Compounds and methods targeting interleukin-19

Abstract

To provide compounds and methods targeting human interleukin-19, including therapeutic antibodies, pharmaceutical compositions and diagnostic applications useful in the field of immune-mediated diseases including psoriasis, atopic dermatitis, psoriatic arthritis, bronchial asthma and diabetic nephropathy.SOLUTION: Provided is an antibody which binds to human interleukin-19, the antibody comprising a light chain variable region (LCVR) and a heavy chain variable region (HCVR). The LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 as well as the HCVR comprises CDRs, HCDR1 and HCDR2, and these are selected from specific sequences.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to the field of medicine. More specifically, the present invention relates to compounds, pharmaceutical compositions, and methods comprising antibodies against human interleukin-19 (IL-19). The compounds and methods of the present invention are expected to be useful in the fields of autoimmune and chronic inflammatory diseases (collectively referred to herein as immune-mediated diseases), particularly diseases such as psoriasis (Ps0), atopic dermatitis (AD), diabetic nephropathy (DN), bronchial asthma (BA), and psoriatic arthritis (PsA), including their treatment and related diagnostic applications. [Background technology]

[0002] Interleukin-19 (IL-19) is a cytokine reported to belong to the interleukin-10 cytokine family (which includes IL-10, 20, 22, and 26, as well as several virally encoded cytokines). IL-19 is involved in the IL-20R complex signaling pathway and is reported to be expressed in resting monocytes, macrophages, B cells, and epithelial cells, including keratinocytes.

[0003] Autoimmune diseases result from the body's immune response to its own tissues. They are often chronic, debilitating, and even fatal. PsO is a chronic autoimmune disease accompanied by systemic symptoms, including psoriatic arthritis, cardiovascular disease, metabolic syndrome, and affective disorders. AD, along with many other forms of chronic autoimmune disease, such as PsO, RA, AxSpA, and PsA, affect the axial and / or peripheral skeleton.

[0004] Current FDA-approved treatments for immune-mediated diseases include corticosteroids, often used to treat acute inflammation, as well as biologics targeting TNFα or interleukin-12 and -23. While these treatments have been shown to be effective in reducing symptoms in some patients, many patients remain non-responsive or lose response to currently available treatments. In autoimmune diseases such as PsO, ixekizumab, an FDA-approved therapeutic antibody targeting IL-17A, has shown that 90% of patients achieved a 75% reduction in the Psoriasis Assessment of Skin Lesions (PASI) score (e.g., PASI 75). However, PASI assessment relies on subject input, which can be difficult to assess in certain circumstances. To date, no objective, sensitive, and reproducible blood-based biomarkers exist to assess and inform the clinical management of PsO and other immune-mediated diseases such as AD, DN, and BA. Thus, there remains an unmet need for compounds, pharmaceutical compositions, and methods useful as therapeutic agents for immune-mediated diseases such as Ps0, AD, BA, DN, and / or in diagnostic applications related thereto. Summary of the Invention

[0005] Thus, in certain embodiments, the present invention provides antibodies against human IL-19. According to some embodiments, the present invention provides antibodies comprising a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises complementarity determining regions (CDRs), LCDR1, LCDR2, and LCDR3, and the HCVR comprises CDRs, HCDR1, HCDR2, and HCDR3, selected from the group of CDR combinations provided in Tables 1, 2, or 3. In some embodiments, the LCVR comprises CDRs, LCDR1, LCDR2, and LCDR3, and the HCVR comprises CDRs, HCDR1, HCDR2, and HCDR3, having an amino acid sequence at least 95% homologous to an amino acid sequence selected from the group of CDR combinations provided in Tables 1, 2, or 3. According to certain embodiments, the present invention also provides antibodies comprising: a. LCVR having the amino acid sequence of SEQ ID NO: 66 and HCVR having the amino acid sequence of SEQ ID NO: 70; b. LCVR having the amino acid sequence of SEQ ID NO: 74 and HCVR having the amino acid sequence of SEQ ID NO: 78; c. LCVR having the amino acid sequence of SEQ ID NO: 82 and HCVR having the amino acid sequence of SEQ ID NO: 86; d. LCVR having the amino acid sequence of SEQ ID NO: 34 and HCVR having the amino acid sequence of SEQ ID NO: 38; e. LCVR having the amino acid sequence of SEQ ID NO: 42 and HCVR having the amino acid sequence of SEQ ID NO: 46; f. an LCVR having the amino acid sequence of SEQ ID NO: 50 and an HCVR having the amino acid sequence of SEQ ID NO: 54, and g. Antibodies comprising an LCVR and an HCVR selected from an LCVR having the amino acid sequence of SEQ ID NO:58 and an HCVR having the amino acid sequence of SEQ ID NO:62 are also provided.

[0006] According to an even more particular embodiment, the present invention also provides a method for treating a skin condition comprising: a. LC having the amino acid sequence of SEQ ID NO: 2 and HC having the amino acid sequence of SEQ ID NO: 6; b. LC having the amino acid sequence of SEQ ID NO: 10 and HC having the amino acid sequence of SEQ ID NO: 14; c. LC having the amino acid sequence of SEQ ID NO: 18 and HC having the amino acid sequence of SEQ ID NO: 22; d. LC having the amino acid sequence of SEQ ID NO: 26 and HC having the amino acid sequence of SEQ ID NO: 30; e. an LC having the amino acid sequence of SEQ ID NO: 310 and an HC having the amino acid sequence of SEQ ID NO: 311, and f. Antibodies are also provided that comprise an LC and an HC selected from, or having amino acid sequences that are at least 95% homologous to, the amino acid sequences of: an LC having the amino acid sequence of SEQ ID NO: 312; and an HC having the amino acid sequence of SEQ ID NO: 313.

[0007] According to certain embodiments, the present invention provides human IL-19 neutralizing antibodies having an LCVR and an HCVR, wherein the LCVR comprises CDRs (LCDR1, LCDR2, and LCDR3), and the HCVR comprises CDRs (HCDR1, HCDR2, and HCDR3), which are selected from or have amino acid sequences having at least 95% homology to the amino acid sequences of the CDR combinations provided in Tables 1, 2, or 3. In certain embodiments, the human IL-19 neutralizing antibodies of the present invention comprise: a. LCVR having the amino acid sequence of SEQ ID NO: 66 and HCVR having the amino acid sequence of SEQ ID NO: 70; b. LCVR having the amino acid sequence of SEQ ID NO: 74 and HCVR having the amino acid sequence of SEQ ID NO: 78; c. LCVR having the amino acid sequence of SEQ ID NO: 82 and HCVR having the amino acid sequence of SEQ ID NO: 86; d. LCVR having the amino acid sequence of SEQ ID NO: 34 and HCVR having the amino acid sequence of SEQ ID NO: 38; e. LCVR having the amino acid sequence of SEQ ID NO: 42 and HCVR having the amino acid sequence of SEQ ID NO: 46; f. an LCVR having the amino acid sequence of SEQ ID NO: 50 and an HCVR having the amino acid sequence of SEQ ID NO: 54, and g. Comprises an LCVR and an HCVR selected from an LCVR having the amino acid sequence of SEQ ID NO: 58 and an HCVR having the amino acid sequence of SEQ ID NO: 62.

[0008] According to an even more particular embodiment, the present invention also provides a method for treating a skin condition comprising: a. LC having the amino acid sequence of SEQ ID NO: 2 and HC having the amino acid sequence of SEQ ID NO: 6; b. LC having the amino acid sequence of SEQ ID NO: 10 and HC having the amino acid sequence of SEQ ID NO: 14; c. LC having the amino acid sequence of SEQ ID NO: 18 and HC having the amino acid sequence of SEQ ID NO: 22; d. an LC having the amino acid sequence of SEQ ID NO: 26 and an HC having the amino acid sequence of SEQ ID NO: 30, and e. an LC having the amino acid sequence of SEQ ID NO: 310 and an HC having the amino acid sequence of SEQ ID NO: 311, and f. Also provided are human IL-19 neutralizing antibodies comprising an LC and an HC selected from, or having amino acid sequences at least 95% homologous to, the amino acid sequences of: an LC having the amino acid sequence of SEQ ID NO: 312; and an HC having the amino acid sequence of SEQ ID NO: 313.

[0009] In embodiments, the antibodies of the invention comprise an IgG1 heavy chain. According to some embodiments, the antibodies further comprise a kappa light chain.

[0010] According to some aspects of the present invention, human IL-19 antibodies, including human IL-19 neutralizing antibodies, are provided that bind to human IL-19 within an epitope region comprising at least one or more of amino acid residues 95-102, 67-75, 125-136, 67-75 and 125-136, 90-100, 42-60, 90-107, 149-160, and 42-60, 90-107, and 149-160 (as determined by the methods described herein) of human IL-19 as set forth in SEQ ID NO: 1. In one embodiment, the present invention provides IL-19 antibodies that bind to human IL-19 within the epitope region of human IL-19 that binds to the antibodies provided herein.

[0011] According to some embodiments, the IL-19 antibodies of the invention are useful for treating immune-mediated diseases. In some more specific embodiments, the immune-mediated disease is at least one of Ps0, AD, PsA, BA, and / or DN. According to other embodiments of the invention, the IL-19 antibodies of the invention are useful for diagnosing autoimmune diseases. In some more specific embodiments, the immune-mediated disease is at least one of Ps0, AD, and / or DN.

[0012] The present invention further provides pharmaceutical compositions comprising an IL-19 antibody of the present invention and one or more pharmaceutically acceptable carriers, diluents, or excipients. Additionally, the present invention provides methods of treating immune-mediated diseases, such as Ps0, AD, and / or DN, comprising administering to a patient in need thereof a pharmaceutical composition of the present invention.

[0013] Additionally, the present invention provides methods for treating immune-mediated diseases, more specifically, methods for treating immune-mediated diseases, including Ps0, AD, PsA, BA, or DN, comprising administering to a patient in need thereof an effective amount of an IL-19 antibody of the present invention.

[0014] The present invention also provides IL-19 antibodies of the present invention for use in therapy. More specifically, the present invention provides IL-19 antibodies of the present invention for use in treating immune-mediated diseases, including Ps0, AD, PsA, and DN. In certain embodiments, the present invention provides use of IL-19 antibodies of the present invention in the manufacture of a medicament for treating one or more immune-mediated diseases, including Ps0, AD, PsA, BA, and DN.

[0015] According to some embodiments, the present invention provides a method for detecting IL-19 in a patient sample, comprising contacting the patient sample with a first antibody that binds to a first epitope region of IL-19, contacting the patient sample with a second antibody that binds to a second epitope region of IL-19 and that has a detectable label, and detecting a signal provided by the detectable label. In some embodiments, the patient sample is one of blood, serum, or plasma. According to some more specific embodiments, the first epitope region of IL-19 overlaps with the second epitope region of IL-19. Furthermore, in some embodiments, the steps of contacting with the first and second antibodies occur simultaneously. In some specific embodiments, the first antibody comprises a combination of LC and HC CDRs provided in Table 1, 2, or 3. In some embodiments, the first antibody comprises a combination of LC and HC CDRs that are 95% homologous to the LC and HC CDRs provided in Table 1, 2, or 3. In some specific embodiments, the second antibody comprises a combination of LC and HC CDRs provided in Table 1, 2, or 3. In some embodiments, the second antibody comprises a combination of LC and HC CDRs that have 95% homology to the LC and HC CDRs provided in Table 1, 2, or 3. In more specific embodiments, the first and second antibodies are not bottled together.

[0016] According to some embodiments of the present invention, there is provided a method for quantifying IL-19 in a patient sample, comprising the steps of contacting the patient sample with a first antibody that binds to a first epitope region of IL-19, contacting the patient sample with a second antibody that binds to a second epitope region of IL-19 and that bears a detectable label, and detecting a signal provided by the detectable label. The method includes contacting the control standard with a first antibody that binds to the same first epitope region of IL-19 (used in contacting the patient sample), contacting the control standard with a second antibody that binds to the same second epitope region of IL-19 (used in contacting the patient sample) and that has a detectable label, and detecting the signal provided by the detectable label. In some embodiments, the patient sample is one of blood, serum, or plasma. According to some more specific embodiments, the first epitope region of IL-19 partially overlaps with the second epitope region of IL-19. Further, in some embodiments, the contacting with the first and second antibodies occurs simultaneously. In some specific embodiments, the first antibody comprises a combination of LC and HC CDRs provided in Table 1, 2, or 3. In some embodiments, the first antibody comprises a combination of LC and HC CDRs that are 95% homologous to the LC and HC CDRs provided in Table 1, 2, or 3. In some specific embodiments, the second antibody comprises a combination of LC and HC CDRs provided in Table 1, 2, or 3. In some embodiments, the second antibody comprises a combination of LC and HC CDRs that have 95% homology to the LC and HC CDRs provided in Table 1, 2, or 3. In more specific embodiments, the first and second antibodies are not bottled together.

[0017] According to some embodiments, methods for diagnosing immune-mediated diseases are provided. Such methods include contacting a patient sample with an IL-19 antibody and detecting binding between IL-19 in the patient sample and the antibody. According to some specific embodiments, the diagnostic method includes diagnosing the patient as having, at risk of, in need of treatment for, and / or at risk of symptoms associated with an immune-mediated disease if the presence of IL-19 in the patient sample is detected above a reference value. According to some more specific embodiments, such methods further include determining the reference value, which includes contacting a control standard with a first antibody that binds to a first epitope region of IL-19 identical to that used in contacting the patient sample; contacting the control standard with a second antibody having a detectable label that binds to a second epitope region of IL-19 identical to that used in contacting the patient sample; and detecting the signal provided by the detectable signal. In some embodiments, the first antibody comprises a combination of LC and HC CDRs as provided in Table 1, 2, or 3. In some embodiments, the first antibody comprises a combination of LC and HC CDRs that are 95% homologous to the LC and HC CDRs provided in Tables 1, 2, or 3. Some embodiments of the methods of diagnosing immune-mediated diseases provided herein further comprise contacting a patient sample with a second IL-19 antibody that binds to a second epitope region of IL-19 and has a detectable label, and detecting the signal provided by the detectable label. In some specific embodiments, the IL-19 antibody comprises a combination of LC and HC CDRs provided in Tables 1, 2, and 3. In some embodiments, the second IL-19 antibody comprises a combination of LC and HC CDRs provided in Tables 1, 2, and 3. In some embodiments, the second antibody comprises a combination of LC and HC CDRs that are 95% homologous to the LC and HC CDRs provided in Tables 1, 2, and 3. According to specific embodiments, the first epitope region of IL-19 overlaps with the second epitope region of IL-19.According to certain embodiments, the first and second antibodies are not bottled together. According to further embodiments, the reference value is about 21 pg / mL. In further embodiments, the immune-mediated disease is one of Ps0, AD, PsA, BA, and DN.

[0018] In yet further embodiments, the present invention provides methods for treating an immune-mediated disease in a patient. Such methods include contacting a patient sample with an IL-19 antibody and detecting binding between IL-19 in the patient sample and the antibody, and diagnosing the patient as having, being at risk for, in need of treatment for, and / or being at risk for an immune-mediated disease if the presence of IL-19 in the patient sample is detected above a reference value. According to some more specific embodiments of the treatment methods provided herein, such methods further include determining the reference value, which includes contacting a control standard with a first antibody that binds to a first epitope region of IL-19 identical to that used in contacting the patient sample, contacting the control standard with a second antibody having a detectable label that binds to a second epitope region of IL-19 identical to that used in contacting the patient sample, and detecting the signal provided by the detectable signal. In some specific embodiments, the IL-19 antibody comprises a combination of LC and HC CDRs provided in Tables 1, 2, and 3. In some embodiments, the IL-19 antibody comprises a combination of LC and HC CDRs that are 95% homologous to the LC and HC CDRs provided in Table 1, 2, or 3. According to some embodiments, the reference value is about 21 pg / mL. In embodiments, the immune-mediated disease is one of Ps0, AD, and DN. In some embodiments, the patient sample is one of blood, serum, or plasma. According to some embodiments, the method further comprises contacting the patient sample with a second IL-19 antibody that binds to a second epitope region of IL-19 and has a detectable label, and detecting the signal provided by the detectable label. In still further embodiments, the second antibody comprises a combination of LC and HC CDRs provided in Table 1, 2, or 3. In some embodiments, the second antibody comprises a combination of LC and HC CDRs that are 95% homologous to the LC and HC CDRs provided in Table 1, 2, or 3. According to certain embodiments, the first and second antibodies are not bottled together. DETAILED DESCRIPTION OF THE INVENTION

[0019] As used herein, an "antibody" is an immunoglobulin molecule comprising two HCs and two LCs interconnected by disulfide bonds. The amino-terminal portion of each LC and HC contains a variable region of approximately 100-120 amino acids primarily responsible for antigen recognition via the CDRs housed within it. The CDRs are interspersed with more conserved regions called framework regions ("FRs"). Each LCVR and HCVR is composed of three CDRs and four FRs arranged from the amino terminus to the carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The three CDRs of the LC are referred to as "LCDR1, LCDR2, and LCDR3," and the three CDRs of the HC are referred to as "HCDR1, HCDR2, and HCDR3." The CDRs contain most of the residues that form specific interactions with antigens. The functional ability of an antibody to bind to a specific antigen is largely determined by the six CDRs. The assignment of amino acids to the CDR domains within the LCVR and HCVR regions of the antibodies of the present invention is based on the well-known Kabat numbering convention (Kabat, et al., Ann. NY Acad. Sci. 190:382-93 (1971); Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, USDapartment of Health and Human Services, NIH Publication No. 91-3242 (1991)) and the North numbering convention (North et al., A New Clustering of Antibody CDR Loop Conformations, Journal of Molecular Biology, 406:228-256 (2011)).

[0020] LCs are classified as kappa or lambda, each characterized by a specific constant region known in the art. HCs are classified as gamma, mu, alpha, delta, or epsilon, defining the antibody's isotype as IgG, IgM, IgA, IgD, or IgE, respectively. Antibodies of the present invention include IgG HCs, which can be further classified into subclasses, e.g., IgG1, IgG2, IgG3, and IgG4. The carboxy-terminal portion of each HC defines a constant region primarily responsible for effector function. Certain embodiments of antibodies of the present invention may contain one or more modifications in the constant region of each HC known in the art, e.g., that enhance or reduce effector function.

[0021] The antibody of the present invention is a monoclonal antibody. A monoclonal antibody is an antibody derived from a single copy or clone (including, for example, any eukaryotic, prokaryotic, or phage clone), not the method by which it is produced. Monoclonal antibodies can be produced, for example, by hybridoma technology, recombinant technology, phage display technology, synthetic technology, such as CDR grafting, or a combination of such technologies or other techniques known in the art.

[0022] Methods for producing and purifying antibodies are well known in the art and can be found, for example, in Harlow and Lane (1988), Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, chapters 5-8 and 15, ISBN 0-87969-314-2. For example, mice or rabbits can be immunized with human IL-19, and the resulting antibodies can be recovered, purified, and their amino acid sequences determined using conventional methods well known in the art. Similarly, thousands of Fab fragments can be screened for interaction with human IL-19, and the resulting interacting fragments can be recovered, purified, and their amino acid sequences determined using conventional methods well known in the art, and phage libraries can be screened from which initial lead antibodies can be constructed. According to possible embodiments, the antibodies of the present invention can be engineered to contain one or more human framework regions surrounding CDRs derived from a non-human antibody. Human framework germline sequences can be obtained, for example, from ImMunoGeneTics (INGT) through their website (http: / / imgt.cines.fr) or from The Immunoglobulin Facts Book by Marie-Paule Lefranc and Gerard Lefranc, Academic Press, 2001, ISBN 012441351.

[0023] In certain embodiments of the invention, the antibody, or nucleic acid encoding the antibody, is provided in isolated form. As used herein, the term "isolated" refers to a protein, polypeptide, or nucleic acid that is free or substantially free from other macromolecular species that are found within a cellular environment.

[0024] The antibodies of the present invention can be used to treat patients. More specifically, the antibodies of the present invention are expected to treat immune-mediated diseases or disorders, including Ps0, AD, PsA, BA, and DN. While the antibodies of the present invention are expected to be useful in treating Ps0, AD, and DN, such antibodies may also be useful in treating other immune-mediated diseases, including RA, AxSpA, and PsA, and / or immune-mediated diseases specifically involving epithelial cells. As used interchangeably herein, "treatment" and / or "treating" and / or "treat" are intended to refer to any process in which there may be a slowing, impeding, arresting, controlling, halting, or reversing the progression of the disorders described herein, but do not necessarily indicate a complete elimination of all symptoms of the disorder. Treatment includes the administration of the antibodies of the invention for the treatment of a human disease or condition that would benefit from reduced IL-19 activity, and includes (a) inhibiting further progression of the disease, i.e., arresting its development, and (b) relieving the disease, i.e., causing regression of the disease or disorder or alleviating its symptoms or complications.

[0025] As used interchangeably herein, the terms "patient," "subject," and "individual" refer to a human. In certain embodiments, the patient is further characterized as having a disease, disorder, or condition (e.g., an autoimmune disorder) that would benefit from reduced IL-19 activity. In other embodiments, the patient is further characterized as being at risk for developing an immune-mediated disease, disorder, or condition that would benefit from reduced IL-19 activity.

[0026] As used herein, a patient "sample" refers to a human sample. Non-limiting sources of samples for use in the present invention include blood, plasma, serum, spinal fluid, lymphatic fluid, biopsy aspirate, ascites, fluid extracts, solid tissue, skin, external sections of the respiratory, intestinal, and genitourinary tract, tears, saliva, milk, tumors, organs, cell cultures, and / or cell culture components.

[0027] As used herein, the term "bind" (or "binds") refers to the interaction of an antibody with an epitope region of human IL-19. The term "epitope region" refers to specific amino acids comprising IL-19 that provide an antigenic determinant capable of specific binding to an IL-19 antibody. The amino acids in the epitope region provide chemically active surface groups on IL-19, form a specific three-dimensional structure of IL-19, and may provide specific charge characteristics. Binding may involve interaction of the antibody with the epitope region through either "conformational" or "linear" epitope binding of the antibody to human IL-19. Presented herein are exemplary embodiments of IL-19 antibodies that bind to linear epitopes on human IL-19, as well as other exemplary embodiments of IL-19 antibodies that bind to conformational epitopes. Conformational and nonconformational / linear epitopes can be distinguished in that binding to conformational epitope regions, but not linear epitope regions, is lost in the presence of denaturing solvents. In certain embodiments, the term "binds" (or binds) to human IL-19 refers to interaction with the epitope region comprising amino acid residues 95-102 of human IL-19, as determined by my method described herein (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1). In further embodiments, the term "binds" (or binds) to human IL-19 refers to interaction with the epitope region comprising amino acid residues 90-100 of human IL-19, as determined by my method described herein (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1). In another specific embodiment, the term "binds" (or "binds") to human IL-19 refers to interaction with an epitope region comprising amino acid residues 67-75 of human IL-19, as determined by my method described in this disclosure (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1).In another embodiment, the term "binds" (or binds) to human IL-19 refers to interaction with the epitope region comprising amino acid residues 125-136 of human IL-19 as determined by my method described herein (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1). In another specific embodiment, the term "binds" (or binds) to human IL-19 refers to interaction with the epitope region comprising amino acid residues 67-75 and 125-136 of human IL-19 as determined by my method described herein (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1). In a further embodiment, the term "binds" (or binds) to human IL-19 refers to interaction with the epitope region comprising amino acid residues 42-60 of human IL-19 as determined by my method described herein (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1). In certain embodiments, the term "bind" (or binds) to human IL-19 refers to interaction with the epitope region comprising amino acid residues 90-107 of human IL-19, as determined by my methods described herein (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1). In certain embodiments, the term "bind" (or binds) to human IL-19 refers to interaction with the epitope region comprising amino acid residues 149-160 of human IL-19, as determined by my methods described herein (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1). In another specific embodiment, the term "bind" (or binds) to human IL-19 refers to interaction with the epitope region comprising amino acid residues 42-60, 90-107, and 149-160 of human IL-19, as determined by my methods described herein (residue numbering based on the exemplary human IL-19 of SEQ ID NO:1). It should be understood that there are known variations of human IL-19, resulting, for example, from splice variants.It is also understood that such known variants may result in altered residue numbering of the residues described herein (e.g., in the relationship of the residue numbering presented in SEQ ID NO: 1). While some variants may have altered residue numbering, the amino acids comprising the epitope region remain the same. As used herein, the term "epitope region" refers to a distinct three-dimensional site on an antigen that is recognized, either completely or partially, by an antibody of the present invention.

[0028] The antibodies of the present invention can be prepared by methods well known in the art and can be incorporated into pharmaceutical compositions comprising an antibody of the present invention and one or more pharmaceutically acceptable carrier(s) and / or diluent(s) (see, e.g., Remington, The Science and Practice of Pharmacy, 22, which provides an overview of formulation techniques generally known to practitioners). nd Edition, Loyd V., Ed., Pharmaceutical Press, 2012). Suitable carriers for pharmaceutical compositions include any material that, when combined with the antibody of the present invention, retains the activity of the molecule and is non-reactive with the patient's immune system. Pharmaceutical compositions containing the antibody of the present invention can be administered via parenteral routes (e.g., subcutaneous, intravenous, intraperitoneal, intramuscular, or transdermal) to patients at risk for or exhibiting the diseases or disorders described herein. The pharmaceutical compositions of the present invention contain an "effective" or "therapeutically effective" amount (used interchangeably herein) of the antibody of the present invention. An effective amount refers to the amount (at the dosage and duration and by means of administration) necessary to achieve the desired therapeutic result. The effective amount of an antibody may vary depending on factors such as the individual's condition, age, sex, and weight, as well as the ability of the antibody to elicit the desired response in the individual. An effective amount is also one in which any toxic or detrimental effects of the antibody of the present invention are outweighed by the therapeutically beneficial effects.

[0029] The term percent homology, as used in this disclosure, in the context of two or more amino acid sequences, refers to two or more sequences that have a specified percentage of amino acid residues that are identical when compared and aligned for maximum correspondence using a sequence comparison algorithm (e.g., BLASTP and BLASTN, or other algorithms available to those skilled in the art) or by visual inspection. Depending on the application, the percent homology can exist over a region of the sequences being compared, e.g., over a functional domain, or over the entire length of the two sequences being compared. As an example, the percent sequence homology can be compared to a reference sequence. For example, when using a sequence comparison algorithm, the test and reference sequences can be input into a computer (and, if necessary, subsequence coordinates can be further specified, along with sequence algorithm program parameters). The sequence comparison algorithm then calculates the percent sequence identity or homology of the test sequence(s) relative to the reference sequence(s) based on the specified program parameters. Exemplary sequence alignment and / or homology algorithms are available through Smith & Waterman, Adv. Appl. Math. 2:482 (1981), Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), GAP, BESTFIT, FASTA, and TFASTA (Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally, Ausubel et al., infra). One example of an algorithm suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm, which is described in Altschul et al., J. Mol. Biol. 215:403-410 (1990).Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov / ).

[0030] The present disclosure also relates to methods of clinical diagnosis, prognosis, or theranosis of a subject performed by a medical professional using the methods disclosed herein. The methods described herein can be performed, for example, by an individual, a medical professional, or a third party, such as a service provider that resolves genotype information from a subject. As described herein, a medical professional can initiate or modify treatment after receiving information related to the diagnostic methods of the present disclosure. For example, a medical professional may recommend a therapy or a change in therapy.

[0031] The antibodies of the present disclosure can be used to isolate, detect, and / or quantify IL-19 by standard techniques, such as affinity chromatography, immunoprecipitation, immunohistochemistry, or ELISA-based assays. Such assays can be used to detect and / or assess the abundance and / or pattern of IL-19 expression for diagnostic, prognostic, or theranostic purposes, e.g., monitoring polypeptide levels in serum, plasma, blood, or tissues as part of a clinical trial procedure to determine the effectiveness of a given therapeutic regimen.

[0032] The IL-19 level or measurement provided by the assay of the present invention can be an absolute value (e.g., concentration within a biological sample) or a relative value (e.g., concentration compared to a reference). As used herein, if the IL-19 detection method indicates that the level or concentration of IL-19 in a patient sample is higher than a reference value, the IL-19 is said to be "increased" in the patient sample. Conversely, if the level or concentration of IL-19 in the patient sample is lower than the reference value, or, for example, the IL-19 value measured in a previous patient sample, the IL-19 is said to be "decreased" in the patient sample.

[0033] As used herein, a "reference value" refers to a known or approximate concentration of IL-19 associated with a specific condition. The reference value concentration level can be an absolute or relative amount, a range of amounts, or a minimum, average, and / or median amount of IL-19. The reference value can also serve as a baseline for IL-19 against which values ​​obtained from patient samples are compared. According to some embodiments, the reference value can include a reference value of about 21 pg / mL.

[0034] As used herein, "control standard" refers to a sample that can be used to compare results obtained from patient samples in the methods of the present invention. A control standard is a cell, tissue, or known protein concentration added to the culture medium. The concentration level of the control standard can be an absolute or relative amount of IL-19, a range of amounts, or a minimum, average, and / or median amount. A control standard can also serve as a baseline of IL-19 to which patient samples are compared. A control standard can include a concentration value from the same patient or a known normal standard of IL-19. According to some embodiments, a control standard can include a reference value of about 21 pg / mL. Furthermore, in some embodiments, a control standard can represent IL-19 concentrations in the form of a standard curve.

[0035] As used herein, the term "capture antibody" or "first antibody" refers to an IL-19 antibody that can bind to and capture IL-19 in a patient sample under suitable conditions such that the capture antibody-IL-19 complex can be separated from the remainder of the sample. In some embodiments, the capture antibody is immobilized. In some embodiments, the capture antibody is labeled with a detectable label. In some embodiments, the capture antibody is immobilized in a "sandwich" immunoassay, in which the capture or first IL-19 antibody binds to a specific or first epitope region of IL-19. In such sandwich immunoassays, a "detection (or second) antibody" is also utilized. According to some embodiments, the detection or second antibody can specifically bind to the capture antibody and can be labeled with a detectable label. In some embodiments, the detection second antibody binds to IL-19 that has already been bound or captured by the capture or first antibody. In such embodiments, the detection antibody binds to IL-19 at a second epitope region and can be labeled with a detectable label.

[0036] As understood in the art, antibodies of the present invention can be conjugated to a "detectable label" to facilitate their detection. As used herein, a detectable label is a moiety, composition, or technique that can be used to detect binding of a detection antibody to a capture antibody-IL-19 complex. According to some embodiments, the detectable label can be directly or indirectly conjugated to the antibody (either for capture or detection, as the case may be). Examples of detectable labels include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase. Examples of suitable prosthetic group complexes include streptavidin / biotin and avidin / biotin. Examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotnazinylamine fluorescein, dansyl chloride, or phycoerythrin. Examples of luminescent materials include luminol. Examples of bioluminescent materials include luciferase, luciferin, and aequorin. And examples of suitable radioactive materials include 125 I, 131 I, 35 S, or 3 H. The antibodies of the present invention may also be useful in pharmacogenomic analyses. Such embodiments can be used to identify individuals who may benefit from specific or modified treatments and / or to monitor the effectiveness of current treatment regimens.

[0037] As used interchangeably herein, the terms "diagnosis" or "diagnosing" refer to methods by which one of ordinary skill in the art can estimate and / or determine the probability ("likelihood") that a patient is or is not afflicted with a given disease or condition. In the context of the present invention, "diagnosing" a patient includes using the results of the assays of the present invention to identify or diagnose an autoimmune disease or autoimmune disease and factors associated with the patient (i.e., the presence or occurrence of an autoimmune disease, or the need for treatment, or the effectiveness of treatment for the patient's autoimmune disease). According to the present invention, diagnosis may also be based on a combination of other clinical signs understood by a medical professional to arrive at a diagnosis. [Example]

[0038] Expression of IL-19 antibodies The murine-derived IL-19 antibodies of the present invention are produced using hybridoma methodology (e.g., as first described by Kohler et al., Nature, 256:495 (1975)). Briefly, mice are immunized with recombinant human IL-19, and lymphocytes capable of producing antibodies that bind to human IL-19 are isolated and fused with a myeloma cell line using a suitable fusing agent to form hybridoma cells (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (Academic Press, 1986)). The hybridomas are seeded and grown in a suitable culture medium, preferably containing one or more substances that inhibit the survival of unfused myeloma cells. The binding specificity of the monoclonal antibodies produced by the hybridomas is then determined by in vitro binding assays (e.g., immunoprecipitation, radioimmunoassay (RIA), or enzyme-linked immunosorbent assay (ELISA)). Preferred hybridomas can be subcloned by limiting dilution procedures and grown by standard methods, including in vivo as ascites tumors in animals (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (Academic Press, 1986)). Monoclonal antibodies secreted by the hybridomas (and / or subclones) are purified according to conventional procedures, such as affinity chromatography (e.g., protein A or protein G-Sepharose) or ion exchange chromatography, hydroxyapatite chromatography, gel electrophoresis, dialysis, etc. Affinity maturation of antibodies can be performed according to methods known in the art.

[0039] The cDNA encoding the antibody of the present invention is sequenced using conventional procedures. The cDNA sequences encoding the heavy and light chains can be cloned and incorporated into a GS (glutamine synthetase) expression vector. The engineered immunoglobulin expression vector can then be stably transfected into CHO cells. As those skilled in the art will understand, mammalian expression of antibodies typically results in glycosylation at the highly conserved N-glycosylation site within the Fc region. Stable clones can be verified for expression of an antibody that specifically binds to human IL-19. Positive clones can be grown in serum-free medium for antibody production in a bioreactor. The medium into which the antibody is secreted can be purified by conventional techniques. For example, the medium can be conveniently applied to a Protein A or G Sepharose FF column equilibrated with a compatible buffer, such as phosphate-buffered saline. The column is washed to remove nonspecifically bound components. The bound antibody is eluted, for example, by a pH gradient, and the antibody fractions are detected by SDS-PAGE or the like and then pooled. The antibody may be concentrated and / or sterile filtered using common techniques. Soluble aggregates and multimers can be efficiently removed by common techniques, including size exclusion, hydrophobic interaction, ion exchange, or hydroxyapatite chromatography. The product may be immediately frozen, for example, at -70°C, or lyophilized. The CDR sequences of exemplary embodiments of affinity-optimized murine-derived IL-19 antibodies of the present invention known in the art are provided in Table 1. [Table 1]

[0040] The rabbit-derived IL-19 antibodies of the present invention are produced by obtaining antibody gene sequences directly from B cells. Briefly, rabbits are immunized with recombinant human IL-19, and mRNA is isolated from antigen-specific B cells enriched from PBMCs. Nucleic acid sequences encoding heavy and light chain variable regions from this library are then cloned into a cell-based display system. Functional binding fragments are isolated from the library, their individual gene sequences are determined, and they are cloned for recombinant IgG expression and purified essentially as described above for mouse-derived IL-19 antibodies. Table 2 provides CDR sequences for exemplary embodiments of the rabbit-derived IL-19 antibodies of the present invention that have been affinity-optimized as known in the art. [Table 2]

[0041] The phage-derived IL-19 antibodies of the present invention are isolated from antibody phage libraries using common techniques, such as those described above in McCafferty et al., Nature, 348:552-554 (1990). Clackson et al., Nature, 352:624-628 (1991) and Marks et al., J. Mol. Biol., 222:581-597 (1991). cDNA sequences encoding the heavy and light chains of the phage-derived antibodies of the present invention may be cloned and manipulated into GS (glutamine synthetase) expression vectors for recombinant expression in competent cell lines, such as CHO cells. CDR sequences of exemplary embodiments of the phage-derived IL-19 antibodies of the present invention are provided in Table 3. [Table 3]

[0042] Binding kinetics and affinity Binding of exemplary IL-19 antibodies of the invention to recombinant human IL-19 (having the amino acid sequence set forth in SEQ ID NO:1) is measured using a Biolayer Interferometry (BLI) assay (using HBS-EP+ running buffer (GE Healthcare, 10 mM HEPES pH 7.4+150 mM NaCl+3 mM EDTA+0.05% surfactant P20) at 25°C) measured on an Octet Red96® instrument available from ForteBio.

[0043] Except as noted, all reagents and materials are from ForteBio (Freemont, CA). An AMQ biosensor is used to immobilize the antibody to be analyzed. Exemplary antibody samples of the present invention (R_1, R_2, R_3, R_4, R_39, M_1, M_2, and M_5) are prepared at 5 μg / mL by dilution in running buffer. Recombinant human IL-19 is prepared at concentrations of 270, 90, 30, 10, 3.33, 1.11, 0.370, and 0 (blank) nM by dilution in running buffer. Each analysis consisted of (1) capturing the antibody sample onto the biosensor for 300 seconds, (2) establishing a baseline by incubating the antibody-loaded biosensor with running buffer for 60 seconds, (3) incubating the antibody-loaded biosensor with serially diluted recombinant human IL-19 for 300 seconds to monitor the association phase, and (4) returning the biosensor to running buffer to monitor the dissociation phase.

[0044] Binding data were processed using standard double referencing and fitted to a 1:1 binding model using Data Analysis v9.0 evaluation software to determine association rates (k on , M -1 s -1 units), dissociation rate (k off , s -1 units), and R max Determine the K (unit: nm). D =k off / k on From the relationship, the equilibrium dissociation constant (K D) was calculated and is in units of moles. The results are provided in Table 4. [Table 4]

[0045] Epitope mapping For high-resolution linear epitope mapping, PEPperCHIP® peptide microarray linear epitope mapping of the exemplary antibody M_1 against human IL-19 was performed according to the manufacturer's instructions. Briefly, the exemplary antibody M-1 was incubated with a custom PEPperCHIP® peptide microarray containing overlapping 12-mer peptide fragments of human IL-19. Scan intensities were resolved using the manufacturer's software. For the exemplary antibody M_1, PEPperCHIP® analysis revealed an epitope consisting of residues 95-102 (EPNPKILR) of SEQ ID NO: 1. Other exemplary murine and rabbit-derived antibodies of the present invention do not yield linear epitopes, demonstrating conformational epitope binding of human IL-19.

[0046] Hydrogen-deuterium exchange coupled with mass spectrometry (HDX-MS) was performed to map the epitope regions of the recombinant human IL-19 protein for the exemplary antibodies M_2, M_3, M_5, and R_39. Briefly, HDX-MS was performed on a Waters nanoACQUITY system equipped with HDX technology, including a LEAP HDX robotic liquid handling system, and mass spectrometry was performed on a Waters Xevo G2-Tof mass spectrometer. Complexes of human IL-19 and the exemplary antibodies M_2, M_3, M_5, and R_39 were prepared at a molar ratio of 1:1.2 in 10 mM sodium phosphate buffer, pH 7.4, containing 150 mM NaCl (1x PBS buffer). Deuterium exchange experiments are initiated by adding 55 μL of DO buffer containing 0.1×PBS to 5 μL of human IL-19 or human IL-19 / antibody complex at 15° C. for various time periods (0 s, 10 s, 1 min, 10 min, 60 min, 120 / 240 min). The reaction is quenched for 2 min at 1° C. using an equal volume of 0.32 M TCEP, 0.1 M phosphate pH 2.5. 50 μL of the quenched reaction is injected onto an online pepsin column (Waters BEH Enzymate) at 14° C. for 4 min at a flow rate of 100 μL / min using 0.2% formic acid in water as the mobile phase. The resulting peptic peptides were then separated on a C18 column (Waters, Acquity UPLC BEH C18, 1.7 μm, 1.0 mm × 50 mm) equipped with a Vanguard trap column using a gradient of 3–85% acetonitrile (containing 0.2% formic acid) over 10 min at a flow rate of 50 μL / min. The separated peptides were then transferred to a Waters Xevo G2 time-of-flight (qTOF) mass spectrometer. The mass spectrometer was operated over a mass acquisition range of m / z 255.00–1950.00 with a scan time of 0.5 s. E , ESI +The XevoG2 was set to collect data in NMR mode. The instrument was calibrated with Glu-fibrinopeptide prior to use. All acquired data was mass-corrected every 30 seconds at a flow rate of 5 μl / min using a 2 μg / ml solution of LeuEnk in 50% ACN, 50% HO, and 0.1% FA (m / z 556.2771). Peptides were initially identified using Waters Protein Lynx Global Server 3.02. Processing parameters were set to a low energy threshold of 100.0 counts, a high energy threshold of 50.0 counts, and an intensity threshold of 1500.0 counts. The resulting peptide list was imported into Waters DynamX 3.0 software, with thresholds of 5 ppm mass error and 20% fragment ions per peptide based on peptide length. The relative deuterium uptake of each peptide was determined by processing the MS data of the deuterated sample along with the non-deuterated control in DynamX.

[0047] Using the described HDX-MS, 90.9-94.8% sequence coverage of the human IL-19 protein is observed. When conjugated with the exemplary antibodies, reduced deuterium incorporation is observed at residues of SEQ ID NO: 1, as shown: M_2 and M_3: residues 67-75 (QIIKPLDVC) and 125-136 (RQCHCRQEATNA); M_5: residues 90-100 (FKDHQEPNPKI); and R_39: residues 42-60 (QEIKRAIQAKDTFPNVTIL), 90-107 (FKDHQEPNPKILRKISSI), and 149-160 (VHAAAIKSLGEL).

[0048] Binning experiment Binning experiments involve monoclonal antibodies competing with each other in a pairwise and combinatorial manner for binding to a specific antigen. A "bin" is a relative concept based on the epitope region represented within the panel of monoclonal antibodies being tested. When tested against other antibodies (or bins of antibodies) in the test panel, two antibodies that are not paired with each other and share the same blocking profile belong to the same bin. Binning of exemplary antibodies of the present invention can be performed by a cross-competition binning assay using Octet Red 96®, available from ForteBio, according to the manufacturer's instructions. Briefly, to determine whether two antibodies share overlapping epitope regions, the exemplary antibodies are labeled with biotin and captured on a streptavidin sensor tip. The coated biosensor tip is then incubated with recombinant human IL-19 to saturate the capture antibody binding sites. The capture antibody-antigen complex is then incubated with a detection antibody. If the detection antibody is able to bind, a change in wavelength is detected. Antibodies with identical binding profiles are grouped together in the same bin. The results are presented in Table 5. [Table 5]

[0049] Neutralization of IL-19 in vitro Antibodies of the invention are expected to neutralize IL-19. Neutralization of IL-19 activity by antibodies of the invention can be assessed by one or more IL-19 / IL-19 receptor binding assay formats, as well as the IL-19 binding assay described below, for example.

[0050] In one example, IL-19 is radiolabeled, for example, with iodine-125 or tritium. Cells expressing an IL-19 receptor, such as IL-20R1 (e.g., primary human cells, such as transformed keratinocytes endogenously expressing the IL-19 receptor, or keratinocytes expressing the IL-19 receptor) are used in the assay, which can be performed in a buffered medium, such as HBSS, containing calcium and magnesium and whole cells. Thus, cells can be incubated with labeled IL-19 in assay buffer for 1-6 hours at 4, 20, or 37°C. The readout provides the amount of label bound to the cells after separating unbound tracer, such as by filtration through a glass fiber filter. Alternatively, neutralization can be assessed by a proximity-based assay using SPA beads. Additionally, neutralization assays utilizing non-radiolabeled IL-19 protein can be used.

[0051] Such neutralization assays involve preincubation (e.g., 1 hour) of the antibody being evaluated with labeled IL-19 (as well as a control sample without the antibody targeting IL-19) before addition to the binding assay. A concentration of labeled IL-19 near the 50% binding level (EC50) can be used, as well as a range of concentrations (e.g., when assessing antibody dose response, such as from about 100 micromolar to about 1 picomolar). Antibody inhibition assessed over a range allows for the determination of potency (IC50).

[0052] According to another method for evaluating IL-19 neutralization by the antibodies of the present invention, IL-19 protein is labeled with a fluorescent dye for flow cytometry (e.g., Alexa-647) and used to label cells such as human keratinocytes. Binding can then be measured using flow cytometry. Antibody neutralization of IL-19 is evaluated by preincubating the antibody with labeled IL-19 (e.g., for 1 hour at 4°C) before adding the mixture to the cells (with staining performed for approximately 3 hours at 4°C). A concentration of fluorescently labeled IL-19 close to the 50% binding level (EC50) can be used, as well as various concentrations (e.g., when evaluating the dose response of the antibody, such as from about 100 micromolar to about 1 picomolar). Antibody inhibition of the binding of labeled IL-19 to its receptor can be reflected by measuring the loss of labeled cells, and the antibody's potency (IC50) can be determined.

[0053] Alternatively, biophysical assays such as biolayer interferometry (BLI) can be used to assess IL-19 neutralization by the antibodies of the present invention. Binding of a ligand immobilized on the surface of the biosensor tip to an analyte in solution increases the optical thickness of the biosensor tip, resulting in a wavelength shift (expressed in nm). According to such an assay, the IL-19 receptor (i.e., IL-20R1) is expressed in a membrane-free manner (e.g., as an Fc-fusion protein, e.g., IL20Rbeta Fc chimeric protein from R&D Systems catalog 1788-IR-050). An AMQ or anti-rabbit conjugate biosensor (ForteBio) is used to immobilize the anti-IL-19 antibody of interest (M_1, M_2, M_3, M_5, and R_39). The immobilized antibody is then incubated with recombinant human IL-19 protein diluted to 100 nM using HBS-EP+ running buffer (GE Healthcare, 10 mM HEPES pH 7.4 + 150 mM NaCl + 3 mM EDTA + 0.05% surfactant P20) for 240-300 seconds. Human IL-19 is assessed by binding to the anti-IL-19 antibody followed by incubation with human IL-20R beta Fc fusion protein for 240-300 seconds. The ability of the antibody to block or neutralize binding of the IL-19 ligand to the soluble receptor is observed as a minimal (<0.025 nm) increase in wavelength during this step of the assay. The results are provided in Table 6. [Table 6]

[0054] Another method for assessing IL-19 neutralization by the antibodies of the present invention involves adding such antibodies preincubated with human IL-19 to human keratinocytes. Exogenous IL-19 to human keratinocytes induces the expression of additional IL-19 and other inflammatory molecules, such as IL-8, CCL20, and S100A7. After preincubation of the antibody and IL-19 (e.g., 1 hour at 4°C), the antibody-IL-19 mixture is added to cultured human keratinocytes. The cells are then cultured for 1 to 48 hours, and one or more of IL-19, IL-8, CCL20, and S100A7 (or other molecules expressed downstream of IL-19) in the supernatant are measured, for example, by ELISA (alternatively, mRNA of the downstream molecule can be measured). Inhibition of IL-19 function by the antibody indicates reduced expression of the downstream molecule by the cultured keratinocytes.

[0055] The PathHunter® eXpress IL20RA / IL20RB Dimerization Assay (DiscoverX product code 93-1027E3) was used to evaluate the ability of exemplary antibodies to block binding of human IL-19 recombinant protein in a cell-based assay format. This assay detects ligand-induced dimerization of the two subunits of a receptor-dimer pair. Cells are designed to co-express one receptor subunit fused to an enzyme donor and a second dimer partner fused to an enzyme acceptor. Binding of an agonist to one receptor subunit induces it to interact with its dimer partner, forcing the complementation of the two enzyme fragments and resulting in the formation of a functional enzyme that hydrolyzes a substrate and generates a chemiluminescent signal. Briefly, cells were seeded at 2500 cells per well and cultured for 4 hours at 37°C / 5% CO2 before adding human IL-19 recombinant protein premixed with various concentrations of exemplary antibodies (M_1 and M_5) ranging from 10 to 0.00001 μg / ml, including a buffer-only control. Human IL-19 recombinant protein with or without the exemplary antibody mixture was then incubated with the cells overnight at 37°C / 5% CO2. Substrate buffer was added to the cells and incubated for 1 hour at room temperature in the dark before luminescence detection. The concentrations of exemplary antibodies resulting in 50% inhibition of signal (IC50) and maximum signal inhibition percentage (% inhibition) are tabulated for eight experiments with the standard error of the mean (SEM) shown below. Results are provided in Table 7. [Table 7]

[0056] IL-19 assay Psoriasis vulgaris is currently measured based on the assessment of total body surface area (BSA) and / or the degree of erythema, thickness, and extent of psoriasis lesions (PASI). However, given the subjective input required by these methods, they may not be linear depending on the severity of skin lesions. No single blood-borne marker capable of assessing overall psoriasis activity has been identified. Therefore, a more objective and reproducible method for determining severity is desirable. The present invention provides a highly sensitive and specific assay for measuring IL-19 levels in patient samples, such as blood, serum, and plasma. As demonstrated herein, the IL-19 assay of the present invention provides an accurate diagnostic tool for predicting treatment response (i.e., a predictive biomarker), disease recurrence (i.e., a prognostic biomarker), disease onset, and disease severity in patients with moderate to severe PsO.

[0057] According to exemplary embodiments, provided herein is a sandwich ELISA assay for sensitive detection of IL-19. The assay utilizes exemplary IL-19 antibodies of the invention, e.g., as described in Tables 1, 2, or 3. According to exemplary embodiments, a first IL-19 antibody (selected from Tables 1, 2, or 3) is utilized as an IL-19 capture antibody, and a second IL-19 antibody (selected from Tables 1, 2, or 3) is utilized as an IL-19 reporter antibody. In some embodiments, the first and second IL-19 antibodies are selected from distinct epitope bins (e.g., in a specific embodiment, exemplary IL-19 antibody M_1 is paired with exemplary IL-19 antibody M_2). According to some embodiments, 1 milligram of a first IL-19 antibody (capture antibody) is biotinylated using the Pierce Biotinylation Kit (catalog number), and 1 milligram of a second IL-19 antibody (reporter antibody) is labeled with ruthenium using a MesoScale Discovery (MSD) kit for electrochemiluminescence (ECL) detection. According to such embodiments, the labeled antibodies are evaluated using MALDI-TOF to ensure suitable labeling, and then diluted in 50% glycerol and stored at -20°C prior to use.

[0058] Streptavidin-coated 96-well MSD plates are washed three times with TBST (Tris-buffered saline containing 10 mmol / L Tris pH 7.40, 1 mL Tween 20 / L, 150 mmol / L NaCl) and then blocked with TBS-T + 1% BSA for 1 hour at room temperature. The plates are washed again, and the wells are then incubated with biotinylated IL-19 capture antibody (1 mg / L) for 1 hour. The plates are then washed again before testing patient samples.

[0059] During testing of patient samples, a standard curve is generated using 50 µL of recombinant human IL-19 control standard (serial diluted IL-19 recombinant protein ranging from 100 to 0.0001 ng / L in assay buffer of 50 mmol / L HEPES, pH 7.40, 150 mmol / L NaCl, 10 µL / L Triton X-100, 5 mmol / L EDTA, and 5 mmol / L EGTA, plus a zero blank). Data from 10 individual standard curves prepared as described herein are used to generate a 10 -1 pg / mL to 10 5The dynamic range of IL-19 in pg / mL is shown (providing high sensitivity and a wide dynamic range for the therapeutic and diagnostic assays provided herein). Patient samples (which, according to the present invention, may include blood, serum, or plasma) are diluted 1:4 with assay buffer and added to each well. The plate is incubated overnight at 4°C. After incubation, the wells are aspirated and washed three times with TBST. 50 μL of ruthenium-labeled IL-19 detection antibody (0.5 mg / L) is then added to the wells for incubation at room temperature for 1 hour. After incubation, the wells are aspirated and washed three times with TBST. 150 μL of 2X MSD read buffer is then added. Ruthenium electrochemiluminescence in the wells is detected using an MSD Sector 6000 plate reader. Data is analyzed, and calibration curve fitting for the IL-19 MSD immunoassay is performed using MesoScale Discovery software. SAS® software version 9.4 (PROC MIXED) uses an unstructured covariance matrix and log 10 A mixed-effects model with transformed IL-19 concentrations (SAS version 9.4 for UNIX, SAS Institute Inc.: Cary, NC, 2016) was used to evaluate the effect of treatment on IL-19 levels. Statistical analyses were generated using the R version 3.3.3 statistical computing environment (www.R-project.org, Vienna, Austria, 2017) with the ggplot and pROC packages.

[0060] IL-19 serum concentrations in Ps0 patients vs. healthy group A study of IL-19 levels in the serum of 125 Ps0 patients before treatment was compared with IL-19 serum levels in 36 healthy volunteer samples. Using an IL-19 assay essentially as described above, the serum IL-19 concentration (pg / mL) of each patient sample was measured with a capture antibody selected from bin 1 (specifically, exemplary IL-19 antibody M_1) and a detection antibody selected from bin 2 (specifically, exemplary IL-19 antibody M_2). The geometric mean of serum IL-19 concentrations in healthy volunteers (n=36) was measured at 11 pg / mL (range 4-51 pg / mL, and 95% confidence level <21 pg / mL), while the geometric mean of serum IL-19 concentrations in Ps0 patients (pre-treatment) (n=112) was measured at 87 pg / mL. Thus, the present invention provides an IL-19 blood-based assay that enables the diagnosis of Ps0 patients.

[0061] PS0 study in anti-IL-17 treatment group A study of IL-19 levels in the serum of 125 Ps0 patients treated with the therapeutic antibody ixekizumab, which targets IL-17, will be conducted. The study will include five treatment groups: 10 mg (n=24), 25 mg (n=23), 75 mg (n=26), or 150 mg (n=28) of ixekizumab or placebo (n=24). All treatment doses will be administered subcutaneously, beginning at week 0 and every two weeks thereafter through week 16 (inclusive). Using the IL-19 assay described above, each patient's serum IL-19 concentration (pg / ml) will be measured at week 0 (pretreatment), week 2, and week 12 using a capture antibody selected from bin 1 (specifically, exemplary IL-19 antibody M_1) and a detection antibody selected from bin 5 (specifically, exemplary IL-19 antibody M_2). Serum IL-19 concentration levels, percent PASI change, and PASI 75 responses are provided in Tables 8-10.

[0062] As shown, 36 of 41 patients (87.8%) who achieved a ≥5-fold reduction in IL-19 levels between weeks 0 and 2 achieved a PASI 75 or higher by week 16 (in contrast, only 24 of 56 patients (42.9%) who achieved a <5-fold reduction in IL-19 levels between weeks 0 and 2 achieved a PASI 75 response by week 16). Furthermore, 37 of 42 patients (88%) who achieved a ≥5-fold reduction in IL-19 levels between weeks 0 and 9 achieved a PASI 75 or higher by week 12 (in contrast, only 22 of 53 patients (41.5%) who achieved a <5-fold reduction in IL-19 levels between weeks 0 and 16 achieved a PASI 75 response by week 16 (data reflect two patients who withdrew between weeks 2 and 12). No significant changes in IL-19 levels were observed in the placebo-treated group over the 16-week study period. [Table 8] Table 8 provides data showing IL-19 measured in treatment groups over 16 weeks of treatment with placebo or various ixekizumab doses. [Table 9] Table 9 provides the number of patients by treatment group who achieved PASI 75 by week 16. [Table 10]

[0063] Table 10 shows the correlation between IL-19 serum levels and PASI in psoriasis patients after 16 weeks of placebo or various ixekizumab treatments (21 ng / L represents the upper limit of the normal range for IL-19 in healthy subjects). The improvement in PASI 100 at 16 weeks was noted following a prior reduction in circulating IL-19 to near-normal concentrations after 2 weeks of treatment.

[0064] The data provided in Tables 8-10 demonstrate that the IL-19 assay of the present invention provides a valuable tool for the diagnosis and therapeutic prognosis of Ps0 patients treated with IL-17 antibodies.

[0065] PS0 study in anti-TNFα treatment group A study of IL-19 levels in the serum of 35 Ps0 patients who were complete responders when treated with the FDA-approved TNFα antagonist entanercept was conducted. Treatment groups were compared with 50 mg of etanercept (n=35) administered every other week or placebo. Both treatment groups were administered subcutaneously. Using the IL-19 assay described above, each patient's serum IL-19 concentration (pg / ml) was measured at weeks 0 (pretreatment), 1, 4, and 12 using a capture antibody selected from bin 1 (specifically, exemplary IL-19 antibody M_1) and a detection antibody selected from bin 2 (specifically, exemplary IL-19 antibody M_2). IL-19 levels were assessed for prognostic value with improvement in PASI at weeks 4 and 12. Serum IL-19 concentration levels are presented in Table 11. The prognostic values ​​at week 4 showing the correlation between IL-19 serum levels and PASI in psoriasis patients (21 ng / L represents the upper limit of the normal range for IL-19 in healthy subjects) are presented in Table 12. The prognostic values ​​at week 12 showing the correlation between IL-19 serum levels and PASI in psoriasis patients (21 ng / L represents the upper limit of the normal range for IL-19 in healthy subjects) are presented in Table 13. [Table 11] [Table 12] [Table 13]

[0066] As noted above, patients treated with TNF antagonists experienced, on average, a median decrease in serum IL-19 of more than 40 pg / mL after 1 week and a median decrease in serum IL-19 of more than 70 pg / mL at week 4. The data provided in Tables 11-13 demonstrate that the IL-19 assay of the present invention provides a valuable tool for the diagnosis and therapeutic prognosis of Ps0 patients treated with TNFα antibodies.

[0067] PS0 study in anti-IL-23 treatment group A study of IL-19 levels in the serum of Ps0 patients treated with mirikizumab, a therapeutic antibody targeting IL-23, will be conducted. Eight treatment arms will be evaluated: 5 mg, 20 mg, 60 mg, 120 mg, 200 mg, 350 mg, and 600 mg of mirikizumab or placebo. Each treatment arm will be administered as a single subcutaneous dose on Day 0. Using the IL-19 assay described above, each patient's serum IL-19 concentration (pg / ml) will be measured between Visits 2 and 12 with a capture antibody selected from Bin 1 (specifically, exemplary IL-19 antibody M_1) and a detection antibody selected from Bin 2 (specifically, exemplary IL-19 antibody M_2). IL-19 levels will also be evaluated for prognostic value with improvement in PASI between Visits 2 and 12. Serum IL-19 concentration levels are presented in Table 14. A comparison of serum levels at Week 8 is presented in Table 15. And the prognostic values ​​at week 8 showing the correlation between IL-19 serum levels and PASI in psoriasis patients (21 ng / L represents the upper limit of the normal range for IL-19 in healthy subjects) are presented in Table 16. The decrease in serum IL-19 correlating with the improvement in PASI score showing that the IL-19 assay of the present invention provides a valuable tool for the diagnosis and therapeutic prognosis of Ps0 patients treated with IL-23 antibodies. [Table 14] [Table 15] [Table 16]

[0068] Ps0 study in the JAK1 and JAK2 kinase inhibitor treatment groups A study of IL-19 levels in the serum of Ps0 patients treated with the therapeutic selective JAK1 and JAK2 inhibitor baricitinib will be conducted. Treatment groups will be evaluated: 2 mg, 4 mg, 8 mg, and 10 mg of baricitinib or placebo. Each treatment group will be administered orally once daily. Using the IL-19 assay described above, serum IL-19 concentrations (pg / ml) for each patient will be measured at baseline and after each treatment with a capture antibody selected from bin 1 (specifically, exemplary IL-19 antibody M_1) and a detection antibody selected from bin 2 (specifically, exemplary IL-19 antibody M_2). IL-19 levels will also be evaluated for prognostic value with improvement in PASI. Serum IL-19 concentration levels are presented in Table 17. PASI prognosis data (week 12) showing the correlation between IL-19 serum levels and PASI in psoriasis patients (21 ng / L represents the upper limit of the normal range for IL-19 in healthy subjects) are presented in Table 18. The data demonstrate that the decrease in serum IL-19 correlated with the improvement in PASI score indicating the IL-19 assay of the present invention provides a valuable tool for the diagnosis and therapeutic prognosis of Ps0 patients treated with JAK1 and JAK2 inhibitors. [Table 17] [Table 18]

[0069] AD study in JAK1 and JAK2 kinase inhibitor treatment groups A study of IL-19 levels in the serum of 123 patients with moderate to severe atopic dermatitis treated with the therapeutic selective JAK1 and JAK2 inhibitor baricitinib will be conducted. Treatment groups will be compared, with 2 mg and 4 mg of baricitinib or placebo. Each treatment group will be administered orally once daily. Using the IL-19 assay described above, each patient's serum IL-19 concentration (pg / ml) will be measured at baseline (before treatment) and at weeks 4 and 16 using a capture antibody selected from bin 1 (specifically, exemplary IL-19 antibody M_1) and a detection antibody selected from bin 2 (specifically, exemplary IL-19 antibody M_2). IL-19 levels will be evaluated for prognostic value associated with improvement in EASI score. Serum IL-19 concentration levels are presented in Table 19. The prognostic value of EASI (week 16) showing correlation of IL-19 serum levels in AD patients (21 ng / L represents the upper limit of the normal range for IL-19 in healthy subjects) is presented in Table 20. The data show that baseline IL-19 concentrations in AD patients were found to be elevated compared to normal (geometric mean of AD patients was 34 pg / mL). The data also show that the decrease in serum IL-19 at weeks 4 and 16 correlating with improvement in EASI score at week 16 indicating the IL-19 assay of the present invention provides a valuable tool for the diagnosis and therapeutic prognosis of Ps0 patients treated with JAK1 and JAK2 inhibitors. [Table 19] [Table 20]

[0070] IL-19 serum concentrations in patients with renal failure and diabetes IL-19 levels were measured in healthy donors (n=20), renal failure patients (n=16), diabetic patients without renal failure (n=20), and diabetic patients with renal failure (n=21). Using the IL-19 assay described above, baseline serum IL-19 concentrations (pg / ml) for each patient were measured with a capture antibody selected from bin 1 (specifically, exemplary IL-19 antibody M_1) and a detection antibody selected from bin 2 (specifically, exemplary IL-19 antibody M_2). The data show that IL-19 levels were significantly elevated in renal failure patients (40±6 pg / mL), diabetic patients without renal failure (17±3 pg / mL), and diabetic patients with renal failure (46±9 pg / mL) compared with healthy donors (8±1 pg / mL). Thus, the IL-19 assay of the present invention provides a valuable tool for the diagnosis and therapeutic prognosis of diabetic and renal failure patients.

[0071] PsA study in anti-IL-17 treatment group A study of IL-19 levels in the serum of 309 PsA patients treated with the therapeutic antibody ixekizumab, which targets IL-17, will be conducted. The study will include three treatment arms: (i) an anti-IL-17 treatment group, receiving 160 mg of ixekizumab at baseline, followed by 80 mg every 2 weeks for 12 weeks thereafter (n=103); (ii) an anti-IL-17 treatment group, receiving 160 mg of ixekizumab at baseline, followed by 80 mg every 4 weeks for 12 weeks thereafter (n=107); or (iii) placebo (n=105). All treatment doses will be administered subcutaneously. Using the IL-19 assay described above, serum IL-19 concentrations (pg / ml) for each patient are measured at weeks 0 (pre-treatment administration), 4, and 12 with a capture antibody selected from bin 1 (specifically, exemplary IL-19 antibody M_1) and a detection antibody selected from bin 2 (specifically, exemplary IL-19 antibody M_2). Serum IL-19 concentration levels are presented in Table 21. PASI prognostic values ​​at weeks 4 and 12 (21 ng / L represents the upper limit of the normal range for IL-19 in healthy subjects), showing the correlation between IL-19 serum levels and PASI in patients, are presented in Tables 22 and 23, respectively. [Table 21] [Table 22] [Table 23]

[0072] Table 21 shows that baseline IL-19 levels in patients with psoriatic arthritis are elevated compared to baseline values ​​in healthy volunteers (represented by the shaded gray area). Placebo treatment does not result in significant changes in IL-19 over the 12-week study. However, both ixekizumab-treated groups demonstrate a reduction in IL-19 to near-normal levels after 4 weeks, and this reduction persists over 12 weeks of treatment. Tables 22 and 23 show the relationship between IL-19 levels and 12-week PASI scores in PsA patients in either the placebo or ixekizumab-treated groups after 4 or 12 weeks. Improvement in PASI 100 at 12 weeks correlated with a reduction in circulating IL-19 concentrations to near-normal levels, with the majority of poor PASI responders in the placebo group. The data provided in Tables 21-23 demonstrate that the IL-19 assay of the present invention provides a valuable tool for the diagnosis and therapeutic prognosis of PsA patients treated with an IL-17 antibody.

[0073] Sequence Listing SEQ ID NO: 1 (human IL-19) MKLQCVSLWLLGTILILCSVDNHGLRRCLISTDMHHEESFQEIKRAIQAKDTFPNVTILSTLETLQIIKPLDVCCVTKNLLAFYVDRVFKDHQEPNPKILRKISSIANSFLYMQKTLRQCQEQRQCHCRQEATNATRVIHDNYDQLEVHAAAIKSLGELDVFLAWINKNHEVMFSA

[0074] SEQ ID NO: 2 (LC of murine-derived IL-19 Ab 1 ("M_1")) DIVMTQSPSSLAMSVGQKVTMSCKSSQSLLSSYNQKNYLAWYQQKPGQSPKLLVYFASTRPPGVPDRFIGSGSGSDFTLTISSVQAEDLADYFCQQHERLPITFGAGTKL ELKRADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

[0075] SEQ ID NO: 3 (LCDR1 of mouse-derived IL-19 Ab 1) KSSQSLLSSYNQKNYLA

[0076] SEQ ID NO: 4 (LCDR2 of mouse-derived IL-19 Ab 1) FASTRPP

[0077] SEQ ID NO: 5 (LCDR3 of mouse-derived IL-19 Ab 1) QQHERLPIT

[0078] SEQ ID NO: 6 (HC of murine-derived IL-19 Ab 1 ("M_1")) EVQLQQSGPVLVKPGASVKMSCKASGYKFTDYFVGWVKQSHGKSLEWIGYVDPENGYTRCNQKFKGKATLTVDKSSSTAYMELNSLTSEDSAVYYCARYDYDWAWFTNWG QGTLVTVSAAKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVPSSTWPSETVTCNVAHPASSTKVDKKIVPRDC GCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTI SKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK

[0079] SEQ ID NO: 7 (HCDR1 of mouse-derived IL-19 Ab 1) GYKFTDYFVG

[0080] SEQ ID NO: 8 (HCDR2 of mouse-derived IL-19 Ab 1) YVDPENGYTRCNQKFKG

[0081] SEQ ID NO: 9 (HCDR3 of mouse-derived IL-19 Ab 1) YDYDWAWFTN

[0082] SEQ ID NO: 10 (LC of murine-derived IL-19 Ab 2 ("M_2")) DIVLTQSPESLAVSLGQRATISCRASESVDNYGISFIHWYQQKPGQPPKLLIYRASNLKSGIPARFSGRGSRTDFTLTINPVETDDVATYYCQQINKDPLTFGAGTKLE LKRADAAPTVSIFPPSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

[0083] SEQ ID NO: 11 (LCDR1 of mouse-derived IL-19 Ab 2) RASESVDNYGISFIH

[0084] SEQ ID NO: 12 (LCDR2 of mouse-derived IL-19 Ab 2) RASNLKS

[0085] SEQ ID NO: 13 (LCDR3 of mouse-derived IL-19 Ab 2) QQINKDPLT

[0086] SEQ ID NO: 14 (HC of murine-derived IL-19 Ab 2 ("M_2")) LVQLQQSDAELVKPGASLKISCKVSGYTFTDHALHWMKQRPEQGLEWIGYIYPRDGSTKYNEKFKGKATLTADRSSSTAYMELNSLTSEDSAVYFCARGWDFAMDYWGQG TSVTVSSAKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVPSSTWPSETVTCNVAHPASSTKVDKKIVPRDCG CKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTI SKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK

[0087] SEQ ID NO: 15 (HCDR1 of mouse-derived IL-19 Ab 2) GYTFTDHALH

[0088] SEQ ID NO: 16 (HCDR2 of mouse-derived IL-19 Ab 2) YIYPRDGSTKYNEKFKG

[0089] SEQ ID NO: 17 (HCDR3 of mouse-derived IL-19 Ab 2) GWDFAMDY

[0090] SEQ ID NO: 18 (LC of murine-derived IL-19 Ab 3 ("M_3")) DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYFCLQYDDFPYTFGGGTKLEIK RADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

[0091] SEQ ID NO: 19 (LCDR1 of mouse-derived IL-19 Ab 3) KASQDINSYLS

[0092] SEQ ID NO: 20 (LCDR2 of murine IL-19 Ab 3) RANRLVD

[0093] SEQ ID NO: 21 (LCDR3 of mouse-derived IL-19 Ab 3) LQYDDFPYT

[0094] SEQ ID NO: 22 (HC of murine IL-19 Ab 3 ("M_3")) QIQLVQSGPELKKPGETVKISCKASGYTFTTYGMSWVKQAPGKGLKWMVWINTYSGVPTYVDDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARRDEGFAYWGQGT LVTVSAAKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVPSSTWPSETVTCNVAHPASSTKVDKKIVPRDCGC KPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTIS KTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK

[0095] SEQ ID NO: 23 (HCDR1 of mouse-derived IL-19 Ab 3) GYTFTTYGMS

[0096] SEQ ID NO: 24 (HCDR2 of mouse-derived IL-19 Ab 3) WINTYSGVPTYVDDFKG

[0097] SEQ ID NO: 25 (HCDR3 of mouse-derived IL-19 Ab 3) RDEGFAY

[0098] SEQ ID NO: 26 (LC of murine IL-19 Ab 4 ("M_4")) DIVMTQSPSSLAMSVGQKVTMSCKSSQSLLSSYNQKNYLAWYQQKPGQSPKLLVYFASTRESGVPDRFIGSGSGSDFTLTISSVQAEDLADYFCQQHYSTPLTFGAGTKL ELKRADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

[0099] SEQ ID NO: 27 (LCDR1 of murine IL-19 Ab 4) KSSQSLLSSYNQKNYLA

[0100] SEQ ID NO: 28 (LCDR2 of murine IL-19 Ab 4) FASTRES

[0101] SEQ ID NO: 29 (LCDR3 of murine IL-19 Ab 4) QQHYSTPLT

[0102] SEQ ID NO: 30 (HC of murine-derived IL-19 Ab 4 ("M_4")) EVQLQQSGPVLVKPGASVKMSCKASGYTFTDYYMNWVKQSHGKSLEWIGFINPYNDDTRCNQKFKGKATLTVDKSSSTAYMELNSLTSEDSAVYYCARYDGYWAWFAYWG QGTLVTVSAAKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVPSSTWPSETVTCNVAHPASSTKVDKKIVPRDC GCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTI SKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK

[0103] SEQ ID NO: 31 (HCDR1 of mouse-derived IL-19 Ab 4) GYTFTDYYMN

[0104] SEQ ID NO: 32 (HCDR2 of mouse-derived IL-19 Ab 4) FINPYNDDTRCNQKFKG

[0105] SEQ ID NO: 33 (HCDR3 of mouse-derived IL-19 Ab 4) YDGYWAWFAY

[0106] SEQ ID NO: 34 (LCVR of rabbit-derived IL-19 Ab 1 ("R_1")) AIDMTQTPASVSEPVGGTVTIKCQASQSISSYLAWYQQKPGQPPKLLIYSASTLASGVPSRFRGSGSGREFTLTISDLECADAATYYCQCHYHGSSYWDNSFGGGTEVVVK

[0107] SEQ ID NO: 35 (LCDR1 of rabbit-derived IL-19 Ab 1) QASQSISSYLA

[0108] SEQ ID NO: 36 (LCDR2 of rabbit-derived IL-19 Ab 1) SASTLAS

[0109] SEQ ID NO: 37 (LCDR3 of rabbit-derived IL-19 Ab 1) QCHYHGSSYWDNS

[0110] SEQ ID NO: 38 (HCVR of rabbit-derived IL-19 Ab 1 ("R_1")) QQLEESGGGLVQPEGSLTLTCTASGFSFSSSYWICWVRQAPGKGLEWLACIDTGVSGDTYYANWAEGRFTISKTSSTTVTLQMTSLTAADTATYFCARDIFGSAIDNSLWGPGTLVTVSS

[0111] SEQ ID NO: 39 (HCDR1 of rabbit-derived IL-19 Ab 1) GFSFSSSYWIC

[0112] SEQ ID NO: 40 (HCDR2 of rabbit-derived IL-19 Ab 1) CIDTGVSGDTYYANWAEG

[0113] SEQ ID NO: 41 (HCDR3 of rabbit-derived IL-19 Ab 1) DIFGSAIDNSL

[0114] SEQ ID NO: 42 (LCVR of rabbit-derived IL-19 Ab 2 (“R_2”)) ADVVMTQTPASVEAAVGGTVTIKCQASESIGNALAWYQQKPGQPPKLLIYDASKLASGVPSRFKGSGSGTQFTLTISDLECADAATYYCQCHYHGSSYWDNSFGGGTEVVVK

[0115] SEQ ID NO: 43 (LCDR1 of rabbit-derived IL-19 Ab 2) QASESIGNALA

[0116] SEQ ID NO: 44 (LCDR2 of rabbit-derived IL-19 Ab 2) DASKLAS

[0117] SEQ ID NO: 45 (LCDR3 of rabbit-derived IL-19 Ab 2) QCHYHGSSYWDNS

[0118] SEQ ID NO: 46 (HCVR of rabbit-derived IL-19 Ab 2 ("R_2")) QQLEESGGGLVQPEGSLTLTCTASGFSFSSSYWICWVRQAPGKGLEWLACIDTGVSGDTYYANWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARDIFGSAIDNSLWGPGTLVTVSS

[0119] SEQ ID NO: 47 (HCDR1 of rabbit-derived IL-19 Ab 2) GFSFSSSYWIC

[0120] SEQ ID NO: 48 (HCDR2 of rabbit-derived IL-19 Ab 2) CIDTGVSGDTYYANWAKG

[0121] SEQ ID NO: 49 (HCDR3 of rabbit-derived IL-19 Ab 2) DIFGSAIDNSL

[0122] SEQ ID NO: 50 (LCVR of rabbit-derived IL-19 Ab 4 ("R_3")) ADVVMTQTPSSVEAAVGGTVTIKCQASQSIGSSLAWYQQKPGQRPKLLIYGASTLASGVPSRFKGSGSGTEFTLTISDLECADAATYYCQCHYHGSSYWDNSFGGGTEVVVK

[0123] SEQ ID NO: 51 (LCDR1 of rabbit-derived IL-19 Ab 3) QASQSIGSSLA

[0124] SEQ ID NO: 52 (LCDR2 of rabbit-derived IL-19 Ab 3) GASTLAS

[0125] SEQ ID NO: 53 (LCDR3 of rabbit-derived IL-19 Ab 3) QCHYHGSSYWDNS

[0126] SEQ ID NO: 54 (HCVR of rabbit-derived IL-19 Ab 4 ("R_3")) QCQSLEESGGGLVEPEGSLTLTCKASGFSFSSSYWICWVRQAPGKGLEWIACTDTFSGDTYYASWAKGRFTISKTSSTTVTLRMTSLTDADTATYFCARDIFGTAVHISLWGPGTLVTVSS

[0127] SEQ ID NO: 55 (HCDR1 of rabbit-derived IL-19 Ab 3) GFSFSSSYWIC

[0128] SEQ ID NO: 56 (HCDR2 of rabbit-derived IL-19 Ab 3) CTDTFSGDTYYASWAKG

[0129] SEQ ID NO: 57 (HCDR3 of rabbit-derived IL-19 Ab 3) DIFGTAVHISL

[0130] SEQ ID NO: 58 (LCVR of rabbit-derived IL-19 Ab 5 ("R_4")) ADVVMTQTPSSVSEPVGGTVTIKCQASQSIYSYLSWYQQKPGQPPKLLIYEASKLASGVPSRFKGSGSGTQFTLTISGVECADAATYYCQQGYSSSNVDNTFGGGTEVVVT

[0131] SEQ ID NO: 59 (LCDR1 of rabbit-derived IL-19 Ab 4) QASQSIYSYLS

[0132] SEQ ID NO: 60 (LCDR2 of rabbit-derived IL-19 Ab 4) EASKLAS

[0133] SEQ ID NO: 61 (LCDR3 of rabbit-derived IL-19 Ab 4) QQGYSSSNVDNT

[0134] SEQ ID NO: 62 (HCVR of rabbit-derived IL-19 Ab 5 ("R_4")) QCQSVEESGGRLVTPGTPLTLTCTVSGIDLSIYAMGWVRQAPGKGLEYIGIIDTTGTAYYARWAKGRFTISKTSATVALKITSPTTEDTATYFCARDSGSLYYGSYALWGPGTLVTVSS

[0135] SEQ ID NO: 63 (HCDR1 of rabbit-derived IL-19 Ab 4) GIDLSIYAMG

[0136] SEQ ID NO: 64 (HCDR2 of rabbit-derived IL-19 Ab 4) IIDTTGTAYYARWAKG

[0137] SEQ ID NO: 65 (HCDR3 of rabbit-derived IL-19 Ab 4) DSGSLYYGSYAL

[0138] SEQ ID NO: 66 (LCVR of phage-derived IL-19 Ab 1 (“P_1”)) EIVMTQSPGTLSLSPGERATLSCRASQSISSGYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFATYYCLQFKSFPLTFGQGTKLEIKR

[0139] SEQ ID NO: 67 (LCDR1 of phage-derived IL-19 Ab 1) RASQSISSGYLA

[0140] SEQ ID NO: 68 (LCDR2 of phage-derived IL-19 Ab 1) GASSRAT

[0141] SEQ ID NO: 69 (LCDR3 of phage-derived IL-19 Ab 1) LQFKSFPLT

[0142] SEQ ID NO: 70 (HCVR of phage-derived IL-19 Ab 1 (“P_1”)) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDGGDYGDMGYWGQGTLVTVSS

[0143] SEQ ID NO: 71 (HCDR1 of phage-derived IL-19 Ab 1) GGTFSSYAIS

[0144] SEQ ID NO: 72 (HCDR2 of phage-derived IL-19 Ab 1) GIIPIFGTANYAQKFQG

[0145] SEQ ID NO: 73 (HCDR3 of phage-derived IL-19 Ab 1) DGGDYGDMGY

[0146] SEQ ID NO: 74 (LCVR of phage-derived IL-19 Ab 2 (“P_2”)) EIVMTQSPDSLAVSLGERATINCKSSQSVLYRSNSKSYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPGSFGPGTKVEIKR

[0147] SEQ ID NO: 75 (LCDR1 of phage-derived IL-19 Ab 2) KSSQSVLYRSNSKSYLA

[0148] SEQ ID NO: 76 (LCDR2 of phage-derived IL-19 Ab 2) WASTRES

[0149] SEQ ID NO: 77 (LCDR3 of phage-derived IL-19 Ab 2) QQYYSTPGS

[0150] SEQ ID NO: 78 (HCVR of phage-derived IL-19 Ab 2 ("P_2")) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISQSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHPERGSRRGPYYYYMDVWGKGTTVTVSS

[0151] SEQ ID NO: 79 (HCDR1 of phage-derived IL-19 Ab 2) GFTFSSYAMS

[0152] SEQ ID NO: 80 (HCDR2 of phage-derived IL-19 Ab 2) AISQSGGSTYYADSVKG

[0153] SEQ ID NO: 81 (HCDR3 of phage-derived IL-19 Ab 2) HPERGSRRGPYYYYMDV

[0154] SEQ ID NO: 82 (LCVR of phage-derived IL-19 Ab 3 (“P_3”)) DIQLTQSPSSLSASLGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQYYDYSPWAFGQGTKLEIKR

[0155] SEQ ID NO: 83 (LCDR1 of phage-derived IL-19 Ab 3) RASQGISSWLA

[0156] SEQ ID NO: 84 (LCDR2 of phage-derived IL-19 Ab 3) AASTLQS

[0157] SEQ ID NO: 85 (LCDR3 of phage-derived IL-19 Ab 3) QQYYDYSPWA

[0158] SEQ ID NO: 86 (HCVR of phage-derived IL-19 Ab 3 (“P_3”)) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGLSLLYYDLSENYFDYWGQ GTTVTVSS

[0159] SEQ ID NO: 87 (HCDR1 of phage-derived IL-19 Ab 3) GFTFSSYAMS

[0160] SEQ ID NO: 88 (HCDR2 of phage-derived IL-19 Ab 3) AISGSGGSTYYADSVKG

[0161] SEQ ID NO: 89 (HCDR3 of phage-derived IL-19 Ab 3) GLSLLYYDLSENYFDY

[0162] SEQ ID NO: 90 (LCDR1 of rabbit-derived IL-19 Ab 5) QASQSIYSYLS

[0163] SEQ ID NO: 91 (LCDR2 of rabbit-derived IL-19 Ab 5) EASKLAS

[0164] SEQ ID NO: 92 (LCDR3 of rabbit-derived IL-19 Ab 5) QQGYSSSNVDNT

[0165] SEQ ID NO: 93 (HCDR1 of rabbit-derived IL-19 Ab 5) GIDLSIYAMG

[0166] SEQ ID NO: 94 (HCDR2 of rabbit-derived IL-19 Ab 5) IIDTTGTAYYARWAKG

[0167] SEQ ID NO: 95 (HCDR3 of rabbit-derived IL-19 Ab 5) DSGSLYYGSYAL

[0168] SEQ ID NO: 96 (LCDR1 of rabbit-derived IL-19 Ab 6) QASESIYSSLA

[0169] SEQ ID NO: 97 (LCDR2 of rabbit-derived IL-19 Ab 6) GASTLAS

[0170] SEQ ID NO: 98 (LCDR3 of rabbit-derived IL-19 Ab 6) QCHYHGSSYWDNS

[0171] SEQ ID NO: 99 (HCDR1 of rabbit-derived IL-19 Ab 6) GFSFSSSYWIC

[0172] SEQ ID NO: 100 (HCDR2 of rabbit-derived IL-19 Ab 6) CTDTFSGDTYYASWAKG

[0173] SEQ ID NO: 101 (HCDR3 of rabbit-derived IL-19 Ab 6) DIFGTAVHISL

[0174] SEQ ID NO: 102 (LCDR1 of rabbit-derived IL-19 Ab 7) QASESIYSSLA

[0175] SEQ ID NO: 103 (LCDR2 of rabbit-derived IL-19 Ab 7) GASTLAS

[0176] SEQ ID NO: 104 (LCDR3 of rabbit-derived IL-19 Ab 7) QCHYHGSSYWDNS

[0177] SEQ ID NO: 105 (HCDR1 of rabbit-derived IL-19 Ab 7) GFSFSSSYWIC

[0178] SEQ ID NO: 106 (HCDR2 of rabbit-derived IL-19 Ab 7) CTDTFSGDTYYASWAKG

[0179] SEQ ID NO: 107 (HCDR3 of rabbit-derived IL-19 Ab 7) DIFGTAVHISL

[0180] SEQ ID NO: 108 (LCDR1 of rabbit-derived IL-19 Ab 8) QASQSIGSSLA

[0181] SEQ ID NO: 109 (LCDR2 of rabbit-derived IL-19 Ab 8) GASTLAS

[0182] SEQ ID NO: 110 (LCDR3 of rabbit-derived IL-19 Ab 8) QCHYHGSSYWDNS

[0183] SEQ ID NO: 111 (HCDR1 of rabbit-derived IL-19 Ab 8) GFSFSSSYWIC

[0184] SEQ ID NO: 112 (HCDR2 of rabbit-derived IL-19 Ab 8) CTDTFSGDTYYASWAKG

[0185] SEQ ID NO: 113 (HCDR3 of rabbit-derived IL-19 Ab 8) DIFGTAVHISL

[0186] SEQ ID NO: 114 (LCDR1 of rabbit-derived IL-19 Ab 9) QASESIYSSLA

[0187] SEQ ID NO: 115 (LCDR2 of rabbit-derived IL-19 Ab 9) GASTLAS

[0188] SEQ ID NO: 116 (LCDR3 of rabbit-derived IL-19 Ab 9) QCHYHGSSYWDNS

[0189] SEQ ID NO: 117 (HCDR1 of rabbit-derived IL-19 Ab 9) GFSFSSSYWIC

[0190] SEQ ID NO: 118 (HCDR2 of rabbit-derived IL-19 Ab 9) CTDTFSGDTYYASWAKG

[0191] SEQ ID NO: 119 (HCDR3 of rabbit-derived IL-19 Ab 9) DIFGTAVHISL

[0192] SEQ ID NO: 120 (LCDR1 of rabbit-derived IL-19 Ab 10) QASQSISSYLA

[0193] SEQ ID NO: 121 (LCDR2 of rabbit-derived IL-19 Ab 10) GASTLAS

[0194] SEQ ID NO: 122 (LCDR3 of rabbit-derived IL-19 Ab 10) QCHYHGSSYWDNS

[0195] SEQ ID NO: 123 (HCDR1 of rabbit-derived IL-19 Ab 10) GFSFSSSYWIC

[0196] SEQ ID NO: 124 (HCDR2 of rabbit-derived IL-19 Ab 10) CTDTFSGDTYYASWAKG

[0197] SEQ ID NO: 125 (HCDR3 of rabbit-derived IL-19 Ab 10) DIFGTAVHISL

[0198] SEQ ID NO: 126 (LCDR1 of rabbit-derived IL-19 Ab 11) QASQSISSYLA

[0199] SEQ ID NO: 127 (LCDR2 of rabbit-derived IL-19 Ab 11) GASTLAS

[0200] SEQ ID NO: 128 (LCDR3 of rabbit-derived IL-19 Ab 11) QSAVYSSSSGYGVP

[0201] SEQ ID NO: 129 (HCDR1 of rabbit-derived IL-19 Ab 11) GFSLSSYDMS

[0202] SEQ ID NO: 130 (HCDR2 of rabbit-derived IL-19 Ab 11) IIDSIGSIWYANWAKG

[0203] SEQ ID NO: 131 (HCDR3 of rabbit-derived IL-19 Ab 11) ESGPINTDYDL

[0204] SEQ ID NO: 132 (LCDR1 of rabbit-derived IL-19 Ab 12) QTSESFYSNNILS

[0205] SEQ ID NO: 133 (LCDR2 of rabbit-derived IL-19 Ab 12) EASKLAS

[0206] SEQ ID NO: 134 (LCDR3 of rabbit-derived IL-19 Ab 12) QSAIYDGSYIVT

[0207] SEQ ID NO: 135 (HCDR1 of rabbit-derived IL-19 Ab 12) GFSLSSYDMS

[0208] SEQ ID NO: 136 (HCDR2 of rabbit-derived IL-19 Ab 12) IIDSIGSIWYANWAKG

[0209] SEQ ID NO: 137 (HCDR3 of rabbit-derived IL-19 Ab 12) ESGPINTDYDL

[0210] SEQ ID NO: 138 (LCDR1 of rabbit-derived IL-19 Ab 13) QASQSISSYLA

[0211] SEQ ID NO: 139 (LCDR2 of rabbit-derived IL-19 Ab 13) GASTLAS

[0212] SEQ ID NO: 140 (LCDR3 of rabbit-derived IL-19 Ab 13) QSAVYSSSSGYGVP

[0213] SEQ ID NO: 141 (HCDR1 of rabbit-derived IL-19 Ab 13) GFSLSSYDMS

[0214] SEQ ID NO: 142 (HCDR2 of rabbit-derived IL-19 Ab 13) IIDSIGSIWYANWAKG

[0215] SEQ ID NO: 143 (HCDR3 of rabbit-derived IL-19 Ab 13) ESGPINTDYDL

[0216] SEQ ID NO: 144 (LCDR1 of rabbit-derived IL-19 Ab 14) QASQSISSYLA

[0217] SEQ ID NO: 145 (LCDR2 of rabbit-derived IL-19 Ab 14) GASTLAS

[0218] SEQ ID NO: 146 (LCDR3 of rabbit-derived IL-19 Ab 14) QSAVYSSSSGYGVP

[0219] SEQ ID NO: 147 (HCDR1 of rabbit-derived IL-19 Ab 14) GFSLSSYDMS

[0220] SEQ ID NO: 148 (HCDR2 of rabbit-derived IL-19 Ab 14) IIDSIGSIWYANWAKG

[0221] SEQ ID NO: 149 (HCDR3 of rabbit-derived IL-19 Ab 14) ESGPINTDYDL

[0222] SEQ ID NO: 150 (LCDR1 of rabbit-derived IL-19 Ab 15) QASESISSYLA

[0223] SEQ ID NO: 151 (LCDR2 of rabbit-derived IL-19 Ab 15) GASTLAS

[0224] SEQ ID NO: 152 (LCDR3 of rabbit-derived IL-19 Ab 15) QGYFGDYIYG

[0225] SEQ ID NO: 153 (HCDR1 of rabbit-derived IL-19 Ab 15) GFSLTSYAMS

[0226] SEQ ID NO: 154 (HCDR2 of rabbit-derived IL-19 Ab 15) IIGSPGTTGYATWAKG

[0227] SEQ ID NO: 155 (HCDR3 of rabbit-derived IL-19 Ab 15) GWFYYGMAL

[0228] SEQ ID NO: 156 (LCDR1 of rabbit-derived IL-19 Ab 16) PXQEHLTP

[0229] SEQ ID NO: 157 (LCDR2 of rabbit-derived IL-19 Ab 16) GASTLAX

[0230] SEQ ID NO: 158 (LCDR3 of rabbit-derived IL-19 Ab 16) QGYFGDYIYG

[0231] SEQ ID NO: 159 (HCDR1 of rabbit-derived IL-19 Ab 16) GFSLTSYAMS

[0232] SEQ ID NO: 160 (HCDR2 of rabbit-derived IL-19 Ab 16) IIGSPGTTGYATWAKG

[0233] SEQ ID NO: 161 (HCDR3 of rabbit-derived IL-19 Ab 16) GWFYYGMAL

[0234] SEQ ID NO: 162 (LCDR1 of rabbit-derived IL-19 Ab 17) QASESISSYLA

[0235] SEQ ID NO: 163 (LCDR2 of rabbit-derived IL-19 Ab 17) GASTLAS

[0236] SEQ ID NO: 164 (LCDR3 of rabbit-derived IL-19 Ab 17) QGYFGDYIYG

[0237] SEQ ID NO: 165 (HCDR1 of rabbit-derived IL-19 Ab 17) GFSLTSYAMS

[0238] SEQ ID NO: 166 (HCDR2 of rabbit-derived IL-19 Ab 17) IIGSPGTTGYATWAKG

[0239] SEQ ID NO: 167 (HCDR3 of rabbit-derived IL-19 Ab 17) GWFYYGMAL SEQ ID NO: 168 (LCDR1 of rabbit-derived IL-19 Ab 18) QASESISSYLA

[0240] SEQ ID NO: 169 (LCDR2 of rabbit-derived IL-19 Ab 18) GASTLAS

[0241] SEQ ID NO: 170 (LCDR3 of rabbit-derived IL-19 Ab 18) QGYFGDYIYG

[0242] SEQ ID NO: 171 (HCDR1 of rabbit-derived IL-19 Ab 18) GFSLTSYAMS

[0243] SEQ ID NO: 172 (HCDR2 of rabbit-derived IL-19 Ab 18) IIGSPGTTGYATWAKG

[0244] SEQ ID NO: 173 (HCDR3 of rabbit-derived IL-19 Ab 18) GWFYYGMAL

[0245] SEQ ID NO: 174 (LCDR1 of rabbit-derived IL-19 Ab 19) QASESISSYLA

[0246] SEQ ID NO: 175 (LCDR2 of rabbit-derived IL-19 Ab 19) GASTLAS

[0247] SEQ ID NO: 176 (LCDR3 of rabbit-derived IL-19 Ab 19) QGYFGDYIYG

[0248] SEQ ID NO: 177 (HCDR1 of rabbit-derived IL-19 Ab 19) GFSLTSYAMS

[0249] SEQ ID NO: 178 (HCDR2 of rabbit-derived IL-19 Ab 19) IIGSPGTTGYATWAKG

[0250] SEQ ID NO: 179 (HCDR3 of rabbit-derived IL-19 Ab 19) GWFYYGMAL

[0251] SEQ ID NO: 180 (LCDR1 of rabbit-derived IL-19 Ab 20) QASESISSYLA

[0252] SEQ ID NO: 181 (LCDR2 of rabbit-derived IL-19 Ab 20) GASTLAS

[0253] SEQ ID NO: 182 (LCDR3 of rabbit-derived IL-19 Ab 20) QGYFGDYIYG

[0254] SEQ ID NO: 183 (HCDR1 of rabbit-derived IL-19 Ab 20) GFSLTSYAMS

[0255] SEQ ID NO: 184 (HCDR2 of rabbit-derived IL-19 Ab 20) IIGSPGTTGYATWAKG

[0256] SEQ ID NO: 185 (HCDR3 of rabbit-derived IL-19 Ab 20) GWFYYGMAL

[0257] SEQ ID NO: 186 (LCDR1 of rabbit-derived IL-19 Ab 21) QASQSISNYLS

[0258] SEQ ID NO: 187 (LCDR2 of rabbit-derived IL-19 Ab 21) WASNLAS

[0259] SEQ ID NO: 188 (LCDR3 of rabbit-derived IL-19 Ab 21) LGEFSCSSADCFA

[0260] SEQ ID NO: 189 (HCDR1 of rabbit-derived IL-19 Ab 21) GFDLSNYAMT

[0261] SEQ ID NO: 190 (HCDR2 of rabbit-derived IL-19 Ab 21) AIHGSGVTDCASWTRG

[0262] SEQ ID NO: 191 (HCDR3 of rabbit-derived IL-19 Ab 21) ESAGINTDYDL

[0263] SEQ ID NO: 192 (LCDR1 of rabbit-derived IL-19 Ab 22) QASQSISNYLS

[0264] SEQ ID NO: 193 (LCDR2 of rabbit-derived IL-19 Ab 22) WASNLAS

[0265] SEQ ID NO: 194 (LCDR3 of rabbit-derived IL-19 Ab 22) LGEFSCSSADCFA

[0266] SEQ ID NO: 195 (HCDR1 of rabbit-derived IL-19 Ab 22) GFDLSNYAMT

[0267] SEQ ID NO: 196 (HCDR2 of rabbit-derived IL-19 Ab 22) AIHGSGVTDCASWTRG

[0268] SEQ ID NO: 197 (HCDR3 of rabbit-derived IL-19 Ab 22) ESAGINTDYDL

[0269] SEQ ID NO: 198 (LCDR1 of rabbit-derived IL-19 Ab 23) QASKSIGSYLS

[0270] SEQ ID NO: 199 (LCDR2 of rabbit-derived IL-19 Ab 23) RASTLAS

[0271] SEQ ID NO: 200 (LCDR3 of rabbit-derived IL-19 Ab 23) QAYYGDYIYD

[0272] SEQ ID NO: 201 (HCDR1 of rabbit-derived IL-19 Ab 23) GFSLSSYPMS

[0273] SEQ ID NO: 202 (HCDR2 of rabbit-derived IL-19 Ab 23) IIGSTGSTGYANWAKG

[0274] SEQ ID NO: 203 (HCDR3 of rabbit-derived IL-19 Ab 23) GWFYYGLDL

[0275] SEQ ID NO: 204 (LCDR1 of rabbit-derived IL-19 Ab 24) QASQSIGSYLS

[0276] SEQ ID NO: 205 (LCDR2 of rabbit-derived IL-19 Ab 24) RASTLAS

[0277] SEQ ID NO: 206 (LCDR3 of rabbit-derived IL-19 Ab 24) QAYYGDYIYD

[0278] SEQ ID NO: 207 (HCDR1 of rabbit-derived IL-19 Ab 24) GFSLSSYPMS

[0279] SEQ ID NO: 208 (HCDR2 of rabbit-derived IL-19 Ab 24) IIGSTGSTGYANWAKG

[0280] SEQ ID NO: 209 (HCDR3 of rabbit-derived IL-19 Ab 24) GWFYYGLDL

[0281] SEQ ID NO: 210 (LCDR1 of rabbit-derived IL-19 Ab 25) QASQSIGSYLA

[0282] SEQ ID NO: 211 (LCDR2 of rabbit-derived IL-19 Ab 25) DASDLAS

[0283] SEQ ID NO: 212 (LCDR3 of rabbit-derived IL-19 Ab 25) QSAVYDSSYVVT

[0284] SEQ ID NO: 213 (HCDR1 of rabbit-derived IL-19 Ab 25) GFSLSSYDMS

[0285] SEQ ID NO: 214 (HCDR2 of rabbit-derived IL-19 Ab 25) ISDSLGTTWYANWAKG

[0286] SEQ ID NO: 215 (HCDR3 of rabbit-derived IL-19 Ab 25) ESGDIRIDYDL

[0287] SEQ ID NO: 216 (LCDR1 of rabbit-derived IL-19 Ab 26) QASQSIGSYLA

[0288] SEQ ID NO: 217 (LCDR2 of rabbit-derived IL-19 Ab 26) DASDLAS

[0289] SEQ ID NO: 218 (LCDR3 of rabbit-derived IL-19 Ab 26) QSAVYDSSYVVT

[0290] SEQ ID NO: 219 (HCDR1 of rabbit-derived IL-19 Ab 26) GFSLSSYDMS

[0291] SEQ ID NO: 220 (HCDR2 of rabbit-derived IL-19 Ab 26) ISDSLGTTWYANWAKG

[0292] SEQ ID NO: 221 (HCDR3 of rabbit-derived IL-19 Ab 26) ESGDIRIDYDL

[0293] SEQ ID NO: 222 (LCDR1 of rabbit-derived IL-19 Ab 27) QASQSIGSYLA

[0294] SEQ ID NO: 223 (LCDR2 of rabbit-derived IL-19 Ab 27) DASDLAS

[0295] SEQ ID NO: 224 (LCDR3 of rabbit-derived IL-19 Ab 27) QSAVYDSSYVVT

[0296] SEQ ID NO: 225 (HCDR1 of rabbit-derived IL-19 Ab 27) GFSLSSYDMS

[0297] SEQ ID NO: 226 (HCDR2 of rabbit-derived IL-19 Ab 27) ISDSLGTTWYANWAKG

[0298] SEQ ID NO: 227 (HCDR3 of rabbit-derived IL-19 Ab 27) ESGDIRIDYDL

[0299] SEQ ID NO: 228 (LCDR1 of rabbit-derived IL-19 Ab 28) QASQSIGSYLA

[0300] SEQ ID NO: 229 (LCDR2 of rabbit-derived IL-19 Ab 28) DASDLAS

[0301] SEQ ID NO: 230 (LCDR3 of rabbit-derived IL-19 Ab 28) QSAVYDSSYVVT

[0302] SEQ ID NO: 231 (HCDR1 of rabbit-derived IL-19 Ab 28) GFSLSSYDMS

[0303] SEQ ID NO: 232 (HCDR2 of rabbit-derived IL-19 Ab 28) ISDSLGTTWYANWAKG

[0304] SEQ ID NO: 233 (HCDR3 of rabbit-derived IL-19 Ab 28) ESGDIRIDYDL

[0305] SEQ ID NO: 234 (LCDR1 of rabbit-derived IL-19 Ab 29) QASQSLNINYLS

[0306] SEQ ID NO: 235 (LCDR2 of rabbit-derived IL-19 Ab 29) SASTLAS

[0307] SEQ ID NO: 236 (LCDR3 of rabbit-derived IL-19 Ab 29) QQSVNYGRVDNI

[0308] SEQ ID NO: 237 (HCDR1 of rabbit-derived IL-19 Ab 29) GFTISNYHMS

[0309] SEQ ID NO: 238 (HCDR2 of rabbit-derived IL-19 Ab 29) RIVSYGGTYYANWAKG

[0310] SEQ ID NO: 239 (HCDR3 of rabbit-derived IL-19 Ab 29) DSSGSGFSFAL

[0311] SEQ ID NO: 240 (LCDR1 of rabbit-derived IL-19 Ab 30) QASQSITTSYLS

[0312] SEQ ID NO: 241 (LCDR2 of rabbit-derived IL-19 Ab 30) KASTLAS

[0313] SEQ ID NO: 242 (LCDR3 of rabbit-derived IL-19 Ab 30) QQSHNYGRVDNI

[0314] SEQ ID NO: 243 (HCDR1 of rabbit-derived IL-19 Ab 30) GFTISNYHMS

[0315] SEQ ID NO: 244 (HCDR2 of rabbit-derived IL-19 Ab 30) RIVSYGGTYYANWAKG

[0316] SEQ ID NO: 245 (HCDR3 of rabbit-derived IL-19 Ab 30) DSSGSGFSFAL

[0317] SEQ ID NO: 246 (LCDR1 of rabbit-derived IL-19 Ab 31) QASQSITTSYLS

[0318] SEQ ID NO: 247 (LCDR2 of rabbit-derived IL-19 Ab 31) KASTLAS

[0319] SEQ ID NO: 248 (LCDR3 of rabbit-derived IL-19 Ab 31) QQSHNYGRVDNI

[0320] SEQ ID NO: 249 (HCDR1 of rabbit-derived IL-19 Ab 31) GFTISNYHMS

[0321] SEQ ID NO: 250 (HCDR2 of rabbit-derived IL-19 Ab 31) RIVSYGGTYYANWAKG

[0322] SEQ ID NO: 251 (HCDR3 of rabbit-derived IL-19 Ab 31) DSSGSGFSFAL

[0323] SEQ ID NO: 252 (LCDR1 of rabbit-derived IL-19 Ab 32) QASQSITTSYLS

[0324] SEQ ID NO: 253 (LCDR2 of rabbit-derived IL-19 Ab 32) KASTLAS

[0325] SEQ ID NO: 254 (LCDR3 of rabbit-derived IL-19 Ab 32) QQSHNYGRVDNI

[0326] SEQ ID NO: 255 (HCDR1 of rabbit-derived IL-19 Ab 32) GFTISNYHMS

[0327] SEQ ID NO: 256 (HCDR2 of rabbit-derived IL-19 Ab 32) RIVSYGGTYYANWAKG

[0328] SEQ ID NO: 257 (HCDR3 of rabbit-derived IL-19 Ab 32) DSSGSGFSFAL

[0329] SEQ ID NO: 258 (LCDR1 of rabbit-derived IL-19 Ab 33) QASQSITTSYLS

[0330] SEQ ID NO: 259 (LCDR2 of rabbit-derived IL-19 Ab 33) KASTLAS

[0331] SEQ ID NO: 260 (LCDR3 of rabbit-derived IL-19 Ab 33) QQSHNYGRVDNI

[0332] SEQ ID NO: 261 (HCDR1 of rabbit-derived IL-19 Ab 33) GFTISNYHMS

[0333] SEQ ID NO: 262 (HCDR2 of rabbit-derived IL-19 Ab 33) RIVSYGGTYYANWAKG

[0334] SEQ ID NO: 263 (HCDR3 of rabbit-derived IL-19 Ab 33) DSSGSGFSFAL

[0335] SEQ ID NO: 264 (LCDR1 of rabbit-derived IL-19 Ab 34) QASQNIYSNLA

[0336] SEQ ID NO: 265 (LCDR2 of rabbit-derived IL-19 Ab 34) KASTLAS

[0337] SEQ ID NO: 266 (LCDR3 of rabbit-derived IL-19 Ab 34) QAYVGNYIYT

[0338] SEQ ID NO: 267 (HCDR1 of rabbit-derived IL-19 Ab 34) GFSLSSYPMS

[0339] SEQ ID NO: 268 (HCDR2 of rabbit-derived IL-19 Ab 34) IIGSSGSIGYASWAKG

[0340] SEQ ID NO: 269 (HCDR3 of rabbit-derived IL-19 Ab 34) GWFYYGMDL

[0341] SEQ ID NO: 270 (LCDR1 of rabbit-derived IL-19 Ab 35) QASQSIGSNLA

[0342] SEQ ID NO: 271 (LCDR2 of rabbit-derived IL-19 Ab 35) RASTLAS

[0343] SEQ ID NO: 272 (LCDR3 of rabbit-derived IL-19 Ab 35) QGYYGDGIYG

[0344] SEQ ID NO: 273 (HCDR1 of rabbit-derived IL-19 Ab 35) GFSLSSYPMS

[0345] SEQ ID NO: 274 (HCDR2 of rabbit-derived IL-19 Ab 35) LIGSSGTIYFATWAKG

[0346] SEQ ID NO: 275 (HCDR3 of rabbit-derived IL-19 Ab 35) GWFYYGMDL

[0347] SEQ ID NO: 276 (LCDR1 of rabbit-derived IL-19 Ab 36) QASQSISSWLS

[0348] SEQ ID NO: 277 (LCDR2 of rabbit-derived IL-19 Ab 36) GASTLAS

[0349] SEQ ID NO: 278 (LCDR3 of rabbit-derived IL-19 Ab 36) QSYYYISSSSYT

[0350] SEQ ID NO: 279 (HCDR1 of rabbit-derived IL-19 Ab 36) GFSLSSYPMS

[0351] SEQ ID NO: 280 (HCDR2 of rabbit-derived IL-19 Ab 36) LIGSSGTIYFATWAKG

[0352] SEQ ID NO: 281 (HCDR3 of rabbit-derived IL-19 Ab 36) GWFYYGMDL

[0353] SEQ ID NO: 282 (LCDR1 of rabbit-derived IL-19 Ab 37) QASQSISSYLA

[0354] SEQ ID NO: 283 (LCDR2 of rabbit-derived IL-19 Ab 37) SASTLAS

[0355] SEQ ID NO: 284 (LCDR3 of rabbit-derived IL-19 Ab 37) QCHYHGSSYWDNS

[0356] SEQ ID NO: 285 (HCDR1 of rabbit-derived IL-19 Ab 37) GFSFSSSYWIC

[0357] SEQ ID NO: 286 (HCDR2 of rabbit-derived IL-19 Ab 37) CIDTGVSGDTYYANWAEG

[0358] SEQ ID NO: 287 (HCDR3 of rabbit-derived IL-19 Ab 37) DIFGSAIDNSL

[0359] SEQ ID NO: 288 (LCDR1 of rabbit-derived IL-19 Ab 38) QASQNIYSNLA

[0360] SEQ ID NO: 289 (LCDR2 of rabbit-derived IL-19 Ab 38) GASNLES

[0361] SEQ ID NO: 290 (LCDR3 of rabbit-derived IL-19 Ab 38) QGGYSGGIYA

[0362] SEQ ID NO: 291 (HCDR1 of rabbit-derived IL-19 Ab 38) GFSLTRHAMS

[0363] SEQ ID NO: 292 (HCDR2 of rabbit-derived IL-19 Ab 38) AIHGSGVTDYASWAKG

[0364] SEQ ID NO: 293 (HCDR3 of rabbit-derived IL-19 Ab 38) GSGL

[0365] SEQ ID NO: 294 (LCVR of rabbit-derived IL-19 Ab 39 ("R_39")) DIVMTQTPASVEAAVGGTVTIKCQASQSIYRYLSWYQQKPGQRPKLLIYGASNLASGVSSRFKGSGSGTEFTLTISDLECADAATYYCQSYYYSSSSGYGNVFGGGTEVVVK

[0366] SEQ ID NO: 295 (LCDR1 of rabbit-derived IL-19 Ab 39) QASQSIYRYLS

[0367] SEQ ID NO: 296 (LCDR2 of rabbit-derived IL-19 Ab 39) GASNLAS

[0368] SEQ ID NO: 297 (LCDR3 of rabbit-derived IL-19 Ab 39) QSYYYSSSSGYGNV

[0369] SEQ ID NO: 298 (HCVR of rabbit-derived IL-19 Ab 39 ("R_39")) QEQLKESGGGLVQPGGSLKLSCKASGFDLSSYGVSWVRQAPGKGLEWIGYIDPVFGSTYYANWVNGRFTISSDNAQNTLYLQLNSLTAADTATYFCARGSGYVYYGYTYDLWGPGTLVTVSS

[0370] SEQ ID NO: 299 (HCDR1 of rabbit-derived IL-19 Ab 39) GFDLSSYGVS

[0371] SEQ ID NO: 300 (HCDR2 of rabbit-derived IL-19 Ab 39) YIDPVFGSTYYANWVNG

[0372] SEQ ID NO: 301 (HCDR3 of rabbit-derived IL-19 Ab 39) GSGYVYYGYTYDL

[0373] SEQ ID NO: 302 (LCVR of murine-derived IL-19 Ab 5 ("M_5")) DIVMTQSPSSLAMSVGQKVTMSCKSSQSLLSSYNQKNYLAWYQRKPGQSPKLLVYFASQRATGVPDRFIGSGSGSDFTLTISSVQAEDLADYFCQQHTRLPITFGAGTKLELK

[0374] SEQ ID NO: 303 (LCDR1 of murine IL-19 Ab 5) KSSQSLLSSYNQKNYLA

[0375] SEQ ID NO: 304 (LCDR2 of murine IL-19 Ab 5) FASQRAT

[0376] SEQ ID NO: 305 (LCDR3 of murine IL-19 Ab 5) QQHTRLPIT

[0377] SEQ ID NO: 306 (HCVR of murine-derived IL-19 Ab 5 ("M_5")) EVQLQQSGPVLVKPGASVKMSCKASGYPFNDYFLGWVKQSHGKSLEWIGSINPDNDYTMSNQKFKGKATLTVDKSSSTAYMELNSLTSEDSAVYYCARYDYDWAWFAHWGQGTLVTVSA

[0378] SEQ ID NO: 307 (HCDR1 of mouse-derived IL-19 Ab 5) GYPFNDYFLG

[0379] SEQ ID NO: 308 (HCDR2 of mouse-derived IL-19 Ab 5) SINPDNDYTMSNQKFKG

[0380] SEQ ID NO: 309 (HCDR3 of mouse-derived IL-19 Ab 5) YDYDWAWFAH

[0381] SEQ ID NO: 310 (LC of rabbit-derived IL-19 Ab 39 ("R_39")) DIVMTQTPASVEAAVGGTVTIKCQASQSIYRYLSWYQQKPGQRPKLLIYGASNLASGVSSRFKGSGSGTEFTLTISDLECADAATYYCQSYYYSSSSGYGNVFGGGTE VVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC

[0382] SEQ ID NO: 311 (HC of rabbit-derived IL-19 Ab 39 ("R_39")) QEQLKESGGGLVQPGGSLKLSCKASGFDLSSYGVSWVRQAPGKGLEWIGYIDPVFGSTYYANWVNGRFTISSDNAQNTLYLQLNSLTAADTATYFCARGSGYVYYGYTYDL WGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTC SKPTCPPPELLGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKT ISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPAVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK

[0383] SEQ ID NO: 312 (LC of murine-derived IL-19 Ab 5 ("M_5")) DIVMTQSPSSLAMSVGQKVTMSCKSSQSLLSSYNQKNYLAWYQRKPGQSPKLLVYFASQRATGVPDRFIGSGSGSDFTLTISSVQAEDLADYFCQQHTRLPITFGAGTKLELKRADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

[0384] Sequence number 313 (HC of mouse-derived IL-19 Ab 5 (「M_5」)) EVQLQQSGPVLVKPGASVKMSCKASGYPFNDYFLGWVKQSHGKSLEWIGSINPDNDYTMSNQKFKGKATLTVDKSSSTAYMELNSLTSEDSAVYYCARYDYDWAWFAHWGQGTLVTVSAAKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVPSSTWPSETVTCNVAHPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK

Claims

1. 1. An antibody that binds to human IL-19, the antibody comprising a light chain variable region (LCVR) and a heavy chain variable region (HCVR), the LCVR comprising complementarity determining regions (CDRs), LCDR1, LCDR2, and LCDR3, and the HCVR comprising CDRs, HCDR1, HCDR2, which are a. a group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 provided in Table 1; b. a group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 provided in Table 2, or c. The group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 provided in Table 3 An antibody selected from the group consisting of

2. 1. An antibody that binds to human IL-19, the antibody comprising a light chain variable region (LCVR) and a heavy chain variable region (HCVR), the LCVR comprising complementarity determining regions (CDRs), LCDR1, LCDR2, and LCDR3, and the HCVR comprising CDRs, HCDR1, HCDR2, which are a. a group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 having at least 95% amino acid sequence homology to the amino acid sequence of the group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 provided in Table 1; b. a group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 that have at least 95% amino acid sequence homology to the amino acid sequence of the group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 provided in Table 2; or c. A group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 that have at least 95% amino acid sequence homology to the amino acid sequences of the group of LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 provided in Table 3. An antibody selected from the group consisting of

3. A light chain variable region (LCVR) and a heavy chain variable region (HCVR), which a. the LCVR having the amino acid sequence of SEQ ID NO:66 and the HCVR having the amino acid sequence of SEQ ID NO:70; b. the LCVR having the amino acid sequence of SEQ ID NO: 74 and the HCVR having the amino acid sequence of SEQ ID NO: 78; c. the LCVR having the amino acid sequence of SEQ ID NO: 82 and the HCVR having the amino acid sequence of SEQ ID NO: 86; d. the LCVR having the amino acid sequence of SEQ ID NO: 34 and the HCVR having the amino acid sequence of SEQ ID NO: 38; e. the LCVR having the amino acid sequence of SEQ ID NO: 42 and the HCVR having the amino acid sequence of SEQ ID NO: 46; f. the LCVR having the amino acid sequence of SEQ ID NO:50 and the HCVR having the amino acid sequence of SEQ ID NO:54; g. the LCVR having the amino acid sequence of SEQ ID NO:58 and the HCVR having the amino acid sequence of SEQ ID NO:62; h. the LCVR having the amino acid sequence of SEQ ID NO:294 and the HCVR having the amino acid sequence of SEQ ID NO:298; and i. the LCVR having the amino acid sequence of SEQ ID NO: 302 and the HCVR having the amino acid sequence of SEQ ID NO: 306 The antibody of claim 1 or 2, selected from the group consisting of:

4. A light chain variable region (LCVR) and a heavy chain variable region (HCVR), which a. the LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO:66, and the HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO:70; b. the LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 74, and the HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 78; c. the LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 82, and the HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 86; d. the LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 34, and the HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 38; e. the LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 42, and the HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 46; f. the LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 50, and the HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 54; g. said LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO:58, and said HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO:62; h. the LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 294, and the HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 298; i. the LCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 302, and the HCVR having an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 306; The antibody according to claims 1 to 3, which is selected from the group consisting of

5. The antibody of any one of claims 1 to 4, further comprising an IgG1 heavy chain.

6. The antibody of any one of claims 1 to 5, further comprising a kappa light chain.

7. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 95-102 of human IL-19 as set forth in SEQ ID NO:

1.

8. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 90-100 of human IL-19 as set forth in SEQ ID NO:

1.

9. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 67-75 of human IL-19 as set forth in SEQ ID NO:

1.

10. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 125-136 of human IL-19 as set forth in SEQ ID NO:

1.

11. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 42-60 of human IL-19 as set forth in SEQ ID NO:

1.

12. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 90-107 of human IL-19 as set forth in SEQ ID NO:

1.

13. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 149-160 of human IL-19 as set forth in SEQ ID NO:

1.

14. The antibody according to any one of claims 7 to 13, wherein the epitope region is a linear epitope of human IL-19.

15. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 42-60, and residues 90-107, and residues 149-160 of human IL-19 as set forth in SEQ ID NO:

1.

16. An antibody that binds to human IL-19 within an epitope region comprising amino acids within residues 67-75 and 125-136 of human IL-19 as set forth in SEQ ID NO:

1.

17. The antibody of any one of claims 7 to 16, wherein the antibody neutralizes human IL-19 activity.

18. The antibody has a titer of at least about 2.90 x 10 －９ The antibody of any one of claims 7 to 17, which binds to human IL-19 with an affinity of

19. A method for treating an immune-mediated disease, comprising administering to a patient in need thereof an effective amount of an antibody according to any one of claims 1 to 18.

20. 20. The method of claim 19, wherein the immune-mediated disease is one of Pso, AD, PsA, and nephropathy.

21. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 18 and one or more pharma- ceutically acceptable carriers, diluents or excipients.

22. 22. A method of treating an immune-mediated disease, comprising administering to a patient in need thereof the pharmaceutical composition of claim 21.

23. 23. The method of claim 22, wherein the immune-mediated disease is one of Pso, AD, PsA, and nephropathy.

24. The antibody according to any one of claims 1 to 18 for use in therapy.

25. The antibody according to any one of claims 1 to 18 for use in the treatment of an immune-mediated disease.

26. 26. The antibody of claim 25, wherein the immune-mediated disease is selected from the group consisting of Pso, AD, PsA, and nephropathy.

27. An antibody according to any one of claims 1 to 18 for use in the manufacture of a medicament for said treatment of an immune-mediated disease.

28. 28. The antibody of claim 27, wherein the immune-mediated disease is selected from the group consisting of Pso, AD, PsA, and nephropathy.

29. 1. A method for detecting IL-19 in a patient sample, comprising: contacting the patient sample with a first antibody, wherein the first antibody binds to a first epitope region of IL-19; contacting the patient sample with a second antibody, wherein the second antibody binds to a second epitope region of IL-19, and wherein the second antibody comprises a detectable label; detecting a signal provided by said detectable label.

30. 1. A method for quantifying IL-19 in a patient sample, comprising: contacting the patient sample with a first antibody, wherein the first antibody binds to a first epitope region of IL-19; contacting the patient sample with a second antibody, wherein the second antibody binds to a second epitope region of IL-19, and wherein the second antibody comprises a detectable label; detecting a signal provided by the detectable label of the second antibody contacted with the patient sample; contacting a control with a first antibody, said first antibody binding to the same first epitope region of IL-19 as used in contacting said patient sample; contacting the control with a second antibody comprising a detectable label, wherein the second antibody binds to the same second epitope region of IL-19 as that used in contacting the patient sample; detecting a signal provided by the detectable signal of the second antibody contacted with the patient sample.

31. 1. A method for diagnosing a patient as having, at risk for, in need of treatment for, or at risk for a condition associated with an immune-mediated disease, comprising: contacting the patient sample with a first antibody, wherein the first antibody binds to a first epitope region of IL-19; contacting the patient sample with a second antibody, wherein the second antibody binds to a second epitope region of IL-19, and wherein the second antibody comprises a detectable label; detecting a signal provided by the detectable label; and diagnosing the patient as having, at risk for, in need of treatment for, or at risk for a condition associated therewith, if the presence of IL-19 in the patient sample is detected above a reference level.

32. contacting a control with a first antibody, said first antibody binding to the same first epitope region of IL-19 as used in contacting said patient sample; contacting the control with a second antibody comprising a detectable label, wherein the second antibody binds to the same second epitope region of IL-19 as that used in contacting the patient sample; detecting the signal provided by the detectable signal, 32. The method of claim 31 , wherein the diagnostic step comprises a greater detectable signal from the second antibody contacted with the patient sample compared to the detectable signal from the second antibody contacted with the control standard.

33. 1. A method of treating one of Ps0, AD, PsA, or nephropathy in a patient, comprising: contacting the patient sample with a first antibody, wherein the first antibody binds to a first epitope region of IL-19; contacting the patient sample with a second antibody, wherein the second antibody binds to a second epitope region of IL-19, and wherein the second antibody comprises a detectable label; detecting a signal provided by the detectable label; treating the patient if the presence of IL-19 in the patient sample is detected above a reference level; The method, wherein said treating step comprises treating said patient with a therapeutic agent that targets at least one of TNFα, IL-17, IL-19, IL-23, or JAK.

34. contacting a control with a first antibody, said first antibody binding to the same first epitope region of IL-19 as used in contacting said patient sample; contacting the control with a second antibody comprising a detectable label, wherein the second antibody binds to the same second epitope region of IL-19 as that used in contacting the patient sample; detecting the signal provided by the detectable signal, 34. The method of claim 33, wherein the treatment step comprises a greater detectable signal from the second antibody contacted with the patient sample compared to the detectable signal from the second antibody contacted with the control.

35. The method of any of claims 29 to 34, wherein the patient sample is one of blood, plasma, or serum.

36. The method of any one of claims 29 to 35, wherein the first antibody is immobilized on a substrate.

37. The method of any of claims 29 to 36, wherein the first epitope region of IL-19 partially overlaps with the second epitope region of IL-19.

38. The method of any of claims 29 to 37, wherein the steps of contacting the patient sample with the first antibody and contacting the patient sample with the second antibody occur simultaneously.

39. The method according to any one of claims 29 to 38, wherein the first antibody is an antibody according to claims 1 to 18.

40. The method according to any of claims 29 to 39, wherein the second antibody is an antibody according to claims 1 to 18, with the proviso that it is not identical to the first antibody.

41. The first epitope region of IL-19 comprises amino acids within one of the following residues of human IL-19 set forth in SEQ ID NO: 1: 95-102; 90-100; 67-75; 125-136; 42-60; 90-107; 149-160; 67-75 and 125-136; or 42-60, 90-107 and 149-160; and the second epitope region of IL-19 comprises amino acids within one of the following residues of human IL-19 set forth in SEQ ID NO: 1:

41. The method of any of claims 29 to 40, wherein the epitope region comprises amino acids within a different one of the following residues of human IL-19 set forth in SEQ ID NO:1: 95-102; 90-100; 67-75; 125-136; 42-60; 90-107; 149-160; 67-75 and 125-136; or 42-60, 90-107 and 149-160.

42. 1. A method for diagnosing a patient as having, at risk for, in need of treatment for, or at risk for a condition associated with an immune-mediated disease, comprising: A method comprising the steps of contacting a patient sample with an antibody that binds to an epitope region of IL-19 and detecting binding between IL-19 in said patient sample and said antibody.

43. 43. The method of claim 42, wherein the patient sample is one of blood, plasma, or serum.

44. quantitating said IL-19 in said patient sample; The method of any of claims 42 or 43, further comprising the step of comparing the concentration of IL-19 in the patient sample with a reference value.

45. The method according to any one of claims 34 to 36, wherein the antibody is an antibody according to claims 1 to 11.

46. The method of any of claims 42-45, wherein the reference level is about 0.21 pg / mL.

47. 1. A method of treating one of Ps0, AD, PsA, or nephropathy, comprising: contacting a patient sample with an antibody that binds human IL-19 and detecting binding between IL-19 in the patient sample and the antibody; treating one of Ps0, AD, PsA, or nephropathy if the presence of IL-19 in the patient sample is detected above a reference level; The method, wherein said treating step comprises treating said patient with a therapeutic agent that targets one of TNFα, IL-17, IL-19, IL-23, or JAK.

48. 48. The method of claim 47, wherein the patient sample is one of blood, plasma, or serum.

49. The method according to any one of claims 47 or 48, wherein the antibody is an antibody according to claims 1 to 11.

50. 50. The method of any of claims 47-49, wherein the reference level is about 21 pg / mL.

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