A method for treating psoriasis using recombinant interleukin-23P19 antibodies.

Abstract

The present invention relates to a method for the prevention or treatment of psoriasis in a subject, comprising administering an IL-23p19 antibody to the subject, wherein a first dose of the IL-23p19 antibody is administered at weeks 0, 4, and 8, respectively, and thereafter a second dose of the IL-23p19 antibody is administered every 8 weeks to 20 weeks; wherein the first dose is 200 mg, and the second dose is 50 mg to 250 mg, preferably 100 mg to 200 mg.

Description

Technical Field

[0001] The present invention relates to the field of disease treatment. More particularly, the present invention relates to a method for treating psoriasis using an interleukin-23p19 antibody (IL-23p19 antibody).

Background Art

[0002] Psoriasis is an immune-mediated, chronic, recurrent, inflammatory, systemic disease affected by genetic and environmental factors, and can occur in all age groups regardless of gender. Typical clinical symptoms of psoriasis include scaly erythema or plaques distributed locally or extensively, without infection, difficult to treat, and often persistent throughout life. Psoriasis is classified into psoriasis vulgaris (including guttate psoriasis and plaque psoriasis), pustular psoriasis, erythrodermic psoriasis, and psoriatic arthritis.

[0003] Currently, the worldwide prevalence of psoriasis is about 2%, 80-90% of patients suffer from psoriasis vulgaris, and about one-third of them are moderate to severe cases. The prevalence of psoriasis varies greatly around the world. In China, the reported prevalence of psoriasis was 0.123% in 1984, and 0.47% in a survey of six Chinese cities in 2008. Based on this, it is estimated that there are approximately 6 million or more psoriasis patients in China.

[0004] Currently, the main systemic treatments for psoriasis in China include methotrexate (MTX), cyclosporine A, retinoids, and biological agents. In recent years, monoclonal antibody biological agents targeting inflammatory cytokines have been increasingly used to treat severe psoriasis that is poorly responsive to conventional systemic drug therapy, significantly impacts quality of life, and is accompanied by obvious joint symptoms. These biological agents include tumor necrosis factor α (TNF-α) antagonists (etanercept, infliximab, adalimumab), IL-12 / 23 antagonists (ustekinumab), and IL-17A antagonists (secukinumab). Guselkumab (Johnson & Johnson), risankizumab (AbbVie), and tildrakizumab (Merck & Co.) are humanized IgG1 monoclonal antibodies that bind to the IL-23p19 subunit and have been developed in recent years. They have shown remarkable efficacy in the treatment of plaque psoriasis and are approved in many countries for the treatment of moderate to severe plaque psoriasis. In December 2019, guselkumab was also approved in China for the treatment of adult patients with moderate to severe plaque psoriasis who are indicated for systemic therapy.

[0005] The introduction of IL-17 and IL-23p19 monoclonal antibody drugs has revolutionized psoriasis treatment. IL-23p19 monoclonal antibodies have become one of the best biologic options for psoriasis treatment due to their long-term efficacy, safety, and ease of use. However, biologics are not yet widely available among psoriasis patients in China, and there remains a significant demand for effective, safe, and low-cost domestically produced biologics. [Overview of the Initiative] [Means for solving the problem]

[0006] The present invention provides a method for treating psoriasis using an IL-23p19 antibody to satisfy the above needs. The method of the present invention can significantly improve the patient's skin lesions, has good overall safety and tolerability, and shows excellent patient compliance.

[0007] In a first aspect, the present invention provides a dosing regimen for administering IL-23p19 antibody to subjects requiring the prevention or treatment of psoriasis. This regimen includes: administering a first dose of IL-23p19 antibody at weeks 0, 4, and 8, respectively, and then administering a second dose of IL-23p19 antibody every 8 to 20 weeks (preferably every 8 to 16 weeks, more preferably every 10 to 14 weeks, even more preferably every 11 to 13 weeks, e.g., every 12 weeks), where the first dose is 200 mg, and the IL-23p19 antibody is one of the following six CDRs: - Heavy chain VH CDR1 containing or consisting of GYTFTSYLMH (SEQ ID NO: 1); - Heavy chain VH CDR2 containing or consisting of YINPYNEGTN (SEQ ID NO: 2); - Heavy chain VH CDR3 containing or consisting of NWDLPY (SEQ ID NO: 3); - Light chain VL CDR1 containing or consisting of RASQSISDYLH (SEQ ID NO: 4); - Light chain VL CDR2 containing or consisting of YASQSMS (SEQ ID NO: 5); and - Contains or comprises a light chain VL CDR3 containing QQGHSFPFT (SEQ ID NO: 6), Here, the CDR boundary is determined, for example, by the AbM scheme.

[0008] In a second aspect, the present invention provides a method for preventing or treating psoriasis in a subject. The method comprises the step of administering an IL-23p19 antibody to the subject according to the following dosing schedule: administering a first dose of the IL-23p19 antibody at weeks 0, 4, and 8, respectively; and then administering a second dose of the IL-23p19 antibody every 8 to 20 weeks (preferably every 8 to 16 weeks, more preferably every 10 to 14 weeks, even more preferably every 11 to 13 weeks, e.g., every 12 weeks), where the first dose is 200 mg, and the IL-23p19 antibody is one of the following six CDRs: - Heavy chain VH CDR1 containing or consisting of GYTFTSYLMH (SEQ ID NO: 1); - Heavy chain VH CDR2 containing or consisting of YINPYNEGTN (SEQ ID NO: 2); - Heavy chain VH CDR3 containing or consisting of NWDLPY (SEQ ID NO: 3); - Light chain VL CDR1 containing or consisting of RASQSISDYLH (SEQ ID NO: 4); - Light chain VL CDR2 containing or consisting of YASQSMS (SEQ ID NO: 5); and - Contains or comprises a light chain VL CDR3 containing QQGHSFPFT (SEQ ID NO: 6), Here, the CDR boundary is determined, for example, by the AbM scheme.

[0009] In a third aspect, the present invention provides an IL-23p19 antibody for the prevention or treatment of psoriasis in a subject, wherein the IL-23p19 antibody is administered to the subject according to the following dosing schedule: a first dose of the IL-23p19 antibody is administered at weeks 0, 4, and 8, respectively; thereafter, a second dose of the IL-23p19 antibody is administered every 8 to 20 weeks (preferably every 8 to 16 weeks, more preferably every 10 to 14 weeks, even more preferably every 11 to 13 weeks, e.g., every 12 weeks), wherein the first dose is 200 mg, wherein the IL-23p19 antibody is one of the following six CDRs: - Heavy chain VH CDR1 containing or consisting of GYTFTSYLMH (SEQ ID NO: 1); - Heavy chain VH CDR2 containing or consisting of YINPYNEGTN (SEQ ID NO: 2); - Heavy chain VH CDR3 containing or consisting of NWDLPY (SEQ ID NO: 3); - Light chain VL CDR1 containing or consisting of RASQSISDYLH (SEQ ID NO: 4); - Light chain VL CDR2 containing or consisting of YASQSMS (SEQ ID NO: 5); and - Contains or comprises a light chain VL CDR3 containing QQGHSFPFT (SEQ ID NO: 6), Here, the CDR boundary is determined, for example, by the AbM scheme.

[0010] In a fourth aspect, the present invention provides a unit dosage form comprising the IL-23p19 antibody described herein for use in the prevention or treatment of psoriasis by administering the IL-23p19 antibody according to the administration schedule of the present invention.

[0011] In a fifth aspect, the present invention provides a kit comprising the IL-23p19 antibody described herein and a package insert printed with instructions for the use of the IL-23p19 antibody to prevent or treat psoriasis by administering the IL-23p19 antibody according to the dosage schedule of the present invention.

[0012] In all aspects of the present invention described above, administering a second dose every 8 to 20 weeks, for example every 12 weeks, during the maintenance period can improve patient medication compliance, reduce fear of injections, alleviate physical and psychological burden, and thereby help maintain long-term remission in the patient.

[0013] Other embodiments of the present invention will become apparent by referring to the detailed description below. [Modes for carrying out the invention]

[0014] Before describing the present invention in detail, it should be understood that the present invention is not limited to the specific methods or experimental conditions described herein, because such methods and conditions may change. Furthermore, the terms used herein are for the purpose of describing specific embodiments and are not intended to be limiting.

[0015] definition Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art. For the purposes of the present invention, the following terms are defined below.

[0016] The term "approximately" used with a number is intended to encompass numbers within a range of 5% less than the specified number and 5% more than the specified number. In short, the term "approximately" means ±5% of the number it is connected to. The terms "and / or" should be understood to mean either one of the options or one of the two or more options when used to connect two or more choices.

[0017] In this specification, the terms “comprise” or its variations “comprises” and “comprising,” or “include” or its variations “includes” and “including,” mean to include, but not to exclude, other elements, values, or steps. Wherever the terms “comprise” or its variations “comprises” and “comprising,” or “include” or its variations “includes” and “including,” are used in this specification, unless otherwise specified, they also include “consist of” or “consisting of” the elements, values, or steps described; that is, the terms “comprise” and its variations “comprises” and “comprising,” or “include” and its variations “includes” and “including,” also include “consist of” and its variations “consisting of.” For example, when referring to an antibody variable region that “contains” a particular sequence, it is intended to also include the antibody variable region consisting of that particular sequence.

[0018] The p19 subunit of IL-23 (also referred to herein as "IL-23p19" and "p19 subunit") is a polypeptide having 189 amino acids, including a 21-amino acid leader sequence and containing four α helices named A, B, C, and D that are closely arranged in an up-up-down-down topology (Oppmann et al., Immunity 13:715 (2000), SEQ ID NO: 181). The four helices are connected via three polypeptide loops. The A-B and C-D loops are relatively long and modeled to connect parallel helices. The short B-C loop connects the antiparallel B and C helices. The p19 subunit of IL-23 is a member of the IL-6 family of helical cytokines. This cytokine family binds to its cognate receptor via three conserved epitopes (sites I, II, III; Bravo and Heath (2000) EMBO J. 19:2399-2411). The p19 subunit interacts with three cytokine receptor subunits to form a functional signaling complex. When expressed intracellularly, the p19 subunit first forms a complex with the p40 subunit, which is shared by the p19 subunit and IL-12. The p19p40 complex is secreted from the cell as a heterodimeric protein and is called IL-23. In one embodiment, the IL-23p19 of the present invention is derived from human (NCBI: AAG37232) or cynomolgus monkey (NCBI: AEY84629).

[0019] As used herein, the terms "anti-IL-23p19 antibody", "anti-IL-23p19", "IL-23p19 antibody", or "antibody that binds to IL-23p19" or "IL-23p19-binding antibody" are used interchangeably and refer to an antibody that can bind with sufficient affinity to the (human or cynomolgus monkey) IL-23p19 subunit or a fragment thereof and can be used as a diagnostic and / or therapeutic agent targeting (human or cynomolgus monkey) IL-23p19.

[0020] As used herein, the term "antibody" is used in the broadest sense and refers to a protein containing an antigen-binding site, including natural and artificial antibodies having various structures such as full-length antibodies, antigen-binding antibody fragments, or multispecific antibodies (e.g., bispecific antibodies), but not limited thereto.

[0021] As used herein, the terms "whole antibody", "full-length antibody", "complete antibody", and "intact antibody" are used interchangeably and refer to a glycoprotein in which at least two heavy chains (H) and two light chains (L) are linked by disulfide bonds. Each heavy chain consists of a heavy-chain variable region (abbreviated as VH herein) and a heavy-chain constant region. The heavy-chain constant region consists of three domains, CH1, CH2, and CH3. Each light chain consists of a light-chain variable region (abbreviated as VL herein) and a light-chain constant region. The light-chain constant region consists of one domain, CL. The VH region and VL region are further subdivided into regions in which hypervariable regions, also known as complementarity-determining regions (CDRs), and more conserved regions, also known as framework regions (FRs), are interspersed. Each VH or VL consists of three CDRs and four FRs, which are arranged in the following order from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The constant region is not directly involved in the process of antibody binding to an antigen but exhibits many effector functions.

[0022] As used herein, the terms "complementarity-determining region", "CDR region", or "CDR" are used interchangeably and refer to a region in an antibody variable domain that has a highly variable sequence, forms a structurally defined loop ("hypervariable loop"), and / or contains antigen-contact residues ("antigen-contact site"). CDRs are mainly responsible for binding to antigen epitopes. The CDRs of the heavy and light chains are generally called CDR1, CDR2, and CDR3 and are numbered in order from the N terminus. The CDRs located in the heavy-chain variable domain of an antibody are called HCDR1, HCDR2, and HCDR3, and the CDRs located in the light-chain variable domain of an antibody are called LCDR1, LCDR2, and LCDR3.

[0023] In specific amino acid sequences of the light chain variable region or heavy chain variable region, the precise amino acid sequence boundaries of each CDR can be determined using one or a combination thereof of known antibody CDR numbering systems, including, for example, the Chothia method based on the three-dimensional structure of the antibody and the topology of the CDR loop (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)), the Kabat method based on the mutability of the antibody sequence (Kabat et al., Sequences of Proteins of Immunological Interest, 4th edition, USD Department of Health and Human Services, National Institutes of Health (1987)), the AbM method (University of Bath), the Contact method (University College London), and the International Immunogenetic Database (IMGT) (World Wide Web). This includes images (imgt.cines.fr / ), as well as a North CDR definition based on affinity propagation clustering using a large number of crystal structures.

[0024] An example of an AbM scheme is as follows:

[0025] [Table 1]

[0026] Unless otherwise specified, when referring to residue positions in the antibody variable region (including heavy chain variable region residues and light chain variable region residues) in this invention, it refers to positions numbered according to the Kabat numbering system (Kabat et al., Sequences of Proteins of Immunological Interest, 5th edition, Public Health Service, National Institutes of Health, Bethesda, Md. (1991)).

[0027] In one embodiment, the CDR boundary of the antibody of the present invention was determined by the AbM scheme. As used herein, the term “antigen-binding fragment” refers to a molecule distinct from an intact antibody, containing a portion of an intact antibody, and binding to the antigen to which the intact antibody binds. Examples of antigen-binding fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2, diabodies, linear antibodies, single-chain antibodies (e.g., scFv), single-domain antibodies, bivalent or bispecific antibodies or fragments thereof, camelid antibodies, and bispecific or polyspecific antibodies formed from antibody fragments.

[0028] In this specification, the term “psoriasis” refers to a non-infectious disease of unknown cause, and it is generally believed that the immune system is involved in the development of psoriasis. Psoriasis has a genetic predisposition and can be triggered by external factors such as infections. Psoriasis includes, but is not limited to, psoriasis vulgaris (including guttate psoriasis and plaque psoriasis), pustular psoriasis, erythrodermic psoriasis, and psoriatic arthritis (e.g., psoriatic arthritis). The psoriasis described herein may be mild, moderate, or severe, and moderate and severe psoriasis ("moderate to severe psoriasis") carries a high risk of complications such as ischemic heart disease, stroke, hypertension, dyslipidemia, diabetes, and Crohn's disease. Preferably, the psoriasis described herein is moderate to severe psoriasis, for example, moderate to severe plaque psoriasis. Psoriasis often manifests as one or more red, silvery-white, shiny plaques localized on the scalp, elbows, knees, back, or buttocks. The skin between the eyebrows, armpits, navel, perianal area, and the skin at the junction of the buttocks and lower back may also be affected. Psoriasis can also manifest as deformed, thickened, or indented nails. Depending on the affected area, psoriasis may be classified as, for example, scalp psoriasis, nail psoriasis, palmoplantar psoriasis, or genital psoriasis.

[0029] As used herein, the term “unit dose formulation” refers to a formulation containing a fixed amount of IL-23p19 antibody administered to a patient at the time of administration. Preferably, the unit dose formulation described herein is used for parenteral administration and is contained, for example, in an injection vial, ampoule, or pre-filled syringe, which contains a solution or lyophilized powder containing IL-23p19 antibody.

[0030] In this specification, "lyophilized powder" refers to powder prepared by lyophilization, which is used for immediate administration to a subject after being diluted with a suitable solvent for injection (e.g., sterile water for injection, sodium chloride injection, glucose injection, etc.).

[0031] In this specification, the term "parenteral administration" means a method of administration other than enteral and topical administration, such as injection or infusion, including but not limited to injection and infusion into veins, muscles, arteries, spinal cavities, joint capsules, orbits, hearts, skin, abdominal cavity, trachea, subcutaneous tissue, subcutaneous tissue, joints, subarticular capsules, subarachnoid, spinal cavity, epidural, and sternal spaces.

[0032] In this specification, the term "subject" refers to an animal. Preferably, the subject refers to a mammal, including, for example, primates (e.g., humans, monkeys, gorillas, etc.), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, mice, etc. More preferably, the subject is a human.

[0033] In this specification, the term "Week 0" refers to the time of the first administration of IL-23p19 antibody. In this specification, the term "Week 4" refers to four weeks after the first administration of IL-23p19 antibody. In this specification, the term "Week 8" refers to eight weeks after the first administration of IL-23p19 antibody. Other similar terms should be understood similarly.

[0034] In this specification, the terms “treatment” or “to treat” mean to alleviate or cure psoriasis or its symptoms, and to slow or halt the progression of psoriasis or its symptoms.

[0035] In this specification, the terms “prevention” or “preventing” mean delaying or preventing the onset of psoriasis or its symptoms. In this specification, the term "first dose" refers to 200 mg of IL-23p19 antibody as described herein, and the first dose can be administered to a subject by administering one or more unit dosage forms.

[0036] In this specification, the term “second dose” means 50 mg to 250 mg, preferably 100 mg to 200 mg, of the IL-23p19 antibody described herein, for example, 100 mg, 150 mg, or 200 mg, and the second dose can be administered to a subject by administering one or more unit dosage forms.

[0037] In this specification, the term "PASI" refers to the Psoriasis Area and Severity Index. PASI is an established tool for measuring the effectiveness of psoriasis medications and can be used to provide a numerical score (ranging from 0 to 72) for any psoriasis condition. A higher PASI value indicates a greater severity of psoriasis.

[0038] As used herein, the term “sPGA” refers to a static physician comprehensive assessment used to evaluate the psoriatic skin lesions of a subject at a specific point in time, and the general scoring criteria for sPGA are a 4-point or 5-point scoring system. For the 4-point scoring system, the specific scoring criteria include: 0 = clear; 1 = very mild; 2 = mild; 3 = moderate; 4 = severe. For the 5-point scoring system, the specific scoring criteria include: 0 = clear; 1 = very mild; 2 = mild; 3 = moderate; 4 = prominent; 5 = severe. A higher sPGA score indicates a more severe psoriatic skin lesion.

[0039] As used herein, the term "IGA" refers to the investigator global assessment. Similar to sPGA6, IGA is used to assess a subject's psoriasis skin lesions at a specific point in time, and has a common scoring scale of 4 or 5 points. For the 4-point scoring scale, the specific scoring criteria include: 0 = clear; 1 = very mild; 2 = mild; 3 = moderate; 4 = severe. For the 5-point scoring scale, the specific scoring criteria include: 0 = clear; 1 = very mild; 2 = mild; 3 = moderate; 4 = prominent; 5 = severe. A higher IGA score indicates a more severe psoriasis skin lesion.

[0040] Administration plan and treatment method In a first aspect, the present invention provides a dosing regimen for administering an IL-23p19 antibody to subjects requiring the prevention or treatment of psoriasis. This regimen includes: administering a first dose of the IL-23p19 antibody at weeks 0, 4, and 8, respectively, and then administering a second dose of the IL-23p19 antibody every 8 to 20 weeks (preferably every 8 to 16 weeks, more preferably every 10 to 14 weeks, even more preferably every 11 to 13 weeks, for example every 12 weeks), where the first dose is 200 mg.

[0041] In a second aspect, the present invention provides a method for the prevention or treatment of psoriasis in a subject. The method comprises the step of administering an IL-23p19 antibody to the subject according to the following dosing schedule: administering a first dose of the IL-23p19 antibody at weeks 0, 4, and 8, respectively; and then administering a second dose of the IL-23p19 antibody every 8 to 20 weeks (preferably every 8 to 16 weeks, more preferably every 10 to 14 weeks, even more preferably every 11 to 13 weeks, for example every 12 weeks), where the first dose is 200 mg.

[0042] In the two embodiments described above, the IL-23p19 antibody is administered to the subject according to the following administration schedule: a first dose of the IL-23p19 antibody is administered at weeks 0, 4, and 8, respectively, and then a second dose of the IL-23p19 antibody is administered every 12 weeks, for example at weeks 20, 32, 44, 56, and 68, where the first dose is 200 mg.

[0043] In the two embodiments described above, the IL-23p19 antibody is administered to the subject according to the following administration schedule: a first dose of the IL-23p19 antibody is administered at weeks 0, 4, and 8, respectively, and then a second dose of the IL-23p19 antibody is administered every 12 weeks, for example at weeks 20, 32, 44, 56, and 68, where the first dose is 200 mg and the second dose is 50 mg to 250 mg, preferably 100 mg to 200 mg.

[0044] In specific embodiments of the two embodiments described above, the IL-23p19 antibody is administered to the subject according to the following dosing schedule: a first dose of the IL-23p19 antibody is administered at weeks 0, 4, and 8, respectively, and then a second dose of the IL-23p19 antibody is administered every 12 weeks, for example at weeks 20, 32, 44, 56, and 68, where the first dose is 200 mg and the second dose is 50 mg to 250 mg, preferably 100 mg to 200 mg, for example 100 mg, 120 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, or 200 mg, more preferably 100 mg or 200 mg.

[0045] In specific embodiments of the two aspects described above, administration is performed by injection, preferably by subcutaneous injection. In preferred embodiments of the two embodiments described above, the IL-23p19 antibody is contained in a pre-filled syringe, preferably containing an IL-23p19 antibody solution at a concentration of 100 mg / mL or 200 mg / mL.

[0046] In specific embodiments of the two aspects described above, the psoriasis is psoriasis vulgaris, preferably moderate to severe psoriasis vulgaris. The IL-23p19 antibody used in the administration scheme or method of the present invention is an antibody that specifically binds to IL-23p19 and has the following six CDRs: - Heavy chain VH CDR1 containing or consisting of GYTFTSYLMH (SEQ ID NO: 1); - Heavy chain VH CDR2 containing or consisting of YINPYNEGTN (SEQ ID NO: 2); - Heavy chain VH CDR3 containing or consisting of NWDLPY (SEQ ID NO: 3); - Light chain VL CDR1 containing or consisting of RASQSISDYLH (SEQ ID NO: 4); - Light chain VL CDR2 containing or consisting of YASQSMS (SEQ ID NO: 5); and - Contains or comprises a light chain VL CDR3 containing QQGHSFPFT (SEQ ID NO: 6), Here, the CDR boundary is determined, for example, by the AbM scheme.

[0047] In one embodiment, the heavy chain of the IL-23p19 antibody used in the administration scheme or method of the present invention includes an N-glycosylation site, which is asparagine at position 295 of the heavy chain. Therefore, in one embodiment, the IL-23p19 antibody used in the administration scheme or method of the present invention is a glycosylated antibody, for example, an antibody that is glycosylated with asparagine at position 295.

[0048] In one embodiment, the IL-23p19 antibody used in the administration scheme or method of the present invention comprises a heavy chain variable region VH and / or a light chain variable region VL, wherein the heavy chain variable region comprises or consists of the sequence described in 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 described in 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. In one embodiment, the IL-23p19 antibody used in the administration scheme or method of the present invention comprises a heavy chain and / or a light chain, wherein the heavy chain comprises or consists of the sequence described in 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 described in SEQ ID NO: 10, or a sequence having at least 90%, 95%, 98%, or 99% identity thereto. In one embodiment, the IL-23p19 antibody used in the administration scheme or method of the present invention is an IgG1 type antibody comprising a heavy chain and a light chain as defined in the present invention. In one embodiment, the IL-23p19 antibody used in the administration scheme or method of the present invention comprises or consists of two described heavy chains and two described light chains, for example, two identical heavy chains and two identical light chains. Array (Sequence ID 9) QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWMGYINPYNEGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARNWDLPYWGQGTLV TVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG Array (Sequence ID 10) DIQMTQSPSSLSASVGDRVTITCRASQSISDYLHWYQQKPGKAPKLLIKYASQSMSGVPSRFSGSGSGSDFTLTISSLQPEDFATYYCQQGHSFPFTFGQGTKLEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Preferably, the IL-23p19 antibody used in the administration scheme and method of the present invention is the IL-23p19 antibody 17D1-YTE disclosed in the patent application PCT application number PCT / CN2019 / 121261 (International filing date: November 27, 2019, International Publication number WO2020 / 108530A1), which comprises a heavy chain consisting of the sequence described in SEQ ID NO: 9 and a light chain consisting of the sequence described in SEQ ID NO: 10. The contents of this patent application are fully described herein and are therefore incorporated herein by reference.

[0049] In one embodiment, the IL-23p19 antibody used in the administration plan or method of the present invention comprises the heavy chain described in SEQ ID NO: 9 and the light chain described in SEQ ID NO: 10. In one embodiment, the IL-23p19 antibody used in the administration scheme or method of the present invention is a full-length antibody. In one embodiment, the IL-23p19 antibody used in the administration scheme and method of the present invention further comprises an antigen-binding fragment.

[0050] In one embodiment, the IL-23p19 antibody used in the administration scheme or method of the present invention is recombinantly expressed in HEK293 cells or CHO cells. The IL-23p19 antibody used in the administration plan or method of the present invention may be formulated into a formulation for administration. Preferably, the IL-23p19 antibody can be formulated according to the formulation of a formulation and preparation method containing the IL-23p19 antibody disclosed in the patent application PCT application number PCT / CN2021 / 093219 (International filing date: 12 May 2021, International Publication number WO2021 / 228113A1). For example, a formulation containing IL-23p19 antibody comprises IL-23p19 antibody at a concentration of 100.0 mg / mL, 0.76 mg / mL histidine, 1.08 mg / mL histidine hydrochloride, 50.00 mg / mL sorbitol, and 0.5 mg / mL polysorbate 80, with a pH of 6.0 ± 0.5 (5.9 to 6.5, e.g., 6.0, 6.1, 6.2, 6.3, 6.4, or 6.5), preferably pH 6.0 ± 0.3. The contents of this patent application are fully described herein and are therefore incorporated herein by reference.

[0051] Unit dose formulation The unit dose formulation contains IL-23p19 antibody. Preferably, the unit dose formulation contains 50 mg to 500 mg of IL-23p19 antibody, for example, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 300 mg, 350 mg, 400 mg, or 500 mg. More preferably, the unit dose formulation contains 50 mg to 200 mg of IL-23p19 antibody, for example, 50 mg, 100 mg, or 200 mg. This unit dose formulation is used for the prevention or treatment of psoriasis by administration according to the dosage schedule of the present invention. Psoriasis is, for example, psoriasis vulgaris, preferably moderate to severe psoriasis vulgaris.

[0052] The unit dose formulations described herein are preferably used for parenteral administration, such as by injection, preferably by subcutaneous injection. The unit dose formulations may be injection vials, ampoules, or pre-filled syringes and contain a solution or lyophilized powder containing IL-23p19 antibody. More preferably, the unit dose formulations described herein are pre-filled syringes for parenteral administration containing a solution or lyophilized powder containing 50 to 200 mg, for example, 50 mg, 100 mg, or 200 mg, preferably 50 mg to 100 mg, of IL-23p19 antibody.

[0053] In one embodiment, the IL-23p19 antibody is contained in a pre-filled syringe, which preferably contains an IL-23p19 antibody solution at a concentration of 100 mg / mL or 200 mg / mL.

[0054] kit The kit contains an IL-23p19 antibody. Preferably, the kit contains the above-described unit dose formulation and further includes a package insert printed with instructions for administering the IL-23p19 antibody according to the administration schedule of the present invention in the prevention or treatment of psoriasis.

[0055] This kit is used for the prevention or treatment of psoriasis by administering IL-23p19 antibodies according to the administration schedule of the present invention. Psoriasis is, for example, plaque psoriasis, preferably moderate to severe plaque psoriasis.

[0056] use The IL-23p19 antibody described herein can be used for the prevention or treatment of psoriasis. Accordingly, the present invention further relates to the use of the IL-23p19 antibody in the manufacture of a medicament for the prevention or treatment of psoriasis in a subject, wherein the IL-23p19 antibody is administered to the subject according to the administration schedule described above. Psoriasis is, for example, psoriasis vulgaris, preferably moderate to severe psoriasis vulgaris. [Examples]

[0057] 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 is obtained, and this antibody consists of a heavy chain comprising the sequence described in SEQ ID NO: 9 and a light chain comprising the sequence described in SEQ ID NO: 10.

[0058] In short, the antibody was recombinantly expressed in CHO cells, the IL-23p19 antibody sample for the pH screening experiment of the present invention was obtained by purification using affinity chromatography, and the IL-23p19 antibody sample for the formulation screening experiment of the present invention was obtained by purification using cation exchange chromatography.

[0059] Example 2. Preparation of a formulation containing IL-23p19 antibody. 2.1 Experimental Procedure A formulation containing the IL-23p19 antibody used in the present invention was prepared 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; the IL-23p19 antibody purified in Example 1 was ultrafiltered and transferred to the above buffers with different pH values; the protein content was adjusted to 50 mg / ml; the obtained solution was filtered, dispensed into vials, and the caps were closed.

[0060] The resulting formulation contains: 100 mg / ml recombinant anti-IL-23p19 antibody, 0.76 mg / ml histidine, 1.08 mg / ml histidine hydrochloride, 50.00 mg / ml sorbitol, 0.50 mg / ml polysorbate 80, and pH 6.0.

[0061] Example 3. Clinical Trial 3.1 Research purpose Main purpose: - To evaluate the efficacy of subcutaneous injection of IL-23p19 antibody compared to placebo in the treatment of moderate to severe plaque psoriasis.

[0062] Secondary purpose: - To evaluate the safety of IL-23p19 antibodies in the treatment of moderate to severe plaque psoriasis; - To evaluate the efficacy of IL-23p19 in the long-term treatment of moderate to severe plaque psoriasis; - To evaluate the population pharmacokinetic characteristics of IL-23p19 in patients with moderate to severe plaque psoriasis; - To evaluate the immunogenicity of IL-23p19 in patients with moderate to severe plaque psoriasis; - To evaluate the impact of IL-23p19 treatment on health-related quality of life in patients with moderate to severe plaque psoriasis; - To evaluate the efficacy of IL-23p19 as a treatment for scalp psoriasis in patients with scalp psoriasis at baseline; - To evaluate the efficacy of IL-23p19 as a treatment for nail lesions in patients with onychopsoriasis at baseline; - To evaluate the efficacy of IL-23p19 as a treatment for palmoplantar psoriasis in patients with palmoplantar psoriasis at baseline; - To evaluate the efficacy of IL-23p19 as a treatment for genital psoriasis in patients with genital psoriasis at baseline; and - To investigate the efficacy of IL-23p19 on baseline PsA activity scores in patients with psoriatic arthritis (PsA).

[0063] 3.2 Principles of Research Design The recommended dosing regimen for IL-23p19 antibody is based on data analysis from a single-dose study (CIL-23P19 antibody A101) and a repeated-dose study (CIL-23P19 antibody A201) already conducted in healthy Chinese subjects, and includes, in particular, 1) clinical safety outcomes; 2) exposure-primary endpoint efficacy analysis; and 3) PopPK / PASI modeling and simulation. The proposed recommended dosing regimen is as follows: 200 mg of IL-23P19 antibody is administered subcutaneously at weeks 0, 4, and 8, followed by 100 mg or 200 mg of IL-23p19 antibody every 12 weeks thereafter.

[0064] The specific evidence is as follows: The IL-23p19 antibody demonstrated good safety: In both single-dose studies in healthy individuals and repeated-dose studies in psoriasis patients, overall safety was good, with no significant increase in the incidence of adverse events compared to the placebo group, and no dose-dependent safety events were observed.

[0065] Increased exposure (mean concentration) during loading doses increased the proportion of patients achieving the primary endpoint (PASI90 at week 16): Increasing the mean concentration of IL-23P19 antibody within 16 weeks (Cavg, 16w) increased the proportion of psoriasis patients achieving PASI90 at week 16. Simulation results from a robust PopPK / PASI model predict that 57.5% of psoriasis patients will achieve PASI90 at week 16 with subcutaneous injections of 200 mg of IL-23P19 antibody at weeks 0, 4, and 8.

[0066] Maintenance dosing at extended intervals (administered every 12 weeks, Q12W) sustained long-term efficacy in psoriasis patients: Based on simulation results of a robust PopPK / PASI model, maintenance dosing of 100 mg and 200 mg Q12W, respectively, is expected to result in long-term (week 52) PASI90 in 83% and 88% of subjects; these two long-term maintenance dosing regimens were expected to be the most convenient treatment plans for psoriasis patients and provide a treatment plan that achieves stable efficacy.

[0067] Based on the above analysis, the proposed recommendation is as follows: Administer 200 mg of IL-23P19 antibody subcutaneously at weeks 0, 4, and 8, followed by 100 mg Q12W or 200 mg Q12W subcutaneously for subsequent clinical studies.

[0068] 3.3 Research Design This study is a multicenter, randomized, double-blind, placebo-controlled study with the primary objective of evaluating the efficacy of subcutaneous injection of IL-23P19 antibody compared to placebo in the treatment of moderate to severe plaque psoriasis. The target population consists of men and women aged 18 to 75 years who were diagnosed with plaque psoriasis, with or without psoriatic arthritis, at least 6 months prior to the first dose of the study drug. Candidates must be diagnosed with plaque psoriasis with an sPGA of 3 or higher, a PASI of 12 or higher, and a body surface area (BSA) of 10% or higher. The planned enrollment for this study is 500 patients with moderate to severe plaque psoriasis.

[0069] After a 4-week screening period, eligible participants will be randomly assigned in a 1:2:2 ratio to either the placebo group, IL-23P19 antibody group 1 (an initial dose of 200 mg of IL-23P19 antibody followed by 200 mg every 12 weeks), or IL-23P19 antibody group 2 (an initial dose of 200 mg of IL-23P19 antibody followed by 100 mg every 12 weeks). Participants will be stratified based on their history of using biological agents for psoriasis treatment.

[0070] Placebo group: Subcutaneous injections of placebo at weeks 0, 4, and 8, and subcutaneous injections of 200 mg of IL-23P19 antibody at weeks 16, 20, 24, 32, and 44.

[0071] • IL-23P19 antibody group 1: Subcutaneous injections of 200 mg of IL-23P19 antibody are administered at weeks 0, 4, and 8, followed by subcutaneous injections of 200 mg of IL-23P19 antibody every 12 weeks, i.e., at weeks 20, 32, and 44. To maintain blinding, placebo is administered subcutaneously at weeks 16 and 24.

[0072] • IL-23P19 antibody group 2: Subcutaneous injections of 200 mg of IL-23P19 antibody are administered at weeks 0, 4, and 8, followed by subcutaneous injections of 100 mg of IL-23P19 antibody every 12 weeks, i.e., at weeks 20, 32, and 44. To maintain blinding, placebo is administered subcutaneously at weeks 16 and 24.

[0073] Participants will receive their final dose at week 44, and follow-up examinations and evaluations for the double-blind treatment period will continue until week 52. Following the double-blind treatment period, there will be a 16-week follow-up period, with the final follow-up taking place at week 68.

[0074] Selection Criteria Eligible subjects must meet all of the following selection criteria: (1) Must be a male or female between the ages of 18 and 75.

[0075] (2) Having been diagnosed with psoriasis vulgaris for at least six months, regardless of whether or not psoriatic arthritis is present; (3) During the screening period and at baseline, the affected body surface area (BSA) is 10% or more, the Psoriasis Area and Severity Index (PASI) score is 12 or higher, and the Static Comprehensive Physician Assessment (sPGA) score is 3 or higher; (4) Indication of phototherapy and / or systemic treatment for psoriasis; and (5) The subjects must fully understand the purpose of the study, have a basic understanding of the pharmacological effects and potential adverse reactions of the investigational drug, and be able to voluntarily sign informed consent in accordance with the spirit of the Declaration of Helsinki.

[0076] Exclusion criteria (1) If you have been diagnosed with psoriasis other than plaque psoriasis (guttate psoriasis, pustular psoriasis, erythrodermic psoriasis); (2) If diagnosed with drug-induced psoriasis (e.g., psoriasis caused by beta-blockers, calcium channel blockers, etc.); (3) A history of treatment with IL-23P19 antibody or IL-23 targeted therapy; (4) If, within two weeks of the first dose of the study drug, there is a history of treatment with topical medications that may affect the assessment of psoriasis (including, but not limited to, corticosteroids, vitamin D3 derivatives, retinoids, calcineurin inhibitors, keratolytics, and combination formulations); (5) If, within four weeks of the first dose of the study drug, there is a history of treatment with systemic medications that may affect the assessment of psoriasis (including, but not limited to, methotrexate, cyclosporine, retinoids, azathioprine, leflunomide, mycophenolate mofetil, sulfasalazine, corticosteroids, JAK inhibitors such as tofacitinib and baricitinib, or herbal medicines or Chinese patented drugs for psoriasis); (6) If the patient has a history of treatment with a tumor necrosis factor-alpha (TNF-α) antagonist (including, but not limited to, etanercept, infliximab, or adalimumab) within three months prior to the first dose of the study drug (or within five half-lives of the drug); (7) If the patient has a history of IL-17 targeted therapy (including, but not limited to, secukinumab and ixekizumab) within six months prior to the first dose of the study drug (or within five half-lives of the drug); (8) If the patient has a history of treatment with natalizumab or a B-cell or T-cell modulator (e.g., rituximab, abatacept, or visilizumab) within 12 months prior to the first dose of the study drug; (9) Any person who has received phototherapy for psoriasis within one month prior to the first dose of the study drug, and / or who does not intend to avoid prolonged sun exposure and other ultraviolet exposure during the study period; (10) If there is evidence of a serious, progressive, and uncontrolled cardiovascular, neuromuscular, hematological, respiratory, hepatic or gastrointestinal, urinary tract, neurological, or psychiatric disorder; (11) If you have had an opportunistic infection (e.g., herpes zoster (severe or recurrent), active cytomegalovirus, Pneumocystis carinii, histoplasma, aspergillus, mycobacterium, etc.) within six months prior to the screening period; (12) A history of recurrent or chronic infection, including but not limited to chronic kidney infection, chronic chest infection (e.g., bronchiectasis), recurrent urinary tract infection, and open wounds, draining wounds, or infected skin wounds; (13) A history of a serious infection (e.g., sepsis, pneumonia, pyelonephritis) within two months prior to the screening period, or a history of hospitalization or intravenous antibiotic treatment due to an infection; (14) If the patient has a malignant tumor or a history of malignant tumor (except for squamous cell carcinoma of the skin, basal cell carcinoma, or cervical intraepithelial neoplasia that has been successfully resected and for which there is no evidence of recurrence or metastasis within the last five years); (15) If you have a lymphoproliferative disorder, have had one in the past, or have symptoms or signs suggestive of a lymphoproliferative disorder (e.g., lymphadenopathy and / or splenomegaly) within five years prior to the screening period; (16) If a subject has a history of active tuberculosis or clinical symptoms suggestive of tuberculosis (including, but not limited to, pulmonary tuberculosis, lymphoid tuberculosis, or tuberculous pleurisy), and the subject undergoes interferon-gamma release assay (IGRA) and chest X-ray (anterior-posterior and lateral) for tuberculosis screening, then for subjects without symptoms of active tuberculosis or radiological evidence of tuberculosis: - If the IGRA result is negative, the subject is eligible for registration; - If the IGRA result is inconclusive, retesting is possible, and subjects with persistent inconclusive results will be ineligible for registration; and - If the IGRA result is positive, the subject will receive prophylactic anti-tuberculosis treatment for at least one month, after which they can undergo re-screening and evaluation. Subjects who are asymptomatic, have good resistance to anti-tuberculosis drugs, and are willing to receive complete prophylactic anti-tuberculosis treatment during the study period will be eligible for enrollment based on the principal investigator's assessment.

[0077] (17) Any person who has received the Bacillus Calmette-Guérin (BCG) vaccine within 12 months prior to the first dose of the study drug, or who is scheduled to receive the BCG vaccine during the study period or within 12 months after the final study treatment; (18) Any person who has received a live vaccine or bacterial vaccine within three months prior to the first dose of the study drug, or who is scheduled to receive a live vaccine or bacterial vaccine during the study period or within three months after the final study treatment; (19) Any person who has received treatment with an investigational biological agent within six months prior to the first dose of the investigational drug, or who has received any experimental treatment within 30 days or within five half-lives of the investigational drug, or who is currently participating in a clinical study; (20) During the screening period and at baseline, the results of routine blood tests and blood biochemistry tests must meet the following conditions: - If any of the indicators for hemoglobin, red blood cells, white blood cells, neutrophils, or platelets falls below the lower limit of normal (LLN) and the principal investigator determines that the abnormality is clinically significant, - One of the following indicators is more than twice the upper limit of normal (ULN): alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), or direct bilirubin (DBIL). - When creatinine (Cr) exceeds ULN, and If the indicator falls within the range required by the protocol during re-examination, the subject will be deemed eligible for registration.

[0078] (21) If, during the screening period, the virus test result meets any of the following criteria: - Tests positive for human immunodeficiency virus (HIV) antibodies; - If the patient is positive for hepatitis C virus (HCV) antibodies and has no history of successful treatment, where successful treatment is defined as becoming negative for HCV RNA after completing at least 24 weeks of antiviral therapy; - Hepatitis B virus (HBV) screening includes at least hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb), and the test results for these three indicators must be: HBsAg positive; or if HBsAg is negative and only HBcAb is positive, then HBV DNA testing is required, and the HBV DNA result must be positive. - If syphilis-specific antibodies are positive (excluding those whose non-specific antibody titers became negative after standard syphilis treatment); - If a clinically significant abnormality is observed in a 12-lead electrocardiogram (ECG) during the screening period: QTcF greater than 450 milliseconds, shortening or prolonging of the PR interval, second- or third-degree atrioventricular block, premature excitation syndrome and / or prolonged QT syndrome, or a serious arrhythmia requiring treatment; (22) If you have a history of severe allergic reactions to drugs or food, and / or hypersensitivity to the test drug or other components; (23) If there is a history of alcohol or drug abuse within 12 months prior to the screening period; (24) Women who are pregnant or breastfeeding, or women of reproductive age who have tested positive for pregnancy during the screening period or before administration; (25) Any person who plans to become pregnant during the study period or within six months after administration of the study drug, or who does not intend to use an effective method of contraception (e.g., condoms) approved by the principal investigator during the study period; and (26) If the principal investigator determines, for any reason, that the subject is unsuitable to participate in this study.

[0079] 3.4 Definition of research completion Participants are considered to have completed the study upon completing their follow-up examination at week 68 of the study. If a treatment / research project is terminated prematurely for any reason before its completion, the research will be considered incomplete.

[0080] The end of the study is defined as the completion of the 68-week follow-up examination for the last participant. 3.4.1 Clinical criteria for discontinuation / early termination of the study This study may be suspended or terminated early if there is sufficient reasonable grounds. The party suspending or terminating the study must provide written notice to the subjects, the principal investigator, the sponsor, and the regulatory authorities stating the reasons for the suspension or termination. If the study is terminated or terminated early, the principal investigator must promptly notify the subjects and the ethics committee (EC) and provide the reasons for the termination or termination. Where applicable, the principal investigator must contact the subjects and inform them of any changes to scheduled appointments.

[0081] Situations requiring the suspension or interruption of research include, but are not limited to, the following: • If an unexpected and significant or unacceptable risk to the subject is identified; • If the evidence of effectiveness indicates the discontinuation / termination of the study; • Failure to meet protocol compliance requirements; • When the data required for evaluation is incomplete and / or insufficient; and • If there are plans to change or discontinue the development of the investigational drug.

[0082] The study may only continue if safety, protocol compliance, and data quality issues are resolved and the requirements of the ethics committee and / or the National Medical Products Administration are met. If the sponsor decides to discontinue supplying the investigational drug, sufficient notice will be given to allow for appropriate adjustments to the treatment of the subjects.

[0083] 3.5 Indicators related to effectiveness evaluation: 3.5.1 PASI The Psoriasis Area and Severity Index (PASI) is an established tool for measuring the effectiveness of psoriasis medications. PASI provides a numerical score ranging from 0 to 72 for all stages of psoriasis. It linearly combines the percentage of body surface area affected with the severity of erythema, induration, and scaling in four body parts. PASI assessments at follow-up consultations should ideally be performed by the same physician who assessed the PASI for the same patient during the screening period / baseline.

[0084] This evaluation item is based on the percentage decrease from baseline and is typically summarized as the result of a binomial distribution based on the achievement rate of an X% decrease (or PASIx), where X is 50, 75, 90, or 100. Thus, PASI90 refers to an improvement of 90% or more in the PASI score from baseline; PASI75 refers to an improvement of 75% or more in the score from baseline; and PASI100 refers to a 100% improvement in the score from baseline.

[0085] To calculate PASI, the area of ​​four major body parts is assessed: head (h), trunk (t), upper limbs (u), and lower limbs (l), which account for 10%, 30%, 20%, and 40% of the body surface area, respectively.

[0086] The affected area of ​​these four sites is represented by the following numbers: 0 = No effect; 1 = less than 10%; 2 = 10% to less than 30%; 3 = 30% to less than 50%; 4 = 50% to less than 70%; 5 = 70% to less than 90%; 6 = 90% to 100%.

[0087] The severity of skin lesions, indicated by erythema (E), induration (I), and scaling (S), is assessed on a scale of 0 to 4, where 0 indicates no effect on the skin, 1 indicates mild, 2 indicates moderate, 3 indicates severe, and 4 indicates extremely severe; scores for each of the four areas are recorded individually.

[0088] The following points should be considered as an aid to domain assessment: a. The neck is considered part of the head; b. The axilla and groin are considered part of the trunk; and c. The buttocks are considered part of the lower limb.

[0089] PASI=0.1*(Eh+Ih+Sh)Ah+0.3*(Et+It+St)At+0.2*(Eu+Iu+Su)Au+0.4*(El+Il+Sl)Al 3.5.2 sPGA The Static Psoriasis Assessment (sPGA) is a record of a physician's assessment of the subject's psoriasis condition, and includes the following aspects: induration, scaling, and erythema. The sPGA score is obtained by dividing the sum of the scores of the three items by 3.

[0090] Induration (I) (Average value of all skin lesions; National Psoriasis Foundation (NPF) standard card used for measurement) 0 = No evidence of plaque elevation 1 = Tiny plaque elevation, 0.25 mm 2 = Mild plaque elevation, 0.5 mm 3 = Moderate plaque elevation, 0.75 mm 4 = Significant plaque elevation, 1 mm 5 = Severe plaque elevation, ≥1.25mm Erythema (E) (Average value for all skin lesions) 0 = No evidence of erythema; hyperpigmentation may be present. 1 = Faint erythema 2 = Mild redness 3 = Moderate redness 4 = vivid red 5 = Dark red to crimson Scaling (S) (average value for all skin lesions) 0 = No signs of scales 1 = Very small scales; sporadic scales accounting for less than 5% of all skin lesions. 2 = Mild; fine scales are predominant. 3 = Moderate; coarse scales are predominant. 4 = Prominent; thick, non-sticky scales are dominant. 5 = Severe; predominantly very thick, sticky scales. I + E + S = / 3 = (Overall average value) sPGA (Static Physician Overall Assessment) was evaluated based on the overall average score: sPGA was evaluated based on the overall average score: 0 = Clear, excluding some residual pigmentation. 1 = extremely small; most individuals have a skin lesion score of 1; 2 = Mild; most individuals have a skin lesion score of 2; 3 = Moderate; most individuals have a skin lesion score of 3; 4 = Prominent: Most individuals have a skin lesion score of 4; 5 = Severe; most individuals have a skin lesion score of 5.

[0091] sPGA evaluations for patients during follow-up consultations should ideally be performed by the same physician who performed the sPGA evaluation for the same patients during the screening period / baseline. A higher sPGA score indicates a greater severity of psoriatic skin lesions.

[0092] 3.5.3 DLQI The Skin Disease-Related Quality of Life Index (DLQI) is a tool for assessing skin disease-related quality of life (AY Finlay and GK Khan) used to evaluate the impact of a disease on a subject's quality of life. It is a 10-question questionnaire used to assess six different aspects of quality of life: symptoms and emotions, daily activities, leisure activities, work or school standards, personal relationships, and treatment. In a consultation involving DLQI assessment, the DLQI assessment in study is performed prior to all other consultation processes (such as examinations, treatments, psoriasis assessment, adverse event collection, and concomitant medication collection).

[0093] 3.5.4 PSSI The Scalp Psoriasis Severity Index (PSSI) assessment is performed only on subjects who have scalp psoriasis at baseline. The PSSI records the area of ​​scalp psoriasis, as well as the induration, scaling, and erythema of the scalp psoriasis lesions. Similar to the PASI, the PSSI numerical score ranges from 0 to 72. At follow-up examinations, the PSSI assessment of subjects should ideally be performed by the same physician who performed the PSSI assessment of the same subjects during the screening period / baseline.

[0094] 3.5.5 NAPSI The Nail Psoriasis Severity Index (NAPSI) should only be evaluated in patients who have concomitant nail psoriasis at baseline. The NAPSI assesses damage to the nail matrix and nail bed, with a total score ranging from 0 to 80. At follow-up examinations, the NAPSI should ideally be performed by the same physician who performed the NAPSI evaluation for the same patients during the screening period / baseline.

[0095] 3.5.6 PPASI The Palmoplantar Psoriasis Area and Severity Index (PPASI) should only be assessed in subjects with palmoplantar psoriasis at baseline. The PPASI assesses palmar and plantar psoriasis, with a total score ranging from 0 to 72. PPASI assessments at follow-up visits should ideally be performed by the same physician who assessed the PPASI for the same subjects during the screening period / baseline.

[0096] 3.5.7 sPGA-G The static physician-assisted genital assessment (sPGA-G) should only be performed on subjects with genital psoriasis at baseline. The sPGA-G is a local assessment of genital psoriasis using the sPGA assessment criteria. At follow-up visits, the sPGA-G assessment should ideally be performed by the same physician who performed the sPGA-G assessment on the same subject during the screening period / baseline.

[0097] 3.5.8 Disease activity of PsA The assessment of psoriatic arthritis disease activity is used only in subjects with psoriatic arthritis at baseline and is performed using the overall PsA disease activity assessment. This assessment must be performed independently by the physician and the subject. At follow-up examinations, the PsA disease activity assessment of the subject should be performed by the same physician who performed the baseline PsA disease activity assessment of the same subject. To record the assessment of psoriatic arthritis disease activity, a Visual Analogue Scale (VAS) is used by both the "subject" and the "physician". The VAS assessment by the subject ranges from "very good (0 cm)" to "very poor (10 cm)", and the VAS assessment by the physician ranges from "no arthritis activity (0 cm)" to "arthritis and its activity (10 cm)".

[0098] 3.5.9 Photography of skin lesions To obtain additional data for efficacy evaluation, photographs of the subject's skin condition (excluding the perineum) were taken at each efficacy evaluation.

[0099] 3.6 Research Evaluation Criteria At week 16, IL-23P19 antibody group 1 and IL-23P19 antibody group 2 were combined and compared with the placebo group.

[0100] Primary endpoints for effectiveness: - Percentage of subjects who achieved a PASI improvement of 90% or more by week 16 (PASI90); and - The percentage of subjects for which sPGA achieved a clear score (0 points) or minimum score (1 point) in week 16.

[0101] Important secondary endpoints regarding effectiveness: - Percentage of subjects who achieved a PASI improvement of 75% or more by week 16 (PASI75); - Percentage of subjects who achieved 100% improvement in PASI by week 16 (PASI100); - Percentage of players who achieved sPGA Clear (0 points) in week 16; - Percentage of subjects whose QLQI score reached 0 / 1 by week 16; Other secondary efficacy endpoints: - Percentage of subjects who achieved a PASI improvement of 90% or more by week 52 (PASI90); - Percentage of subjects who achieved a PASI improvement of 75% or more by week 52 (PASI75); - Percentage of subjects who achieved 100% improvement in PASI by week 52 (PASI100); - Percentage of participants who achieved sPGA Clear (0 points) in week 52; - Percentage of participants who achieved sPGA Clear (0 points) or Minimum (1 point) by week 52; - Change from baseline in DLQI at week 52; - The percentage of subjects who achieved PASI90, PASI75, PASI100, sPGA0, or sPGA0 / 1 at different time points, and the percentage of subjects who achieved DLQI0 / 1 at different time points; - Median PASI improvement at different time points; - Change from baseline in PSSI at different time points (only for subjects with scalp psoriasis at baseline); - Change from baseline in NAPSI at different time points (only for subjects with nail psoriasis at baseline); - Change from baseline in PPASI at different time points (only for subjects with palmoplantar psoriasis at baseline); - Changes from baseline in sPGA-G at different time points (only for subjects with genital psoriasis at baseline); and - Change from baseline in the Global Assessment of Disease Activity for PsA at different time points (only for subjects who had psoriatic arthritis at baseline).

[0102] Pharmacokinetic evaluation items: Elimination half-life (t 1 / 2 Characterization of the pharmacokinetic properties of IL-23p19, including but not limited to ), clearance (CL), and volume of distribution (V).

[0103] Safety evaluation items: All adverse events, including serious adverse events. Changes in vital signs, physical examination, clinical tests, electrocardiogram, etc., before and after administration.

[0104] Immunogenicity assessment: Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (Nab). 3.7 Clinical trial results (1) Blinded data In this Phase III clinical study, 500 subjects have been enrolled so far, including 100 in the placebo group and 200 each in IL-23P19 antibody group 1 and IL-23P19 antibody group 2. At week 16, 326 of the 500 subjects achieved PASI90 and 390 achieved sPGA0 / 1.

[0105] In the 500 registered participants, no serious or unacceptable toxic side effects were observed, and patient compliance was good. (2) Estimation results based on blinded data Currently, this clinical trial is ongoing, but the 500 enrolled participants have achieved the primary clinical endpoint at 16 weeks. Therefore, the blinded data collected from these 500 participants have not been disclosed. However, based on the prior art and these blinded data, the efficacy, safety, and good compliance of administering the IL-23P19 antibody according to the dosing regimen of the present invention have been well demonstrated in the treatment of moderate to severe plaque psoriasis.

[0106] According to prior art (Kenneth B Gordon et al., Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomized, placebo-controlled and ustekinumab-controlled phase 3 trials, Lancet. August 25, 2018; 392(10148): pp. 650-661), in a phase 3 clinical study of the same-target risankizumab in patients with moderate to severe plaque psoriasis (PASI≧12 and sPGA≧3), the proportion of patients achieving PASI90 at week 16 was 4.9% or 2.0% in the placebo group, and the proportion of patients achieving sPGA0 / 1 was 7.8% or 5.1% in the placebo group.

[0107] Based on the highest percentage of subjects achieving PASI90 in the placebo group, which was 4.9%, it was estimated that in the Phase III clinical trial of this application, the maximum number of subjects achieving PASI90 in the placebo group of 100 subjects was 5 (=100*4.9%). Of these 326 subjects who achieved PASI90, 321 (=326-5) came from two treatment groups (i.e., IL-23P19 antibody group 1 and IL-23P19 antibody group 2). Therefore, the percentage of subjects achieving PASI90 in the 400 subjects from the two treatment groups was 80.3% (=321 / 400).

[0108] Based on the highest percentage of subjects achieving sPGA0 / 1 in the placebo group, which was 7.8%, it was estimated that 8 subjects (=100*7.8%) achieved sPGA0 / 1 in the 100 subjects in the placebo group in the Phase III clinical trial of this application. Of these 390 subjects who achieved sPGA0 / 1, 382 subjects (=390-8) came from two treatment groups (i.e., IL-23P19 antibody group 1 and IL-23P19 antibody group 2). Therefore, the percentage of subjects achieving sPGA0 / 1 in the 400 subjects from the two treatment groups was 95.5% (=382 / 400).

[0109] [Table 2]

[0110] Therefore, based on the blinded data obtained from 500 subjects in this Phase III clinical trial, it can be estimated that 80.3% of subjects achieved PASI90 at week 16, and 95.5% achieved sPGA0 / 1 at week 16. Compared to the percentage of subjects achieving PASI90 and sPGA0 / 1 at week 16 with the same target antibodies, guselkumab (Johnson & Johnson) and risankizumab (AbbVie), the IL-23p19 antibody showed superior therapeutic efficacy.

[0111] Furthermore, the current blinded results of this Phase III clinical trial showed good safety when the IL-23p19 antibody was used according to the administration plan of the present invention for the treatment of moderate to severe plaque psoriasis, with no unacceptable toxic side effects observed in 500 subjects.

[0112] Exemplary embodiments of the present invention are described above. Those skilled in the art will understand that these disclosures are merely illustrative and that various other substitutions, adaptations, and modifications are possible within the scope of the invention. Accordingly, the present invention is not limited to the specific embodiments listed herein.

Claims

1. A method for the prevention or treatment of psoriasis in the subject: The treatment plan involves administering a first dose of IL-23p19 antibody at weeks 0, 4, and 8, and then administering a second dose of IL-23p19 antibody every 8 to 20 weeks, wherein the IL-23p19 antibody has the following six CDRs: - Heavy chain VH CDR1 containing or consisting of GYTFTSYLMH (SEQ ID NO: 1); - Heavy chain VH CDR2 containing or consisting of YINPYNEGTN (SEQ ID NO: 2); - Heavy chain VH CDR3 containing or consisting of NWDLPY (SEQ ID NO: 3); - Light chain VL CDR1 containing or consisting of RASQSISDYLH (SEQ ID NO: 4); - Light chain VL CDR2 containing or consisting of YASQSMS (SEQ ID NO: 5); and - Contains or comprises a light chain VL CDR3 containing QQGHSFPFT (SEQ ID NO: 6), Here, the first dose is 200 mg, and the second dose is 50 mg to 250 mg, preferably 100 mg to 200 mg, for example, 100 mg, 120 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, or 200 mg, in this dosage plan; The method comprising the step of administering an IL-23p19 antibody to a subject in accordance with [the specified method].

2. The method according to claim 1, comprising the step of administering IL-23p19 antibody to a subject according to a dosage plan, in which a first dose of IL-23p19 antibody is administered at week 0, week 4, and week 8, and thereafter a second dose of IL-23p19 antibody is administered every 8 to 16 weeks, preferably every 10 to 14 weeks, more preferably every 11 to 13 weeks.

3. The method according to claim 1 or 2, comprising the step of administering IL-23p19 antibody to a subject according to a dosing plan, in which a first dose of IL-23p19 antibody is administered at weeks 0, 4, and 8, respectively, and thereafter a second dose of IL-23p19 antibody is administered every 12 weeks.

4. The method according to any one of claims 1 to 3, comprising the step of administering IL-23p19 antibody to a subject according to a dosage plan, in which a first dose of IL-23p19 antibody is administered at weeks 0, 4, and 8, respectively, and then a second dose of IL-23p19 antibody is administered at weeks 20, 32, and 44, respectively.

5. The method according to any one of claims 1 to 4, wherein the second dose is 100 mg or 200 mg.

6. The method according to any one of claims 1 to 5, wherein administration is performed by injection, preferably by subcutaneous injection.

7. The method according to any one of claims 1 to 6, wherein the IL-23p19 antibody is contained in a pre-filled syringe containing an IL-23p19 antibody solution at a concentration of 100 mg / mL or 200 mg / mL.

8. The method according to any one of claims 1 to 7, wherein the psoriasis is psoriasis vulgaris, preferably moderate to severe psoriasis vulgaris.

9. The method according to any one of claims 1 to 8, wherein the heavy chain of the IL-23p19 antibody includes an N-glycosylation site which is asparagine at position 295 of the heavy chain.

10. The method according to any one of claims 1 to 9, wherein the 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 the sequence described in SEQ ID NO: 7, or a sequence having at least 90%, 95%, 98%, or 99% identity thereto, and the light chain variable region comprising or consisting of the sequence described in SEQ ID NO: 8, or a sequence having at least 90%, 95%, 98%, or 99% identity thereto.

11. The method according to any one of claims 1 to 10, wherein the IL-23p19 antibody is an IgG1 antibody comprising a heavy chain and a light chain, the heavy chain comprising or consisting of the sequence described in SEQ ID NO: 9, or a sequence having at least 90%, 95%, 98%, or 99% identity thereto, and the light chain comprising or consisting of the sequence described in SEQ ID NO: 10, or a sequence having at least 90%, 95%, 98%, or 99% identity thereto.

12. The method according to any one of claims 1 to 11, wherein the IL-23p19 antibody comprises the heavy chain described in SEQ ID NO: 9 and the light chain described in SEQ ID NO: 10; for example, the IL-23p19 antibody comprises the two heavy chains described in SEQ ID NO: 9 and the two light chains described in SEQ ID NO: 10, or comprises the IL-23p19 antibody according to any one of claims 1 to 11.

13. The method according to any one of claims 1 to 12, wherein the IL-23p19 antibody is recombinantly expressed in HEK293 cells or CHO cells.

14. The method according to any one of claims 1 to 13, wherein the IL-23p19 antibody is contained in a pharmaceutical formulation comprising 100.0 mg / mL of IL-23p19 antibody, 0.76 mg / mL of histidine, 1.08 mg / mL of histidine hydrochloride, 50.00 mg / mL of sorbitol, and 0.5 mg / mL of polysorbate 80, with a pH of 6.0 ± 0.5, preferably 6.0 ± 0.

3.

15. A unit dose formulation for use in the prevention or treatment of psoriasis, preferably psoriasis vulgaris, more preferably moderate to severe psoriasis vulgaris, by the method according to any one of claims 1 to 14, comprising 50 mg to 500 mg, preferably 50 mg to 200 mg, for example, 50 mg to 100 mg of IL-23p19 antibody.

16. (1) 50 mg to 500 mg, preferably 50 mg to 200 mg, for example 50 mg to 100 mg of IL-23p19 antibody in one or more unit dose formulations; and (2) a kit comprising a printed instruction leaflet for the use of the anti-IL-23p19 antibody according to the method of any one of claims 1 to 14 in the prevention or treatment of psoriasis, preferably psoriasis vulgaris, more preferably moderate to severe psoriasis vulgaris.

17. Use of the unit dose formulation according to claim 15 or the kit according to claim 16 in the manufacture of a pharmaceutical product for the prevention or treatment of psoriasis.

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