request 17

In comparison to claim 1 of the main request, claim 1 of this request has been further restricted by a limitation of the autoimmune disease and by a further amendment, namely:

"...an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Grave's disease

v. SLE (systemic lupus erythematosus)

vi. Sjogren's syndrome

vii. pernicious anemia

viii. chronic active (lupoid) hepatitis

ix. optic neuritis;

[deleted: x.rheumatoid arthritis (RA)]

wherein the pH controlled release pharmaceutical composition is in the form of a tablet based on granules,

wherein the granules are prepared by mixing and granulating the active substance at a concentration of 10 to 90% with ethylcellulose at a concentration between 2 to 40% and polyethylene glycol (PEG) at a concentration of 1 to 40%,

and wherein the tablet is enteric coated.".

Auxiliary request 18

In comparison to claim 1 of the main request, claim 1 of this request has been further restricted by a limitation of the autoimmune disease and by a further amendment, namely:

"...an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Grave's disease

v. SLE (systemic lupus erythematosus)

vi. Sjogren's syndrome

vii. pernicious anemia

viii. chronic active (lupoid) hepatitis

[deleted: x.rheumatoid arthritis (RA)]

ix. optic neuritis;

wherein the pH controlled release pharmaceutical composition is in the form of a tablet based on granules,

wherein the granules are prepared by mixing and granulating the active substance at a concentration of 10 to 90% with ethylcellulose at a concentration between 2 to 40% and polyethylene glycol (PEG) at a concentration of 1 to 40%,

and wherein the tablet is enteric coated;

wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and,

within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released.".

Auxiliary request 19

In comparison to claim 1 of the main request, claim 1 of this request has been further restricted by a limitation of the autoimmune disease and by a further amendment, namely:

"...an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Grave's disease

v. SLE (systemic lupus erythematosus)

vi. Sjogren's syndrome

vii. pernicious anemia

viii. chronic active (lupoid) hepatitis

[deleted: x.rheumatoid arthritis (RA)]

ix. optic neuritis;

wherein the pharmaceutical composition is in the form of a tablet obtained by a process comprising the following steps:

a) granulating a mixture of 50 g dimethyl fumarate with 12 g ethylcellulose and 3 g polyethylene glycol 400 dissolved in 150 ml ethanol 96 %, passing the granulate through a 1.0 mm sieve, drying at 50°C to 60°C over 30 min and repeating passing of the granulate through a 1.0 mm sieve to obtain a DMF-granulate;

b) granulating a mixture of lactose and microcrystalline cellulose in equal shares with 2 % povidone dissolved in water, passing the granulate through a 1.0 mm sieve, drying at 50°C to 60°C over 30 min and repeating passing of the granulate through a 1.0 mm sieve to obtain a placebo granulate;

c) mixing 60 parts of the DMF-granulate produced according to step a) with38 parts of the placebo-granulate produced according to step b) for 30minutes in a mixer; and adding one part colloidal silicon dioxide and one part magnesium stearate and mixing the blend for 5 minutes;

or

mixing 60 parts of the DMF-granulate produced according to step a) with 37parts of the placebo-granulate produced according to step b) for 30 minute sin a mixer; and adding one part carboxymethylcellulose, one part colloidal silicon dioxide and one part magnesium stearate and mixing the blend for 5 10 minutes;

d) compressing the blend to obtain tablets with a diameter of 10 mm. a weight of 260 mg and a hardness of about 50 N; and

e) providing the tablets produced according to step d) with an enteric coating.".

Auxiliary request 20

"1. A pH controlled release pharmaceutical composition for oral use which consists of dimethylfumarate as the active substance, wherein the composition is provided with an enteric coating wherein the composition is for administration twice daily and wherein the amount in a dosage form is 240 mg substance [deleted: wherein the daily dosage is ][deleted: 480 mg][deleted: active substance given in one to three doses] for use in the treatment of psoriatic arthritis, neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Grave's disease

v. SLE (systemic lupus erythematosus)

vi. Sjögren's syndrome

vii. pernicious anemia

viii. chronic active (lupoid) hepatitis

[deleted: x. rheumatoid arthritis (RA)]

ix. optic neuritis.".

Auxiliary request 21

In comparison to claim 1 of auxiliary request 20, claim 1 of auxiliary request 21 has been further restricted by the suppression of "psoriatic arthritis" as disease to be treated, namely "...for use in the treatment of [deleted: psoriatic arthritis,] neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from...".

Auxiliary request 22

In comparison to claim 1 of auxiliary request 20, claim 1 of auxiliary request 22 has been further amended by the introduction of the following feature: "...wherein the composition includes a diffusion-controlled drug delivery system, an osmotic pressure controlled drug delivery system, or an erodible drug delivery system".

Auxiliary request 23

In comparison to claim 1 of auxiliary request 20, claim 1 of auxiliary request 23 has been further amended by the introduction of the following feature: "...wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a rotating basket for a capsule and a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and,

within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released."

Auxiliary request 24

In comparison to claim 1 of auxiliary request 20, claim 1 of auxiliary request 24 has been further amended by the introduction of the following feature: "...wherein the pH controlled release pharmaceutical composition is in the form of a tablet based on granules, wherein the granules are prepared by mixing and granulating the active substance at a concentration of 10 to 90% with ethylcellulose at a concentration between 2 to 40% and polyethylene glycol (PEG) at a concentration of 1 to 40%, and wherein the tablet is enteric coated".

Auxiliary request 25

In comparison to claim 1 of auxiliary request 20, claim 1 of auxiliary request 25 has been further amended by the introduction of the following feature: "...wherein the pH controlled release pharmaceutical composition is in the form of a tablet based on granules,

wherein the granules are prepared by mixing and granulating the active substance at a concentration of 10 to 90% with ethylcellulose at a concentration between 2 to 40% and polyethylene glycol (PEG) at a concentration of 1 to 40%,

and wherein the tablet is enteric coated;

wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and,

within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released."

Auxiliary request 26

"1. A pH controlled release pharmaceutical composition for oral use which consists of dimethylfumarate as the active substance, wherein the composition is provided with an enteric coating wherein the composition is for administration twice daily and wherein the amount in a dosage form is 240 mg substance [deleted: wherein the daily dosage is ][deleted: 480 mg][deleted: active substance given in one to three doses] for use in the treatment of[deleted: psoriatic arthritis, neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from]

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

[deleted: iii. juvenile-onset diabetes mellitus]

[deleted: iv. Hashimoto's thyroiditis]

[deleted: v. Grave's disease]

[deleted: vi. SLE (systemic lupus erythematosus)]

[deleted: vii. Sjögren's syndrome]

[deleted: viii. pernicious anemia]

[deleted: ix. chronic active (lupoid) hepatitis]

[deleted: x. rheumatoid arthritis (RA)]

[deleted: xi. optic neuritis."]

Auxiliary request 27

In comparison to claim 1 of auxiliary request 26, claim 1 of auxiliary request 27 has been further amended by the introduction of the following feature: "...wherein the composition includes a diffusion-controlled drug delivery system, an osmotic pressure controlled drug delivery system, or an erodible drug delivery system".

Auxiliary request 28

In comparison to claim 1 of auxiliary request 26, claim 1 of auxiliary request 28 has been further amended by the introduction of the following feature: "...wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a rotating basket for a capsule and a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and,

within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released."

VI. A communication from the Board, dated 17 January 2020, was sent to the parties. In it the Board expressed its preliminary opinion and stated inter alia that the main request did not meet the requirements of Article 76(1) EPC.

VII. With a letter dated 5 May 2020, the appellant filed new auxiliary requests 1-12 and 1A, 2A, 5A-7A, 9A-12A (corresponding respectively to auxiliary requests 3A, 10A, 9A, 11A, 12A, 2A, 4A-6A filed with letter of 1 August 2018).

The subject-matter of claim 1 of the auxiliary requests 1-12 read as follows, the difference with respect to claim 1 of the main request being indicated in bold.

Auxiliary requests 1

"1. A pH controlled release pharmaceutical composition for oral use which consists of dimethyl fumarate as the active substance, wherein the composition is provided with an enteric coating, wherein the daily dosage is 480 mg active substance given in one to three doses, for use in the treatment of psoriatic arthritis, neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from

i. polyarthritis

ii. multiple sclerosis (MS)

iii. juvenile-onset diabetes mellitus

iv. Hashimoto's thyroiditis

v. Graves' disease

vi. SLE (systemic lupus erythematosus)

vii. Sjogren's syndrome

viii. pernicious anemia

ix. chronic active (lupoid) hepatitis

x. rheumatoid arthritis (RA)

xi. optic neuritis^

wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a rotating basket for a capsule and a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and,

within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released."

Auxiliary request 2

"1.A pH controlled release pharmaceutical composition for oral use which consists of dimethyl fumarate as the active substance, wherein the composition is provided with an enteric coating, wherein the composition is for administration twice daily and wherein the amount in a dosage form is 240 mg active substance [deleted: wherein the amount in a dosage form is 480 mg active subsatnce given in one to three doses,] for use in the treatment of psoriatic arthritis, neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from

i. polyarthritis

ii. multiple sclerosis (MS)

iii. juvenile-onset diabetes mellitus

iv. Hashimoto's thyroiditis

v. Graves' disease

vi. SLE (systemic lupus erythematosus)

vii. Sjogren's syndrome

viii. pernicious anemia

ix. chronic active (lupoid) hepatitis

x. rheumatoid arthritis (RA)

xi. optic neuritis;

wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a rotating basket for a capsule and a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and, within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released."

Auxiliary request 3

The subject-matter of claim 1 of auxiliary request 3 differs from claim 1 of the main request only through the dosage regimen, namely "...wherein the composition is for administration twice daily and wherein the amount in a dosage form is 240 mg active substance...".

Auxiliary request 4

The subject-matter of claim 1 of auxiliary request 4 differs from claim 1 of the main request by the dosage regimen, namely "...wherein the composition is for administration twice daily and wherein the amount in a dosage form is 240 mg active substance..." and by the suppression of "i. polyarthritis" from the list of autoimmune diseases.

Auxiliary request 5

The subject-matter of claim 1 of auxiliary request 5 differs from claim 1 of the main request by the dosage regimen, namely "...wherein the composition is for administration twice daily and wherein the amount in a dosage form is 240 mg active substance..." and by the addition of the feature "...wherein the composition includes a diffusion-controlled drug delivery system, an osmotic pressure controlled drug delivery system, or an erodible drug delivery system".

Auxiliary request 6

The subject-matter of claim 1 of auxiliary request 6 differs from claim 1 of the main request in the definition of the dosage regimen, namely "...wherein the composition is for administration twice daily and wherein the amount in a dosage form is 240 mg active substance..." and by the addition of the feature "...wherein the pH controlled release pharmaceutical composition is in the form of a tablet based on granules, wherein the granules are prepared by mixing and granulating the active substance at a concentration of 10 to 90% with ethylcellulose at a concentration between 2 to 40% and polyethylene glycol (PEG) at a concentration of 1 to 40%, and wherein the tablet is enteric coated".

Auxiliary request 7

The subject-matter of claim 1 of auxiliary request 7 differs from claim 1 of the main request in the definition of dosage regimen, namely "...wherein the composition is for administration twice daily and wherein the amount in a dosage form is 240 mg active substance..." and by the addition of the features:

- "...wherein the pH controlled release pharmaceutical composition is in the form of a tablet based on granules, wherein the granules are prepared by mixing and granulating the active substance at a concentration of 10 to 90% with ethylcellulose at a concentration between 2 to 40% and polyethylene glycol (PEG) at a concentration of 1 to 40%, and wherein the tablet is enteric coated...", and

- "wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and,

within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released."

Auxiliary request 8

The subject-matter of claim 1 of auxiliary request 8 differs from claim 1 of the main request in the suppression of psoriatic arthritis and polyarthritis as diseases to be treated:

"1. A pH controlled release pharmaceutical composition for oral use which consists of dimethyl fumarate as the active substance, wherein the composition is provided with an enteric coating, wherein the daily dosage is 480 mg active substance given in one to three doses, for use in the treatment of [deleted: psoriatic arthritis,] neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from

[deleted: i. polyarthritis]

i. multiple sclerosis (MS)

ii. juvenile-onset diabetes mellitus

iii. Hashimoto's thyroiditis

iv. Graves' disease

v. SLE (systemic lupus erythematosus)

vi. Sjogren's syndrome

vii. pernicious anaemia

viii. chronic active (lupoid) hepatitis

ix. rheumatoid arthritis (RA)

x. optic neuritis."

Auxiliary request 9

The subject-matter of claim 1 of auxiliary request 9 differs from claim 1 of the main request in the addition of the feature "...wherein the composition includes a diffusion-controlled drug delivery system, an osmotic pressure controlled drug delivery system, or an erodible drug delivery system".

Auxiliary request 10

The subject-matter of claim 1 of auxiliary request 10 differs from claim 1 of the main request in the addition of the features "...wherein the pH controlled release pharmaceutical composition is in the form of a tablet based on granules, wherein the granules are prepared by mixing and granulating the active substance at a concentration of 10 to 90% with ethylcellulose at a concentration between 2 to 40% and polyethylene glycol (PEG) at a concentration of 1 to 40%, and wherein the tablet is enteric coated",

Auxiliary request 11

The subject-matter of claim 1 of auxiliary request 11 differs from claim 1 of the main request in the addition of the features:

- "...wherein the pH controlled release pharmaceutical composition is in the form of a tablet based on granules, wherein the granules are prepared by mixing and granulating the active substance at a concentration of 10 to 90% with ethylcellulose at a concentration between 2 to 40% and polyethylene glycol (PEG) at a concentration of 1 to 40%, and wherein the tablet is enteric coated;..." and

- "...wherein the release of dimethyl fumarate - when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37°C and a rotation speed of 100 rpm using a paddle dissolution apparatus for a tablet - is as follows:

within the first 3 hours after start of the test at the most 70% w/w of the total amount of dimethyl fumarate contained in the composition is released, and,

within the first 4 hours after start of the test at the most 92% w/w of the total amount of dimethyl fumarate contained in the composition is released."

Auxiliary request 12

The subject-matter of claim 1 of auxiliary request 12 differs from claim 1 of the main request in the addition of the features:

"...wherein the pharmaceutical composition is in the form of a tablet obtained by a process comprising the following steps:

a) granulating a mixture of 50 g dimethyl fumarate with 12 g ethylcellulose and 3 g polyethylene glycol 400 dissolved in 150 ml ethanol 96 %, passing the granulate through a 1.0 mm sieve, drying at 50°C to 60°C over 30 min and repeating passing of the granulate through a 1.0 mm sieve to obtain a DMF-granulate;

b) granulating a mixture of lactose and microcrystalline cellulose in equal shares with 2 % povidone dissolved in water, passing the granulate through a 1.0 mm sieve, drying at 50°C to 60°C over 30 min and repeating passing of the granulate through a 1.0 mm sieve to obtain a placebo granulate;

c) mixing 60 parts of the DMF-granulate produced according to step a) with38 parts of the placebo-granulate produced according to step b) for 30minutes in a mixer, and adding one part colloidal silicon dioxide and one part magnesium stearate and mixing the blend for 5 minutes,

or

mixing 60 parts of the DMF-granulate produced according to step a) with 37parts of the placebo-granulate produced according to step b) for 30 minutesin a mixer, and adding one part carboxymethylcellulose, one part colloidal silicon dioxide and one part magnesium stearate and mixing the blend for 5 10 minutes,

d) compressing the blend to obtain tablets with a diameter of 10 mm, a weight of 260 mg and a hardness of about 50 N, and

e) providing the tablets produced according to step d) with an enteric coating."

The subject-matter of claim 1 of all auxiliary requests 1A, 2A, 5A-7A, 9A-12A differed from claim 1 of the corresponding numbered auxiliary requests 1, 2, 5-7, 9-12, in the addition of the feature "psoriasis", namely "for use in the treatment of psoriasis, psoriatic arthritis, neurodermatitis, inflammatory bowel disease, or an autoimmune disease selected from...".

VIII. Oral proceedings took place on 6 September 2021 by videoconference.

IX. The arguments of the appellant may be summarised as follows:

Main request - Article 76(1) EPC

With regard to the daily dosage (feature (d) of claim 1), it was disclosed in the passage at page 36, lines 13-23, of the parent application. This passage presented the information on possible daily dosages in the form of a limited number of ranges defined by specific end points, among them 480 mg. According to the established case law, end points of ranges were explicitly disclosed. Moreover, the claims as filed contained a pointer to a daily dosage of 480 mg, which was achieved by administration of 240 mg twice daily. In particular, this followed from claims 27, 30, 32, 33 and 37 from the parent application. Also, from the fact that a claim was directed to this specific dosage, it was clear that this dosage was a preferred embodiment and therefore did not constitute a selection.

With regard to the list of diseases to be treated (feature (e) of claim 1), the original claims 44 and 45 contained the same list of diseases, and the original description also referred to these same diseases. In the description, however, the diseases were split into two groups. A first group to be found at pages 37-38 of the parent application, where the only difference between the conditions referred to in the present claim and the disclosure in the indicated passage was the deletion of one condition, namely psoriasis. The deletion of this condition could not lead to singling out of any subject-matter. The second group of diseases were referred to at page 38, which group was not recited in the present claim. Omitting these conditions from the claim did not amount to selecting any specific condition. The list of conditions remained generic. It had a reduced size, which was not objectionable. The possibility of deleting members from lists was also in line with the considerations of the Enlarged Board in G 2/10 in the context of disclaiming subject-matter. It was further noted that the primary focus of the invention was the treatment of autoimmune, inflammatory, or hyperproliferative conditions. The conditions according to the second group would not have been classified as autoimmune, inflammatory, or hyperproliferative conditions per se, as confirmed by Professor Page in HBP 14. Thus, the treatment of the conditions of the second group was a less preferred aspect of the original disclosure. The present claim related to the more preferred aspect.

With regard to the combination of features, the treatment of the conditions was by administering the compositions to patients at a daily dosage of the active substance. The skilled person would read information on conditions and on dosing in combination, and understand that in the passage at page 36, lines 16 to 23, of the parent application, a daily dosage of 480 mg DMF given in one to three doses was explicitly disclosed as an alternative dosage for the whole range of conditions. There was nothing in the parent application which would link particular daily dosages to particular conditions. To the contrary, the skilled person would have concluded that patients would benefit from a systemic therapy using dimethylfumarate at the same labelled dose independent of the specific disease. An additional pointer was provided by original claims 44 and 45, which referred to claims 1 to 43 and thus also to claims 27, 32, and 37. The original claims supported the treatment of all conditions, including those referred to in the present claim, by two times 240 mg daily, i.e a daily dosage of 480 mg dimethylfumarate.

Admission of auxiliary requests 1A, 2A, 5A-7A, 9A, 10A-12A into the proceedings

In all these requests, the term "psoriasis" was reintroduced in claim 1. This change did not create a new case.

Auxiliary requests 1 and 1A- Article 76(1) EPC

The same arguments submitted for the man request applied to these requests.

Auxiliary request 2 - Article 76(1) EPC

The claim according to auxiliary request 2 differed from the claim according to auxiliary request 1 with respect to the dosing feature, and required that the composition was for administration twice daily and the amount in a dosage form was 240 mg active substance.

The amended feature of twice daily followed from the combination of original claims 30, 32, and the amount in a dosage form of 240 mg active substance followed from original claims 33 and 37. Finally, the diseases to be treated followed from original claim 45, as discussed. Combining original claims to define a narrower claim was common practice and supported by the case law.

The further auxiliary requests- Article 76(1) EPC

The claim according to auxiliary requests 3, 4, 5, 5A, 6, 6A, 7, 7A contained the dosing feature also present in the claim of auxiliary request 2. The same arguments applied to all auxiliary requests.

X. The arguments of the respondents may be summarised as follows:

Main request - Article 76(1) EPC

According to respondent 01, the claimed dosage regimen constituted a selection, since none the disclosed small ranges was identified as being preferred, and its selection alone violated the requirements of Article 76(1) EPC. The dosage regimen depended also on the disease to be treated. Moreover, the diseases to be treated constituted a further selection, in view of the omission of some diseases from original claims 44 and 45 or from the description. The combination of these features lacked a direct and unambiguous disclosure in the parent application.

Respondents 03, 04, 05, 10, 11 essentially submitted the same arguments.

Admission of auxiliary requests 1A, 2A, 5A-7A, 9A, 10A-12A into the proceedings

According to respondent 01, by not submitting these requests in opposition proceedings, the appellant prevented the opposition division to take a decision on said requests. These requests should therefore not be admitted.

Respondent 05 considered that none of said requests would overcome the deficiencies of the main request, and should accordingly not be admitted.

Respondent 10 added that the appellant should not have been able to present a new case on appeal with a scope of claims which it had the opportunity to present during opposition proceedings.

Respondent 11 considered also that it should not be admitted to open a discussion that should have taken place in opposition proceedings.

Auxiliary requests 1 and 1A- Article 76(1) EPC

The same arguments submitted in relation to the main request applied to these requests.

Auxiliary request 2 - Article 76(1) EPC

According to respondent 01, all dosage regimen which were present in the original claims were equally ranking. The new dosage regimen of "240 mg" was an arbitrary selection of the subject-matter of original claim 37. The same arguments applied for "twice daily" which originated from claim 32. There was no pointer for these selections and their combination and there were no convergent lists of preference which could have justified these selections.

Respondent 03 pointed furthermore out that the original claims 44 and 45 relating to the diseases, comprised the term "any one of" the previous claims and did refer not to a specific dosage regimen.

Respondents 5 and 10 argued that the claimed dosage regimen and the claimed diseases originated from multiple options which had the same level of preference, and that there was not any combination which could be singled out in comparison to the other combinations.

The further auxiliary requests- Article 76(1) EPC

The same arguments submitted for the main request and for auxiliary request 2 applied to the remaining requests.

XI. Requests

The appellant requested that the decision under appeal be set aside and the patent be maintained according to the set of claims filed as main request with the statement of grounds of appeal on 1 August 2018, or alternatively on the basis of one of auxiliary requests 1-12 and 1A, 2A, 5A-7A, 9A, 10A-12A filed with letter of 5 May 2020 or auxiliary requests 13-28 filed with the statement of grounds of appeal on 1 August 2018 (each "A" request immediately following the request with the corresponding number). The appellant also requested a remittal to the opposition division division for further prosecution of all issues except for basis in the parent application and the application as filed.

Respondents 01, 03, 04, 05, 10 and 11 requested that the appeal be dismissed.

The respondent 05 also requested that auxiliary requests 2A, 5A-7A, 12A filed with letter of 5 May 2020 not be admitted into the proceedings.

Respondents 01, 10 and 11 also requested that auxiliary requests 1A, 2A, 5A-7a, 9A, 10A-12A filed with letter of 5 May 2020 not be admitted into the proceedings.

The opponents 09, 06 and 07 withdrew their opposition with letters dated respectively 5 June 2018, 6 December 2018 and 16 October 2020.

The respondents 02 and 08 did not file any request nor submissions in the appeal proceedings.