A safe and effective method for treating ulcerative colitis with anti-IL12 / IL23 antibodies.

Abstract

This provides treatment methods for ulcerative colitis. [Solution] The present invention describes a method and composition for the clinically proven safe and effective treatment of ulcerative colitis, particularly moderate to severe active ulcerative colitis, in patients who have an insufficient response to or poor tolerance to conventional or existing therapies involving intravenous and / or subcutaneous administration of anti-IL-12 / IL-23p40 antibodies.

Claims

1. This includes administering a pharmaceutical composition containing an anti-IL-12 / IL-23p40 antibody to a target. Treatment of moderate to severe active ulcerative colitis (UC) in patients who require it. A method for performing the procedure, wherein the antibody includes a heavy chain variable region and a light chain variable region, and the heavy chain variable region The region is the complementarity-determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO: 1, and the C region of SEQ ID NO:

2. The DRH2 amino acid sequence and the CDRH3 amino acid sequence of SEQ ID NO: 3 are included, and the light chain is variable. The region is the complementarity-determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO: 4, and SEQ ID NO: 5 The antibody comprises the CDRL2 amino acid sequence and the CDRL3 amino acid sequence of SEQ ID NO: 6, and the antibody The above-mentioned subject is given intravenously, preferably at week 0 of treatment, approximately 6.0 mg / kg of the subject's body weight or It is administered at a dose of 130 mg per administration, subcutaneously to the subject, preferably for 8 weeks of treatment. The antibody is administered to the eye at a dose of 90 mg per administration, and at the maintenance dose, at 8 weeks... The drug is administered every 8 weeks after the treatment, or every 12 weeks after the treatment at the 8th week, and the subject is 、 (a) Symptomatic remission, (b) Partial Mayo remission, (c) Mayo rectal bleeding subscore is 0, (d) Mayo bowel movement frequency subscore is 0 or 1, (e) The average absolute number of feces decreases by at least 3, (f) Reduction in the amount of corticosteroids used and / or administered, (g) Corticosteroid-free symptomatic remission, (h) Corticosteroid-free partial Mayo remission, (i) Normalization of fecal lactoferrin, (j) Normalization of fecal calprotectin levels, (k) The total score on the Inflammatory Bowel Disease Questionnaire (IBDQ) is 16 points or less from the baseline during the induction period. Improvement on, (l) IBDQ remission, (m) SF-36 PCS score improves by 5 points or more from the baseline during the introductory phase, (n) SF-36 MCS score improves by 5 points or more from baseline during the introductory phase. At 92 weeks, based on meeting one or more clinical endpoints selected from the group consisting of the following: Responders to treatment The aforementioned method.

2. The antibody comprises the heavy chain variable region of the amino acid sequence of SEQ ID NO: 7 and the amino acid sequence of SEQ ID NO:

8. The method according to claim 1, comprising the light chain variable region of the acid sequence.

3. The antibody consists of the heavy chain of the amino acid sequence of SEQ ID NO: 10 and the light chain of the amino acid sequence of SEQ ID NO:

11. The method according to claim 1, including the method described in claim 1.

4. The pharmaceutical composition for intravenous administration contains 10 mM L-histidine, 8.5% (w / v ) Sucrose, 0.04% (w / v) polysorbate 80, 0.4 mg / mL L- It contains methionine and 20 μg / mL of EDTA disodium salt dihydrate at pH 6.

0. The method according to any one of claims 1 to 3, further comprising a solution.

5. The pharmaceutical composition for subcutaneous administration contains 6.7 mM L-histidine, 7.6% (w / v A solution containing sucrose (0.004% w / v) polysorbate 80 at pH 6.

0. The method according to claim 4, further comprising a liquid.

6. The method according to claim 4, wherein the subject is a delayed responseer.

7. The aforementioned subjects include anti-TNF, vedolizumab, corticosteroids, and azathioprine (AZA At least one therapy selected from the group consisting of ), and 6-mercaptopurine (6MP). Either previously failed to, or were intolerant to, or the subject is Corticos The method according to claim 4, which exhibits teroid dependence.

8. The method according to claim 4, wherein the subject is identified as having mucosal healing that has continued from week 0 to at least week 92.

9. Treatment of moderate to severe active ulcerative colitis (UC) is provided to those who require it. A pharmaceutical composition comprising an anti-IL-12 / IL-23p40 antibody for the purpose of performing the procedure, wherein the antibody This includes a heavy chain variable region and a light chain variable region, and the heavy chain variable region is used for the complementarity determination of Sequence ID No.

1. The amino acid sequence of region heavy chain 1 (CDRH1), the amino acid sequence of CDRH2 in SEQ ID NO: 2, and the The CDRH3 amino acid sequence in sequence number 3 is included, and the light chain variable region is the complementarity determination region of sequence number 4. The amino acid sequence of the regional light chain 1 (CDRL1), the amino acid sequence of CDRL2 of SEQ ID NO: 5, and the sequence The subject includes the CDRL3 amino acid sequence number 6, (a) Symptomatic remission, (b) Partial Mayo remission, (c) Mayo rectal bleeding subscore is 0, (d) Mayo bowel movement frequency subscore is 0 or 1, (e) The average absolute number of feces decreases by at least 3, (f) Reduction in the amount of corticosteroids used and / or administered, (g) Corticosteroid-free symptomatic remission, (h) Corticosteroid-free partial Mayo remission, (i) Normalization of fecal lactoferrin, (j) Normalization of fecal calprotectin levels, (k) The total score on the Inflammatory Bowel Disease Questionnaire (IBDQ) is 16 points or less from the baseline during the induction period. Improvement on, (l) IBDQ remission, (m) SF-36 PCS score improves by 5 points or more from the baseline during the introductory phase, (n) SF-36 MCS score improves by 5 points or more from baseline during the introductory phase. At 92 weeks, based on meeting one or more clinical endpoints selected from the group consisting of the following: Responders to treatment The aforementioned pharmaceutical composition.

10. The antibody comprises the heavy chain variable region of the amino acid sequence of SEQ ID NO: 7 and the amino acid sequence of SEQ ID NO:

8. The pharmaceutical composition according to claim 9, comprising a variable light chain region of the column.

11. The antibody comprises the heavy chain of the amino acid sequence of SEQ ID NO: 10 and the amino acid sequence of SEQ ID NO: 11 The pharmaceutical composition according to claim 9, comprising a light chain.

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