Use of recombinant anti-interleukin 23p19 subunit antibodies in the treatment of inflammatory bowel disease

Abstract

The present invention relates to a method using recombinant anti-interleukin-23p19 subunit antibodies to treat inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, and more particularly to a dosing regimen using anti-IL-23p19 antibodies to prevent or treat mild ulcerative colitis and moderate to severe ulcerative colitis.

Description

Technical Field

[0001] The present invention generally relates to the use of anti-IL-23p19 antibodies in the treatment of inflammatory bowel diseases, including ulcerative colitis (e.g., mild to moderate to severe ulcerative colitis) and Crohn's disease, and particularly to dosing regimens for treating said diseases.

Background Art

[0002] Inflammatory bowel disease (IBD) is a idiopathic inflammatory bowel disease that affects the ileum, rectum, and colon, and clinical symptoms include diarrhea, abdominal pain, and bloody stools. Inflammatory bowel diseases include ulcerative colitis (UC) and Crohn's disease (CD). Ulcerative colitis (UC) is a chronic inflammatory disease characterized by inflammation of the colon and rectum. Typical symptoms include recurrent diarrhea, abdominal pain, and mucopurulent bloody stools accompanied by tenesmus. UC seriously threatens physical health and also affects daily life and psychology. UC is clinically classified into a primary type and a chronic relapsing type. UC is relatively common in Europe and North America, and the morbidity rate in China is lower than that of Westerners, but the number of patients has shown a rapid increase in the past 20 years, with a morbidity rate of 11.6 / 100,000 people, and it mostly occurs in the young to middle-aged population. Crohn's disease (CD) is a chronic inflammatory granulomatous disease that affects the entire digestive tract. As a non-continuous full-thickness inflammation, it most frequently occurs in the terminal ileum and adjacent colon. The main lesion is a gastrointestinal ulcer, which may cause intestinal stenosis and perforation, and shows a high tendency of recurrence risk. The incidence rate of Crohn's disease has shown a significant upward trend in the past 10 years.

[0003] Clinical treatment for ulcerative colitis (UC) primarily involves drug therapy and surgery. Mercaptopurine-based drugs are the most traditional immunosuppressants, but they have a high incidence of side effects. In the field of biological therapy, anti-TNF-α monoclonal antibodies are used in patients who do not respond to hormone therapy or immunosuppressant therapy, hormone-dependent patients, and patients who are intolerant to the aforementioned drugs. Infliximab (IFX) was previously the only biological agent approved in China for the treatment of UC and cyclophosphamide (CD). In May 2019, ustekinumab (Stelara®) was added to the second list of emergency import new drugs by the NMPA and is now used to treat moderate to severe active Crohn's disease (CD) in adult patients who have poor response, no response, or intolerance to conventional therapy or tumor necrosis factor α (TNF-α) antagonists. In March 2020, vedolizumab (Entyvio®) was approved by the NMPA and is now used in China for moderate to severe active ulcerative colitis (UC) and cardiopulmonary disease (CD) in adult patients who have poor response, no response, or intolerance to conventional therapies or tumor necrosis factor-alpha (TNF-α) inhibitors. Therefore, various biological agents targeting specific immune pathways have been studied as potential treatments for UC. Vedolizumab, an anti-tumor necrosis factor-alpha (anti-TNFα) monoclonal antibody and a recently developed integrin receptor antagonist, has already received approval from the U.S. Food and Drug Administration and the European Medicines Agency.

[0004] IL-23 (interleukin-23) is a heterodimer cytokine belonging to the IL-12 family, possessing a p40 subunit similar to IL-12 and a unique p19 subunit. The IL-23 heterodimer binds to the IL-23 receptor (IL-23R) and the β1 subunit of the IL-12 receptor (IL-12Rβ1), activating signaling pathways. Although IL-23 and IL-12 are closely related, these two cytokines play different biological roles, promoting the responses of Th1 and Th17 cells, respectively. Alone or in combination with other cytokines such as transforming growth factor (TGF-β), IL-6, or IL-1β, they can induce differentiation of naive CD4+ T cells into Th17 cells, promoting the proliferation, differentiation, and maintenance of Th17 and innate immune cells. Stimulation of Th17 cells produces IL-17, IL-22, tumor necrosis factor (TNF)-α, and granulocyte-macrophage-colony stimulating factor (GM-CSF), which stimulate inflammation and other immune-mediated pathological processes in local tissues through a wide range of immune-mediated inflammatory states. Chronic inflammation resulting from IL-23 / Th17 / IL-17 dysregulation is the pathophysiological basis of various autoimmune diseases, including psoriasis, ulcerative colitis, Crohn's disease, rheumatoid arthritis, multiple sclerosis, and asthma. Several companies are working on developing IL-23-targeted therapies for a wide range of diseases. Ustekinumab, a monoclonal antibody approved by the U.S. Food and Drug Administration for the treatment of psoriasis, psoriatic arthritis, and CD, was the first biologic to demonstrate clinical benefit in autoimmune diseases. Because ustekinumab binds to the shared p40 subunit of IL-12 and IL-23, it targets both cytokines rather than just IL-23. Inhibiting the IL-12 pathway may potentially limit the clinical activity of p40-targeting antibodies because it hinders interferon-mediated inhibition of Th17 cell production against Th1 cell induction.Drugs that specifically target the IL-23p19 subunit have shown clinical activity in psoriasis and CD (Kopp T et al., Nature, Vol. 521, No. 7551, pp. 222-226, 2015; Sands BE et al., Journal of Crohn's and Colitis, Vol. 9, Supplementary Issue 1, pp. S15-S16, 2015).

[0005] Conventional drugs or biological agents approved for the treatment of ulcerative colitis may have insufficient, no, or intolerable treatment rates, and may also have various types and degrees of side effects. [Overview of the project]

[0006] The inventors unexpectedly discovered that administration of anti-IL-23p19 antibodies, particularly according to the administration regimen of the present invention, yielded satisfactory clinical response and remission rates in patients with inflammatory bowel diseases, including ulcerative colitis and Crohn's disease. The results showed good therapeutic efficacy, no significant or unacceptable adverse events, acceptable and manageable safety, good tolerability, and good patient compliance.

[0007] The present invention also addresses the above needs by providing a method for treating ulcerative colitis using an anti-IL-23p19 antibody.

[0008] Therefore, in a first embodiment, a method is provided for preventing or treating inflammatory bowel disease, such as ulcerative colitis or Crohn's disease, in a patient, comprising administering the anti-IL-23p19 antibody of the present invention to the patient in need.

[0009] In a second embodiment, the use of the anti-IL-23p19 antibody of the present invention is provided for the prevention or treatment of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease.

[0010] In a third embodiment, the present invention provides an anti-IL-23p19 antibody used for the prevention or treatment of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease.

[0011] In a fourth embodiment, the use of the anti-IL-23p19 antibody of the present invention is provided in the preparation of agents for preventing or treating inflammatory bowel diseases such as ulcerative colitis or Crohn's disease.

[0012] In a fifth embodiment, a pharmaceutical composition is provided comprising an effective amount of the anti-IL-23p19 antibody of the present invention and one or more pharmaceutically acceptable excipients.

[0013] In a sixth embodiment, a kit is provided comprising an effective amount of the anti-IL-23p19 antibody of the present invention and a printed instruction leaflet containing instructions on the use of the antibody in the prevention or treatment of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease.

[0014] In a seventh embodiment, a single-dose unit containing an effective amount of the anti-IL-23p19 antibody of the present invention is provided.

[0015] In an eighth embodiment, the use of a kit in the preparation of drugs for the prevention or treatment of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease is provided.

[0016] In certain embodiments of the present invention, a method for preventing or treating inflammatory bowel disease is provided. Preferably, the inflammatory bowel disease is ulcerative colitis (e.g., mild, moderate, or severe ulcerative colitis) or Crohn's disease.

[0017] In a particular embodiment of the present invention, a method for preventing or treating ulcerative colitis is provided. Preferably, the ulcerative colitis is moderate to severe.

[0018] In a particular embodiment of the present invention, the method comprises administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which 100-1000 mg / dose of anti-IL-23p19 antibody is administered once or multiple times to patients who require an induction dose, b) The maintenance therapy phase involves administering a maintenance dose of anti-IL-23p19 antibody to each patient at a dose of 100-1000 mg / dose, once or multiple times, with the first maintenance dose administered 2-8 weeks after the final dose of the induction dose. The amino acid sequence of the heavy chain CDR1 of the antibody includes or consists of SEQ ID NO: 1, the amino acid sequence of the heavy chain CDR2 includes or consists of SEQ ID NO: 2, the amino acid sequence of the heavy chain CDR3 includes or consists of SEQ ID NO: 3, the amino acid sequence of the light chain CDR1 of the antibody includes or consists of SEQ ID NO: 4, the amino acid sequence of the light chain CDR2 includes or consists of SEQ ID NO: 5, and the amino acid sequence of the light chain CDR3 includes or consists of SEQ ID NO: 6.

[0019] In certain embodiments of the present invention, the induction dose is administered by intravenous injection and / or the maintenance dose is administered by subcutaneous injection.

[0020] In a particular embodiment of the present invention, once a clinical response is obtained by administering the induction dose, the patient enters the maintenance therapy phase.

[0021] In certain embodiments of the present invention, the induction dose is administered 1 to 3 times, preferably 3 times.

[0022] In a particular embodiment of the present invention, when an induction dose is administered multiple times, the induction dose is administered at intervals of four weeks.

[0023] In a particular embodiment of the present invention, when a maintenance dose is administered multiple times, the maintenance dose is administered at intervals of 4 to 8 weeks.

[0024] In certain embodiments of the present invention, the first maintenance dose is administered 2 to 8 weeks after the last induction dose. Preferably, the first maintenance dose is administered 4 weeks after the last induction dose.

[0025] In certain embodiments of the present invention, the method comprises administering an anti-IL-23p19 antibody to a patient in need thereof, wherein the dosing regimen is a) an induction therapy phase of administering an induction dose of the anti-IL-23p19 antibody at 100-1000 mg per administration to the patient in need thereof three times at 4-week intervals; and b) a maintenance therapy phase of administering a maintenance dose of the anti-IL-23p19 antibody to the patient at 100-1000 mg per administration at 4-8 week intervals, wherein the first maintenance dose is administered at 2-8 weeks after the final administration of the induction dose; comprising wherein the amino acid sequence of the heavy chain CDR1 of the antibody comprises or consists of SEQ ID NO: 1, the amino acid sequence of the heavy chain CDR2 of the antibody comprises or consists of SEQ ID NO: 2, the amino acid sequence of the heavy chain CDR3 of the antibody comprises or consists of SEQ ID NO: 3, the amino acid sequence of the light chain CDR1 of the antibody comprises or consists of SEQ ID NO: 4, the amino acid sequence of the light chain CDR2 of the antibody comprises or consists of SEQ ID NO: 5, the amino acid sequence of the light chain CDR3 of the antibody comprises or consists of SEQ ID NO: 6, and the CDRs have boundaries defined by the AbM rules.

[0026] In certain embodiments of the present invention, the ulcerative colitis is moderate to severe ulcerative colitis. In another specific embodiment, the ulcerative colitis is mild ulcerative colitis.

[0027] In certain embodiments of the present invention, the induction dose is administered by intravenous injection. Preferably, the induction dose is administered by intravenous infusion.

[0028] In certain embodiments of the present invention, the maintenance dose is administered by subcutaneous injection.

[0029] In certain embodiments of the present invention, the induction dose of the anti-IL-23p19 antibody is administered three times by intravenous infusion at 4-week intervals.

[0030] In certain embodiments of the present invention, a maintenance dose of anti-IL-23p19 antibody is administered to patients who require it by subcutaneous injection at 4-week intervals.

[0031] In certain embodiments of the present invention, a maintenance dose of anti-IL-23p19 antibody is administered to patients who require it by subcutaneous injection at 8-week intervals.

[0032] In a particular embodiment of the present invention, the induction dose in the method is 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg.

[0033] In a particular embodiment of the present invention, the induction dose in the method is 200 mg.

[0034] In a particular embodiment of the present invention, the induction dose in the method is 600 mg.

[0035] In a particular embodiment of the present invention, the maintenance dose in the method is administered at intervals of four weeks following the administration of the first maintenance dose.

[0036] In a particular embodiment of the present invention, the first maintenance dose in the method is administered four weeks after the final dose of the induction dose.

[0037] In certain embodiments of the present invention, the maintenance dose in the method is 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg.

[0038] In a particular embodiment of the present invention, the maintenance dose in the method is 200 mg.

[0039] In a particular embodiment of the present invention, the administration regimen in the method includes administering an induction dose of anti-IL-23p19 antibody to a patient requiring such an antibody at 4-week intervals, three times, if the patient does not achieve a clinical response 2 to 8 weeks after the final dose of the induction dose, an extension induction dose of 100 to 1000 mg / dose is administered three times, and if a clinical response is achieved with the extension induction dose, the patient enters a maintenance therapy phase.

[0040] In a specific embodiment of the present invention, if no clinical response is obtained 4 weeks after the final dose of the induction dose, an extension induction dose of 100-1000 mg per dose is administered three times.

[0041] In a particular embodiment of the present invention, the extended induction dose is administered at intervals of four weeks.

[0042] In certain embodiments of the present invention, the extended induction dose is administered by intravenous infusion.

[0043] In a particular embodiment of the present invention, the first extended induction dose is administered 4 weeks after the final dose of the m induction dose.

[0044] In certain embodiments of the present invention, the extended induction dose in the method is 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg.

[0045] In a particular embodiment of the present invention, the extended induction dose in the method is 600 mg.

[0046] In certain embodiments of the present invention, the first maintenance dose after the extended induction period is administered 2 to 8 weeks after the last dose of the extended induction dose.

[0047] In a particular embodiment of the present invention, the first maintenance dose after the extended induction period is administered 4 weeks after the last dose of the extended induction dose.

[0048] In a specific embodiment of the present invention, after the extended induction period, a maintenance dose of anti-IL-23p19 antibody is administered to patients who require it by subcutaneous injection at 4-week intervals. Furthermore, the maintenance dose is 100 to 1000 mg.

[0049] In certain embodiments of the present invention, the method includes administering a maintenance dose of 100 mg / dose, 200 mg / dose, 300 mg / dose, 400 mg / dose, 500 mg / dose, 600 mg / dose, 700 mg / dose, 800 mg / dose, 900 mg / dose, or 1000 mg / dose after the extended induction period.

[0050] In a particular embodiment of the present invention, the method includes administering a maintenance dose of 200 mg / dose after the extended induction period.

[0051] The method of the present invention comprises administering at least one induction dose of anti-IL-23p19 antibody to a patient as needed during the induction phase in order to induce a desired therapeutic effect, including clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief. If the patient achieves the desired therapeutic effect at the end of the induction phase, then at least one maintenance dose is administered to the patient thereafter to maintain at least one therapeutic effect (clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief) obtained during the induction phase.

[0052] There is no minimum or maximum duration for the induction phase, but it is generally 4, 8, or 12 weeks, and the end of the induction phase is evaluated 4 or 8 weeks after the final dose of the induction dose. For example, a 4-week induction phase may include administering the induction dose in week 0 and evaluating the end of the induction phase in week 4. An 8-week induction phase may include administering the induction dose in weeks 0 and 4 and evaluating the end of the induction phase in week 8. A 12-week induction phase may include administering the induction dose in weeks 0, 4, and 8 and evaluating the end of the induction phase in week 12.

[0053] In a particular embodiment of the present invention, the heavy chain of the anti-IL-23p19 antibody includes an N-glycosylation site located at the 295th asparagine position of the heavy chain.

[0054] In a particular embodiment of the present invention, the anti-IL-23p19 antibody in the method comprises a heavy chain variable region VH and a light chain variable region VL, wherein the heavy chain variable region comprises or consists of the sequence of SEQ ID NO: 7 or a sequence having at least 90%, 95%, 98%, or 99% identity thereto, and the light chain variable region comprises or consists of the sequence of SEQ ID NO: 8 or a sequence having at least 90%, 95%, 98%, or 99% identity thereto.

[0055] In a particular embodiment of the present invention, the anti-IL-23p19 antibody in the method is an IgG1 antibody, preferably comprising a heavy chain and a light chain, wherein the heavy chain comprises or consists of a sequence having at least 90%, 95%, 98%, or 99% identity with SEQ ID NO: 9, and the light chain comprises or consists of a sequence having at least 90%, 95%, 98%, or 99% identity with SEQ ID NO: 10.

[0056] In certain embodiments of the present invention, the anti-IL-23p19 antibody comprises a heavy chain shown in SEQ ID NO: 9 and a light chain shown in SEQ ID NO: 10, for example, the anti-IL-23p19 antibody comprises two heavy chains shown in SEQ ID NO: 9 and two light chains shown in SEQ ID NO: 10, or consists of two heavy chains shown in SEQ ID NO: 9 and two light chains shown in SEQ ID NO: 10.

[0057] In certain embodiments of the present invention, the anti-IL-23p19 antibody is recombinantly expressed in HEK 293 cells or CHO cells.

[0058] In certain embodiments of the present invention, the invention further relates to a kit comprising an effective amount of the anti-IL-23p19 antibody, preferably including a printed instruction leaflet with instructions regarding the administration of the anti-IL-23p19 antibody to an individual for the prevention or treatment of inflammatory bowel disease such as ulcerative colitis or Crohn's disease.

[0059] The present invention further provides a single-dose unit comprising an effective amount of the anti-IL-23p19 antibody of the present invention and a kit containing the effective amount of the anti-IL-23p19 antibody of the present invention.

[0060] In certain embodiments of the present invention, the use of a kit in the preparation of a drug for preventing or treating inflammatory bowel diseases such as ulcerative colitis or Crohn's disease is further included.

[0061] The present invention provides a method for preventing or treating inflammatory bowel diseases such as ulcerative colitis or Crohn's disease using an anti-IL-23p19 antibody, which, when administered once every four or eight weeks during the maintenance phase, can improve patient compliance with the medication, reduce patient fear of injections, alleviate patient physical and psychological burden, and help maintain long-term remission.

[0062] In another specific embodiment of the method of the present invention, the patient is a person receiving initial treatment with a biological agent.

[0063] In a specific candidate embodiment of the method of the present invention, the patient is a person with a history of treatment with biological agents.

[0064] This embodiment of the method of the present invention includes administering one, two, or three additional induction doses (referred to as “extended induction doses”) to distinguish them from the initial induction dose if the patient does not achieve a clinical response at the end of the initial induction period. The doses and dosing intervals of the extended induction period are generally the same as those of the initial induction period. However, modifications may be made if the healthcare professional has grounds to believe that the modification would benefit the patient, such as increasing the dose or frequency of administration of anti-IL-23p19 antibody. If the patient achieves a clinical response at the end of the extended induction period, at least one maintenance dose of anti-IL-23p19 antibody is administered to maintain the clinical response, such as clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief, or any other necessary therapeutic effect. The patient receives the first maintenance dose 4 to 12 weeks after the last dose of the extended induction dose. This 4 to 12-week period takes into account the temporal variation between the last dose of the extended induction dose and the evaluation of the end of the extended induction period. This variation may be due to variations in the dosing frequency during the extended induction period. For example, the administration frequency during the extended induction phase is at 4-week intervals, and the evaluation of the end of the extended induction phase is performed 4 weeks after the last dose of the extended induction dose. If the patient achieves a clinical response, the first maintenance dose can be administered at the end of the induction phase evaluation visit (i.e., 4 weeks after the last dose of the extended induction dose) or at a follow-up visit scheduled shortly thereafter. Alternatively, the administration frequency during the extended induction phase is at 8-week intervals, and the evaluation of the end of the extended induction phase is performed 8 weeks after the last dose of the extended induction dose. If the patient achieves clinical remission, the first maintenance dose can be administered at the end of the induction phase evaluation visit (i.e., 8 weeks after the last dose of the extended induction dose) or at a follow-up visit scheduled shortly thereafter.

[0065] Other embodiments of the present invention will become apparent by referring to the following detailed description. Detailed Description of the Invention

[0066] Before describing the present invention in detail, it should be understood that the present invention is not limited to the specific methods and experimental conditions described herein, as these can be modified. Furthermore, the terms used herein are solely for the purpose of describing specific embodiments and are not intended to be limiting. Definitions

[0067] Unless otherwise defined, all technical and scientific terms used herein have meanings that are generally understood by those skilled in the art. For the purposes of the present invention, the following terms have been defined.

[0068] When used in conjunction with a number, the term "approximately" means to encompass a range of numbers that have a lower limit of 5% lower and an upper limit of 5% higher than the specified number.

[0069] When the term "and / or" is used in relation to two or more options, it is understood to mean either one of the options or two or more of the options.

[0070] In this specification, the terms “inclusion” or “contains” are intended to include the elements, integers, or procedures described, but not to exclude other elements, integers, or procedures. In this specification, when the terms “inclusion” or “contains” are used, unless otherwise specified, they also include combinations of the elements, integers, or procedures described. For example, when an antibody variable region “contains” a specific sequence is mentioned, it means including the antibody variable region consisting of that sequence.

[0071] The IL-23 p19 subunit (also referred to herein as "IL-23p19" and "p19 subunit") is a polypeptide comprising a 21-amino acid leader sequence (Oppmann et al., Immunity 13: 715 (2000), SEQ ID NO: 181) and four packed α-helices called A, B, C, and D, having an over-over-under-under topology. The four helices are linked by three polypeptide loops. The AB and CD loops are relatively long to link parallel helices. The short BC loop links the antiparallel B and C helices. The IL-23 p19 subunit is a member of the IL-6 family of helical cytokines. The cytokine family binds to its homologous receptors via three conserved epitopes (sites I, II, and III; Bravo and Heath (2000) EMBO J.19: 2399-2411). The p19 subunit interacts with the three cytokine receptor subunits to form a potent signaling complex. When expressed intracellularly, the p19 subunit first forms a complex with the p40 subunit, and the p19 subunit shares the p40 subunit with IL-12. The p19p40 complex is secreted from the cell as a heterodimeric protein called IL-23. In certain embodiments, the IL-23p19 of the present invention is derived from humans (NCBI: AAG37232) or cynomolgus monkeys (NCBI: AEY84629).

[0072] In this specification, the terms “anti-IL-23p19 antibody,” “anti-IL-23p19,” “IL-23p19 antibody,” or “antibody that binds to IL-23p19” refer to an antibody that binds with sufficient affinity to (human or cynomolgus monkey) IL-23p19 subunits or fragments and can be used as a diagnostic and / or therapeutic agent targeting (human or cynomolgus monkey) IL-23p19.

[0073] In this specification, the term “antibody” is used in its broadest sense to refer to a protein containing an antigen-binding site, and includes, but is not limited to, full-length antibodies and antigen-binding fragments of antibodies, as well as natural and artificial antibodies of various structures.

[0074] The terms "whole antibody," "full-length antibody," "complete antibody," or "full-length antibody" can be used interchangeably and refer to a glycoprotein containing at least two heavy chains (H) and two light chains (L) linked together by disulfide bonds. Each heavy chain consists of a variable heavy chain region (abbreviated as VH in this specification) and a constant heavy chain region. The constant heavy chain region consists of three domains: CH1, CH2, and CH3. Each light chain consists of a variable light chain region (abbreviated as VL in this specification) and a constant light chain region. The constant light chain region consists of one domain, CL. The VH and VL regions are further divided into hypervariable regions (complementarity-determining regions (CDRs)) and relatively conserved regions (framework regions (FRs)) inserted between them. Each VH and VL consists of three CDRs and four FRs, arranged in the order FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4 from the amino group terminus to the carboxyl group terminus. The constant regions do not directly participate in antibody antigen binding but exhibit various effector functions.

[0075] The term "complementarity-determining region," "CDR region," or "CDR" refers to a region in the antibody variable domain whose sequence is hypervariable and which forms structurally determined loops ("hypervariable loops") and / or antigen contact residues ("antigen contact sites"). CDRs are primarily responsible for binding to antigen epitopes. Heavy chain and light chain CDRs are generally called CDR1, CDR2, and CDR3, and are numbered from the N-terminus. CDRs located in the antibody heavy chain variable domain are called HCDR1, HCDR2, and HCDR3, and CDRs located in the antibody light chain variable domain are called LCDR1, LCDR2, and LCDR3.

[0076] In a given light chain variable region or heavy chain variable region amino acid sequence, the precise amino acid sequence boundary of each CDR can be determined by one or a combination of numerous well-known antibody CDR assignment systems. For example, the aforementioned assignment system can be defined by Chothia (Chothia et al. (1989) Nature 342: 877-883; Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins", Journal of Molecular Biology, 273, 927-948 (1997)), based on the three-dimensional structure of antibodies and the topology of the CDR loop; Kabat (Kabat et al., Sequences of Proteins of Immunological Interest, 4th edition, US Department of Health and Human Services, National Institutes of Health (1987)), AbM (University of Bath), Contact (University College London), the international ImMunoGeneTics database (IMGT) (www.imgt.cines.fr / ), and North CDR, based on affinity propagation clustering using numerous crystal structures.

[0077] An example of an AbM rule is as follows:

[0078] [Table 1]

[0079] Unless otherwise specified, in this invention, when referring to residue positions in the variable region of an antibody (including heavy chain variable region residues and light chain variable region residues), it refers to the numbered positions according to the Kabat numbering system (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)).

[0080] In certain embodiments, the CDR of the antibody of the present invention has a boundary defined by the AbM rule.

[0081] The term "antibody fragment" refers to a molecule that, unlike a complete antibody, contains a portion of a complete antibody and binds to the antigen to which the complete antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2, bivalent antibodies, linear antibodies, single-chain antibodies (such as scFv), single-domain antibodies, bivalent or bispecific antibodies or their fragments, camelid antibodies, and bispecific or multispecific antibodies formed from antibody fragments.

[0082] In this specification, the term "antigen-binding fragment" refers to a molecule that, unlike a complete antibody, contains a portion of a complete antibody and binds to the antigen to which the complete antibody binds. Examples of antigen-binding fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2, bivalent antibodies, linear antibodies, single-chain antibodies (such as scFv), single-domain antibodies, bivalent or bispecific antibodies or their fragments, camelid antibodies, and bispecific or multispecific antibodies formed from antibody fragments.

[0083] The terms "pharmaceutical composition" or "formulation" refer to a composition suitable for administration to animals, preferably mammals (including humans), comprising at least one active ingredient and at least one inactive ingredient, such as a pharmaceutically acceptable excipient. The pharmaceutical compositions of the present invention are preferably in extra-gastrointestinal administration forms, such as solutions, suspensions, lyophilized powders, and concentrated solutions.

[0084] The term "kit" refers to one or more individual pharmaceutical compositions (where at least one pharmaceutical composition contains an effective amount of anti-IL-23p19 antibody) and a package insert containing instructions for the use of the anti-IL-23p19 antibody for the prevention or treatment of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease, particularly in accordance with the administration regimen of the present invention. The kit may contain other therapeutic agents having the same or different activity. If the kit contains multiple individual pharmaceutical compositions, it should be understood that each pharmaceutical composition may contain a different dose and / or be administered via a different route.

[0085] In this specification, the term “single-dose unit” refers to a single-dose drug dosage form containing the antibody of the present invention, which is administered to a patient at the time of administration, and includes, for example, injection vials, ampoules, pre-filled syringes or pre-filled injectors containing a solution or lyophilized powder of the drug.

[0086] The terms “patient” and “subject” are used interchangeably and refer to animals. Preferably, the patient or subject is a mammal such as a primate (e.g., human, monkey, gorilla), cattle, sheep, goat, horse, dog, cat, rabbit, rat, or mouse. More preferably, the patient or subject is a human.

[0087] The term "patient or subject receiving initial treatment with a biological agent" refers to a patient or subject who has no prior history of treatment with a biological agent, and such biological agents include, for example, anti-tumor necrosis factor-α (TNF-α) antagonists such as adalimumab and infliximab, and anti-integrin antibodies such as vedolizumab and other experimental biological agents.

[0088] In this specification, the term “extra-gastrointestinal administration” refers to methods of administration other than enteral and local administration, typically by injection or infusion, and includes, but is not limited to, injections and infusions administered intravenously, intramuscularly, intra-arterially, intrathecally, intra-articularly, intra-orbitally, intracardiacly, intradermally, intraperitoneally, transtracheally, subcutaneously, subcuticularly, intra-articularly, sub-articularly, subarachnoidally, intraspinally, epidurally, and intrasternally.

[0089] The term "pharmaceutically acceptable" means that the following substances, compositions, dosage forms, etc., do not exhibit excessive toxicity, irritation, allergic reactions, or other undesirable properties in mammals, particularly humans, and that the benefit-risk ratio is reasonable when administered to animals or humans.

[0090] The term "pharmaceutically acceptable excipient" refers to a component in a drug formulation other than the active ingredient that is non-toxic to the organism. Examples of pharmaceutically acceptable carriers include, but are not limited to, adhesives, disintegrants, lubricants, solvents, dispersion media, buffers, excipients, antioxidants, preservatives, or flavoring agents.

[0091] The term "effective dose" refers to the amount that effectively achieves the desired therapeutic or preventive effect in the required dosage and for the required duration. The effective dose is determined by the attending physician or veterinarian and varies depending on factors such as the compound, the condition being treated, the severity of the disease being treated, the individual's age and associated health status, the route and form of administration, and the judgment of the attending physician or veterinarian. Generally, the "preventive effective dose" is less than the "therapeutic effective dose."

[0092] The term "treatment" refers to reducing or alleviating the severity of at least one symptom or condition, slowing or preventing its progression, or curing a condition.

[0093] The term "prevention" refers to delaying or preventing the onset of a disease or its symptoms.

[0094] The term "inflammatory bowel disease" refers to a spontaneous inflammatory bowel disorder affecting the ileum, rectum, and colon, which clinically manifests as diarrhea, abdominal pain, and bloody stools.

[0095] The term "ulcerative colitis" refers to a continuous inflammation of the colonic mucosa and submucosa, primarily affecting the rectum and colon, and is classified into mild, moderate, and severe based on the severity of the disease. The modified Mayo scoring system can be used to assess the severity and activity of ulcerative colitis.

[0096] The term "Crohn's disease" refers to a chronic inflammatory granulomatous disease of unknown cause that affects the entire gastrointestinal tract, characterized by discontinuous, full-thickness inflammation, with gastrointestinal ulcers being the primary lesion.

[0097] The term "Week 0" refers to the time when the IL-23p19 antibody was first administered. The term "Week 4" refers to the fourth week from the time the IL-23p19 antibody was first administered. The term "Week 8" refers to the eighth week from the time the IL-23p19 antibody was first administered. Other similar terms are understood similarly.

[0098] In this specification, the "modified Mayo score" is based on the Mayo scoring system for evaluating the severity and activity of ulcerative colitis (Schreder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987; 317(26):16 25-9). Following the recommendations of the U.S. Food and Drug Administration (FDA), it consists of three items—stool frequency, bloody stool, and endoscopic findings—and is scored from 0 to 9, without using a comprehensive assessment by a physician.

[0099] In this specification, the term "symptom Mayo score" refers to the modified Mayo score, which excludes endoscopic findings, and is assigned a score from 0 to 6.

[0100] In this specification, the term “partial Mayo score” refers to the Mayo score excluding endoscopic findings, i.e., the score including bowel movements, bloody stool, and the physician’s overall assessment. It is used only for the assessment of clinical recurrence and not as an indicator of efficacy.

[0101] In this specification, “clinical remission” is the primary endpoint of the study and is defined as a modified Mayo score of 0 for bloody stools, ≤1 for bowel movement frequency, and ≤1 for endoscopic findings.

[0102] In this specification, the term “clinical response” means that the modified Mayo score is reduced by 30% or more and by 2 or more points from baseline, the bloody stool score is reduced by 1 or more points from baseline, or the score for the relevant sub-item is 0 or 1.

[0103] In this specification, the term "symptom relief" refers to a bowel movement frequency score of 0 or 1 and a bloody stool score of 0.

[0104] In this specification, the term "endoscopic remission" refers to an endoscopic score of 0 or 1 on the modified Mayo score. An endoscopic score of 0 is considered to be complete endoscopic remission.

[0105] In this specification, the term "mucosal healing" refers to endoscopic remission and remission of the central imaging Geboes score on histopathological imaging.

[0106] In this specification, the term “induction dose” refers to the initial dose of anti-IL-23p19 antibody administered to a patient to achieve clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief. The “induction dose” may be a single dose. The “induction dose” may also be multiple doses. In this specification, the term “induction dose” typically refers to the dose administered during the induction phase, unless otherwise specified or the context clearly contradicts it.

[0107] In this specification, the term “induction therapy period” refers to the period during which the “induction dose” is administered to achieve clinical remission, clinical response, endoscopic remission, mucosal healing and / or symptom relief.

[0108] In this specification, the term “extended induction period” refers to a period of treatment in patients who have not achieved clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief during the initial induction therapy period, and which includes administering anti-IL-23p19 antibodies to achieve clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief. The “extended induction period” may be 4 weeks, 8 weeks, or 12 weeks.

[0109] In this specification, the term “extended induction dose” refers to an additional induction dose of anti-IL-23p19 antibody, which is administered to patients in order to achieve clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief in patients who have not achieved clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief during the initial induction therapy period. The “extended induction dose” may be a single dose or multiple doses. There is no minimum or maximum duration to the induction period, but it is generally 4 weeks, 8 weeks, or 12 weeks. The end of the extended induction period is usually evaluated 4 or 8 weeks after the final dose of the extended induction dose. The “extended induction dose” is administered during the extended induction therapy period.

[0110] In this specification, the term “maintenance (therapy) phase” refers to the period during which an anti-IL-23p19 antibody is administered to a patient to maintain a desired therapeutic effect, including clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief. The “maintenance phase” begins following the induction therapy phase or extended induction therapy phase, when the desired therapeutic effect, including clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief, has been achieved.

[0111] In this specification, the term “maintenance dose” refers to a subsequent dose of anti-IL-23p19 antibody administered to maintain or prolong a desired therapeutic effect, including clinical remission, clinical response, endoscopic remission, mucosal healing, and / or symptom relief. The “maintenance dose” is administered after the induction dose. The “maintenance dose” may be a single dose or multiple doses. The first dose in the maintenance phase after the completion of the induction phase is referred to as the “first maintenance dose.”

[0112] In some embodiments, the administration regimen of the present invention comprises an induction phase and a subsequent maintenance phase, the induction phase and the maintenance phase as described herein.

[0113] In some other embodiments, the administration regimen of the present invention comprises an induction phase, a subsequent extended induction phase, and a subsequent maintenance phase, the induction phase, extended induction phase, and maintenance phase as described herein.

[0114] In some embodiments, the Mayo score is assessed at the end of the induction therapy period, preferably using a modified Mayo score. In particular, the Mayo score is assessed at weeks 11-12, preferably using a modified Mayo score.

[0115] In some embodiments, a Mayo score evaluation is performed at the end of the extended implementation period, preferably adopting a modified Mayo score. In particular, a Mayo score evaluation is performed in weeks 23-24, preferably adopting a modified Mayo score.

[0116] In some embodiments, a safety follow-up period of 8 weeks is performed after the final dose of the maintenance dose.

[0117] In some embodiments, the administration regimen of the present invention is a) An induction therapy phase in which 100-1000 mg / dose of anti-IL-23p19 antibody is administered once or multiple times to patients who require an induction dose, b) The patient is administered one or more maintenance doses of anti-IL-23p19 antibody at a dose of 100-1000 mg / dose, with the first maintenance dose administered 2-8 weeks after the last dose of the induction dose, and Includes.

[0118] In some embodiments, the induction therapy phase includes administering one or more induction doses of anti-IL-23p19 antibody to the patient at a dose of 100 to 1000 mg per dose. Preferably, the induction dose is administered by intravenous injection. More preferably, the induction dose is administered by intravenous infusion.

[0119] In a specific embodiment of the present invention, a clinical response is obtained by administering the induction dose, and the patient enters the maintenance therapy phase.

[0120] In some embodiments, the induction dose may be administered once or multiple times, for example, once, twice, three times, or four times. Preferably, the induction dose is administered one to three times. More preferably, the induction dose is administered three times. When the induction dose is administered multiple times, the doses are administered at four-week intervals. It should be understood that the induction doses may be equal or unequal.

[0121] In certain embodiments, patients achieve a clinical response 2 to 8 weeks after the final dose of the induction dose during the induction phase and enter the maintenance phase. In some embodiments, the first maintenance dose is administered 2 to 8 weeks after the final dose of the induction dose. Preferably, the first maintenance dose is administered 4 weeks after the final dose of the induction dose.

[0122] In some embodiments, the maintenance therapy phase involves administering the patient one or more maintenance doses of anti-IL-23p19 antibody at 100 to 1000 mg per dose. Preferably, the maintenance dose is administered by subcutaneous injection.

[0123] In certain embodiments, the maintenance dose may be administered once or multiple times. In certain embodiments, when the maintenance dose is administered multiple times, the doses are administered at intervals of 4 to 8 weeks. Preferably, the maintenance dose is administered at intervals of 4 or 8 weeks. It should be understood that when the maintenance dose is administered multiple times, the doses may be equal or unequal. In particular, the maintenance therapy period is 32 weeks, starting from the administration of the first maintenance dose.

[0124] In a particular embodiment of the present invention, the method involves administering an anti-IL-23p19 antibody to a patient in need, the administration regimen comprising administering an induction dose of the anti-IL-23p19 antibody to the patient in need three times at 100-1000 mg / dose at 4-week intervals.

[0125] In a particular embodiment of the present invention, the method includes administering a maintenance dose of anti-IL-23p19 antibody to the patient at intervals of 4 to 8 weeks, with the first maintenance dose administered 2 to 8 weeks after the last dose of the induction dose.

[0126] In a particular embodiment, the administration regimen of the present invention is a) An induction therapy phase in which patients requiring the treatment receive an induction dose of anti-IL-23p19 antibody at 100-1000 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody at intervals of 4 to 8 weeks, 100 to 1000 mg / dose, with the first maintenance dose administered 2 to 8 weeks after the last dose of the induction dose. Includes.

[0127] In a specific embodiment of the present invention, the anti-IL-23p19 antibody is an antibody that specifically binds to IL-23p19, and the following six CDRs: - A heavy chain VH CDR1 containing or consisting of GYTFTSYLMH (SEQ ID NO: 1), - A heavy chain VH CDR2 containing YINPYNEGTN (SEQ ID NO: 2) or consisting of the same sequence, - A heavy chain VH CDR3 containing or consisting of NWDLPY (Sequence ID 3), - A light chain VL CDR1 containing or consisting of RASQSISDYLH (SEQ ID NO: 4), - A light chain VL CDR2 containing or consisting of YASQSMS (Sequence ID 5), - A light chain VL CDR3 containing or consisting of QQGHSFPFT (sequence number 6), Includes.

[0128] In particular, the CDR has boundaries defined by the AbM rule.

[0129] In certain specific embodiments, the inflammatory bowel disease is ulcerative colitis (UC) or Crohn's disease (CD).

[0130] In certain specific embodiments, the UC is moderate to severe ulcerative colitis, which includes, but is not limited to, moderate to severe active ulcerative colitis (modified Mayo score of 4-9 and endoscopic score of 2 or higher). In certain specific embodiments, the UC is mild ulcerative colitis.

[0131] In a specific embodiment, the method involves administering an induction dose of anti-IL-23p19 antibody to a patient requiring it three times by intravenous infusion at four-week intervals.

[0132] In certain specific embodiments, the method involves administering a maintenance dose of anti-IL-23p19 antibody to patients requiring it by subcutaneous injection at intervals of 4 to 8 weeks, for example, at intervals of 4, 6, 7, or 8 weeks.

[0133] In certain specific embodiments, the induction dose in the method is 100 to 1000 mg, for example, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg. It should be understood that the induction dose may be within the range of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg, or any two of these. For example, 200 to 900 mg, 200 to 800 mg, 200 to 600 mg, etc. In certain specific embodiments, the induction dose is 200 mg. In another specific embodiment, the induction dose is 600 mg.

[0134] In certain specific embodiments, the maintenance dose may be administered once or multiple times. It should be understood that the maintenance dose may be equal or unequal. When the maintenance dose is administered multiple times, the maintenance dose is administered at intervals of 2 to 8 weeks. In certain specific embodiments, the maintenance dose in the method is administered at intervals of 2 to 8 weeks after the first administration of the maintenance dose, for example, at intervals of 2, 3, 4, 5, 6, 7, or 8 weeks. In particular, the maintenance dose is administered at intervals of 4 or 8 weeks. In particular, the maintenance therapy period is 32 weeks, starting from the first administration of the maintenance dose.

[0135] In certain specific embodiments, the first maintenance dose in the method is administered 2 to 8 weeks after the last dose of the induction dose, for example, at 2, 3, 4, 5, 6, 7, or 8 weeks. Preferably, the first maintenance dose is administered 4 weeks after the last dose of the induction dose during the induction therapy phase.

[0136] In certain specific embodiments, the maintenance dose in the method is 100 to 1000 mg, for example, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg. It should be understood that the maintenance dose may be within the range of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg, or any two of these. Examples include 200 to 900 mg, 200 to 800 mg, 200 to 600 mg, etc. In particular, the maintenance dose is 200 mg.

[0137] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody by intravenous infusion at 100-1000 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 to 8 weeks, with the first maintenance dose administered 2 to 8 weeks after the last dose of the induction dose, as part of the maintenance therapy phase. Includes.

[0138] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody by intravenous infusion at 200-600 mg / dose at 4-week intervals, b) Maintenance therapy phase: The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 to 8 weeks, with the first maintenance dose administered 2 to 8 weeks after the last dose of the induction dose. Includes.

[0139] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody by intravenous infusion at 200 mg to 600 mg per dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 2 to 8 weeks after the last dose of the induction dose, as part of the maintenance therapy phase. Includes.

[0140] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody three times by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 2 to 8 weeks after the last dose of the induction dose, and the maintenance therapy phase is as follows: Includes.

[0141] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody three times by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 4 weeks after the last dose of the induction dose, and the maintenance therapy phase is as follows: Includes.

[0142] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody three times by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 2 to 8 weeks after the last dose of the induction dose, and the maintenance therapy phase continuing until week 44. Includes.

[0143] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody three times by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 2 weeks after the last dose of the induction dose, and the maintenance therapy phase continuing until week 44. Includes.

[0144] In a particular specific embodiment, the method further, a) At the end of the induction therapy period, evaluate the Mayo score at weeks 11-12. b) During the maintenance therapy phase, subjects who showed a clinical response at weeks 12-13 were randomly divided again in a 1:1 ratio to receive either 200 mg of anti-IL-23p19 antibody subcutaneously every 4 weeks or 200 mg of anti-IL-23p19 antibody subcutaneously every 8 weeks. Administration was continued until week 44, and safety monitoring was continued until week 52. Includes.

[0145] In a particular specific embodiment, the method further, a) At the end of the induction therapy period, the Mayo score was assessed at week 12 to evaluate the subject's efficacy response to the investigational drug. b) At the start of the maintenance therapy phase, subjects who showed a clinical response at week 12 were randomly divided again in a 1:1 ratio to receive either 200 mg of anti-IL-23p19 antibody subcutaneously every 4 weeks or 200 mg of anti-IL-23p19 antibody subcutaneously every 8 weeks. Administration was continued until week 44, and safety monitoring was continued until week 52. Includes.

[0146] In certain embodiments, the administration regimen of the present invention further comprises an extended induction period (or extended induction therapy period) performed after the induction therapy period and before the maintenance therapy period as described herein. In certain embodiments, the patient receives an extended induction period because they have not achieved a clinical response 2 to 8 weeks after the final dose of the induction dose in the induction therapy period.

[0147] In a particular embodiment, the administration regimen of the present invention includes an extended induction phase performed after the induction phase and before the maintenance phase: a1) Extended induction phase: The patient is administered an extended induction dose of anti-IL-23p19 antibody at a dose of 100-1000 mg per dose, once or multiple times. Preferably, once a clinical response is obtained with the administration of the extended induction dose, the patient enters the maintenance therapy phase.

[0148] In certain embodiments, the extended induction dose is administered by intravenous injection. More preferably, the extended induction dose is administered by intravenous infusion.

[0149] In certain embodiments, the first extended induction dose is administered 2 to 8 weeks after the last dose of the induction dose during the induction therapy period, preferably 2, 3, 4, 5, 6, 7, or 8 weeks after the last dose of the induction dose, and more preferably 4 weeks after the last dose of the induction dose.

[0150] In certain embodiments, the extended induction dose may be administered once or multiple times, for example, once, twice, three times, or four times. Preferably, the extended induction dose is administered one to three times. More preferably, the extended induction dose is administered three times. It should be understood that the extended induction dose may be equal or unequal. In some embodiments, when the extended induction dose is administered multiple times, the doses are administered at 4-week intervals.

[0151] In certain embodiments, if a clinical response is obtained by administering an extended induction dose, the patient can receive maintenance therapy.

[0152] In certain embodiments, patients achieve a clinical response 2 to 8 weeks after the final dose of the extended induction dose during the extended induction phase and receive treatment during the maintenance phase.

[0153] In a particular embodiment, the administration regimen in the method includes administering an induction dose of anti-IL-23p19 antibody three times at 4-week intervals to a patient requiring the induction dose, followed by an extended induction therapy phase in which, if the patient does not achieve a clinical response 2 to 8 weeks after the final dose of the induction dose, an extension induction dose of 100 to 1000 mg / dose is administered three times, and if a clinical response is achieved with the extension induction dose, the patient enters the maintenance therapy phase.

[0154] In a particular embodiment, the administration regimen in the method includes administering an induction dose of anti-IL-23p19 antibody three times at 4-week intervals to a patient requiring the induction dose, followed by an extended induction therapy phase in which, if the patient does not achieve a clinical response 4 weeks after the final dose of the induction dose, an extension induction dose of 100-1000 mg / dose is administered three times, and if a clinical response is achieved with the extension induction dose, the patient enters the maintenance therapy phase.

[0155] In certain specific embodiments, each extended induction dose in the method is 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg. It should be understood that the extended induction dose may be within a range consisting of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg, or any two of these. For example, 200-900 mg, 200-800 mg, 200-600 mg, etc. In particular, the extended induction dose is 600 mg.

[0156] In some embodiments, the administration regimen of the present invention further includes a maintenance therapy period performed after the extended induction period described herein. In particular, this maintenance therapy period is essentially the same as the maintenance therapy period performed after the induction period described herein.

[0157] In some embodiments, the administration regimen of the present invention is a) An induction therapy phase in which 100-1000 mg / dose of anti-IL-23p19 antibody is administered once or multiple times to patients who require an induction dose, a1) The patient is administered an extended induction dose of anti-IL-23p19 antibody at a dose of 100-1000 mg / dose, once or multiple times. Preferably, when a clinical response is obtained with the administration of the extended induction dose, the patient enters the maintenance therapy phase. b) The patient is administered one or more maintenance doses of anti-IL-23p19 antibody at a dose of 100-1000 mg / dose, with the first maintenance dose administered 2-8 weeks after the last dose of the induction dose, and Includes.

[0158] In some embodiments, the maintenance therapy phase includes administering a maintenance dose of anti-IL-23p19 antibody to the patient at a dose of 100-1000 mg per dose, once or multiple times. Preferably, the maintenance dose is administered by subcutaneous injection.

[0159] In certain specific embodiments, the maintenance dose may be administered once or multiple times. It should be understood that the maintenance dose may be equal or unequal. When the maintenance dose is administered multiple times, the doses are administered at intervals of 2 to 8 weeks, for example, 2, 3, 4, 5, 6, 7, or 8 weeks. In particular, the maintenance dose is administered at intervals of 4 or 8 weeks. Specifically, the maintenance therapy period is 32 weeks, starting from the first administration of the maintenance dose.

[0160] In certain specific embodiments, the administration regimen in the method further includes administering a first maintenance dose 2 to 8 weeks after the last dose of the extension induction dose, for example, 2, 3, 4, 5, 6, 7, or 8 weeks after the extension induction dose. Preferably, the first maintenance dose is administered 4 weeks after the last dose of the extension induction dose during the extension induction period.

[0161] In a specific embodiment, the method involves administering a maintenance dose of anti-IL-23p19 antibody to patients who require it, by subcutaneous injection at 4-week intervals after the extended induction period.

[0162] In certain specific embodiments, the method further comprises the fact that the maintenance dose administered after the extended induction period is 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg. It should be understood that the maintenance dose may be in the range of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg, or any two of these. For example, 200-900 mg, 200-800 mg, 200-600 mg, etc. In particular, the maintenance dose is 200 mg.

[0163] In certain specific embodiments, the administration regimen in the method further includes allowing subjects who have not achieved a clinical response at week 12 to choose an extended induction period in which they receive 600 mg of anti-IL-23p19 antibody by intravenous infusion at weeks 12, 16, and 20.

[0164] In a specific embodiment, subjects who have achieved a clinical response after administration of an extended induction dose enter the maintenance therapy phase, in which the first maintenance dose is 200 mg of anti-IL-23p19 antibody administered subcutaneously 4 weeks after the last dose of the extended induction dose, and is continued for 56 weeks.

[0165] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody three times by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 4 weeks after the last dose of the induction dose, and the maintenance therapy phase is as follows: The CDRs include, where the amino acid sequence of the heavy chain CDR1 of the antibody includes or consists of SEQ ID NO: 1, the amino acid sequence of the heavy chain CDR2 includes or consists of SEQ ID NO: 2, the amino acid sequence of the heavy chain CDR3 includes or consists of SEQ ID NO: 3, the amino acid sequence of the light chain CDR1 of the antibody includes or consists of SEQ ID NO: 4, the amino acid sequence of the light chain CDR2 includes or consists of SEQ ID NO: 5, the amino acid sequence of the light chain CDR3 includes or consists of SEQ ID NO: 6, and the CDRs have boundaries defined by the AbM rule.

[0166] In a specific embodiment, the administration regimen in the method further includes administering an induction dose of anti-IL-23p19 antibody three times at 4-week intervals to the patient in need, and if the patient does not achieve a clinical response 4 weeks after the last dose of the induction dose, administering an extension induction dose of 600 mg / dose three times to the patient, and if the patient achieves a clinical response with the extension induction dose, entering the maintenance therapy phase. Here, the first maintenance dose is administered by subcutaneous injection of 200 mg of anti-IL-23p19 antibody 4 weeks after the last dose of the extension induction dose, and is continued until week 56. Here, the amino acid sequence of the heavy chain CDR1 of the antibody includes or consists of SEQ ID NO: 1, the amino acid sequence of the heavy chain CDR2 includes or consists of SEQ ID NO: 2, the amino acid sequence of the heavy chain CDR3 includes or consists of SEQ ID NO: 3, the amino acid sequence of the light chain CDR1 of the antibody includes or consists of SEQ ID NO: 4, the amino acid sequence of the light chain CDR2 includes or consists of SEQ ID NO: 5, the amino acid sequence of the light chain CDR3 includes or consists of SEQ ID NO: 6, and the CDRs have boundaries defined by the AbM rule.

[0167] In a particular embodiment, the administration regimen of the present invention is a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody three times by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, a1) An extended induction phase in which patients requiring it are administered an extended induction dose of anti-IL-23p19 antibody by intravenous infusion at 600 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 4 weeks after the last dose of the extension induction dose, and the maintenance therapy phase continuing until week 56. Includes.

[0168] In a particular embodiment, the administration regimen includes administering an anti-IL-23p19 antibody to a patient in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring treatment are administered an induction dose of anti-IL-23p19 antibody by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, and the Mayo score is performed at week 12 to evaluate the subject's efficacy response to the anti-IL-23p19 antibody. b) In the maintenance therapy phase, subjects who showed a clinical response at week 12 were randomly divided again and administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, 200 mg / dose, until week 44, with safety monitoring continued until week 52. c) Subjects who did not achieve a clinical response at week 12 may choose an extended induction period in which 600 mg of anti-IL-23p19 antibody is administered intravenously at weeks 12, 16, and 20, and the Mayo score is performed at week 24 to evaluate the subject's efficacy response to the anti-IL-23p19 antibody. d) In the maintenance therapy phase, subjects who showed a clinical response in the extended induction phase at 24 weeks will enter the maintenance therapy phase, continuing with 200 mg of anti-IL-23p19 antibody by subcutaneous injection at 4-week intervals until 56 weeks, and safety monitoring will continue until 64 weeks. In the maintenance therapy phase, subjects who showed a clinical response at 24 weeks will be excluded from the study. Includes.

[0169] In certain specific embodiments, the administration method is either subcutaneous injection or intravenous infusion.

[0170] In certain specific embodiments, subjects are patients who have received treatment with at least one biological agent, or patients receiving treatment with a biological agent for the first time: a. Patients who have received treatment with at least one biological agent refer to patients who have a history of treatment with anti-integrin antibodies such as antitumor necrosis factor-α (TNF-α) antagonists such as adalimumab and infliximab, vedolizumab, or other experimental biological agents, and who have had poor treatment response, no response, or intolerance to the above treatments. b. Subjects receiving treatment with a biological agent for the first time must meet at least one of the following conditions: - Poor therapeutic response, no response, or intolerance to oral administration of 5-aminosalicylic acid. - Poor therapeutic response to or intolerance of oral glucocorticoid therapy, - Poor response to or intolerance to immunomodulatory drugs (mercaptopurine or azathioprine), - Poor therapeutic response to or intolerance to treatment / experimental therapy with JAK (Janus Kinases) inhibitors.

[0171] In certain embodiments, the heavy chain of the anti-IL-23p19 antibody of the present invention includes an N-glycosylation site located at asparagine position 295 of the heavy chain. Therefore, in certain embodiments, the anti-IL-23p19 antibody of the present invention is a glycosylated antibody, for example, an antibody glycosylated at asparagine position 295.

[0172] In a specific embodiment, the anti-IL-23p19 antibody comprises a heavy chain variable region VH and a light chain variable region VL, wherein the heavy chain variable region includes or consists of the sequence of SEQ ID NO: 7 or a sequence having at least 90%, 95%, 98%, or 99% identity thereto, and the light chain variable region includes or consists of the sequence of SEQ ID NO: 8 or a sequence having at least 90%, 95%, 98%, or 99% identity thereto. Array (sequence number 7) QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWMGYINPYNEGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARNWDLPYWGQGTLVTVSS; Array (array number 8) DIQMTQSPSSLSASVGDRVTITCRASQSISDYLHWYQQKPGKAPKLLIKYASQSMSGVPSRFSGSGSGSDFTLTISSLQPEDFATYYCQQGHSFPFTFGQGTKLEIK.

[0173] In certain embodiments, the IL-23p19 antibody of the present invention comprises a heavy chain and / or a light chain, wherein the heavy chain comprises or consists of the sequence of SEQ ID NO: 9 or a sequence having at least 90%, 95%, 98%, or 99% identity thereto, and the light chain comprises or consists of the sequence of SEQ ID NO: 10 or a sequence having at least 90%, 95%, 98%, or 99% identity thereto. In certain specific embodiments, the IL-23p19 antibody is an IgG1 antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises or consists of the sequence of SEQ ID NO: 9 or a sequence having at least 90%, 95%, 98%, or 99% identity thereto, and the light chain comprises or consists of the sequence of SEQ ID NO: 10 or a sequence having at least 90%, 95%, 98%, or 99% identity thereto. In certain embodiments, the IL-23p19 antibody of the present invention comprises two heavy chains and two light chains, for example, two identical heavy chains and two identical light chains, or consists of them.

[0174] In certain embodiments, the IL-23p19 antibody of the present invention comprises a heavy chain shown in SEQ ID NO: 9 and a light chain shown in SEQ ID NO: 10. For example, the IL-23p19 antibody comprises two heavy chains shown in SEQ ID NO: 9 and two light chains shown in SEQ ID NO: 10, or consists of two heavy chains shown in SEQ ID NO: 9 and two light chains shown in SEQ ID NO: 10.

[0175] Array (Sequence ID 9) QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWMGYINPYNEGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARNWDLPYWGQGTLV TVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG Array (Sequence ID 10) DIQMTQSPSSLSASVGDRVTITCRASQSISDYLHWYQQKPGKAPKLLIKYASQSMSGVPSRFSGSGSGSDFTLTISSLQPEDFATYYCQQGHSFPFTFGQGTKLEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Preferably, the IL-23p19 antibody is anti-IL-23p19 antibody 17D1-YTE, which comprises the heavy chain sequence shown in SEQ ID NO. 9 and the light chain sequence shown in SEQ ID NO. 10, as published in PCT application number PCT / CN2019 / 121261 (International filing date: November 27, 2019, International publication number WO2020 / 108530A1). Incorporating the entire patent application into this specification has the same effect as enumerating its entire contents herein.

[0176] In a particular embodiment, the anti-IL-23p19 antibody comprises the heavy chain sequence shown in SEQ ID NO: 9 and the light chain sequence shown in SEQ ID NO: 10.

[0177] In certain embodiments, the IL-23p19 antibody of the present invention is a full-length antibody. In certain embodiments, the IL-23p19 antibody of the present invention also includes an antigen-binding fragment.

[0178] In certain specific embodiments, the anti-IL-23p19 antibody is recombinantly expressed in HEK 293 cells or CHO cells.

[0179] The IL-23p19 antibody of the present invention can be formulated and administered. For example, a formulation of the anti-IL-23p19 antibody of the present invention is 100.0 mg / mL of anti-IL23p19 subunit antibody, 0.76 mg / mL of histidine, 1.08 mg / mL of histidine hydrochloride, 50.00 mg / mL of sorbitol, 0.5 mg / mL of polysorbate 80, and pH 6.0. Preferably, the formulation of the IL-23p19 antibody can be prepared by the method described in the formulation containing the IL-23p19 antibody, its preparation method and use, published in PCT application number PCT / CN2021 / 093219 (International filing date: May 12, 2021, International publication number WO2021 / 228113A1). Incorporating the entire patent application herein has the same effect as its entire contents being enumerated herein.

[0180] Single-dose unit A single-dose unit comprising an effective amount, preferably a fixed dose of 100 mg to 1000 mg, of the anti-IL-23p19 antibody of the present invention. The single-dose unit is administered according to the administration regimen of the present invention for the prevention or treatment of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease.

[0181] The unit dose formulations described herein are preferably for extra-gastrointestinal administration, such as injections including intravenous injection (including intravenous infusion) or subcutaneous injection. The unit dosage form may be an injection vial, ampoule, or pre-filled syringe containing a solution or lyophilized powder of the IL-23p19 antibody. More preferably, the unit dose formulations described herein are pre-filled syringes used for extra-gastrointestinal administration containing a solution or lyophilized powder of the IL-23p19 antibody.

[0182] In certain embodiments, the IL-23p19 antibody is contained in a pre-filled syringe, preferably containing a 200 mg / mL or 600 mg / mL IL-23p19 antibody solution.

[0183] kit A kit comprising an effective amount of the anti-IL-23p19 antibody of the present invention, further comprising a package insert printed with instructions for the use of the anti-IL-23p19 antibody in an individual for the prevention or treatment of ulcerative colitis.

[0184] use Use of the anti-IL-23p19 antibody, single-dose unit, and kit of the present invention in the preparation of agents used for the prevention or treatment of inflammatory bowel diseases such as ulcerative colitis, Crohn's disease, or colitis (especially moderate to severe ulcerative colitis).

[0185] The terms used herein are for the sole purpose of describing specific embodiments and are not intended to limit the invention. The scope of the invention is limited only by the appended claims.

[0186] Unless otherwise stated, all technical and scientific terms used herein have the same meanings as those ordinarily understood by a person of the art in the field of the invention. In this specification, technical and scientific terms not specifically defined have the meanings as ordinarily understood by a person of the art in the field of the invention.

[0187] Any embodiments, technical features, and definitions described herein can be combined in any way to form embodiments that are not directly described in the specification but are consistent with the spirit of the invention, and these embodiments are also included within the scope of the invention.

[0188] The administration regimens described herein (including the activator IL-23p19 antibody, dosage, method of administration, administration interval, number of administrations or duration of administration, etc.) and any features thereof are applicable to any aspect of the present invention, for example, the first to eighth aspects described above. Furthermore, any embodiments, technical features, definitions, and any combination thereof described in one aspect herein are similarly applicable to other aspects, for example, the first to eighth aspects. For example, any embodiments, technical features, definitions, and any combination thereof described in the first or second aspect herein are similarly applicable to other aspects, for example, the third to eighth aspects. Examples The following examples are for illustrative purposes only. These examples are merely illustrative and do not limit the scope of the invention or the claims. Similarly, the invention is not limited to the specific preferred embodiments described herein. Those skilled in the art can modify the invention without departing from the spirit and scope of the invention. Example 1. Preparation and purification of IL-23p19 antibody In accordance with PCT application number PCT / CN2019 / 121261, an antibody 17D1-YTE that specifically binds to IL-23p19 was obtained. This antibody has a heavy chain sequence shown in SEQ ID NO: 9 and a light chain sequence shown in SEQ ID NO: 10. PCT application number PCT / CN2019 / 121261 is incorporated herein by reference in its entirety.

[0189] In summary, antibodies were recombinantly expressed in CHO cells, purified by affinity chromatography to obtain IL-23p19 antibody samples for use in the present invention, and further purified by cation exchange chromatography to obtain IL-23p19 antibody samples for use in the present invention. Example 2. Preparation of the formulation 2.1 Experimental Procedure The formulation of the antibody preparation of the present invention was examined in accordance with PCT application number PCT / CN2021 / 093219. Specifically, 20 mM sodium citrate and 150 mM sodium chloride were prepared, the pH was adjusted with hydrochloric acid, and the purified IL-23p19 antibody from Example 1 was replaced with the buffers of the above different pH values ​​by ultrafiltration to adjust the protein content to 50 mg / ml. After filtration, the solution was dispensed into vials, sealed, and capped.

[0190] The determined antibody injection formulation was: 100 mg / ml recombinant anti-interleukin 23p19 subunit antibody, 0.76 mg / ml histidine, 1.08 mg / ml histidine hydrochloride, 50.00 mg / ml sorbitol, 0.50 mg / ml polysorbate 80, pH 6.0 ± 0.3. The antibody injection formulation of the present invention was prepared according to this formulation and sealed in vials in quantities of 100 mg (1 mL) per vial in Xilin bottles. The antibody injection formulation of the present invention was prepared according to this formulation and sealed in vials. The product is a clear to slightly milky white, colorless to pale yellow liquid and free of foreign matter. This injection formulation was used in Example 3.

[0191] Corresponding placebo: Injectable solution, volume: 1 mL / vial. Additives: 0.76 mg / ml histidine, 1.08 mg / ml histidine hydrochloride, 50.00 mg / ml sorbitol, 0.5 mg / ml polysorbate 80, pH 6.0. The product is sealed in a vial and is a clear to slightly milky white, colorless to pale yellow liquid free of foreign matter. This injectable formulation was used as a placebo in Example 3. Example 3. Clinical trial The anti-IL-23p19 antibody of the present invention demonstrated favorable safety and tolerability in a Phase I clinical trial involving healthy volunteers. No Grade 3 or higher adverse events (TRAEs) were observed during the treatment period. TRAEs with an incidence of 5% or higher included injection site erythema (20.0%), upper respiratory tract infection (14.3%), and rhinorrhea (11.1%), which were essentially consistent with existing research results for the same targeted drug, and no new safety risks were identified. These results support further clinical efficacy and safety studies of the anti-IL-23p19 antibody. 3.1 Purpose of the clinical trial Main purpose: To evaluate the efficacy of anti-IL-23p19 antibody induction therapy in achieving clinical remission in patients with moderate to severe active ulcerative colitis (UC).

[0192] Secondary purpose: To evaluate the effectiveness of anti-IL-23p19 antibody induction therapy in achieving clinical response, symptom relief, endoscopic remission, and mucosal healing in patients with moderate to severe active ulcerative colitis. To evaluate the effectiveness of anti-IL-23p19 antibody maintenance therapy in achieving clinical response, symptom relief, endoscopic remission, and mucosal healing in patients with moderate to severe active ulcerative colitis. To evaluate the impact of induction and maintenance therapy with anti-IL-23p19 antibodies on health-related quality of life in patients with moderate to severe active colorectal disease. To evaluate the safety of anti-IL-23p19 antibody induction and maintenance therapy in patients with moderate to severe active ulcerative colitis. To evaluate the pharmacokinetic characteristics of anti-IL-23p19 antibodies in patients with moderate to severe active ulcerative colitis. To evaluate the immunogenicity of anti-IL-23p19 antibodies in patients with moderate to severe active ulcerative colitis. 3.2 Principles of Clinical Trial Design 3.2.1. Rationale for dose selection Considering the characteristics of UC as an indication and the mechanism of action of the IL-23 molecular pathway, and taking into account clinical safety, efficacy, and ease of administration, we recommend that in Phase II clinical trials, the intravenous infusion dose during induction therapy be 200 mg Q4W and 600 mg Q4W, and the subcutaneous injection dose during maintenance therapy be 200 mg Q4W and 200 mg Q8W. 3.3 Clinical trial design This clinical trial is a multicenter, randomized, double-blind, placebo-controlled Phase II study evaluating the efficacy and safety of induction and maintenance therapy with an anti-IL-23p19 antibody in patients with moderate to severe active ulcerative colitis (modified Mayo score of 4–9 and endoscopic score of ≥2). Approximately 150 subjects will be randomly assigned, of which approximately 30–50% will have received treatment with at least one biologic agent, and approximately 50–70% will be receiving treatment with a biologic agent for the first time. After screening within 6 weeks, patients with moderate to severe active ulcerative colitis who meet the eligibility criteria will be randomly assigned in a 1:1:1 ratio to one of three induction therapy groups, with prior treatment history with biologic agents being used as a stratification factor.

[0193] Induction Therapy Phase: During the 12-week induction therapy phase, the efficacy and safety of induction therapy with intravenous infusion of anti-IL-23p19 antibody will be evaluated in eligible patients. Subjects will be randomly assigned to either the placebo group, the 200 mg intravenous infusion group of anti-IL-23p19 antibody, or the 600 mg intravenous infusion group of anti-IL-23p19 antibody, and will receive the treatment at weeks 0, 4, and 8. At week 12, the subjects' efficacy response to the investigational drug will be evaluated.

[0194] Maintenance Therapy Phase: During this phase, the efficacy and safety of subcutaneous injection of anti-IL-23p19 antibody maintenance therapy will be evaluated for the target patients. Subjects who showed a clinical response at week 12 will continue to participate in the maintenance therapy phase, and subjects who received placebo during the induction phase will continue to receive placebo subcutaneously every four weeks during the maintenance phase. Subjects who received anti-IL-23p19 antibody during the induction phase will be randomly assigned in a 1:1 ratio to receive either 200 mg of anti-IL-23p19 antibody subcutaneously every four weeks, or 200 mg of anti-IL-23p19 antibody 8 weeks later followed by subcutaneous injection. Administration will continue until week 44, and safety monitoring will continue until week 52. During the maintenance therapy phase, subjects who received 200 mg of anti-IL-23p19 antibody subcutaneously every eight weeks will receive placebo subcutaneously at weeks 16, 24, 32, and 40 to maintain blinding.

[0195] Extended Therapy Phase: Subjects who did not achieve a clinical response at week 12 may choose to enter the extended phase. All subjects entering the extended phase, regardless of whether they received placebo or anti-IL-23p19 antibody during the induction phase, will receive intravenous infusions of 600 mg of anti-IL-23p19 antibody from the extended phase (week 12), at weeks 16, and at week 20. At the evaluation at week 24, the efficacy response to the anti-IL-23p19 antibody in these subjects will be assessed. Subjects who achieve a clinical response will receive subcutaneous injections of 200 mg of anti-IL-23p19 antibody every four weeks until week 56, and safety monitoring will continue until week 64. Subjects who achieve a clinical response will terminate the trial.

[0196] Subjects and principal investigators will maintain blinding throughout the induction and maintenance phases of the trial until its completion. The extension phase will be an open-label trial. For example, the antibody injection formulation and placebo prepared in Example 2 will be used in this trial. 3.4 Test population Selection Criteria Only subjects who meet all of the following selection criteria will be included in this clinical trial. (1) Must be a male or female between the ages of 18 and 75. (2) Endoscopic findings supporting ulcerative colitis and histopathological findings supporting the diagnosis of ulcerative colitis, and at least three months have passed since the diagnosis of ulcerative colitis. (3) Having moderate to severe ulcerative colitis, with a modified Mayo score of 4 or higher and an endoscopic score of 2 or higher. (4) The patient must have received treatment with at least one biological agent, or be receiving treatment with a biological agent for the first time. 4a. Patients who have received treatment with at least one biological agent include, for example, patients who have a history of treatment with anti-integrin antibodies such as antitumor necrosis factor-α (TNF-α) antagonists such as adalimumab and infliximab, or vedolizumab or other experimental biological agents, and who have shown poor response, no response, or intolerance to the above treatments.

[0197] - Poor therapeutic response: If symptoms or vital signs of active disease persist despite receiving induction therapy (or induction therapy at the experimental dose recommended in the drug's package insert) according to the induction regimen.

[0198] - No response: If symptoms or vital signs of active disease appear during maintenance therapy after a previous clinical benefit has been achieved.

[0199] - Intolerance: When the dosage is reduced or treatment is discontinued due to side effects related to the above-mentioned medication. 4b. Subjects receiving treatment with a biological agent for the first time must meet one of the following conditions: - Poor therapeutic response, no response, or intolerance to oral 5-aminosalicylic acid therapy: This is defined as persistent symptoms or vital signs of active disease after induction therapy with mesalazine at a dose of at least 2 g / day (or an equivalent dose) for at least two weeks, or the appearance of symptoms or vital signs of active disease during maintenance therapy, or intolerance due to drug-related side effects.

[0200] - Poor response to or intolerance to oral glucocorticoid therapy: This is defined as persistent symptoms or vital signs of active disease after at least two weeks of oral induction therapy with prednisone at a dose of at least 30 mg / day (or an equivalent dose), or intolerance due to glucocorticoid-related side effects.

[0201] - Hormone therapy dependence: Defined as a condition in which the glucocorticoid dose cannot be reduced to less than 10 mg / day of prednisone (or an equivalent dose) until symptoms or vital signs of active disease disappear within 3 months of starting glucocorticoid therapy, or a condition in which relapse occurs within 3 months of completing one treatment period of glucocorticoid therapy.

[0202] - Poor therapeutic response to or intolerance to immunomodulatory drugs (mercaptopurine or azathioprine): This is defined as persistent symptoms or vital signs of active disease after more than 3 months of treatment with mercaptopurine at doses of 0.75 mg / kg / day or more, or azathioprine at doses of 1 mg / kg / day or more, or intolerance due to drug-related side effects.

[0203] - Poor therapeutic response or intolerance to treatment / experimental therapy with JAK (Janus Kinases) inhibitors: This is defined as persistent symptoms or vital signs of active disease, or intolerance due to drug-related side effects, despite use of the labeled or experimental dose of a JAK inhibitor for at least two months. (5) When an investigational drug is first used, the UC-related treatment drug must meet the following requirements: - Administration of TNF-α antagonists must be discontinued for at least 8 weeks.

[0204] - The anti-integrin antibody vedolizumab has been discontinued for at least 12 weeks.

[0205] - Administration of other experimental biological agents must have been discontinued for at least 8 weeks.

[0206] - If you are receiving oral aminosalicylic acid preparations (sulfasalazine or other 5-aminosalicylic acids), you must maintain the prescribed dose for at least two weeks. If you have discontinued the medication, at least two weeks must have passed since discontinuation.

[0207] - If oral glucocorticoids are being administered orally, the prescribed dose must be maintained for at least two weeks. If administration has been discontinued, at least two weeks must have passed since discontinuation.

[0208] - If you are currently receiving conventional immunomodulatory drugs (mercaptopurine, azathioprine, or methotrexate), you must have been continuing treatment for at least 12 weeks and maintaining the prescribed dose for at least 4 weeks. If you have discontinued treatment, at least 4 weeks must have passed since discontinuation.

[0209] - Cyclosporine, tacrolimus, pimecrolimus, 6-thioguanine, thalidomide, mycophenolate mofetil, JAK inhibitors / experimental therapies must have been discontinued for at least 4 weeks.

[0210] - Rectal corticosteroids (administered rectally or sigmoid colon via foam, enema, or suppository) and injectable corticosteroids must have been discontinued for at least two weeks.

[0211] - At least two weeks must have passed since discontinuation of rectal aminosalicylic acid (administered as a foam, enema, or suppository into the rectum or sigmoid colon).

[0212] - At least two weeks must have passed since discontinuing the use of herbal medicine preparations (oral or enema).

[0213] - At least two weeks must have passed since discontinuing extracorporeal nutrition.

[0214] - At least two weeks must have passed since discontinuing antibiotic therapy for ulcerative colitis.

[0215] - At least two weeks must have passed since the discontinuation of selective leukocytocyte adsorption therapy.

[0216] - At least four weeks must have passed since discontinuation of any other experimental therapies. (6) You fully understand the purpose of the clinical trial, have a basic understanding of the pharmacological effects and potential side effects of the investigational drug, and sign the consent form of your own free will in accordance with the Declaration of Helsinki.

[0217] Exclusion criteria Only subjects who do not meet any of the following criteria will be included in this clinical trial. (1) Patients with a history of treatment with IL-12 / 23 and / or IL-23-targeting biological agents. (2) Persons diagnosed with ischemic colitis, infectious colitis, radiation colitis, microscopic colitis, atypical colitis, or those suspected of having Crohn's disease. (3) Individuals with ulcerative colitis (UC) lesions confined to the rectum or extending to the colon less than 15 cm in length. (4) Individuals showing signs of toxic megacolon at the time of screening. (5) Individuals with a history or findings of colonic dysplasia, adenomatous polyps (not resected before clinical trial registration), or gastrointestinal tumors. (6) A person with a history of extensive colectomy, subtotal colectomy, total colectomy, ileostomy, or colostomy for ulcerative colitis. (7) Individuals who require surgery for ulcerative colitis, or who have scheduled elective surgery during the clinical trial period. (8) Patients who have undergone surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, intestinal stenosis, abdominal abscess, or pancreatic abscess within two months prior to screening, or who require surgery for any of these conditions within two weeks prior to screening. (9) A person with a recent diagnosis of a severe, progressive, or uncontrolled cardiovascular, hematological, endocrine, renal, hepatic, respiratory, neurological, or psychiatric disorder. (10) A person who has had a severe or recurrent herpes zoster, active cytomegalovirus infection, Pneumocystis pneumocystis jirovecii infection, histoplasmosis, aspergillosis, or mycobacterium infection within the six months prior to screening. (11) Patients who have tested positive for Clostridioides difficile during the screening period or within four months prior to the first dose, and who have not experienced persistent symptoms of infection with this pathogen (treatment and retesting may be performed during the screening period, if time permits). (12) A person with a history of recurrent or chronic infection, including chronic kidney infection, chronic pleural infection, or recurrent urinary tract infection. (13) Patients with a history of serious infections (e.g., sepsis, severe pneumonia, pyelonephritis, etc.), or patients who have been hospitalized or received intravenous antibiotic treatment for an infection within one month prior to screening (except for mild upper respiratory tract infections, simple urinary tract infections, etc., which may be acceptable at the discretion of the principal investigator). (14) Patients who have or have a history of lymphoproliferative disorders, including lymphoma, or who have symptoms or signs of a lymphoproliferative disorder, such as lymphadenopathy and / or splenomegaly. (15) Persons with a malignant tumor or a history of malignant tumor (excluding basal cell carcinoma, squamous cell carcinoma of the skin, or cervical intraepithelial neoplasia that has been successfully resected within the five years prior to screening and shows no signs of recurrence or metastasis). (16) Individuals who, at the time of screening, have findings / symptoms of untreated latent or active tuberculosis, or a history of active tuberculosis. However, this excludes individuals who do not have findings / symptoms of active tuberculosis but have a positive QuantiFERON-TB test (or a positive T-SPOT test for tuberculosis infection if a QuantiFERON-TB test result is unavailable) and who have received appropriate anti-latent tuberculosis treatment before the first dose. (17) At the time of screening, individuals whose clinical test results meet any of the following criteria: - Individuals whose hemoglobin level is less than 80 g / L, or whose white blood cell, neutrophil, or platelet count is below the lower limit of normal value (LLN), and whose abnormal values ​​are determined by the principal investigator to be clinically significant.

[0218] - Individuals whose arbitrary indicators of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin (TBIL) exceed twice the upper limit of normal value (ULN).

[0219] - Individuals whose creatinine (Cr) levels exceed the ULN (Ultimately Unsustainable Nose) level. (18) Individuals whose viral test results at the time of screening meet any of the following criteria:

[0220] - Individuals who test positive for human immunodeficiency virus (HIV) antibodies.

[0221] - For individuals who are positive for hepatitis C virus (HCV) antibodies but have no history of successful treatment, successful treatment is defined as remaining HCVRNA-negative for 24 weeks or more after receiving antiviral therapy.

[0222] - Hepatitis B virus (HBV) screening includes at least hepatitis B surface antigens (HbsAg), hepatitis B surface antibodies (HbsAb), and hepatitis B core antibodies (HbcAb). The screening is for individuals whose hepatitis B surface antigen test is positive, or, if the hepatitis B surface antigen test is negative but only HbcAb is positive, or if the HBV DNA test result is positive. (19) Any person who has participated in another clinical trial and received the investigational drug within four weeks prior to screening, or whose half-life is within five of the investigational drug's half-lives, or who is scheduled to participate in another clinical trial during the trial period. (20) Persons who have received a BCG vaccine within 12 months prior to the first dose of the investigational drug, or who are scheduled to receive a BCG vaccine during the clinical trial or within 12 months after the last dose of the investigational drug. (21) Persons who have received a live vaccine or bacterial vaccine within three months prior to the first dose of the investigational drug, or who are scheduled to receive a live vaccine or bacterial vaccine during the clinical trial or within three months after the last dose of the investigational drug. (22) Persons suspected of having an allergic constitution as a result of the hearing, or persons with a history of severe drug or food allergies, and / or a history of hypersensitivity to the investigational drug or its components. (23) Anyone with a history of alcohol or drug abuse within 12 months prior to screening. (24) Pregnant or breastfeeding women, or women of childbearing age who have tested positive on a pregnancy test before screening and before administration. (25) Patients who are planning to give birth during the clinical trial period or within six months after administration of the investigational drug, or who do not wish to use any method of contraception (e.g., condoms) that the physician deems appropriate during the clinical trial period. (26) Any other person whom the principal investigator deems unsuitable to participate in this clinical trial. 3.5 Definition of Clinical Trial Completion A subject's trial is considered complete when the final follow-up observation is completed. If the treatment / trial is discontinued early for any reason before the trial is considered complete, the trial is considered incomplete. Trial completion refers to the completion of the final follow-up observation for the last subject. 3.5.1. Clinical Criteria for Discontinuation of Clinical Trials This clinical trial may be temporarily suspended or terminated early if there are sufficient justifiable reasons. The party suspending or terminating the trial must notify the subjects, the principal investigator, the funding agency, and the regulatory authorities in writing and document the reasons for suspension or termination. If the trial is terminated or stopped early, the principal investigator must promptly notify the subjects and the Ethics Committee (EC) and explain the reasons for termination or termination. Where applicable, the principal investigator will contact the subjects to inform them of any changes to their scheduled visits.

[0223] Situations requiring cancellation or termination include, but are not limited to, the following:

[0224] If an unexpected, significant, or unacceptable risk to the subject is identified.

[0225] If the efficacy-related evidence explains why the clinical trial should be terminated / discontinued.

[0226] Failure to meet compliance requirements for the clinical trial protocol.

[0227] If the data for evaluation is incomplete and / or insufficient.

[0228] If the clinical trial protocol is changed, or if the development of the investigational drug is discontinued.

[0229] The clinical trial can only be continued if safety, adherence to the clinical trial protocol, and data quality issues are resolved and the requirements of the EC and / or the National Medical Products Administration are met.

[0230] If a clinical trial sponsor decides to discontinue providing the investigational drug, they must provide sufficient notice to allow for appropriate adjustments to the subjects' treatment. 3.6 Efficacy-related evaluation 3.6.1. Mayo Score The "Modified Mayo Score" is based on the Mayo scoring system, which assesses the severity and activity of ulcerative colitis. Following the recommendations of the U.S. Food and Drug Administration (FDA), it does not use a comprehensive assessment by a physician. Instead, it consists of three items: bowel movement frequency, bloody stools, and endoscopic findings, and is scored on a scale of 0 to 9.

[0231] Bowel movement frequency sum and bloody stool data are collected for three consecutive days within one week prior to score follow-up, and the average values ​​over these three days are used as the bowel movement frequency and bloody stool score at the time of score follow-up. Days that meet the following criteria are excluded from the calculation: a. If medication for constipation or diarrhea has been administered. b. Procedures or bowel preparation days that affect bowel frequency and / or bloody stools (e.g., enemas, liquid diets, laxatives). c. Two days after administration of a gastrointestinal motility inhibitor (e.g., diphenoxylate hydrochloride, atropine, loperamide, or other opioid drugs). d. Two days after a colonoscopy.

[0232] The term "symptom Mayo score" refers to a modified Mayo score that excludes endoscopic findings, and is assigned a score from 0 to 6.

[0233] The term "partial Mayo score" refers to the Mayo score excluding endoscopic findings, i.e., including bowel movements, bloody stool, and the physician's overall assessment. It is used only to assess clinical recurrence and is not an indicator of efficacy.

[0234] "Clinical remission" is the primary endpoint of the study and is defined as a modified Mayo score of 0 for bloody stools, ≤1 for bowel movement frequency, and ≤1 for endoscopic findings.

[0235] The term "clinical response" refers to a modified Mayo score decrease of 30% or more and 2 points or more from baseline, a bloody stool score decrease of 1 point or more from baseline, or a score of 0 or 1 for the relevant subitem.

[0236] The term "symptom relief" refers to a bowel movement frequency score of 0 or 1 and a bloody stool score of 0.

[0237] The term "endoscopic remission" refers to an endoscopic score of 0 or 1 on the modified Mayo score scale. An endoscopic score of 0 is considered complete endoscopic remission.

[0238] The term "mucosal healing" refers to endoscopic remission and remission of the central imaging Geboes score (Geboes, K., Riddell, R., Ost, A., Jensfelt, B., Persson, T. & Lofberg, R. 2000. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut, 47, 404-9). 3.6.2. Endoscopic examination / Histopathological examination Endoscopic examinations are performed at follow-up stages during the clinical trial process, and biopsy specimens are collected from the inflamed areas of ulcerative colitis (UC) during the endoscopy. To ensure data quality and standardization and reduce evaluation bias, endoscopic scores and histopathological interpretation scores are evaluated in the central laboratory.

[0239] Recorded data and endoscopic images from the entire endoscopic examination process are transmitted to the central laboratory, where trained gastroenterologists interpret the images according to established interpretation rules. Endoscopic scores in the modified Mayo score used during the clinical trial are obtained from the radiologists in the central laboratory.

[0240] The histopathological score evaluation of the colon is performed in the central laboratory. A trained specialist in gastrointestinal endoscopy reads the slides in the central laboratory according to the reading rules and performs a score evaluation of the histopathological findings of the biopsy specimens using the Geboes index.

[0241] Two biopsy specimens are taken from representative sites 15 - 20 cm from the anal verge. If this site is not a representative site of mucosal inflammation, biopsy specimens may be taken from other representative sites. The maximum number of biopsy specimens that can be taken at one time is 6. Fresh biopsy specimens are submitted to the central laboratory.

[0242] The term "relaxation of the Geboes index" refers to simultaneously meeting the requirements that grade 0 is 0.3 or less, grade 1 is 1.1 or less, grade 2A is 2A.3 or less, and grades 2B, 3, 4, and grade five are 0. 3.6.3. Inflammatory Bowel Disease Questionnaire The Inflammatory Bowel Disease Questionnaire (IBDQ) is a validated Patient-Reported Outcome (PRO) assessment tool used to evaluate the health-related QOL of patients with inflammatory bowel disease, including ulcerative colitis (Guyatt, 1989). The questionnaire consists of 32 questions and evaluates four aspects of the patient's life: bowel symptoms, general symptoms, emotional ability, and social ability. The score range is from 32 to 224 points, indicating that the higher the score, the higher the QOL. 3.6.4. Short Form Health Survey The SF-36 scale, also known as the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), is a QOL assessment tool filled out by subjects and is widely used to evaluate the health-related QOL (quality of life) of subjects (Ware, Sherbourne, 1992), providing a concise and comprehensive health assessment. The SF-36 scale consists of 36 items and includes eight health concepts: physical function, role physical, bodily pain, general health perception, vitality, social function, role emotional, and mental health. The score range is from 0 to 100 points, and a higher score indicates better physical function and / or health status. 3.6.5. Clinical recurrence During the maintenance or extended subcutaneous administration period, subjects who meet the following criteria are considered to have had a clinical recurrence: An increase of 2 or more points in the partial Mayo score from the maintenance therapy baseline (the first subcutaneous administration in the extended period), with an absolute value of the partial Mayo score of 4 or more, or An absolute value of the partial Mayo score of 7 or more. For subjects who have had a clinical recurrence, rescue therapy can be performed. 3.7 Safety evaluation Laboratory tests: including general blood tests, blood biochemistry, general urine tests, viral serology tests, tuberculosis bacteria, pregnancy tests, Clostridium difficile tests, etc.

[0243] Clinical examinations: including physical examinations, vital sign examinations, 12-lead electrocardiograms (ECGs), severe allergic reactions, infusion reactions, injection site reactions, cardiovascular events, mental disorder-related events, etc. 3.8 Pharmacokinetic analysis Approximately 3.5 mL of whole blood was collected, serum was separated, aliquoted and frozen, and used for PK analysis. The antibody concentration in serum was measured using the ELISA method. For PK parameters, summary statistical analyses (C max , AUC, V, T 1 / 2 , CL, etc. were included, and these were) performed. 3.9 Immunogenicity analysis Approximately 5 mL of whole blood was collected, serum was separated, aliquoted, and frozen for ADA and NAb analysis. Antibody concentrations were measured using immunogenic samples as needed. The positive rates for anti-drug antibodies (ADA) and neutralizing antibodies (NAb) were compiled and calculated for each therapy group. 3.10 Clinical Trial Results To date, 141 subjects have been enrolled in this clinical trial. During the induction phase, 94 subjects received either 200 mg or 600 mg of the antibody, and 47 subjects received a placebo (the ratio of subjects in the 200 mg group, 600 mg group, and placebo group was 1:1:1). At the end of the induction phase (week 12), 72 subjects showed a clinical response, and 19 subjects achieved clinical remission. No significant or unacceptable toxic side effects were observed in the enrolled subjects, and patient compliance was good.

[0244] Blinded data in this trial were estimated by referencing the placebo group achievement rates of other products in similar population trials. Assuming a clinical response rate of 29.9% in the placebo group, the number of subjects with a clinical response in the placebo group was 47 × 29.9% = 14. The number of subjects with a clinical response in the antibody therapy group (including 200 mg and 600 mg) was 72 - 14 = 58 (i.e., the total number of subjects with a clinical response minus the number of subjects with a clinical response in the placebo group). Therefore, the clinical response rate in the antibody therapy group was 58 / 72 = 61.7%. This rate is approximately equivalent to the rate at the end of the induction phase for Guselkumab, another anti-IL-23p19 subunit antibody. Similarly, the clinical remission rate in the antibody therapy group (including 200 mg and 600 mg) was estimated to be 16.0%.

[0245] The blinded data from this clinical trial showed that administration of IL-23p19 subunit antibodies according to the administration regimen of the present invention demonstrated active therapeutic efficacy, good safety, and patient compliance for ulcerative colitis, particularly moderate to severe ulcerative colitis.

[0246] The above describes exemplary embodiments of the present invention. Those skilled in the art will understand that these disclosures are merely illustrative and that various substitutions, adaptations, and modifications are possible within the scope of the invention. Therefore, the present invention is not limited to the specific embodiments described herein.

Claims

1. A method for preventing or treating inflammatory bowel disease, preferably ulcerative colitis or Crohn's disease, comprising administering an anti-IL-23p19 antibody to patients in need, wherein the administration regimen is: a) An induction therapy phase in which the anti-IL-23p19 antibody is administered once or multiple times at an induction dose of 100-1000 mg / dose, b) The patient is administered one or more maintenance doses of anti-IL-23p19 antibody at a dose of 100-1000 mg / dose, with the first maintenance dose administered 2-8 weeks after the last dose of the induction dose, and Includes, The method wherein the amino acid sequence of the heavy chain CDR1 of the antibody includes or consists of SEQ ID NO: 1, the amino acid sequence of the heavy chain CDR2 includes or consists of SEQ ID NO: 2, the amino acid sequence of the heavy chain CDR3 includes or consists of SEQ ID NO: 3, the amino acid sequence of the light chain CDR1 of the antibody includes or consists of SEQ ID NO: 4, the amino acid sequence of the light chain CDR2 includes or consists of SEQ ID NO: 5, and the amino acid sequence of the light chain CDR3 includes or consists of SEQ ID NO:

6.

2. The method according to claim 1, wherein the induction dose is administered by intravenous injection and / or the maintenance dose is administered by subcutaneous injection.

3. The method according to claim 1 or 2, wherein, once a clinical response is obtained with the administration of the aforementioned induction dose, the patient enters a maintenance therapy phase.

4. The method according to any one of claims 1 to 3, wherein the induction dose is administered 1 to 3 times, preferably 3 times.

5. The method according to any one of claims 1 to 4, wherein, when an induction dose is administered multiple times, the induction dose is administered at intervals of 4 weeks, and / or when a maintenance dose is administered multiple times, the maintenance dose is administered at intervals of 4 to 8 weeks.

6. The method according to any one of claims 1 to 5, wherein the first maintenance dose is administered 2 to 8 weeks, preferably 4 weeks, after the last dose of the induction dose.

7. A method for preventing or treating ulcerative colitis (UC), comprising administering an anti-IL-23p19 antibody to patients in need, wherein the administration regimen is: a) An induction therapy phase in which patients requiring the treatment receive an induction dose of anti-IL-23p19 antibody at 100-1000 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody at intervals of 4 to 8 weeks, with the first maintenance dose administered 2 to 8 weeks after the last dose of the induction dose, and Includes, The method according to any one of claims 1 to 6, wherein the amino acid sequence of the heavy chain CDR1 of the antibody includes or consists of SEQ ID NO: 1, the amino acid sequence of the heavy chain CDR2 includes or consists of SEQ ID NO: 2, the amino acid sequence of the heavy chain CDR3 includes or consists of SEQ ID NO: 3, the amino acid sequence of the light chain CDR1 of the antibody includes or consists of SEQ ID NO: 4, the amino acid sequence of the light chain CDR2 includes or consists of SEQ ID NO: 5, and the amino acid sequence of the light chain CDR3 includes or consists of SEQ ID NO:

6.

8. The method according to claim 7, wherein UC is moderate to severe ulcerative colitis.

9. The method according to claim 7 or 8, wherein the induction dose is administered by intravenous injection and / or the maintenance dose is administered by subcutaneous injection.

10. The method according to any one of claims 1 to 9, wherein, during the induction therapy phase, an induction dose of anti-IL-23p19 antibody is administered three times by intravenous infusion at 4-week intervals to patients who require it.

11. The method according to any one of claims 1 to 10, wherein, during the maintenance therapy phase, a maintenance dose of anti-IL-23p19 antibody is administered to patients who require it by subcutaneous injection at intervals of 4 or 8 weeks.

12. The method according to any one of claims 1 to 11, wherein the induction dose administered is in the range of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg, or any two thereof.

13. The method according to any one of claims 1 to 11, wherein each induction dose is 200 mg.

14. The method according to any one of claims 1 to 11, wherein each induction dose is 600 mg.

15. The method according to any one of claims 1 to 14, wherein the maintenance dose is administered at intervals of 4 weeks or 8 weeks after the administration of the first maintenance dose.

16. The method according to any one of claims 1 to 15, wherein the first maintenance dose is administered four weeks after the final dose of the induction dose.

17. The method according to any one of claims 1 to 16, wherein each maintenance dose is in the range of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg, or any two thereof.

18. The method according to any one of claims 1 to 16, wherein each maintenance dose is 200 mg.

19. The aforementioned administration regimen is a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody three times by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 2 weeks after the last dose of the induction dose, and the maintenance therapy phase continuing until week 44. The method according to any one of claims 1 to 18, including the method described in any one of claims 1 to 18.

20. The aforementioned administration regimen includes an extended induction phase which is performed after the induction phase and before the maintenance phase. The method according to any one of claims 1 to 9, wherein the patient is administered an extended induction dose of anti-IL-23p19 antibody at a dose of 100 to 1000 mg per dose, once or multiple times, and preferably, when a clinical response is obtained with the administration of the extended induction dose, the patient enters the maintenance therapy phase.

21. The method according to claim 20, wherein the extended induction dose is administered by intravenous injection.

22. The method according to claim 20 or 21, wherein the extended induction dose is administered 1 to 3 times, preferably 3 times.

23. The method according to any one of claims 20 to 22, wherein, when the extended induction dose is administered multiple times, the extended induction dose is administered at intervals of four weeks.

24. The method according to any one of claims 1 to 23, wherein the administration regimen is administered three times to a patient requiring an induction dose of anti-IL-23p19 antibody at 4-week intervals, and if the patient does not achieve a clinical response 2 to 8 weeks after the final dose of the induction dose, an extended induction phase is further comprising administering an extended induction dose of 100 to 1000 mg / dose three times, and if a clinical response is achieved with the extended induction dose, the patient enters the maintenance therapy phase.

25. The method according to claim 24, wherein if the patient does not obtain a clinical response four weeks after the final dose of the induction dose, an extended induction dose of 100 to 1000 mg per dose is administered three times, and if a clinical response is obtained with the extended induction dose, the patient enters the maintenance therapy phase.

26. The method according to any one of claims 20 to 25, wherein the first extended induction dose is administered four weeks after the last dose of the induction dose during the induction therapy period.

27. The method according to any one of claims 20 to 26, wherein each extended induction dose is in the range of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg, or any two thereof.

28. The method according to claim 27, wherein each extended induction dose is 600 mg.

29. The method according to any one of claims 20 to 28, wherein, after the extended induction period, the first maintenance dose is administered 2 to 8 weeks after the last dose of the extended induction dose.

30. The method according to claim 29, wherein, after the extended induction period, the first maintenance dose is administered 4 weeks after the last dose of the extended induction dose.

31. The method according to any one of claims 20 to 30, wherein, after the extended induction period, a maintenance dose of anti-IL-23p19 antibody is administered to patients who require it by subcutaneous injection at intervals of 4 weeks, at a dose of 100 to 1000 mg per dose.

32. The method according to any one of claims 20 to 31, wherein the maintenance dose administered after the extended induction period is in the range of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg, or any two thereof.

33. The method according to claim 32, wherein each maintenance dose is 200 mg.

34. The aforementioned administration regimen is a) An induction therapy phase in which patients requiring it are administered an induction dose of anti-IL-23p19 antibody three times by intravenous infusion at 200 mg / dose or 600 mg / dose at 4-week intervals, a1) An extended induction phase in which patients requiring it are administered an extended induction dose of anti-IL-23p19 antibody by intravenous infusion at 600 mg / dose at 4-week intervals, b) The patient is administered a maintenance dose of anti-IL-23p19 antibody by subcutaneous injection at intervals of 4 or 8 weeks, with the first maintenance dose administered 4 weeks after the last dose of the extension induction dose, and the maintenance therapy phase continuing until week 56. The method according to any one of claims 1 to 33, including the method described in any one of claims 1 to 33.

35. The method according to any one of claims 1 to 34, wherein the heavy chain of the anti-IL-23p19 antibody includes an N-glycosylation site located at the 295th asparagine position of the heavy chain.

36. The method according to any one of claims 1 to 35, wherein the anti-IL-23p19 antibody comprises a heavy chain variable region VH and a light chain variable region VL, the heavy chain variable region comprising or consisting of a sequence shown in SEQ ID NO: 7 or having at least 90%, 95%, 98%, or 99% identity thereto, and the light chain variable region comprising or consisting of a sequence shown in SEQ ID NO: 8 or having at least 90%, 95%, 98%, or 99% identity thereto.

37. The method according to any one of claims 1 to 36, wherein the anti-IL-23p19 antibody is an IgG1 antibody, and preferably the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises or consists of a sequence having at least 90%, 95%, 98%, or 99% identity with SEQ ID NO: 9, and the light chain comprises or consists of a sequence having at least 90%, 95%, 98%, or 99% identity with SEQ ID NO:

10.

38. The method according to any one of claims 1 to 37, wherein the anti-IL-23p19 antibody comprises a heavy chain shown in SEQ ID NO: 9 and a light chain shown in SEQ ID NO: 10, for example, the anti-IL-23p19 antibody comprises two heavy chains shown in SEQ ID NO: 9 and two light chains shown in SEQ ID NO: 10, or consists of two heavy chains shown in SEQ ID NO: 9 and two light chains shown in SEQ ID NO:

10.

39. The method according to any one of claims 1 to 38, wherein the anti-IL-23p19 antibody is recombinantly expressed in HEK 293 cells or CHO cells.

40. An anti-IL-23p19 antibody used for the prevention or treatment of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease, wherein the amino acid sequence of the heavy chain CDR1 of the antibody includes or consists of SEQ ID NO: 1, the amino acid sequence of the heavy chain CDR2 includes or consists of SEQ ID NO: 2, the amino acid sequence of the heavy chain CDR3 includes or consists of SEQ ID NO: 3, the amino acid sequence of the light chain CDR1 of the antibody includes or consists of SEQ ID NO: 4, the amino acid sequence of the light chain CDR2 includes or consists of SEQ ID NO: 5, the amino acid sequence of the light chain CDR3 includes or consists of SEQ ID NO: 6, and the administration regimen of the antibody is a) An induction therapy phase in which the anti-IL-23p19 antibody is administered once or multiple times at an induction dose of 100-1000 mg / dose, b) The patient is administered one or more maintenance doses of anti-IL-23p19 antibody at a dose of 100-1000 mg / dose, with the first maintenance dose administered 2-8 weeks after the last dose of the induction dose, and The antibody, which includes the antibody.

41. The anti-IL-23p19 antibody used in the use described in claim 40, wherein the administration regimen is defined in any one of claims 2 to 7 and 9 to 34, and / or the anti-IL-23p19 antibody is defined in any one of claims 35 to 39.

42. The use of an anti-IL-23p19 antibody in the preparation of a drug for the prevention or treatment of inflammatory bowel disease such as ulcerative colitis or Crohn's disease, wherein the amino acid sequence of the heavy chain CDR1 of the antibody includes or consists of SEQ ID NO: 1, the amino acid sequence of the heavy chain CDR2 includes or consists of SEQ ID NO: 2, the amino acid sequence of the heavy chain CDR3 includes or consists of SEQ ID NO: 3, the amino acid sequence of the light chain CDR1 of the antibody includes or consists of SEQ ID NO: 4, the amino acid sequence of the light chain CDR2 includes or consists of SEQ ID NO: 5, the amino acid sequence of the light chain CDR3 includes or consists of SEQ ID NO: 6, and the administration regimen of the antibody or drug is a) An induction therapy phase in which the anti-IL-23p19 antibody is administered once or multiple times at an induction dose of 100-1000 mg / dose, b) The patient is administered one or more maintenance doses of anti-IL-23p19 antibody at a dose of 100-1000 mg / dose, with the first maintenance dose administered 2-8 weeks after the last dose of the induction dose, and The use of the antibody, including the aforementioned antibody.

43. The use according to claim 41, wherein the administration regimen is defined in any one of claims 2 to 7 and 9 to 34, and / or the anti-IL-23p19 antibody is defined in any one of claims 35 to 39.

44. A kit comprising an effective amount of the anti-IL-23p19 antibody described in any one of claims 1 to 39, and preferably further comprising a printed instruction leaflet relating to the administration of the anti-IL-23p19 antibody to an individual in the prevention or treatment of an inflammatory bowel disease such as ulcerative colitis or Crohn's disease.

45. Use of the kit according to claim 44 in the preparation of a drug for preventing or treating inflammatory bowel disease such as ulcerative colitis or Crohn's disease.

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