Peptides used in immunotherapy drugs

Abstract

To provide a pharmaceutical composition for treating obesity. [Solution] A pharmaceutical composition for treating obesity is provided, comprising a peptide containing B-A1-T-A2 (formula A), where B is a B cell epitope consisting of the amino acid sequence RNVPPIFNDVYWIAF, A1 is a first auxiliary portion consisting of the amino acid sequence aZ, T is a T cell epitope consisting of the amino acid sequence K(Cha)VAAWTLKAA, and A2 is a second auxiliary portion consisting of 1 to 6 standard amino acids, where a represents D-type alanine, (Cha) represents L-cyclohexylalanine, and Z represents 6-aminohexanoic acid.

Description

[Technical Field]

[0001] This disclosure relates to a technology in the field of immunotherapeutic drugs, specifically a peptide that is injected into a subject's body to generate humoral immunity. [Background technology]

[0002] The purpose of immunotherapies is to induce humoral immunity against the immunotherapie itself when introduced into the target body, and to treat a specific disease or disorder with the antibodies produced as a result. In particular, "treatment" also includes the prevention of a specific disease or disorder. Immunotherapies are similar to vaccines in that they induce antibody production through an antigen-antibody reaction in the target body, but they differ from vaccines in that the antibodies not only have the ability to bind to the immunotherapie itself, but also to specific targets in the body (e.g., specific tissues and cells in the body, or substances produced in metabolic processes), thereby treating specific diseases and disorders and allowing for repeated administration. [Overview of the project] [Problems that the invention aims to solve]

[0003] [Disclosure]

[0004] This disclosure provides a peptide having the function of inducing pre-designed antibodies in the body of a target.

[0005] This disclosure provides compositions for immunotherapeutic drugs containing the peptide.

[0006] This disclosure provides nucleic acid sequences encoding the peptide.

[0007] This disclosure provides the use of the peptide and compositions for immunotherapeutic drugs containing the peptide. [Means for solving the problem]

[0008] According to one aspect of this disclosure, a peptide unit (peptide block) having a length of 23 to 71 mers and being recognized by CD4+ T cells to induce humoral immunity is provided, comprising the following: At least one Th epitope having a length of 8 mer to 32 mer; and At least one B cell epitope Here, the B cell epitope is a fragment or mimotope of apolipoprotein B-100, and the B cell epitope can induce an antibody that targets apolipoprotein B-100.

[0009] In one embodiment, the peptide unit has a length in the range of 26mer to 50mer, and the Th epitope has a length in the range of 11mer to 13mer.

[0010] In one embodiment, the peptide unit comprises one B cell epitope and one Th epitope, and the peptide unit has a length in the range of 26mer to 45mer.

[0011] In one embodiment, the peptide unit comprises one B cell epitope and two Th epitopes (referred to as the first Th epitope and the second Th epitope, respectively), the peptide unit has a length in the range of 37mer to 50mer, and the first Th epitope is linked between the B cell epitope and the second Th epitope.

[0012] In one embodiment, the peptide unit comprises two B cell epitopes (referred to as the first B cell epitope and the second B cell epitope, respectively) and one Th epitope, the peptide unit having a length in the range of 45mer to 50mer, and the second B cell epitope is linked between the first B cell epitope and the Th epitope.

[0013] In one embodiment, the peptide unit comprises two B cell epitopes (referred to as a first B cell epitope and a second B cell epitope, respectively) and one Th epitope, the peptide unit has a length ranging from 45 mer to 50 mer, and the Th epitope is linked between the first B cell epitope and the second B cell epitope.

[0014] The present disclosure provides a nucleic acid encoding a peptide unit, or a peptide that does not comprise non-standard amino acids among peptides.

[0015] The present disclosure provides a peptide in which two or more peptide units and five or less peptide units are linked.

[0016] The present disclosure provides a pharmaceutical composition for treating obesity, comprising a peptide unit or a peptide and an adjuvant.

[0017] The present disclosure provides a method for treating obesity, comprising the step of administering a pharmaceutical composition into the body of a subject.

[0018] The present disclosure provides use of a peptide unit or a peptide for treating obesity.

[0019] The present disclosure provides use of a peptide unit or a peptide for preparing a therapeutic agent for obesity.

[0020] Advantageous Effects of the Invention

[0021] When the peptide provided in the present disclosure is injected into the body of a subject, the peptide has the effect of inducing the production of antibodies having specific physiological functions that specifically bind to a pre-designed antigenic site. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] [Figure 1] FIG. is a graph showing the results of a peptide effect confirmation experiment according to Experimental Example 2, and shows measured values of body weight change for each week of age in each experimental group. [Figure 2] This figure shows the results of the peptide effect confirmation experiment according to Experimental Example 2, and is a graph showing measured values of body weight change by week of age for each experimental group. [Figure 3] This figure shows the results of the peptide effect confirmation experiment according to Experimental Example 2, and is a graph showing measured values of body weight change by week of age for each experimental group. [Figure 4] This figure shows the results of the peptide effect confirmation experiment according to Experimental Example 3, and is a graph showing measured body weight values by week of age of test subjects in each experimental group, wherein "lean" indicates a control group of standard weight, "obese" indicates an obesity group induced by a high-fat diet, "mock" indicates a placebo administration group, and 3H-OTP indicates group 2-1. [Figure 5] This figure shows the results of the peptide effect confirmation experiment according to Experimental Example 3, and is a graph showing measured antibody titer values observed in test subjects for each experimental group, wherein "obese" indicates an obesity group induced by a high-fat diet, "mock" indicates a placebo administration group, and 3H-OTP indicates group 2-1. [Figure 6] This figure shows the results of the peptide effect confirmation experiment according to Experimental Example 3, and is a graph showing measured values of the lipolytic capacity of hormone-sensitive lipase in adipocytes of test subjects for each experimental group, wherein "basal" indicates the case where norepinephrine was not administered, "hormone" indicates the case where norepinephrine was administered, "lean" indicates a control group of standard weight, "obese" indicates an obesity group induced by a high-fat diet, "mock" indicates a placebo administration group, and 3H-OTP indicates group 2-1 ((a) concentration of secreted glycerol per 105 adipocytes, (b) concentration of secreted glycerol per 1 g of adipocytes). [Figure 7] This figure shows the results of the peptide effect confirmation experiment according to Experimental Example 3, and is an image showing measured values of the size of adipocytes of test subjects for each experimental group, wherein "lean" indicates a control group of standard weight and "obese" indicates an obesity group induced by a high-fat diet (each shows a DAPI stained image, a LipidTOX stained image, and a merged image). [Figure 8]This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 3, and is an image showing the measured size of the adipocytes in the test subject for each experimental group (showing DAPI stained images of the nucleus and lipids of adipocytes in each experimental group). "Lean" represents the control group with normal body weight, "Obese" represents the obese group induced by a high-fat diet, "Mock" represents the placebo group, and "3H-OTP" represents group 2-1. [Figure 9] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 3. The graph shows the measured blood lipid concentrations of the test subjects for each experimental group, where TG represents triglycerides, NEFA represents unesterified fatty acids, CHOL represents cholesterol, HDL represents high-density lipoprotein, and LDL represents low-density lipoprotein. [Figure 10] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 4. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. "Underweight" represents the control group with normal body weight, "Obese" represents the obese group induced by a high-fat diet, "Mock" represents the placebo group, 3H-OTP 30μg represents group 3-2, and 3H-OTP 50g represents group 3-1. For reference, a graph for 3H-OTP-2W 50μg, representing group 2-1, is also shown. [Figure 11] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 4. The graph shows the measured antibody titers for each experimental group at different ages of the test subjects. "Lean" represents the control group with normal weight, "Obese" represents the obese group induced by a high-fat diet, "Mock" represents the placebo group, 3H-OTP 30μg represents group 3-2, and 3H-OTP 50g represents group 3-1. [Figure 12] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 5. The graph shows the measured weight of the test subjects at each week of age for each experimental group. "Underweight" represents the control group with normal weight, "Obese" represents the obese group induced by a high-fat diet, and 3H-OTP represents group 4-1. [Figure 13]This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 6. The graph compares the weight of the test subjects at each week of age, measured for each experimental group by age, with the weight at 11 weeks of age and shows the increase in weight at 16 weeks of age. Wild-type (+ / +)-underweight represents the control group with standard weight, wild-type (+ / +) represents group 5-1, heterozygous (+ / -) represents group 5-2, and homozygous (- / -) represents group 5-3. [Figure 14] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 15] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 16] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 17]This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 18] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 19] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 20] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 21]This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 22] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The graph shows the measured body weight of the test subjects at each week of age for each experimental group. Underweight represents the control group with normal body weight, and obese represents the obese group induced by a high-fat diet. P1 represents group 6-1, P2 represents group 6-2, P3 represents group 6-3, P4 represents group 6-4, P5 represents group 6-5, P6 represents group 6-6, P7 represents group 6-7, P8 represents group 6-8, and P9 represents group 6-9. [Figure 23] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The table lists the measured antibody titers for each experimental group at 11 weeks, 16 weeks, and 19 weeks of age. "Lean" indicates the control group with normal weight, and "Obese" indicates the obese group induced by a high-fat diet. P1 indicates group 6-1, P2 indicates group 6-2, P3 indicates group 6-3, P4 indicates group 6-4, P5 indicates group 6-5, P6 indicates group 6-6, P7 indicates group 6-7, P8 indicates group 6-8, and P9 indicates group 6-9. Furthermore, the values ​​identified by the label in the "No" column for each experimental group in each table indicate the experimental results for each individual subject in each experimental group. "ave" indicates the overall mean, "sd" indicates the overall standard deviation, and "se" indicates the overall standard error. [Figure 24]This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The table lists the measured antibody titers for each experimental group at 11 weeks, 16 weeks, and 19 weeks of age. "Lean" indicates the control group with normal weight, and "Obese" indicates the obese group induced by a high-fat diet. P1 indicates group 6-1, P2 indicates group 6-2, P3 indicates group 6-3, P4 indicates group 6-4, P5 indicates group 6-5, P6 indicates group 6-6, P7 indicates group 6-7, P8 indicates group 6-8, and P9 indicates group 6-9. Furthermore, the values ​​identified by the label in the "No" column for each experimental group in each table indicate the experimental results for each individual subject in each experimental group. "ave" indicates the overall mean, "sd" indicates the overall standard deviation, and "se" indicates the overall standard error. [Figure 25] This figure shows the results of the peptide effect confirmation experiment according to Experiment Example 7. The table lists the measured antibody titers for each experimental group at 11 weeks, 16 weeks, and 19 weeks of age. "Lean" indicates the control group with normal weight, and "Obese" indicates the obese group induced by a high-fat diet. P1 indicates group 6-1, P2 indicates group 6-2, P3 indicates group 6-3, P4 indicates group 6-4, P5 indicates group 6-5, P6 indicates group 6-6, P7 indicates group 6-7, P8 indicates group 6-8, and P9 indicates group 6-9. Furthermore, the values ​​identified by the label in the "No" column for each experimental group in each table indicate the experimental results for each individual subject in each experimental group. "ave" indicates the overall mean, "sd" indicates the overall standard deviation, and "se" indicates the overall standard error. [Modes for carrying out the invention]

[0023] The subject matter disclosed herein will be described in more detail below with reference to several specific embodiments and examples. It should be noted that the accompanying drawings encompass only some, and not all, embodiments of the disclosure. The subject matter disclosed herein can be embodied in many different forms and should not be construed as being limited to the specific embodiments described herein. Rather, these embodiments are provided to satisfy the legal requirements to which this disclosure applies. Indeed, many modifications and other embodiments of the disclosure will be conceivable to those skilled in the art to whom the subject matter of this disclosure relates. Therefore, it should be understood that the subject matter disclosed herein is not limited to the specific embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the accompanying claims.

[0024] Definitions of general terms.

[0025] about. As used herein, the term “about” means a quantity that is close to a given quantity, level, value, number, frequency, percentage, dimension, size, volume, weight, or length, and varies to a degree of 30%, 25%, 20%, 25%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% relative to a given quantity, level, value, number, frequency, percentage, dimension, size, volume, weight, or length.

[0026] peptide. As used herein, the term "peptide" refers to a polymer of amino acids. The term peptide refers to a form consisting of a small number of linked amino acids and is primarily used to distinguish it from proteins. While there is no clear criterion for distinguishing between proteins and peptides, as used herein, unless otherwise defined, polymers of approximately 200 amino acids will be called peptides, while those with more amino acids will be called proteins. The term "peptide" may encompass all other meanings recognized by those skilled in the art.

[0027] subject. As used herein, the term "subject" refers to a target organism exposed to a specific substance (e.g., a peptide). A subject may refer to an independent organism (e.g., a human, an animal) or to a partial component of an independent organism (e.g., a tissue, a cell, etc.). This meaning may be interpreted as appropriate depending on the context. Furthermore, the term "subject" may further encompass all meanings recognized by those skilled in the art.

[0028] Immunotherapy drugs. As used herein, the term “immunotherapy” is a concept distinct from general therapeutics or vaccines. Immunotherapy is similar to existing vaccines in that it is injected into the body of a target to induce a humoral immune response to the immunotherapy itself. However, immunotherapy differs from existing vaccines in that the antibodies induced as a result of the humoral immune response have the ability to bind not only to the immunotherapy itself, but also to specific tissues and cells in the body (e.g., cell surface receptors), or specific substances produced during metabolism (e.g., peptides, lipids, proteins, and / or sugars). Thus, immunotherapy can treat specific diseases or disorders and can be administered continuously and repeatedly. Accordingly, immunotherapy generally includes antigens designed to induce antibodies that have the ability to bind to specific target tissues, cells, or substances in the body. Unless otherwise defined, the term “immunotherapy” is interpreted to include all antigens having the above-described function (e.g., peptides, proteins, lipids, sugars, and / or complexes thereof) that can be used as appropriate by those skilled in the art. The term “immunotherapy” is sometimes more specifically referred to as “humoral immunotherapy.” Furthermore, the term "immunotherapy drug" may encompass all meanings recognized by those skilled in the art.

[0029] Treatment or medication. As used herein, the term “treatment” means any direct or indirect action or means to eliminate, alleviate, reduce, suppress, or improve a disease, illness, disorder, and / or symptom of the subject, or any direct or indirect action or means to induce a result that prevents a disease, illness, disorder, and / or symptom of the subject. As used herein, the term “therapeutic agent” means any substance (e.g., a compound or peptide) that can exert a “therapeutic” effect when administered to the subject in an appropriate manner. Furthermore, the terms “treatment” or “therapeutic agent” may include all other meanings recognized by those skilled in the art.

[0030] Immunogenicity. As used herein, the term "immunogenicity" refers collectively to the property of acting as an antigen capable of inducing an immune response, as defined in dictionaries. There are various methods for measuring the immunogenicity of a particular antigen, and these methods can be appropriately adopted or designed depending on the purpose. For example, methods include, but are not limited to, 1) a method for confirming whether IgG, IgA, and / or IgE antibodies are produced in the body of a subject when the antigen is administered to the subject; 2) a method for confirming the timing of the production of IgG, IgA, and / or IgE antibodies according to the administration cycle; 3) a method for confirming the titer of the induced antibody against the antigen; and 4) a method for measuring the effect according to the mechanism of action of the induced antibody, if the mechanism of action is known. The expression "increased immunogenicity" can be used interchangeably with, for example, "increased effect in inducing an immune response," "improved ability to induce antibodies," and "increased efficacy as an immunotherapy," and includes all expressions that a person skilled in the art can appropriately interpret depending on the context.

[0031] mer. As used herein, the term "mer" generally refers to the number of units in a high molecular weight polymer. As used herein, the term "mer" generally refers to a peptide of length N, expressed with a number as "a peptide of length N mers," where N amino acids are polymerized. The unit indicated by the expression "mer" should be interpreted appropriately in context and includes all other meanings that would be recognized by those skilled in the art.

[0032] Standard amino acids. As used herein, the term “standard amino acid” refers to the 20 amino acids synthesized in living organisms through the processes of gene transcription and translation. Specifically, standard amino acids include alanine (Ala, A), arginine (Arg, R), asparagine (Asn, N), aspartic acid (Asp, D), cysteine ​​(Cys, C), glutamic acid (Glu, E), glutamine (Gln, Q), glycine (Gly, G), histidine (His, H), isoleucine (Ile, I), leucine (Leu, L), lysine (Lys, K), methionine (Met, M), phenylalanine (Phe, F), proline (Pro, P), serine (Ser, S), threonine (Thr, T), tryptophan (Trp, W), tyrosine (Tyr, Y), and valine (Val, V). Standard amino acids have corresponding DNA codons and can be represented by the common one- or three-letter abbreviations for amino acids. The terms "standard amino acids" should be interpreted appropriately depending on the context, and they encompass all other meanings that would be recognized by those skilled in the art.

[0033] Non-standard amino acids. As used herein, the term "non-standard amino acid" refers to amino acids other than standard amino acids. Non-standard amino acids include artificial and unnatural amino acids, as well as amino acids that have been chemically modified through post-translational modifications in living organisms. Examples of non-standard amino acids include D-alanine, L-cyclohexylalanine, and 6-aminohexanoic acid. Because non-standard amino acids do not have corresponding DNA codons, they cannot be represented by the one- or three-letter abbreviations of common amino acids; they are represented using other letters and explained by additional explanations. The terms "non-standard amino acid" should be interpreted appropriately in context and include all other meanings that would be recognized by those skilled in the art.

[0034] Description of a peptide sequence. Unless otherwise specified, peptide sequences described herein use single-letter or three-letter abbreviations for amino acids, and are written in the direction from the N-terminus to the C-terminus. For example, RNVP refers to a peptide in which arginine, asparagine, valine, and proline are sequentially linked from the N-terminus to the C-terminus. Another example is Thr-Leu-Lys, which refers to a peptide in which threonine, leucine, and lysine are sequentially linked from the N-terminus to the C-terminus. For amino acids that cannot be represented by a single letter, other letters are used to represent them, and this will be explained by additional explanations.

[0035] When representing a peptide as a structural formula, N- and -C are used to indicate the N-terminus or C-terminus, and parentheses can be used to distinguish the N-terminus and / or C-terminus. For example, when the structural formula of a peptide is represented as (N)-BTA-(C), the "(N)-" at the beginning and the "-(C)" at the end are symbols used to clarify the direction of the N-terminus and C-terminus, unless otherwise specified. This refers to a peptide in which the sequences represented by B, T, and A are linked in the direction from the N-terminus to the C-terminus.

[0036] Background-humoral immunity. Humoral immunity mediated by immunoglobulin M (IgM).

[0037] Among humoral immunity, the IgM-induced immune response is an innate immune function that is mainly activated in the primary immune response and develops rapidly in the early stages of infection. IgM is secreted primarily in pentamer form and theoretically has 10 antigen-binding sites, allowing it to bind to multiple antigens simultaneously. While IgM can bind to a wide variety of antigens in different forms, its binding affinity and avidity are limited by the inherent affinity of IgM itself. Therefore, the affinity and avidity of IgM to antigens are significantly lower than those of antibodies such as IgG, which are produced with the help of helper T cells.

[0038] Limitation of humoral immunity by IgM. While humoral immunity mediated by IgM derivatives plays a crucial role in the initial immune response, the effects of IgM-mediated humoral immunity are considered limited because: 1) the amount of IgM produced by B cells is lower compared to other types of antibodies (e.g., IgG produced by differentiated B cells); 2) the specific binding ability of IgM to antigens is lower than that of IgG; and 3) the degree of secondary immune response is weaker upon re-exposure to the same antigen. Therefore, from the perspective of designing antigens that induce an immune response, if an antigen injected into the target body induces only humoral immunity mediated by IgM, the desired effect is unlikely to be achieved. Consequently, designing antigens that induce humoral immunity mediated by IgG is extremely important.

[0039] Humoral immunity mediated by immunoglobulin G (IgG) 1 - Overview. Humoral immunity that produces IgG primarily occurs in the germinal centers of the spleen or lymph nodes, and this humoral immunity proceeds through the combined action of B cells, helper T cells, and antigen-presenting cells (APCs). The overall process is as follows: 1) B cells recognize the invading antigen (mainly protein or peptide antigens). 2) Antigen-presenting cells endocytose the antigen (or fragments thereof), then cleave the antigen into smaller fragments within the cell, and present some of these fragments on the MHC class II surface of the antigen-presenting cell. 3) Helper T cells recognize the antigen fragments presented on the MHC class II. 4) Helper T cells transmit differentiation signals to B cells (antigen-recognizing cells). 5) The B cells are activated, and some differentiate into plasma cells, producing IgG antibodies with high specific binding ability to the antigen. 6) As a result of the activation of B cells, some cells differentiate into memory B cells and are stored in the body so that they can trigger an immune response that quickly produces IgG antigens if the same antigen invades again.

[0040] Humoral immunity mediated by IgG2 - antigen-recognizing cells. Antigen-presenting cells are a general term for cells that can endocytose protein fragments or peptides, cleave them into shorter peptide fragments, load them onto MHC class II cells, and present them on the surface of the antigen-presenting cell. Major antigen-presenting cells include B cells, macrophages, and dendritic cells. Antigen-presenting cells play a role in transporting endocytized antigen fragments from the infection site to lymph nodes, presenting the antigen fragments to helper T cells via MHC class II cells, and thereby inducing an immune response by activating helper T cells that recognize the antigen fragments.

[0041] Humoral immunity mediated by IgG3 - MHC class II. MHC class II molecules are expressed on the surface of antigen-presenting cells and have a heterodimer structure consisting of α / β chains. Due to its structure, MHC class II can bind to peptides of a certain length and present those peptides. Antigen-presenting cells bind peptide fragments derived from foreign antigens to MHC class II and present these peptide fragments on their cell surface. The expression of human MHC class II involves the HLA gene complex (human leukocyte antigen complex), and among these, gene complexes such as HLA-DP, DQ, and DR are known to be involved in the expression of MHC class II cell surface receptors on the surface of antigen-presenting cells. In humans, it is known that various alleles of the HLA-DR gene exist depending on race, and about 12 types of HLA-DR genes are known to be the most frequently observed alleles.

[0042] Humoral immunity mediated by IgG4 - MHC class II presentation by antigen-presenting cells. Although there are some differences in the literature, the length of peptides presented to MHC class II is known to be in the range of approximately 17mer to 24mer. Therefore, antigen-presenting cells do not present endocytized antigen protein or peptide fragments directly to MHC class II, but rather cleave them into smaller fragments of 17mer to 24mer. Antigen fragments (protein or peptide fragments) endocytized by antigen-presenting cells reside in endosomes, which then fuse with the lysosomes of the antigen-presenting cells. Subsequently, various degrading enzymes present in the lysosomes cleave the antigen fragments into shorter peptides. Examples of degrading enzymes include endopeptidases and exopeptidases. Endopeptidases cleave antigen fragments by acting on peptide bonds within the antigen fragment, while exopeptidases primarily cleave antigen fragments by acting on peptide bonds at both ends. After the above process, when the antigen fragment is cleaved into peptides of appropriate size, some of these peptides bind to MHC class II present in the inner membrane of the lysosome. Lysosomes return to the cell surface and fuse with the cell's plasma membrane, thereby exposing MHC class II molecules and their bound peptide fragments to the surface of the antigen-presenting cell. This entire process is also known as the "antigen-presenting cell antigen presentation process."

[0043] Humoral immunity mediated by IgG5 - helper T cells. Helper T lymphocytes express CD4 and are therefore also known as CD4+ cells. Helper T cells express T cell receptors (TCRs) that have the ability to bind to MHC class II on their surface. T cell receptors generally form a complex with CD3. When an antigen (e.g., a peptide fragment) delivered to the lymph node by an antigen-presenting cell is presented via MHC class II, helper T cells recognize the presented antigen fragment. The T cell receptor-CD3 complex and CD4 are involved in this recognition process. If helper T cells successfully recognize the antigen fragment, they become activated and secrete various cytokines or differentiate themselves. The secreted cytokines are involved in the differentiation of B cells, which will be discussed later.

[0044] IgG6-mediated humoral immunity - differentiation of B cells. Under the influence of cytokines secreted by helper T cells (e.g., interleukin-4 (IL-4)), immunoglobulin class switching occurs in B cells, which changes the isotype of the antibody produced by the B cells (e.g., a change from IgM to IgG). Furthermore, some B cells differentiate into memory B cells and are conserved to induce a rapid immune response when the same antigen invades again, while others differentiate into plasma cells and actively produce IgG antibodies.

[0045] Humoral immunity mediated by IgG7 - conditions for IgG production. For humoral immunity mediated by IgG to develop, two things are essential: 1) the recognition of a specific three-dimensional structure of the antigen by B cells, and 2) the recognition of a fragment of the antigen by helper T cells via MHC class II. Generally, the parts of the antigen recognized by B cells and the parts of the antigen recognized by helper T cells are different from each other and activate immune responses through different pathways. However, it is generally known that an immune response occurs only when the parts recognized by B cells (B cell epitopes) and the parts recognized by helper T cells (Th epitopes) have at least a certain degree of association. For example, B cell epitopes and Th epitopes may be contained in a single molecule, form a conjugate, or have other associations.

[0046] Prior art limitations.

[0047] Considerations when designing peptides that can be used as immunotherapies.

[0048] As described above, immunotherapeutic drugs are required to have the following characteristics: 1) they can stably induce an immune response in the target body; 2) they can uniformly induce only the intended antibodies in the target body, minimizing side effects; and 3) they are easy to synthesize and have reasonable manufacturing costs for commercialization. Therefore, when designing peptides that can be used as immunotherapeutic drugs, it is essential to consider the following three conditions: 1) the peptide must exhibit a certain level of immunogenicity; 2) the peptide must evoke an immune response in the target body that uniformly induces the antigen recognition specificity of the pre-intended antibody and the isotype that governs the physiological function of the antibody; and 3) the peptide must be easy to synthesize, taking economic feasibility into consideration.

[0049] Prior art limitations.

[0050] As disclosed in the previously filed U.S. Patent Application Publication No. 10 / 378,707 and PCT / KR2005 / 000784, as well as in Kim et al. (2016, An apolipoprotein B100 mimotope prevents obesity in mice, Clinical Science 130, 105-116), it is known that antibodies specific to artificially produced peptides having a particular sequence can also bind to the exposed site of the ApoB-100 protein in LDL molecules and thereby function as immunotherapies. Immunotherapies containing peptides have been designed using this property and disclosed in the aforementioned patent applications. However, the prior art has mainly focused on improving the immunogenicity of peptides, for example, by 1) preparing long, continuous identical sequences of peptides (concatemers), and 2) designing immunotherapies by linking helper T cell epitopes (sufficiently long at the protein level) to concatemers. Accordingly, conventionally designed immunotherapies have had limitations: 1) the presence of various epitopes (antigenic determinants) leads to the induction of various types of antibodies, reducing uniformity; and 2) high manufacturing costs make them economically unfeasible.

[0051] The need to establish peptide design methods.

[0052] Regarding peptides used as immunotherapeutic agents, there are no established principles for 1) uniformly inducing only the intended immune response, and 2) designing peptides that are easy to synthesize and have low manufacturing costs. Accordingly, this specification provides technical considerations and design methods for peptides used as immunotherapeutic agents.

[0053] peptide.

[0054] An overview of peptides.

[0055] The peptides provided herein comprise at least one peptide unit (a block of peptide). The peptide unit comprises at least one B cell epitope, at least one Th epitope, and an appropriate number of auxiliary parts. In one embodiment, the peptide may comprise one peptide unit. In another embodiment, the peptide may comprise two or more peptide units.

[0056] Characteristics of Peptide 1 - It contains peptide units.

[0057] A peptide unit is a portion that 1) exhibits immunogenicity above a certain level and 2) is designed to uniformly induce only the pre-intended antibody. Therefore, the peptide units provided herein possess properties suitable for use as immunotherapeutic agents.

[0058] Characteristics of Peptide-2 - The peptide unit is relatively short.

[0059] Peptide units are designed to be relatively short in length, making them easy to synthesize and resulting in low manufacturing costs. Peptides are designed using peptide units as their constituent elements, specifically in the form of one or more linked peptide units. When a peptide contains only a small number of peptide units, the overall length of the peptide is short, which has the advantage of being easy to synthesize. Even in the case of peptides with relatively long sequences containing multiple peptide units, the peptide units themselves are designed to be easily synthesized, so it is possible to prepare the peptide by synthesizing the peptide units in parallel and then linking these peptide units. As a result, the peptides provided herein, in addition to the characteristics of the peptide units described above, possess the characteristic of being easy to synthesize, making them suitable for use as immunotherapeutic agents.

[0060] The function of peptides.

[0061] When this peptide is injected into a target's body, it has the function of uniformly inducing only antibodies that can specifically bind to the B cell epitopes contained in the peptide.

[0062] B cell epitope.

[0063] Definition of a B cell epitope.

[0064] The peptides provided herein contain one or more B-cell epitopes. As used herein, the term B-cell epitope refers to a unit of peptide intentionally designed to induce one type of homogeneous antibody. Therefore, when a peptide containing a B-cell epitope is injected into a subject's body, the result will be that one type of antibody is predominantly induced for each type of B-cell epitope.

[0065] Structure of a B cell epitope.

[0066] A B cell epitope includes a portion that forms a three-dimensional structure and an adjacent portion. The portion that forms the three-dimensional structure is the portion that forms a peptide having a higher-order structure, and this portion is designed so that B cells can recognize the peptide having a higher-order structure and produce antibodies that can specifically bind to the peptide. The adjacent portion directly or indirectly affects the portion that forms the three-dimensional structure and is a portion that stably forms the higher-order structure. Specifically, the adjacent portion may have various functions, such as 1) a function for the portion that forms the three-dimensional structure to form a specific structure, 2) a linker function that does not affect the portion that forms the three-dimensional structure when the B cell epitope is linked to another portion within the peptide unit, and 3) a protective function for the portion that forms the three-dimensional structure, but its functions are not limited to these. In one embodiment, the B cell epitope may have an arrangement in which a first portion that forms the three-dimensional structure and its first adjacent portion are sequentially linked in the order from the N-terminus to the C-terminus. In another embodiment, the B cell epitope may have an arrangement in which a second adjacent portion, a second portion that forms the three-dimensional structure, and a third adjacent portion are sequentially linked in the order from the N-terminus to the C-terminus. In yet another embodiment, the B cell epitope may have an arrangement in which a third portion and a fourth adjacent portion forming a three-dimensional structure are sequentially linked in the direction from the N-terminus to the C-terminus.

[0067] Design of B cell epitope 1 - design of the part that forms the three-dimensional structure.

[0068] A B cell epitope should be able to uniformly induce the production of antibodies that can recognize and specifically bind to the three-dimensional structure of B cells. The three-dimensional structure recognized by B cells can be expressed by appropriate peptides having a higher-order structure. Therefore, B cell epitopes are designed to include a portion that forms a three-dimensional structure, which in turn forms a peptide having a higher-order structure. The portion that forms the three-dimensional structure can form a peptide having a higher-order structure as intended. In one embodiment, the portion that forms the three-dimensional structure may include an α-helix structure. In another embodiment, the portion that forms the three-dimensional structure may include a β-structure. In yet another embodiment, the portion that forms the three-dimensional structure may include an α-helix structure and / or a β-structure. In yet another embodiment, the portion that forms the three-dimensional structure may include a peptide having a tertiary structure. In yet another embodiment, the portion that forms the three-dimensional structure may include a peptide having a quaternary structure.

[0069] Design of B cell epitope 2 - adjacent parts

[0070] When designing B cell epitopes, it is not essential that all sequences form peptides with higher-order structures. In other words, B cell epitopes may be designed to include additional adjacent regions in addition to the regions that form the three-dimensional structure. Adjacent portions can influence the portion forming the three-dimensional structure in order to stably form a higher-order structure. Adjacent portions may have various other functions, and their roles may overlap with those of auxiliary portions. In one embodiment, an adjacent portion may have a linker function. In another embodiment, an adjacent portion may have a protective function for the portion forming the three-dimensional structure. In yet another embodiment, an adjacent portion may have one or more functions.

[0071] Length of a B cell epitope.

[0072] A B cell epitope should 1) be large enough to be recognized by B cells, and 2) have one or a very small number of antibodies that specifically bind to the B cell epitope. The length of the B cell epitope should be limited to an appropriate level. If the length of the B cell epitope is too short, it will not be recognized by B cells and will therefore lack antibody induction ability. On the other hand, if the length of the B cell epitope is too long, various types of antibodies may be induced, potentially deviating from the intended purpose. In one embodiment, the length of the B cell epitope may be about 8 mer, about 9 mer, about 10 mer, about 11 mer, about 12 mer, about 13 mer, about 14 mer, about 15 mer, about 16 mer, about 17 mer, about 18 mer, about 20 mer, about 21 mer, about 22 mer, about 23 mer, about 24 mer, about 25 mer, about 26 mer, about 27 mer, about 28 mer, about 29 mer, or about 30 mer.

[0073] In another embodiment, the length of the B cell epitope may have a value within the two numerical ranges selected in the preceding sentence.

[0074] Embodiments of a B-cell epitope.

[0075] In one embodiment, the B cell epitope may induce an antibody that targets apolipoprotein B-100. In another embodiment, the B cell epitope may be a fragment of apolipoprotein B-100 and / or a mimotope of apolipoprotein B-100. In yet another embodiment, the B cell epitope is Externally exposed sites of apolipoprotein B-100 contained in low-density lipoprotein (LDL); and externally exposed sites of apolipoprotein B-100 contained in very low-density lipoprotein (VLDL), This method is characterized by inducing antibodies that target a selected site.

[0076] A configuration of a B cell epitope.

[0077] In one embodiment, the B cell epitopes are RNVPPIFNDVYWIAF (SEQ ID NO: 6), CRFRGLISLSQVYLS (SEQ ID NO: 7), KTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 8), RNVPPIFNDVY (SEQ ID NO: 9), CRFRGLISLSQ (SEQ ID NO: 10), KTTKQSFDLSVK (SEQ ID NO: 11), RNVPPIFNDVYW (SEQ ID NO: 12), CRFRGLISLSQV (SEQ ID NO: 13), KTTKQSFDLSVKAQYKK (SEQ ID NO: 14), RNVPPIFNDVYWI (SEQ ID NO: 15), CRFRGLISLSQVY (SEQ ID NO: 16), KTTKQSFDLSVKAQYKKN (SEQ ID NO: 17), PIFNDVYWIAF (SEQ ID NO:18), GLISLSQVYLS(SEQ ID NO:19), QSFDLSVKAQYKKNKH(SEQ ID NO:20), PPIFNDVYWIAF(SEQ ID NO:21), RGLISLSQVYLS(SEQ ID NO:22), KQSFDLSVKAQYKKNKH(SEQ ID NO:23), VPPIFNDVYWIAF(SEQ ID NO:24), FRGLISLSQVYLS(SEQ ID NO:25), TKQSFDLSVKAQYKKNKH(SEQ ID NO:26), NVPPIFNDVYWIA(SEQ ID NO:27), RFRGLISLSQVYL(SEQ ID NO:28), TKQSFDLSVKAQYKKN(SEQ ID NO:29), VPPIFNDVYWI(SEQ ID NO:30), FRGLISLSQVY(SEQ ID The peptide contains a sequence selected from the group consisting of NO:31), TKQSFDLSVKAQYKKN (SEQ ID NO:32), PPIFNDVYW (SEQ ID NO:33), RGLISLSQV (SEQ ID NO:34), KQSFDLSVKAQYKK (SEQ ID NO:35), RFRGLISLSQVYLDP (SEQ ID NO:221), and SVCGCPVGHHDVVGL (SEQ ID NO:222).

[0078] In another embodiment, the B cell epitope may be a peptide containing an epitope selected from the group consisting of SEQ ID NOS: 6-35 and 221-222.

[0079] A sequence similar to an example sequence of a B cell epitope.

[0080] In this specification, sequences similar to exemplary sequences of B cell epitopes are disclosed. In one embodiment, a B cell epitope may have a sequence that is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NOS: 6-34 and SEQ ID NO: 221-222. In another embodiment, a B cell epitope may have a sequence that matches the selected sequence to a value greater than the value selected in the preceding sentence. For example, a B cell epitope may have a sequence that is 90% or more identical to SEQ ID NO: 6.

[0081] Th epitope.

[0082] Definition of a Th epitope.

[0083] The Th epitopes in the peptides provided herein refer to the regions of the peptide that, after endocytosis by antigen-presenting cells, bind to MHC class II cells, are presented on the surface of the antigen-presenting cells, and are designed to function in a way that allows them to be recognized by helper T cells (Th, helper T lymphocytes). The process of antigen presentation, in which antigen-presenting cells process endocytized peptides and bind them to MHC class II cells, is as described above. In other words, the Th epitopes are the regions that are recognized by helper T cells when the peptide is injected into the target body, and therefore play a direct role in inducing IgG antibodies against the peptide.

[0084] Design of Th epitope 1-anchor residues.

[0085] Th epitopes are designed to have an anchor residue in their sequence that can bind to MHC class II. Whether or not an anchor residue is included in the sequence is an important factor that affects the function of the Th epitope. In one embodiment, the Th epitope may contain one or more amino acids selected from the group consisting of tyrosine (Y), phenylalanine (F), tryptophan (W), arginine (R), leucine (L), valine (V), isoleucine (I), and methionine (M) as the anchor residue.

[0086] Design of Th epitope 2 - a species-specific Th epitope.

[0087] As a Th epitope, a Th epitope having the ability to bind to MHC class II of a specific species can be selected according to the purpose. In one embodiment, the Th epitope may be a Th epitope having the ability to bind to human MHC class II. In another embodiment, the Th epitope may be a Th epitope having the ability to bind to MHC class II of a species belonging to a mammal. Specifically, the Th epitope may be a Th epitope having the ability to bind to mouse MHC class II.

[0088] Design of Th epitope 3 - gene-specific Th epitope.

[0089] Due to the diverse traits of the HLA gene complex, the structure of MHC class II can vary among races and individuals. Accordingly, it is possible to design Th epitopes that have the ability to bind to HLA-DP, HLA-DQ, and / or HLA-DR, which are MHC class II molecules of specific genetic traits. In one embodiment, the Th epitope may be a peptide sequence having high binding affinity to MHC class II expressed by one or more HLA-DR genes selected from the HLA-DR1 alleles 2w2b, 2w2a, 3, 4w4, 4w14, 5, 7, 52a, 52b, 52c, and 53.

[0090] In one embodiment, the Th epitope may be a peptide sequence having high binding affinity to expressed MHC class II, which is expressed by one or more genes selected from HLA-DQ5, HLA-DR, HLA-DR1 to HLA-DR8, HLA-DR11, HLA-DR13, HLA-DR14, HLA-DRw52, HLA-DR2w15, HLA-DPw4, and HLA-DRB1 subtypes (e.g., 0301, 01, 03, 04, 07, 08, 09, 11, 12, 13, 15, and 0301), as well as HLA-DRB5.

[0091] In another embodiment, the Th epitope may be the sequence named HA307-312 disclosed by Cara C. Wilson et al. (2001, Identification and Antigenicity of Broadly Cross-Reactive and Conserved Human Immunodeficiency Virus Type 1-Derived Helper T-Lymphocyte Epitopes, Journal of Virology, 75(9)4195-4207).

[0092] In yet another embodiment, the Th epitope may be one of the HLA class II restriction epitopes disclosed in Table 2 of Christopher P Desmond et al. (2008, A systematic review of T-cell epitopes in hepatitis B virus: identification, genotypic variation and relevance to antiviral therapeutics, Antiviral Therapy 13:161-175).

[0093] Design of Th epitope 4 - a gene-nonspecific Th epitope.

[0094] Regardless of the traits of the HLA gene complex, Th epitopes capable of binding to various MHC class IIs are known, and it is possible to design Th epitopes that can bind to various MHC class IIs regardless of genetic traits. In one embodiment, the Th epitope may be a sequence named "pan DR-binding peptide" disclosed in U.S. Patent Application No. 305,871.

[0095] Design of Th epitope 5 - elimination of the possibility of it acting as a B cell epitope.

[0096] Th epitopes are designed to be presented by MHC class II on antigen-presenting cells and recognized by helper T cells. Therefore, Th epitopes generally have a very high binding affinity to MHC class II, and thus the probability of a Th epitope acting as a B cell epitope is very low. In other words, Th epitopes are designed not to induce antibodies that specifically bind to the three-dimensional structure of the Th epitope itself.

[0097] Design of the length of the Th epitope

[0098] Th epitopes should be designed to have an appropriate length so that they can bind to one unit of MHC class II. Generally, the length of one unit of a Th epitope that can directly bind to MHC class II is known to be approximately 30 mer (Abbas, AK, Lichtman, A. Hand Pillai, S. Cellular and Molecular Immunology (pp. 124-126), 7th Ed. (2012) Philadelphia PA, Elsevier Saunder, etc.). Furthermore, 1) if the length of the Th epitope is too short, there is a risk that the Th epitope will lose its ability to bind to MHC class II, while 2) if the length of the Th epitope is too long, there is room for the Th epitope to act independently as a B cell epitope, deviating from the intended purpose. Therefore, it is necessary to design Th epitopes of an appropriate length.

[0099] The range of length of the Th epitope.

[0100] In one embodiment, the length of the Th epitope may be 7mer, 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, or 33mer. In another embodiment, the length of the Th epitope may have a value within two numerical ranges selected in the preceding sentence. For example, the length of the Th epitope may be in the range of 8mer to 32mer. In yet another example, the length of the Th epitope may be in the range of 11mer to 13mer.

[0101] Design of the PADRE embodiment of the Th epitope.

[0102] In one embodiment, the Th epitope may be a peptide named “pan DR-binding peptide” as disclosed in U.S. Patent Application No. 305,871. In another embodiment, the Th epitope may be one of the peptides disclosed in Tables VIII A and IX of U.S. Patent No. 6,413,935. In yet another embodiment, the Th epitope may have a peptide sequence satisfying the following structural formula I:

[0103] [Formula I] (N)-Lys-X1-X2-Ala-Ala-X3-Thr-X4-X5-Ala-Ala-(C)

[0104] In the formula, X1 may be, but is not limited to, tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine.

[0105] X2 may be a hydrophobic amino acid, or it may be leucine (Leu) or isoleucine (Ile), but is not limited to these.

[0106] X3 may be an aromatic or cyclic amino acid, or it may be phenylalanine (Phe), tyrosine (Tyr), or histidine (His), but is not limited to these.

[0107] X4 may be an aliphatic long-chain amino acid, or it may be isoleucine (Ile) or valine (Val), but is not limited to these.

[0108] X5 may be a charged amino acid, or it may be arginine (Arg), leucine (Leu), aspartic acid (Asp), glutamine (Gln), or glycine (Gly), but is not limited to these.

[0109] In one embodiment, the Th epitope may have a peptide sequence that satisfies the following structural formula II.

[0110] [Formula II] (N)-X1-X2-Val-X3-Ala-X4-Thr-Leu-Lys-Ala-Ala-(C)

[0111] In the formula, X1 is either lysine (Lys) or arginine (Arg).

[0112] X2 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine.

[0113] X3 is lysine (Lys), tryptophan (Trp), tyrosine (Tyr), arginine (Arg), alanine (Ala), or methionine (Met).

[0114] X4 is either asparagine (Asn), tryptophan (Trp), tyrosine (Tyr), valine (Val), histidine (His), lysine (Lys), or alanine (Ala).

[0115] A configuration embodiment of the Th epitope.

[0116] In one embodiment, the Th epitope is K(Cha)VAAWTLKAA (SEQ ID NO:1), PKYVKQNTLKLAT (SEQ ID NO:2), ILMQYIKANSKFIGI (SEQ ID NO:3), QSIALSSLMVAQAIP (SEQ ID NO:4), ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ (SEQ ID NO:5), PLGFFPDHQL (SEQ ID NO:162), WPEANQVGAGAFGPGF (SEQ ID NO:163), MQWNSTALHQALQDP (SEQ ID NO:164), MQWNSTTFHQTLQDPRVRGLYFPAGG (SEQ ID NO:165), FFLLTRILTI (SEQ ID NO:166), FFLLTRILTIPQSLD (SEQ ID NO:167), TSLNFLGGTTVCLGQ (SEQ ID NO:168), QSPTSNHSPTSCPPIC(SEQ ID NO:169), IIFLFILLLCLIFLLVLLD(SEQ ID NO:170), CTTPAQGNSMFPSC(SEQ ID NO:171), CTKPTDGN(SEQ ID NO:172), WASVRFSW(SEQ ID NO:173), LLPIFFCLW(SEQ ID NO:174), MDIDPYKEFGATVELLSFLP(SEQ ID NO:175), FLPSDFFPSV(SEQ ID NO:176), RDLLDTASALYREALESPEH(SEQ ID NO:177), PHHTALRQAILCWGELMTLA(SEQ ID NO:178), GRETVIEYLVSFGVW(SEQ ID NO:179), EYLVSFGVWIRTPPA(SEQ ID NO:180), VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181), TVVRRRGRSP(SEQ ID NO:182), VGPLTVNEKRRLKLI(SEQ ID NO:183), RHYLHTLWKAGILYK(SEQ ID NO:184), ESRLVVDFSQFSRGN(SEQ ID NO:185), LQSLTNLLSSNLSWL(SEQ ID NO:186), SSNLSWLSLDVSAAF(SEQ ID NO:187), LHLYSHPIILGFRKI(SEQID NO:188)、KQCFRKLPVNRPIDW(SEQ ID NO:189)、LCQVFADATPTGWGL(SEQ ID NO:190)、AANWILRGTSFVYVP(SEQ ID NO:191)、EIRLKVFVLGGCRHK(SEQ ID NO:192) NO:195)、KYVAAWTLKAA(SEQ ID NO:196)、DIEKKIAKMEKASSVFNVVNS(SEQ ID NO:223)、YSGPLKAEIAQRLEDV(SEQ ID NO:224)、K(Cha)VKANTLKAA(SEQ ID NO:225)、K(Cha)VKANTLKAA(SEQ ID NO:225) NO:226)、K(Cha)VKAWTLKAA(SEQ ID NO:227)、K(Cha)VKAWTLKAA(SEQ ID NO:228)、K(Cha)VWANTLKAA(SEQ ID NO:229)、K(Cha)VWANTLKAA(SEQ ID NO:229) NO:230)、K(Cha)VWAYTLKAA(SEQ ID NO:231)、K(Cha)VWAVTLKAA(SEQ ID NO:232)、K(Cha)VYAWTLKAA(SEQ ID NO:233)、K(Cha)VYAWTLKAA(SEQ ID NO:234)、K(Cha)VYAWTLKAA(SEQ ID NO:234) ID NO:235)、K(Cha)VKAHTLKAA(SEQ ID NO:236)、K(Cha)VKAHTLKAA(SEQ ID NO:237)、K(Cha)VAANTLKAA(SEQ ID NO:238)、K(Cha)VAANTLKAA(SEQ ID NO:239)、K(Cha)VAANTLKAA(SEQ ID NO:239) NO:240)、K(Cha)VAAYTLKAA(SEQ ID NO:241)、K(Cha)VAAWTLKAA(SEQ ID NO:242)、K(Cha)VAAKTLKAA(SEQ ID NO:243)、K(Cha)VAAHTLKAA(SEQ ID NO:244)、K(Cha)VAAHTLKAA(SEQ ID NO:244) NO:245)、K(Cha)VAAWTLKAA(SEQ ID NO:246)、、よびK(Cha)VMAATLKAA(SEQ IDA selection may be made from the group consisting of NO:247). In this case, "a" represents D-type alanine, "Z" represents 6-aminohexanoic acid, and "(Cha)" represents L-cyclohexylalanine.

[0117] A sequence similar to an example sequence of a Th epitope.

[0118] This specification discloses sequences similar to exemplary sequences of Th epitopes. In one embodiment, a Th epitope may have sequences having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with SEQ ID NO:1 to SEQ ID NO.5, SEQ ID NO:162 to SEQ ID NO.192, SEQ ID NO:195 to SEQ ID NO.196, and SEQ ID NO:223 to SEQ ID NO.247, sequences satisfying [Formula I] above, or sequences satisfying [Formula II] above. In another embodiment, the Th epitope may have a sequence that matches SEQ ID NO:1 to SEQ ID NO:5, SEQ ID NO:162 to SEQ ID NO:192, SEQ ID NO:195 to SEQ ID NO:196, and SEQ ID NO:223 to SEQ ID NO:247, a sequence that satisfies [Formula I] above, or a sequence that satisfies [Formula II] above. For example, the Th epitope may have a sequence that has 90% or more identity with the sequence of SEQ ID NO:1.

[0119] auxiliary part.

[0120] Definition of auxiliary part.

[0121] The peptides disclosed herein may include one or more auxiliary moieties. An auxiliary moiety is a general term for additional parts that directly or indirectly affect the peptide and can evoke an intended immune response in the target body. The auxiliary moieties may have one or more functions, and the structure and / or position of the peptide sequence can be appropriately designed depending on the purpose.

[0122] Function of auxiliary part 1 - function as a linker.

[0123] The auxiliary portion can function as a linker connecting a B cell epitope and a Th epitope. The B cell epitope and the Th epitope may be directly linked, or they may be linked via the auxiliary portion that functions as a linker. Furthermore, the auxiliary portion may be designed to have a linker function that links multiple units contained in the peptide. In one embodiment, the sequence of the auxiliary portion may be located between the sequence of the B cell epitope and the sequence of the Th epitope. In particular, the auxiliary portion has a linker function that links the B cell epitope and the Th epitope. In another embodiment, the sequence of the auxiliary portion may be located between the sequence of a first peptide unit and the sequence of a second peptide unit in the peptide. In particular, the auxiliary portion has a linker function for linking the first peptide unit and the second peptide unit.

[0124] Function of auxiliary part 2 - function for protection.

[0125] The peptide units provided herein are characterized by having relatively short sequence lengths. Accordingly, when a peptide containing the peptide units is injected into the subject's body, the Th epitope sequence may be degraded before it can be recognized by helper T cells, potentially preventing the intended immune response from occurring. In one embodiment, a protective unit may protect the Th epitope from being cleaved by enzymes in the subject's body. For example, the enzyme in the subject's body may be a peptidase. Specifically, the peptidase may be an exopeptidase and / or an endopeptidase, but is not limited to these. In another embodiment, an auxiliary portion may be ligated to the N-terminus and / or C-terminus of the Th epitope. In particular, the auxiliary portion has the function of protecting the Th epitope. In yet another embodiment, the auxiliary portion may contain at least one non-standard amino acid.

[0126] Function of auxiliary part 3 - function of forming a ring-shaped body.

[0127] The auxiliary moieties may be designed to be attached to both ends of the peptide unit, thereby having the function of enabling the peptide to form a cyclic structure. In one embodiment, the peptide may include a first auxiliary moiety at the N-terminus and a second auxiliary moiety at the C-terminus. In particular, the first and second auxiliary moieties may each contain one or more cysteine ​​(S) molecules. In another embodiment, the peptide may exist as a cyclic structure. In particular, the N-terminus and C-terminus of the peptide may be linked via auxiliary moieties.

[0128] Functions of auxiliary part 3 - other functions.

[0129] The auxiliary portion may have additional functions in addition to those described above. In one embodiment, the auxiliary portion may contain hydrophilic amino acids and may have the function of increasing the solubility of the peptide. In another embodiment, the auxiliary portion may consist of a sequence that is biologically inactive in the body of the subject. In particular, the auxiliary portion may have a dummy function to extend the length of the peptide without affecting the function of the B cell epitope and Th epitope. Specifically, the peptide may, but is not limited to, a His-tag.

[0130] It can perform multiple functions.

[0131] The auxiliary portion may have one or more functions. In one embodiment, the auxiliary portion may have a linker function, a protective function, a ring-forming function, a dummy function, and / or a solubility-enhancing function.

[0132] It may contain non-standard amino acids.

[0133] The auxiliary portion may contain one or more non-standard amino acids. Artificial amino acids may be necessary for the auxiliary portion to perform linker function, protective function, and / or other functions. In one embodiment, the auxiliary portion may contain at least one non-standard amino acid. Specifically, the non-standard amino acid may be one or more non-standard amino acids selected from the group consisting of L-cyclohexylalanine, D-alanine, and 6-aminohexanoic acid, but is not limited to these.

[0134] The length of the auxiliary part.

[0135] Auxiliary parts may be designed to have an appropriate length according to their function. If an auxiliary part has multiple functions, it may be designed to have an appropriate length to perform all of those functions. In one embodiment, the length of the auxiliary portion may be 1mer, 2mer, 3mer, 4mer, 5mer, 6mer, 7mer, 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, or 31mer or longer. In another embodiment, the length of the auxiliary portion may have a value within the two numerical ranges of the preceding sentence. For example, the length of the auxiliary portion may be in the range of 1mer to 8mer. In another example, the length of the auxiliary portion may be in the range of 15mer to 26mer.

[0136] Characteristics of the auxiliary portion - it has little effect on the function of the B cell epitope.

[0137] The auxiliary portion does not significantly affect the function of the peptide units and / or peptides disclosed herein in inducing antibodies that specifically bind to B cell epitopes in the subject body.

[0138] An embodiment of the arrangement of auxiliary parts.

[0139] In one embodiment, the auxiliary parts are Z, aZ, Za, RN, AF, CR, LS, KT, KH, RF, DP, SV, GL, ZRNV (SEQ ID NO:36), aZRN (SEQ ID NO:37), IAFZ (SEQ ID NO:38), AFZa (SEQ ID NO:39), RNVP (SEQ ID NO:40), WIAF (SEQ ID NO:41), ZCRF (SEQ ID NO:42), aZCR (SEQ ID NO:43), YLSZ (SEQ ID NO:44), LSZa (SEQ ID NO:45), CRFR (SEQ ID NO:46), VYLS (SEQ ID NO:47), ZKTT (SEQ ID NO:48), aZKT (SEQ ID NO:49), NKHZ (SEQ ID NO:50), KHZa (SEQ ID The peptides may be selected from the group consisting of NO:51), GSHHHHHHGSDDDDK (SEQ ID NO:52), HHHHHH (SEQ ID NO:53), MRGSHHHHHHGSDDDDKIVD (SEQ ID NO:54), GGGGSGGGGGGSS (SEQ ID NO:55), RRRRRR (SEQ ID NO:159), GSHHHHHHGSDDDDKaZ (SEQ ID NO:193), and ZaGSHHHHHHGSDDDDK (SEQ ID NO:194). In particular, "a" represents D-type alanine and "Z" represents 6-aminohexanoic acid.

[0140] Peptide unit design - the overall picture.

[0141] The following describes possible peptide units and methods for designing their morphologies. Each unit may contain at least one B cell epitope and at least one Th epitope, and may also contain an appropriate number of auxiliary parts. The linking order of the B cell epitope, Th epitope, and auxiliary parts is illustrated for each type. Unless otherwise specified, the design of each part contained in the peptide unit basically follows the design principles described above.

[0142] Design of Unit A.

[0143] Structure and overview of Unit A1.

[0144] In this specification, a peptide unit that includes 1) one B cell epitope and one Th epitope, and 2) one or more auxiliary moieties is referred to as "Unit A". The function of the auxiliary moieties is not particularly limited as long as it does not impair the function of the B cell epitope and the Th epitope, and may be designed as appropriate as needed.

[0145] In one embodiment, unit A may be a unit in which a first B cell epitope and a first Th epitope are sequentially linked in a direction from the N-terminus to the C-terminus.

[0146] Furthermore, unit A may further include a first auxiliary portion. If unit A includes a first auxiliary portion, the sequence of the first auxiliary portion is located N-terminally with respect to the sequence of the first B cell epitope in the sequence of unit A. In particular, the first auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the first auxiliary portion are not limited to these.

[0147] Furthermore, unit A may further include a second auxiliary portion. If unit A includes a second auxiliary portion, the sequence of the second auxiliary portion is located within the sequence of unit A between the sequence of the first B cell epitope and the sequence of the first Th epitope. In particular, the second auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the functions of the second auxiliary portion are not limited to these.

[0148] Furthermore, unit A may further include a third auxiliary part. If unit A includes a third auxiliary part, the arrangement of the third auxiliary part is located C-terminally relative to the arrangement of the first Th epitope in the arrangement of unit A. In particular, the third auxiliary part may have a dummy function, a solubility-enhancing function, a linker function, a protective function and / or a ring-forming function, but the functions of the third auxiliary part are not limited to these.

[0149] In another embodiment, unit A may be a unit in which a second Th epitope and a second B cell epitope are sequentially linked in a direction from the N-terminus to the C-terminus.

[0150] Furthermore, unit A may further include a fourth auxiliary part. If unit A includes a fourth auxiliary part, the arrangement of the fourth auxiliary part is located N-terminally relative to the arrangement of the second Th epitope in the arrangement of unit A. In particular, the fourth auxiliary part may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the fourth auxiliary part are not limited to these.

[0151] Furthermore, unit A may further include a fifth auxiliary portion. If unit A includes a fifth auxiliary portion, the sequence of the fifth auxiliary portion is located within the sequence of unit A between the sequence of the second B cell epitope and the sequence of the second Th epitope. In particular, the fifth auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the fifth auxiliary portion are not limited to these.

[0152] Furthermore, unit A may further include a sixth auxiliary portion. If unit A includes a sixth auxiliary portion, the sequence of the sixth auxiliary portion is located C-terminally relative to the sequence of the second B cell epitope in the sequence of unit A. In particular, the sixth auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the sixth auxiliary portion are not limited to these.

[0153] The structure of the unit A2 formula.

[0154] In one embodiment, unit A is a peptide represented by the following [Formula A] or [Formula A'].

[0155] [Formula A] (N)-A1-B1-A2-T1-A3-(C)

[0156] [Formula A'] (N)-A4-T2-A5-B2-A6-(C)

[0157] B1 and B2 are B cell epitopes and follow the design principles described above.

[0158] T1 and T2 are Th epitopes and follow the design principles described above.

[0159] Sections A1 through A6 are supplementary and can be omitted.

[0160] In particular, A1 to A6 may have dummy functions, solubility-enhancing functions, linker functions, and / or cyclic body-forming functions, but are not limited to these.

[0161] The length of unit A.

[0162] In practice, the length of unit A is approximately 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, 33mer, 34mer, 35mer, 36mer, 37mer, 38mer, 39mer, 40mer, 41mer, 42mer, 43mer, 44mer, 45mer, 46mer, 47mer, 48mer, 49mer, 50mer, 51mer, 52mer, 53mer, 54mer, 55mer, 56mer, 57mer, It may be approximately 58mer, approximately 59mer, approximately 60mer, approximately 61mer, approximately 62mer, approximately 63mer, approximately 64mer, approximately 65mer, approximately 66mer, approximately 67mer, approximately 68mer, approximately 69mer, approximately 70mer, approximately 71mer, approximately 72mer, approximately 73mer, approximately 74mer, approximately 75mer, approximately 76mer, approximately 77mer, approximately 78mer, approximately 79mer, approximately 80mer, approximately 81mer, approximately 82mer, approximately 83mer, approximately 84mer, approximately 85mer, approximately 86mer, approximately 87mer, approximately 88mer, approximately 89mer, approximately 90mer, approximately 91mer, approximately 92mer, approximately 93mer, approximately 94mer, approximately 95mer, approximately 96mer, approximately 97mer, approximately 98mer, approximately 99mer, or approximately 100mer. In another embodiment, unit A length may have a value within two numerical ranges selected in the preceding sentence. For example, the length of unit A may be in the range of approximately 16mer to approximately 30mer. In another example, the length of unit A may be in the range of approximately 23mer to approximately 60mer.

[0163] Unit A - Exemplary design embodiment.

[0164] In one embodiment, unit A may have a sequence in which a first B cell epitope, a first auxiliary portion, and a first Th epitope are sequentially linked. In particular, the first auxiliary portion has a linker function and contains one or more artificial amino acids.

[0165] In another embodiment, unit A may have a sequence in which a second auxiliary portion, a second B cell epitope, a third auxiliary portion, and a second Th epitope are sequentially linked. In particular, the second auxiliary portion is a His-tag, and the third auxiliary portion has linker function and contains one or more artificial amino acids.

[0166] In yet another embodiment, unit A may have a sequence in which a third B cell epitope, a fourth auxiliary portion, a third Th epitope, and a fifth auxiliary portion are sequentially linked. In particular, the fourth auxiliary portion has linker function and protective function, and the fifth auxiliary portion has protective function. The fourth and fifth auxiliary portions each contain one or more artificial amino acids.

[0167] In yet another embodiment, unit A may have an arrangement in which a sixth auxiliary portion, a fourth B cell epitope, a seventh auxiliary portion, a fourth Th epitope, and an eighth auxiliary portion are sequentially linked. In particular, the sixth auxiliary portion is a His-tag, the seventh auxiliary portion has linker and protective functions, and the eighth auxiliary portion has protective functions. The seventh and eighth auxiliary parts each contain one or more artificial amino acids.

[0168] An example of the arrangement of unit A.

[0169] One of the main ingredients is RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:56). NO:57)、CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:58)、KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:59). NO:60)、ZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:61)、RNVPPIFNDVYWIAFK(Cha)VAAWTLKAA(SEQ ID NO:62)、K(Cha)VAAWTLKAARNVPPIFNDVYWIAF(SEQ ID NO:62). NO:63)、RNVPPIFNDVYK(Cha)VAAWTLKAA(SEQ ID NO:64)、PIFNDVYWIAFK(Cha)VAAWTLKAA(SEQ ID NO:65). NO:66); NO:68)、GSHHHHHHGSDDDDKZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:69)、RNVPPIFNDVYWIAFGSHHHHHHGSDDDDKZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:70)、GSHHHHHHGSDDDDKZAK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:71)、GSHHHHHHGSDDDDKCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:71). NO:72) CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZGSHHHHHHGSDDDDK(SEQ IDNO:73)、GSHHHHHHGSDDDDKZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:74)、GSHHHHHHGSDDDDKKTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:75)、KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZGSHHHHHHGSDDDDK(SEQ ID NO:76)、MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:77)、MRGSHHHHHHGSDDDDKIVDGSHHHHHHGSDDDDKRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:78)、MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZGSHHHHHHGSDDDDK(SEQ ID NO:79)、RNVPPIFNDVYWIAFILMQYIKANSKFIGI(SEQ ID NO:80)、RNVPPIFNDVYWIAFILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:81)、CRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZC(SEQ ID NO:82)、RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAACR(SEQ ID NO:161)、RNVPPIFNDVYWIAFXXKXVAAWTLKAAXXGSHHHHHHGSDDDDK(SEQ ID NO:199)、GSHHHHHHGSDDDDKXXKXVAAWTLKAAXXRNVPPIFNDVYWIAF(SEQ ID NO:200)、RNVPPIFNDVYWIAFXXKXVAAWTLKAAXX(SEQ ID NO:204)、RNVPPIFNDVYWIAFKXVAAWTLKAA(SEQ ID NO:205)、RNVPPIFNDVYWIAFKXVAAWTLKAAHHHHHH(SEQ ID NO:206)、RNVPPIFNDVYWIAFXXKXVAAWTLKAACR(SEQ ID NO:208)、RNVPPIFNDVYWIAFXXKFVAAWTLKAAXX(SEQ IDThe unit peptide is selected from the group consisting of NO:210), RNVPPIFNDVYWIAFXXKFVAAWTLKAACR (SEQ ID NO:212), RNVPPIFNDVYWIAFCTKPTDGN (SEQ ID NO:213), RNVPPIFNDVYWIAFLLPIFFCLW (SEQ ID NO:214), RNVPPIFNDVYWIAFFLPSDFFPSV (SEQ ID NO:215), RNVPPIFNDVYWIAFILMQYIKANSKFIGIHHHHHH (SEQ ID NO:219), and RNVPPIFNDVYWIAFMDIDPYKEFGATVELLSFLPHHHHHH (SEQ ID NO:220). In this case, "a" represents D-type alanine, "Z" represents 6-aminohexanoic acid, "(Cha)" represents L-cyclohexyl alanine, and "X" represents any standard amino acid.

[0170] Design of Unit B.

[0171] Structure and overview of Unit B1.

[0172] The peptide units provided herein are referred to as "unit B" if they 1) comprise two B cell epitopes and one Th epitope, 2) the sequence of one of the two B cell epitopes is located between the sequence of the other B cell epitope and the sequence of the Th epitope, and 3) may contain one or more auxiliary moieties. The function of the auxiliary moieties is not particularly limited as long as it does not impair the functions of the B cell epitopes and Th epitopes, and may be designed as appropriate as needed.

[0173] In one embodiment, unit B may be a structure in which a first B cell epitope, a second B cell epitope, and a first Th epitope are sequentially linked in a direction from the N-terminus to the C-terminus.

[0174] Furthermore, unit B may further include a first auxiliary portion. If unit B includes a first auxiliary portion, the sequence of the first auxiliary portion is located N-terminally with respect to the sequence of the first B cell epitope in the sequence of unit B. In particular, the first auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the first auxiliary portion are not limited to these.

[0175] Furthermore, unit B may further include a second auxiliary portion. If unit B includes a second auxiliary portion, the sequence of the second auxiliary portion is located within the sequence of unit B between the sequence of the first B cell epitope and the sequence of the second B cell epitope. In particular, the second auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the functions of the second auxiliary portion are not limited to these.

[0176] Furthermore, unit B may further include a third auxiliary portion. If unit B includes a third auxiliary portion, the sequence of the third auxiliary portion is located within the sequence of unit B between the sequence of the second B cell epitope and the sequence of the first Th epitope. In particular, the third auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the functions of the third auxiliary portion are not limited to these.

[0177] Furthermore, unit B may further include a fourth auxiliary part. If unit B includes a fourth auxiliary part, the arrangement of the fourth auxiliary part is located C-terminally relative to the arrangement of the first Th epitope in the arrangement of unit B. In particular, the fourth auxiliary part may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the fourth auxiliary part are not limited to these.

[0178] In another embodiment, unit B may be a unit in which a second Th epitope, a third B cell epitope, and a fourth B cell epitope are sequentially linked from the N-terminus to the C-terminus.

[0179] Furthermore, unit B may further include a fifth auxiliary part. If unit B includes a fifth auxiliary part, the sequence of the fifth auxiliary part is located N-terminally relative to the sequence of the second Th epitope in the sequence of unit B. In particular, the fifth auxiliary part may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the fifth auxiliary part are not limited to these.

[0180] Furthermore, unit B may further include a sixth auxiliary portion. If unit B includes a sixth auxiliary portion, the sequence of the sixth auxiliary portion is located within the sequence of unit B between the sequence of the second Th epitope and the sequence of the third B cell epitope. In particular, the sixth auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the function of the sixth auxiliary portion is not limited to these.

[0181] Furthermore, unit B may further include a seventh auxiliary portion. If unit B includes a seventh auxiliary portion, the sequence of the seventh auxiliary portion is located within the sequence of unit B between the sequence of the third B cell epitope and the sequence of the fourth B cell epitope. In particular, the seventh auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the functions of the seventh auxiliary portion are not limited to these.

[0182] Furthermore, unit B may further include an eighth auxiliary portion. If unit B includes an eighth auxiliary portion, the sequence of the eighth auxiliary portion is located C-terminally relative to the sequence of the fourth B cell epitope in the sequence of unit B. In particular, the eighth auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the eighth auxiliary portion are not limited to these.

[0183] The structure of the unit B2 formula.

[0184] In one embodiment, unit B is a peptide represented by the following [Formula B] or [Formula B']. [Formula B] (N)-A1-B1-A2-B2-A3-T1-A4-(C) [Formula B'] (N)-A5-T2-A6-B3-A7-B4-A8-(C)

[0185] B1-B4 are B cell epitopes and follow the design principles described above.

[0186] T1 and T2 are Th epitopes and follow the design principles described above.

[0187] Sections A1 through A8 are supplementary and can be omitted.

[0188] In particular, A1 to A8 may have dummy functions, solubility-enhancing functions, linker functions, and / or cyclic body-forming functions, but are not limited to these.

[0189] Length of unit B

[0190] In one embodiment, the length of unit B is approximately 24 mer, 25 mer, 26 mer, 27 mer, 28 mer, 29 mer, 30 mer, 31 mer, 32 mer, 33 mer, 34 mer, 35 mer, 36 mer, 37 mer, 38 mer, 39 mer, 40 mer, 41 mer, 42 mer, 43 mer, 44 mer, 45 mer, 46 mer, 47 mer, 48 mer, 49 mer, 50 mer, 51 mer, 52 mer, 53 mer, 54 mer, 55 mer, 56 mer, 57 mer, 58 mer, 59 mer, 60 mer, 61 mer, It may be approximately 62mer, approximately 63mer, approximately 64mer, approximately 65mer, approximately 66mer, approximately 67mer, approximately 68mer, approximately 69mer, approximately 70mer, approximately 71mer, approximately 72mer, approximately 73mer, approximately 74mer, approximately 75mer, approximately 76mer, approximately 77mer, approximately 78mer, approximately 79mer, approximately 80mer, approximately 81mer, approximately 82mer, approximately 83mer, approximately 84mer, approximately 85mer, approximately 86mer, approximately 87mer, approximately 88mer, approximately 89mer, approximately 90mer, approximately 91mer, approximately 92mer, approximately 93mer, approximately 94mer, approximately 95mer, approximately 96mer, approximately 97mer, approximately 98mer, approximately 99mer, or approximately 100mer. In another embodiment, the length of unit B may have a value within the two numerical ranges selected in the preceding sentence. For example, the length of unit B may be in the range of approximately 24mer to approximately 45mer. In another example, the length of unit A may be in the range of approximately 40mer to approximately 80mer.

[0191] Unit B - Exemplary design embodiment.

[0192] In one embodiment, unit B may have a sequence in which a first auxiliary portion, a first B cell epitope, a second B cell epitope, a second auxiliary portion, and a first Th epitope are sequentially linked. In particular, the first auxiliary portion is a His-tag, and the second auxiliary portion contains one or more artificial amino acids.

[0193] In another embodiment, unit B may have an arrangement in which a third B cell epitope, a fourth B cell epitope, a third auxiliary portion, and a second Th epitope are sequentially linked. In particular, the third auxiliary portion has a linker function and contains one or more artificial amino acids.

[0194] In another embodiment, unit B may have a sequence in which a fourth auxiliary portion, a fifth B cell epitope, a sixth B cell epitope, a fifth auxiliary portion, a third Th epitope, and a sixth auxiliary portion are sequentially linked. In particular, the fourth auxiliary portion is a His-tag, the fifth auxiliary portion has linker function and protective function and contains one or more artificial amino acids, and the sixth auxiliary portion has protective function and contains one or more artificial amino acids.

[0195] In yet another embodiment, unit B may have an arrangement in which a seventh B cell epitope, an eighth B cell epitope, a seventh auxiliary portion, a fourth Th epitope, and an eighth auxiliary portion are sequentially linked. In particular, the seventh auxiliary portion has a linker function and a protective function and contains one or more artificial amino acids, and the eighth auxiliary portion has a protective function and contains one or more artificial amino acids.

[0196] In yet another embodiment, unit B may have a sequence in which an eighth auxiliary portion, a ninth B cell epitope, a ninth auxiliary portion, a tenth B cell epitope, a tenth auxiliary portion, and a fifth Th epitope are sequentially linked. In particular, the eighth auxiliary portion is a His-tag, the ninth auxiliary portion has linker function, and the tenth auxiliary portion has linker function and contains one or more artificial amino acids.

[0197] In yet another embodiment, unit B may have a sequence in which an eleventh B cell epitope, an eleventh auxiliary portion, a twelfth B cell epitope, a twelfth auxiliary portion, and a sixth Th epitope are sequentially linked. In particular, the eleventh auxiliary portion has linker function, and the twelfth auxiliary portion has linker function and contains one or more artificial amino acids.

[0198] In yet another embodiment, unit B may have a sequence in which a 13th B cell epitope, a 13th auxiliary portion, a 14th B cell epitope, a 14th auxiliary portion, a 7th Th epitope, and a 15th auxiliary portion are sequentially linked. In particular, the 13th auxiliary portion has a linker function, the 14th auxiliary portion has a linker function and a protective function and contains one or more artificial amino acids, and the 15th auxiliary portion has a protective function and contains one or more artificial amino acids.

[0199] An example of the arrangement of unit B.

[0200] In one case, unit B is RNVPPIFNDVYWIAFRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:83)、RNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:84) NO:85)、CRFRGLISLSQVYLSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:86). NO:87) CRFRGLISLSQVYLSKTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:88)、KTTKQSFDLSVKAQYKKNKHRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:89)、KTTKQSFDLSVKAQYKKNKHCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:90)、KTTKQSFDLSVKAQYKKNKHKTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:91)、RNVPPIFNDVYWIAFCRFRGLISLSQVYLSK(Cha)VAAWTLKAA(SEQ ID NO:92)、PIFNDVYWIAFGLISLSQVYLSK(Cha)VAAWTLKAA(SEQ ID NO:93)、RNVPPIFNDVYCRFRGLISLSQK(Cha)VAAWTLKAA(SEQ ID NO:93). NO:94)、PIFNDVYWIAFCRFRGLISLSQK(Cha)VAAWTLKAA(SEQ ID NO:95)、PPIFNDVYWRGLISLSQVK(Cha)VAAWTLKAA(SEQ ID NO:96)、RNVPPIFNDVYWIAFCRFRGLISLSQVYLSK(Cha)VAAWTLKAAHHHHHH(SEQ ID NO:96).NO:97), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:98), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAA(SEQ ID NO:99), RNVPPIFDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAA(SEQ ID NO:100), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAA(SEQ ID NO:101), RNVPPIFNDVYWIAFGGGGSGGGGGGSSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAA(SEQ ID NO:102), RNVPPIFNDVYWIAFGGGGSGGGGGGSSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:103), RNVPPIFNDVYWIAFRNVPPIFNDVYWIAFILMQYIKANSKFIGI(SEQ ID NO:104), RNVPPIFNDVYWIAFRNVPPIFNDVYWIAFILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:105), CRNVPPIFNFDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZC(SEQ ID This is a peptide unit selected from the group consisting of NO:106) and RNVPPIFNDVYWIAFCRFRGLISLSQVYLSXXK(Cha)VAAWTLKAAXX (SEQ ID NO:202). In this case, "a" represents D-type alanine, "Z" represents 6-aminohexanoic acid, "(Cha)" represents L-cyclohexylalanine, and "X" represents any standard amino acid.

[0201] Design of the unit C.

[0202] Structure and overview of unit C1.

[0203] The peptide units provided herein are referred to as "unit C" if they 1) comprise two B cell epitopes and one Th epitope, 2) the sequence of the Th epitope is located between the sequence of one of the two B cell epitopes and the sequence of the other B cell epitope, and 3) may include one or more auxiliary moieties. The function of the auxiliary moieties is not particularly limited as long as it does not impair the function of the B cell epitopes and the Th epitope, and may be designed as appropriate as needed.

[0204] In one embodiment, unit C may be a structure in which a first B cell epitope, a first Th epitope, and a second B cell epitope are sequentially linked in a direction from the N-terminus to the C-terminus.

[0205] Furthermore, unit C may further include a first auxiliary portion. If unit C includes a first auxiliary portion, the sequence of the first auxiliary portion is located N-terminally with respect to the sequence of the first B cell epitope within the sequence of unit C. In particular, the first auxiliary part may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the first auxiliary part are not limited to these.

[0206] Furthermore, unit C may further include a second auxiliary portion. If unit C includes a second auxiliary portion, the sequence of the second auxiliary portion is located within the sequence of unit C between the sequence of the first B cell epitope and the sequence of the first Th epitope. In particular, the second auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the functions of the second auxiliary portion are not limited to these.

[0207] Furthermore, unit C may further include a third auxiliary part. If unit C includes a third auxiliary portion, the sequence of the third auxiliary portion is located within the sequence of unit C between the sequence of the first Th epitope and the sequence of the second B cell epitope. In particular, the third auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the functions of the third auxiliary portion are not limited to these.

[0208] Furthermore, unit C may further include a fourth auxiliary portion. If unit C includes a fourth auxiliary portion, the sequence of the fourth auxiliary portion is located C-terminally relative to the sequence of the second B cell epitope in the sequence of unit C. In particular, the fourth auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the fourth auxiliary portion are not limited to these.

[0209] The structure of the unit C2 formula.

[0210] In one embodiment, unit C is a peptide represented by the following formula C. [Formula C] (N)-A1-B1-A2-T1-A3-B2-A4-(C)

[0211] B1 and B2 are B cell epitopes and follow the design principles described above.

[0212] T1 is the Th epitope and follows the design principles described above.

[0213] A1, A2, A3, and A4 are auxiliary sections and can be omitted.

[0214] In particular, A1, A2, A3, and A4 may have dummy functions, solubility-enhancing functions, linker functions, and / or cyclic body-forming functions, but are not limited to these.

[0215] Length in unit C.

[0216] In one embodiment, the length of unit C is approximately 24 mer, 25 mer, 26 mer, 27 mer, 28 mer, 29 mer, 30 mer, 31 mer, 32 mer, 33 mer, 34 mer, 35 mer, 36 mer, 37 mer, 38 mer, 39 mer, 40 mer, 41 mer, 42 mer, 43 mer, 44 mer, 45 mer, 46 mer, 47 mer, 48 mer, 49 mer, 50 mer, 51 mer, 52 mer, 53 mer, 54 mer, 55 mer, 56 mer, 57 mer, 58 mer, 59 mer, 60 mer, and 61 me. r may be approximately 62mer, approximately 63mer, approximately 64mer, approximately 65mer, approximately 66mer, approximately 67mer, approximately 68mer, approximately 69mer, approximately 70mer, approximately 71mer, approximately 72mer, approximately 73mer, approximately 74mer, approximately 75mer, approximately 76mer, approximately 77mer, approximately 78mer, approximately 79mer, approximately 80mer, approximately 81mer, approximately 82mer, approximately 83mer, approximately 84mer, approximately 85mer, approximately 86mer, approximately 87mer, approximately 88mer, approximately 89mer, approximately 90mer, approximately 91mer, approximately 92mer, approximately 93mer, approximately 94mer, approximately 95mer, approximately 96mer, approximately 97mer, approximately 98mer, approximately 99mer, and approximately 100mer. In another embodiment, the length of unit C may have a value within two numerical ranges selected in the preceding sentence. For example, the length of unit C may be in the range of approximately 24mer to approximately 45mer. In another example, the length of unit A may be in the range of approximately 40mer to approximately 80mer.

[0217] Unit C - Exemplary design embodiment.

[0218] In one embodiment, unit C may have a sequence in which a first B cell epitope, a first auxiliary portion, a first Th epitope, a second auxiliary portion, and a second B cell epitope are sequentially linked. In particular, the first and second auxiliary portions have linker function and protective function, respectively. The first and second auxiliary portions each contain one or more artificial amino acids.

[0219] In another embodiment, unit C may have a sequence in which a third auxiliary portion, a third B cell epitope, a fourth auxiliary portion, a second Th epitope, a fifth auxiliary portion, and a fourth B cell epitope are sequentially linked. In particular, the third auxiliary portion is a His-tag, and the fourth and fifth auxiliary portions have linker and protective functions, respectively. The fourth and fifth auxiliary portions each contain one or more artificial amino acids.

[0220] An embodiment of the arrangement of unit C.

[0221] In one embodiment, unit C is RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:107), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:108), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:109), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:110), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:111), RNVPPIFNFDVYWIAFZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:112), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZRNVPPIFNFDVYWIAF(SEQ ID NO:113), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:114), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:115), PIFNDVYWIAFK(Cha)VAAWTLKAACRFRGLISLSQ(SEQ ID NO:116), PPIFNDVYWK(Cha)VAAWTLKAARGLISLSQV(SEQ ID NO:117), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNFDVYWIAF(SEQ ID NO:118), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSILMQYIKANSKFIGIPMGLPQSIALSSLMVAQGGGGSGGGGGSSCRFRGLISLSQVYLS(SEQ ID NO:119), RNVPPIFNDVYWIAFILMQYIKANSKFIGICRFRGLISLSQVYLS(SEQ IDNO:120), RNVPPIFNDVYWIAFZPKYVKQNTLKLATZCRFRGLISLSQVYLS(SEQ ID NO:121), CRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFC(SEQ ID NO:122), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:160), RNVPPIFNDVYWIAFXXKXVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:198), KTTKQSFDLSVKAQYKKNKHXXKXVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:201), RNVPPIFNFDVYWIAFXPKYVKQNTLKLATXCRFRGLISLSQVYLS(SEQ ID NO:203), RNVPPIFNDVYWIAFXXKXVAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:207), RNVPPIFNDVYWIAFXXKFVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:209), RNVPPIFNDVYWIAFXXKFVAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:211), KTTKQSFDLSVKAQYKKNKHZaWPEANQVGAGAFGPGFaZCRFRGLISLSQVYLS(SEQ ID NO:216), KTTKQSFDLSVKAQYKKNKHZaMDIDPYKEFGATVELLSFLPaZCRFRGLISLSQVYLS(SEQ ID This is a peptide unit selected from the group consisting of NO:217) and KTTKQSFDLSVKAQYKKNKHZaILMQYIKANSKFIGIPMGLPQSIALSSLMVAQaZCRFRGLISLSQVYLS (SEQ ID NO:218). In this case, "a" represents D-type alanine, "Z" represents 6-aminohexanoic acid, "(Cha)" represents L-cyclohexylalanine, and "X" represents any standard amino acid.

[0222] Design of unit D.

[0223] Structure and overview of unit D1.

[0224] The peptide units provided herein are referred to as "unit C" if they 1) comprise one B cell epitope and two Th epitopes, 2) the sequence of one of the two Th epitopes is located between the sequence of the other Th epitope and the sequence of the B cell epitope, and 3) may include one or more auxiliary moieties. The function of the auxiliary moieties is not particularly limited as long as it does not impair the function of the B cell epitope and the Th epitope, and may be designed as appropriate as needed.

[0225] In one embodiment, unit D may be a unit in which a first B cell epitope, a first Th epitope, and a second Th epitope are sequentially linked in a direction from the N-terminus to the C-terminus.

[0226] Furthermore, unit D may further include a first auxiliary portion. If unit D includes a first auxiliary portion, the sequence of the first auxiliary portion is located N-terminally with respect to the sequence of the first B cell epitope in the sequence of unit D. In particular, the first auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the first auxiliary portion are not limited to these.

[0227] Furthermore, unit D may further include a second auxiliary portion. If unit D includes a second auxiliary portion, the sequence of the second auxiliary portion is located within the sequence of unit D between the sequence of the first B cell epitope and the sequence of the first Th epitope. In particular, the second auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the functions of the second auxiliary portion are not limited to these.

[0228] Furthermore, unit D may further include a third auxiliary portion. If unit D includes a third auxiliary portion, the arrangement of the third auxiliary portion is located between the arrangement of the first Th epitope and the arrangement of the second Th epitope in the arrangement of unit D. In particular, the third auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the function of the third auxiliary portion is not limited to these.

[0229] Furthermore, unit D may further include a fourth auxiliary part. If unit D includes a fourth auxiliary part, the arrangement of the fourth auxiliary part is located C-terminally relative to the arrangement of the second Th epitope in the unit D sequence. In particular, the fourth auxiliary part may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the fourth auxiliary part are not limited to these.

[0230] In another embodiment, unit D may be a unit in which a third Th epitope, a fourth Th epitope, and a second B cell epitope are sequentially linked from the N-terminus to the C-terminus.

[0231] Furthermore, unit D may further include a fifth auxiliary portion. If unit D includes a fifth auxiliary portion, the sequence of the fifth auxiliary portion is located N-terminally relative to the sequence of the third Th epitope in the unit D sequence. In particular, the fifth auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the fifth auxiliary portion are not limited to these.

[0232] Furthermore, unit D may further include a sixth auxiliary portion. If unit D includes a sixth auxiliary portion, the sequence of the sixth auxiliary portion is located between the sequence of the third Th epitope and the sequence of the fourth Th epitope in the unit D sequence. In particular, the sixth auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the function of the sixth auxiliary portion is not limited to these.

[0233] Furthermore, unit D may further include a seventh auxiliary portion. If unit D includes a seventh auxiliary portion, the sequence of the seventh auxiliary portion is located within the sequence of unit D between the sequence of the fourth Th epitope and the sequence of the second B cell epitope. In particular, the seventh auxiliary part may have a dummy function, a solubility-enhancing function, a linker function, and / or a protective function, but the functions of the seventh auxiliary part are not limited to these.

[0234] Furthermore, unit D may further include an eighth auxiliary portion. If unit D includes an eighth auxiliary portion, the sequence of the eighth auxiliary portion is located C-terminally relative to the sequence of the second B cell epitope in the unit D sequence. In particular, the eighth auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the eighth auxiliary portion are not limited to these.

[0235] The structure of the unit D2 formula.

[0236] In one embodiment, unit B is a peptide represented by the following [Formula D] or [Formula D']. [Formula D] (N)-A1-B1-A2-T1-A3-T2-A4-(C) [Formula D'] (N)-A5-T3-A6-T4-A7-B2-A8-(C)

[0237] B1 and B2 are B cell epitopes and follow the design principles described above.

[0238] T1-T4 are Th epitopes and follow the design principles described above.

[0239] Sections A1-A8 are supplementary and can be omitted.

[0240] In particular, A1 to A8 may have dummy functions, solubility-enhancing functions, linker functions, and / or cyclic body-forming functions, but are not limited to these.

[0241] Length in unit D

[0242] When used in an example, the length of unit D is approximately 24 mer, 25 mer, 26 mer, 27 mer, 28 mer, 29 mer, 30 mer, 31 mer, 32 mer, 33 mer, 34 mer, 35 mer, 36 mer, 37 mer, 38 mer, 39 mer, 40 mer, 41 mer, 42 mer, 43 mer, 44 mer, 45 mer, 46 mer, 47 mer, 48 mer, 49 mer, 50 mer, 51 mer, 52 mer, 53 mer, 54 mer, 55 mer, 56 mer, 57 mer, 58 mer, 59 mer, 60 mer, 61 mer. , In another example, the length of unit A may be in the range of approximately 40mer to approximately 80mer.

[0243] Unit D - Exemplary design embodiment.

[0244] In one embodiment, unit D may have a sequence in which a first auxiliary portion, a first B cell epitope, a second auxiliary portion, a first Th epitope, a third auxiliary portion, and a second Th epitope are sequentially linked. In particular, the first auxiliary portion is a His-tag, and the second and third auxiliary portions each have linker functions. The second and third auxiliary portions each contain one or more artificial amino acids.

[0245] In another embodiment, unit D may have a sequence in which a fourth auxiliary portion, a second B cell epitope, a fifth auxiliary portion, a third Th epitope, a sixth auxiliary portion, a fourth Th epitope, and a seventh auxiliary portion are sequentially linked. In particular, the fourth auxiliary portion is a His-tag, the fifth and sixth auxiliary portions each have a linker function, and the seventh auxiliary portion has a protective function. The fifth, sixth, and seventh auxiliary portions each contain one or more artificial amino acids.

[0246] In yet another embodiment, unit D includes a third B cell epitope, an eighth auxiliary portion, a fifth Th epitope, a ninth auxiliary portion, and a sixth Th epitope. In particular, the eighth and ninth auxiliary portions each have linker functions. The eighth and ninth auxiliary portions each have protective functions and each contains one or more artificial amino acids.

[0247] In yet another embodiment, unit D includes a fourth B cell epitope, a tenth auxiliary portion, a seventh Th epitope, an eleventh auxiliary portion, an eighth Th epitope, and a twelfth auxiliary portion. In particular, the tenth and eleventh auxiliary portions each have a linker function. The twelfth auxiliary portion has a protective function. The tenth, eleventh, and twelfth auxiliary portions each contain one or more artificial amino acids.

[0248] An example of the arrangement of unit D.

[0249] In one embodiment, the unit D is RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGI(SEQ ID NO:123), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ ILMQYIKANSKFIGI(SEQ ID NO:124), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGI(SEQ ID NO:125), ILMQYIKANSKFIGIZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:126), ILMQYIKANSKFIGIZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:127), ILMQYIKANSKFIGIZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:128), PIFNDVYWIAFK(Cha)VAAWTLKAAK(Cha)VAAWTLKAA(SEQ ID NO:129), PPIFNDVYWK(Cha)VAAWTLKAAK(Cha)VAAWTLKAA(SEQ ID NO:130), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGI(SEQ ID NO:131), MRGSHHHHHHGSDDDDKIVDILMQYIKANSKFIGIZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:132), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGI(SEQ ID NO:133), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSILMQYIKANSKFIGIPMGLPQSIALSSLMVAQGGGGSGGGGGGSSILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:134), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZK(Cha)LAAFTIRAAaZ(SEQ IDThis is a unit peptide selected from the group consisting of NO:135) and CRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIC (SEQ ID NO:136). In this case, "a" represents D-type alanine, "Z" represents 6-aminohexanoic acid, "(Cha)" represents L-cyclohexylalanine, and "X" represents any standard amino acid.

[0250] Design of the unit E.

[0251] Structure and overview of unit E1.

[0252] The peptide units provided herein are defined as "unit E" if 1) they comprise two B cell epitopes and two Th epitopes, 2) the sequence of each of the two Th epitopes is located between the sequence of one of the two B cell epitopes and the sequence of the other B cell epitope, and 3) they may contain one or more auxiliary moieties. The function of the auxiliary moieties is not particularly limited as long as it does not impair the function of the B cell epitopes and Th epitopes, and may be designed as appropriate as needed.

[0253] In one embodiment, unit E may be a structure in which a first B cell epitope, a first Th epitope, a second Th epitope, and a second B cell epitope are sequentially linked from the N-terminus to the C-terminus.

[0254] Furthermore, unit E may further include a first auxiliary portion. If unit E includes a first auxiliary portion, the sequence of the first auxiliary portion is located N-terminally with respect to the sequence of the first B cell epitope in the unit E sequence. In particular, the first auxiliary portion may have a dummy function, a solubility-enhancing function, a linker function, and / or a ring-forming function, but the functions of the first auxiliary portion are not limited to these.

[0255] Furthermore, unit E may include a second auxiliary part. When the unit E includes a second auxiliary portion, the sequence of the second auxiliary portion is located between the sequence of the first B cell epitope and the sequence of the first Th epitope within the unit E sequence. In particular, the second auxiliary portion may have, but is not limited to, a dummy function, a solubility improving function, a linker function, and / or a protective function.

[0256] Furthermore, the unit E may further include a third auxiliary portion. When the unit E includes a third auxiliary portion, the sequence of the third auxiliary portion is located between the sequence of the first Th epitope and the sequence of the second Th epitope within the sequence of the unit E. In particular, the third auxiliary portion may have, but the function of the third auxiliary portion is not limited to, a dummy function, a solubility improving function, a linker function, and / or a protective function.

[0257] Furthermore, the unit E may further include a fourth auxiliary portion. When the unit E includes a fourth auxiliary portion, the sequence of the fourth auxiliary portion is located between the sequence of the second B cell epitope and the sequence of the second B cell epitope within the unit E sequence. In particular, the fourth auxiliary portion may have, but the function of the fourth auxiliary portion is not limited to, a dummy function, a solubility improving function, a linker function, and / or a protective function.

[0258] Furthermore, the unit E may further include a fifth auxiliary portion. When the unit E includes a fifth auxiliary portion, the sequence of the fifth auxiliary portion is located on the N-terminal side relative to the sequence of the second B cell epitope within the unit E sequence. In particular, the fifth auxiliary portion may have, but the function of the fifth auxiliary portion is not limited to, a dummy function, a solubility improving function, a linker function, and / or a cyclization formation function.

[0259] Structure of unit E2-formula

[0260] In one embodiment, the unit E is a peptide represented by the following [Formula E]. [Formula E] (N)-A1-B1-A2-T1-A3-T2-A4-B2-A5-(C)

[0261] B1 and B2 are B cell epitopes and follow the design principles described above.

[0262] T1 and T2 are Th epitopes and follow the design principles described above.

[0263] A1, A2, A3, A4, and A5 are auxiliary parts and can be omitted.

[0264] In particular, A1, A2, A3, A4, and A5 may have dummy functions, solubility-enhancing functions, linker functions, and / or cyclic body-forming functions, but are not limited to these.

[0265] Length in units of E.

[0266] In one embodiment, the length of unit E is approximately 32 mer, approximately 33 mer, approximately 34 mer, approximately 35 mer, approximately 36 mer, approximately 37 mer, approximately 38 mer, approximately 39 mer, approximately 40 mer, approximately 41 mer, approximately 42 mer, approximately 43 mer, approximately 44 mer, approximately 45 mer, approximately 46 mer, approximately 47 mer, approximately 48 mer, approximately 49 mer, approximately 50 mer, approximately 51 mer, approximately 52 mer, approximately 53 mer, approximately 54 mer, approximately 55 mer, approximately 56 mer, approximately 57 mer, approximately 58 mer, approximately 59 mer, approximately 60 mer, approximately 61 mer, approximately 62 mer, approximately 63 mer, approximately 64 mer, approximately 65 mer. It may be approximately 66mer, approximately 67mer, approximately 68mer, approximately 69mer, approximately 70mer, approximately 71mer, approximately 72mer, approximately 73mer, approximately 74mer, approximately 75mer, approximately 76mer, approximately 77mer, approximately 78mer, approximately 79mer, approximately 80mer, approximately 81mer, approximately 82mer, approximately 83mer, approximately 84mer, approximately 85mer, approximately 86mer, approximately 87mer, approximately 88mer, approximately 89mer, approximately 90mer, approximately 91mer, approximately 92mer, approximately 93mer, approximately 94mer, approximately 95mer, approximately 96mer, approximately 97mer, approximately 98mer, approximately 99mer, or approximately 100mer. In another embodiment, the length of unit E may have a value within two numerical ranges selected in the preceding sentence. For example, the length of unit E may be in the range of approximately 32mer to approximately 60mer. In another example, the length of unit A may be in the range of approximately 50mer to approximately 100mer.

[0267] Unit E - Exemplary design embodiment.

[0268] In one embodiment, unit E may have a sequence in which a first auxiliary portion, a first B cell epitope, a second auxiliary portion, a first Th epitope, a third auxiliary portion, a second Th epitope, a fourth auxiliary portion, and a second B cell epitope are sequentially linked. In particular, the first auxiliary portion is a His-tag. The second and fourth auxiliary portions have linker function and protective function, respectively. The third auxiliary portion has linker function. The second, third, and fourth auxiliary portions contain one or more artificial amino acids.

[0269] In another embodiment, unit E may have a sequence in which a third B cell epitope, a fifth auxiliary portion, a third Th epitope, a sixth auxiliary portion, a fourth Th epitope, a seventh auxiliary portion, and a fourth B cell epitope are sequentially linked. In particular, the fifth and seventh auxiliary portions have linker and protective functions, respectively. The sixth auxiliary portion has a linker function. The fifth, sixth, and seventh auxiliary portions contain one or more artificial amino acids.

[0270] An example of the arrangement of unit E.

[0271] In one embodiment, unit E is RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF(SEQ ID NO:137), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGICRFRGLISLSQVYLS(SEQ ID NO:138), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:139), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF(SEQ ID NO:140), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGICRFRGLISLSQVYLS(SEQ ID NO:141), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:142), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF(SEQ ID NO:143), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGICRFRGLISLSQVYLS(SEQ ID NO:144), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:145), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF(SEQ IDThis peptide unit is selected from the group consisting of NO:146), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSILMQYIKANSKFIGIPMGLPQSIALSSLMVAQILMQYIKANSKFIGIPMGLPQSIALSSLMVAQGGGGSGGGGGGSSCRFRGLISLSQVYLS (SEQ ID NO:147), PIFNDVYWIAFK(Cha)VAAWTLKAAK(Cha)VAAWTLKAACRFRGLISLSQ (SEQ ID NO:148), PPIFNDVYWK(Cha)VAAWTLKAAK(Cha)VAAWTLKAARGLISLSQV (SEQ ID NO:149), and CRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAFC (SEQ ID NO:150). In this case, "a" represents D-type alanine, "Z" represents 6-aminohexanoic acid, and "(Cha)" represents L-cyclohexylalanine.

[0272] Peptide design.

[0273] Peptide design - overview.

[0274] The peptides provided herein can be designed using one or more of the peptide units disclosed above. These peptides may contain one or more peptide units, and may contain one or more types of peptide units. For example, peptides can be designed by: 1) using only one peptide unit; 2) designing a concatemer by linking multiple peptide units of the same type having the same sequence; 3) designing a peptide in a chain-like form by linking one or more types of peptide units having different sequences; 4) combining the design methods described in 1) to 3) above; or 5) designing a cyclic peptide by linking both ends of peptides designed by the above methods, but the design methods are not limited to these. Each design method will be described in detail below.

[0275] Single unit design.

[0276] The peptide may be designed to contain only one of the above peptide units. In one embodiment, the peptide may comprise one peptide unit selected from the group consisting of unit A, unit B, unit C, unit D, and unit E. In particular, the peptide unit has the configuration described above.

[0277] Concatemer design 1 - Overview.

[0278] A peptide can be designed in the form of a concatemer in which a plurality of peptide units having the same sequence are linked. A peptide designed in concatemer form consists of 1) one type of peptide unit, and 2) a plurality of peptide units having identical or equivalent sequences.

[0279] In particular, the expression two peptide units "having equivalent sequences" refers to 1) the case where an auxiliary moiety is present at the N-terminus and / or C-terminus of each of the two peptides, and 2) when such an auxiliary moiety is present, the case where the remaining sequences are identical even if the sequences of the auxiliary moieties differ between the two. For example, when a first peptide has a sequence in which a first auxiliary moiety and a first unit A are linked in the direction from the N-terminus to the C-terminus, a second peptide has a sequence in which the first unit A and the first auxiliary moiety are linked in the direction from the N-terminus to the C-terminus, a third peptide has a sequence in which a second auxiliary moiety, the first unit A, and a third auxiliary moiety are linked in the direction from the N-terminus to the C-terminus, and a fourth peptide has the sequence of the first unit A, the first to fourth peptides are said to have equivalent sequences.

[0280] In one embodiment, the peptide may comprise one in which a first peptide unit and a second peptide unit are sequentially linked. In particular, the first peptide unit is a peptide unit selected from the group consisting of unit A, unit B, unit C, unit D and unit E, and the second peptide unit has a sequence identical or equivalent to that of the first peptide unit.

[0281] In another embodiment, the peptide may include a sequence in which a third peptide unit, a fourth peptide unit, and a fifth peptide unit are sequentially linked. In particular, the third peptide unit is a peptide unit selected from the group consisting of units A, B, C, D, and E, and the fourth and fifth peptide units each have the same or equivalent sequence as the third peptide unit.

[0282] In yet another embodiment, the peptide may include a sequence in which a sixth peptide unit, a seventh peptide unit, an eighth peptide unit, and a ninth peptide unit are linked together. In particular, the third peptide unit is a peptide unit selected from the group consisting of units A, B, C, D, and E, and the seventh, eighth, and ninth peptide units each have the same or equivalent sequence as the sixth peptide unit.

[0283] Concatemer Design 2-Format

[0284] In one embodiment, the peptide may be a peptide represented by the following formula [Formula 1]. [Formula 1] (N)-U1-U2-…-U n -(C) In the formula, U1~U n Each of these is a peptide unit selected from the group consisting of units A, B, C, D, and E, and these units have the constituent elements of the peptide unit described above.

[0285] U1~U n They have the same or equivalent sequence.

[0286] n is an integer greater than or equal to 2.

[0287] Concatemer Design 3 - Exemplary Arrangement

[0288] In one embodiment, the peptide is MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:151), RNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:152), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID The peptide is selected from the group consisting of NO:153), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGI (SEQ ID NO:154), and RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAFRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF (SEQ ID NO:155). In this case, "a" represents D-type alanine, "Z" represents 6-aminohexanoic acid, and "(Cha)" represents L-cyclohexylalanine.

[0289] Chain-reaction design 1 - Overview

[0290] Peptides can be designed in a chain-like form in which multiple peptide units having different sequences are linked together. A peptide designed in a chain-like form consists of 1) at least one type of peptide unit and 2) multiple peptide units having different sequences.

[0291] In one embodiment, the peptide may include a first peptide unit and a second peptide unit linked together sequentially. In particular, the first peptide unit and the second peptide unit are peptide units selected from the group consisting of units A, B, C, D, and E, and the first peptide unit and the second peptide unit have different sequences from each other.

[0292] In another embodiment, the peptide may include a third peptide unit, a fourth peptide unit, and a fifth peptide unit linked together in sequence. In particular, the third peptide unit, the fourth peptide unit, and the fifth peptide are each peptide units selected from the group consisting of units A, B, C, D, and E, and the third peptide unit, the fourth peptide unit, and the fifth peptide unit have different sequences from each other.

[0293] In yet another embodiment, the peptide may include a sequence in which a sixth peptide unit, a seventh peptide unit, an eighth peptide unit, and a ninth peptide unit are linked together. In particular, the sixth peptide unit, the seventh peptide unit, the eighth peptide unit, and the ninth peptide unit are each peptide units selected from the group consisting of units A, B, C, D, and E, and the sixth peptide unit, the seventh peptide unit, the eighth peptide unit, and the ninth peptide unit have different sequences from each other.

[0294] Bead-link design, type 2

[0295] In one embodiment, the peptide may be a peptide represented by the following formula [Formula 2]. [Formula 2] (N)-U1-U2-…-U n -(C)

[0296] In the formula, U1~U n Each of these is a peptide unit selected from the group consisting of units A, B, C, D, and E, and these units have the constituent elements of the peptide unit described above.

[0297] U1~U n These have the same or equivalent sequence.

[0298] n is an integer greater than or equal to 2.

[0299] Bead-like design 3 - Exemplary arrangement

[0300] In one embodiment, the peptide may be RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ (SEQ ID NO:156), where "a" represents D-type alanine, Z represents 6-aminohexanoic acid, and (Cha) represents L-cyclohexylalanine.

[0301] Combination Design 1 - Overview

[0302] Peptides may be designed by appropriately combining the above-described 1) single-unit design, 2) concatemer design, and 3) chain design. In one embodiment, a peptide may be designed by first designing a unit peptide according to the above design method, and then linking a plurality of unit peptides together.

[0303] In one embodiment, the peptide may be formed by sequentially linking a first unit peptide and a second unit peptide. In particular, the first unit peptide and the second unit peptide each have peptide components according to one of the following: a single-unit design, a concatemer design, or a chain design, and the sequences of the first unit peptide and the second unit peptide are different from each other.

[0304] In another embodiment, the peptide may be a sequence of a third unit peptide, a fourth unit peptide, and a fifth unit peptide linked together. In particular, the third unit peptide, the fourth unit peptide, and the fifth unit peptide each have peptide components according to one of the following: a single-unit design, a concatemer design, and a chain design, and the sequences of the third unit peptide, the fourth unit peptide, and the fifth unit peptide are different from each other.

[0305] In yet another embodiment, the peptide may be formed by sequentially linking a sixth unit peptide, a seventh unit peptide, an eighth unit peptide, and a ninth unit peptide. In particular, the sixth, seventh, eighth, and ninth unit peptides each have peptide components according to one of the following: a single-unit design, a concatemer design, or a chain design, and the sequences of the sixth, seventh, eighth, and ninth unit peptides are different from each other.

[0306] Combination Design 2-Format

[0307] In one embodiment, the peptide may be a peptide represented by the following formula [Formula 3]. [Formula 3] (N)-P1-P2-…-P n -(C)

[0308] In the formula, P1~P n These are unit peptides designed using a method selected from the group consisting of single-unit design, concatemer design, and chain design, and they possess the peptide designs and components described above.

[0309] n is an integer greater than or equal to 2.

[0310] Combination Design 3 - Exemplary Arrangement

[0311] In one embodiment, the peptide is RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFZRNVPPI FNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIZRNVPPIFNDVY WIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGICRFRGLISLSQVYLS (SEQ ID NO:157), and RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFCRFRGLI This peptide is selected from the group consisting of SLSQVYLSZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFZRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIZRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ ILMQYIKANSKFIGICRFRGLISLSQVYLS (SEQ ID NO: 158). In this case, "a" represents D-type alanine, "Z" represents 6-aminohexanoic acid, and "(Cha)" represents L-cyclohexylalanine.

[0312] Design of a ring-shaped body.

[0313] Peptides may be designed to form a cyclic structure. Since a cyclic structure improves the stability of a peptide within the target body, improved efficacy can be expected when a cyclic peptide is used as an immunotherapy drug. In one embodiment, with respect to a peptide designed by a design method selected from the group consisting of single-unit design, concatemer design, chain design, and combination design methods, the peptide may be further designed to have auxiliary moieties at its N-terminus and C-terminus that have the function of forming a cyclic structure. In another embodiment, with respect to a peptide designed by a design method selected from the group consisting of single-unit design, concatemer design, chain design, and combination design methods, the peptide may further include an auxiliary moiety and be designed to form a cyclic structure via the auxiliary moiety.

[0314] Other designs.

[0315] In addition to the design methods described above, peptides may be designed by other methods as needed. In one embodiment, with respect to peptides designed by a design method selected from the group consisting of single-unit design, concatemer design, chain design, and combination design methods, the peptide may further comprise one or more auxiliary moieties, one or more B cell epitopes, and / or one or more Th epitopes.

[0316] Disclosed peptide units and / or sequences similar to peptides.

[0317] This specification discloses peptide units and / or peptides having sequences similar to those disclosed in the sections “Unit A Design,” “Unit B Design,” “Unit C Design,” “Unit D Design,” “Unit E Design,” and “Peptide Design.”

[0318] In one embodiment, the peptide unit may have a sequence that is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of the sequences disclosed in the sections “Unit A Design”, “Unit B Design”, “Unit C Design”, “Unit D Design”, and “Unit E Design”. In another embodiment, the peptide unit may have a sequence that matches, at least numerically, with any one of the sequences disclosed in the sections “Unit A Design”, “Unit B Design”, “Unit C Design”, “Unit D Design”, and “Unit E Design”, as selected in the preceding sentence. In yet another embodiment, the peptide unit may have a sequence that has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with any one selected from SEQ ID NO:56~SEQ ID NO:150, SEQ ID NO:160~SEQ ID NO:161, and SEQ ID NO:198~SEQ ID NO:220. In yet another embodiment, the peptide unit may have a sequence that matches, at least numerically, with one of the disclosed sequences selected from SEQ ID NO:56~SEQ ID NO:150, SEQ ID NO:160~SEQ ID NO:161, and SEQ ID NO:198~SEQ ID NO:220, as selected in the preceding sentence. For example, the peptide unit may have a sequence that is 90% or more identical to SEQ ID NO:56.

[0319] In yet another embodiment, the peptide may have a sequence that is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of the sequences disclosed in the "Peptide Design" section. In yet another embodiment, the peptide may have a sequence that matches any one of the sequences disclosed in the "Peptide Design" section by at least the number selected in the preceding sentence. In yet another embodiment, the peptide may have a sequence that is 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one selected from SEQ ID NO:151 to SEQ ID NO:158. In yet another embodiment, the peptide may have a sequence that matches any one of SEQ ID NO:151 to SEQ ID NO:158 by at least the numerical value selected in the preceding sentence. For example, the peptide may have a sequence that is 90% or more identical to SEQ ID NO:151.

[0320] Use of peptides.

[0321] Peptide Uses - Overview.

[0322] The peptides provided herein are suitable as immunotherapies because, when introduced into a target body, they have the following properties: 1) they induce the production of antibodies that specifically bind to intentionally designed B cell epitopes, and 2) they induce the production of homogeneous antibodies. Therefore, these peptides can be used as immunotherapies. In one embodiment, the peptides provided herein can be used as immunotherapies for obesity. In another embodiment, peptide units and / or peptides containing them provided herein can be used for the treatment of obesity.

[0323] The use of peptides for the treatment of obesity.

[0324] The peptides provided herein include B cell epitopes. In one embodiment, the B cell epitopes may be those included in SEQ ID NOS:41-75. In particular, B cell epitopes are known to induce antibodies capable of binding to ApoB-100 (U.S. Patent Application No. 10 / 378,707, PCT / KR2005 / 000784, and Kim et al., 2016, An apolipoprotein B100 mimotope prevents obesity in mice, Clinical Science 130, 105-116). It is known from the above prior art that antibodies capable of binding to ApoB-100, when induced by B cell epitopes in the body of a subject, have an immunotherapeutic effect against obesity. Accordingly, the use of peptides and methods thereof for the treatment of obesity are disclosed herein. To illustrate the immunotherapeutic effects of peptides on obesity, U.S. Patent Application No. 10 / 378,707, PCT / KR2005 / 000784, and Kim et al., 2016, An apolipoprotein B100 mimotope prevents obesity in mice, Clinical Science 130, 105-116 are incorporated herein by reference. In the event of any conflict between the references and the statements herein, the statements herein should be construed as prevailing.

[0325] A pharmaceutical composition containing peptides.

[0326] This specification discloses pharmaceutical compositions comprising the above-described peptide. The peptide can be used as an immunotherapy and shares similarities with vaccines in that, upon injection into the body, it induces humoral immunity. Therefore, those skilled in the art may include in the peptide-containing pharmaceutical composition appropriate components that can be added for the administration of a common vaccine and / or to enhance the effect of inducing an immune response. For example, the pharmaceutical composition may, but is not limited to, formulated peptides, pharmaceutically acceptable carriers, supplements, and / or adjuvants. Specifically, the pharmaceutical composition includes water, physiological saline, dextrose, ethanol, glycerol, sodium chloride, dextrose, mannitol, sorbitol, lactose, gelatin, albumin, aluminum hydroxide, Freund's incomplete and complete adjuvants (Pifco Laboratories, Detroit, Michigan), Merck Adjuvant 65 (Merck and Company, Inc., Loway, New Jersey), aluminum hydroxide gel (Alum), or aluminum salts, such as aluminum phosphate, AS04 series, MF, squalene, MF59, QS21, calcium, iron or zinc salts, acylated tyrosine, acylated fructose insoluble suspension, cation or anion-derived polysaccharides, polyphosphazene, biodegradable microspheres, Quil A, toll-like receptor (TLR) agonists, and PHAD[Avanti polar Lipid Inc. may include monophosphoryl lipid A (synthetic), monophosphoryl lipid A (MPL, monophosphoryl lipid A), synthetic lipid A, lipid A mimics or analogues, aluminum salts, cytokines, saponins, prolactin, growth hormone deoxycholic acid, beta-glucan, polyribonucleotide, muramyl dipeptide (MDP) derivatives, CpG oligo, gram-negative bacterial lipopolysaccharide (LPS), polyphosphazene, emulsions, virosomens, cocriates, poly(lactide-co-glycolide) (PLG) microparticles, poloxamer particles, microparticles, liposomes, or appropriate combinations thereof.

[0327] A method for producing peptides.

[0328] The peptides provided herein can be prepared by known methods that can be employed by those skilled in the art, and the method of preparation is not particularly limited. In one embodiment, the peptides may be prepared by recombinant protein preparation methods. In another embodiment, the peptides may be chemically synthesized. Specifically, the peptides can be synthesized by liquid-phase peptide synthesis, solid-phase peptide synthesis, convergence of low molecular weight peptide fragments, etc., but the method is not limited to these.

[0329] A nucleic acid that codes for a peptide unit and / or a peptide.

[0330] Nucleic acids that encode peptide units and / or peptides - Overview.

[0331] This specification discloses nucleic acids that encode peptide units and / or peptides disclosed above (hereinafter referred to as "coding nucleic acids"). The peptide units and peptides disclosed herein may contain non-standard amino acids, but there are no codons in nature that correspond to non-standard amino acids. Therefore, non-standard amino acids cannot be encoded in a general manner. Accordingly, these non-standard amino acids must be replaced with appropriate standard amino acids and encoded in the form of nucleic acids. If the peptide units and / or peptides do not contain non-standard amino acids, coding nucleic acids can be designed using nucleic acid codons corresponding to each standard amino acid.

[0332] For the purposes of this specification, peptide units and / or peptides containing non-standard amino acids substituted with appropriate standard amino acids, as well as peptide units and / or peptides containing only standard amino acids, will be referred to as the encoded target peptide, and the DNA and / or RNA encoding the encoded target peptide will be referred to as the coding nucleic acid. In particular, if the peptide unit and / or peptide does not contain non-standard amino acids, the peptide unit and / or peptide has the same amino acid sequence as the encoded target peptide.

[0333] As used herein, the term “encoded target peptide” is a conceptual term introduced to facilitate the description of the resulting coding nucleic acid and is independent of any method or procedure for preparing the coding nucleic acid.

[0334] Design of the encoded target peptide.

[0335] If the peptide units and peptides disclosed herein contain non-standard amino acids, the encoded target peptide is designed by replacing the peptide with an appropriate standard amino acid. If the peptide units and peptides disclosed herein do not contain non-standard amino acids, the encoded corresponding target peptide has the same sequence as the peptide units and peptide. In one embodiment, the encoded target peptide may have non-standard amino acids replaced with any standard amino acids. In another embodiment, the encoded target peptide may have non-standard amino acids replaced with standard amino acids having the same or equivalent function. In yet another embodiment, the encoded target peptide may have the same sequence as the peptide units and / or peptide. In particular, the peptide units and / or peptide are characterized by not having non-standard amino acids.

[0336] Embodiments for designing the encoded target peptide - including PADRE.

[0337] The peptide units and peptides disclosed herein include one or more Th epitopes. In particular, if the Th epitope is a sequence named PADRE as disclosed in U.S. Patent Application No. 305,871, it may include the non-standard amino acid L-cyclohexylalanine. According to the literature, L-cyclohexylalanine is thought to have both the function of protecting PADRE from peptidolytic enzymes and the function of an anchor residue that can bind to MHC class II. Therefore, the target peptide to be encoded is designed by replacing L-cyclohexylalanine with a suitable standard amino acid having the same or equivalent function. In one embodiment, L-cyclohexylalanine may be substituted with any standard amino acid. In another embodiment, L-cyclohexylalanine may be substituted with phenylalanine or tyrosine. In yet another embodiment, the sequence of the target peptide encoded by PADRE may be KFVAAWTLKAA (SEQ ID NO: 195), KYVAAWTLKAA (SEQ ID NO: 196), or KXVAAWTLKAA (SEQ ID NO: 197), where X refers to any standard amino acid.

[0338] Embodiments of the sequence of the encoded target peptide.

[0339] In one embodiment, the sequence of the encoded target peptide is RNVPPIFNDVYWIAFXXKXVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:198), RNVPPIFNDVYWIAFXXKXVAAWTLKAAXXGSHHHHHHGSDDDDK(SEQ ID NO:199), GSHHHHHHGSDDDDKXXKXVAAWTLKAAXXRNVPPIFNDVYWIAF(SEQ ID NO:200), KTTKQSFDLSVKAQYKKNKHXXKXVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:201), RNVPPIFNDVYWIAFCRFRGLISLSQVYLSXXK(Cha)VAAWTLKAAXX(SEQ ID NO:202), RNVPPIFNDVYWIAFXPKYVKQNTLKLATXCRFRGLISLSQVYLS(SEQ ID NO:203), RNVPPIFNDVYWIAFXXKXVAAWTLKAAXX(SEQ ID NO:204), RNVPPIFNDVYWIAFKXVAAWTLKAA(SEQ ID NO:205), RNVPPIFNDVYWIAFKXVAAWTLKAAHHHHHH(SEQ ID NO:206), RNVPPIFNDVYWIAFXXKXVAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:207), RNVPPIFNDVYWIAFXXKXVAAWTLKAACR(SEQ ID NO:208), RNVPPIFNDVYWIAFXXKFVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:209), RNVPPIFNFDVYWIAFXXKFVAAWTLKAAXX(SEQ ID Selected from NO:210), RNVPPIFNDVYWIAFXXKFVAAWTLKAACRFRGLISLSQVYLS (SEQ ID NO:211), and RNVPPIFNDVYWIAFXXKFVAAWTLKAACR (SEQ ID NO:212). In this case, "X" represents any standard amino acid.

[0340] Design of coding nucleic acid 1 - based on nucleic acid codons.

[0341] The coding nucleic acids disclosed herein refer to nucleic acid codons that encode a target peptide to be encoded. Since all sequences of the target peptide to be encoded are standard amino acids, coding nucleic acids are designed based on nucleic acid codons corresponding to each amino acid of the target peptide to be encoded. In particular, since one or more nucleic acid codons may correspond to one standard amino acid, it is ultimately possible to design two or more coding nucleic acids that encode one target peptide to be encoded. In one embodiment, the coding nucleic acid may be a DNA and / or RNA codon that encodes the target peptide to be encoded. In another embodiment, the coding nucleic acid may have a DNA and / or RNA sequence that can bind complementarily to the DNA and / or RNA codon that encodes the target peptide to be encoded.

[0342] The coding nucleic acid sequence may be codon-optimized, which will be explained in more detail below.

[0343] Design of coding nucleic acid 2 - codon optimization.

[0344] As described above, by simply concatenating the nucleic acid codons corresponding to each amino acid of the target peptide to be encoded, it is possible to design multiple coding nucleic acids for a single target peptide. Since there are an average of 1 to 6 nucleic acid codons corresponding to each standard amino acid, the number of possible nucleic acid codon combinations increases exponentially as the amino acid sequence length increases. However, not all of these combinations are equally important. In general, there are nucleic acid codon combinations that can better express the target peptide encoded in a cell, and these combinations may differ depending on the higher-order structure of the sequence itself, the type of target cell into which the coding nucleic acid is injected, and other factors. Discovering such nucleic acid codon combinations and designating them as the coding nucleic acid sequence is called codon optimization. For a single target peptide to be encoded, there is not necessarily only one codon-optimized sequence; there may be two or more codon-optimized sequences.

[0345] In one embodiment, the coding nucleic acid may have a codon-optimized DNA and / or RNA sequence. In another embodiment, the coding nucleic acid may have a non-codon-optimized DNA and / or RNA sequence.

[0346] Codon optimization of coding nucleic acid 1 - Consideration of the higher-order structure of coding nucleic acid.

[0347] Codon optimization of coding nucleic acids may be performed considering the higher-order structure of the nucleic acid sequence itself. In one embodiment, the coding nucleic acid may be codon-optimized considering the GC content of the sequence. In another embodiment, the coding nucleic acid sequences were approximately less than 1%, approximately 1%, approximately 2%, approximately 3%, approximately 4%, approximately 5%, approximately 6%, approximately 7%, approximately 8%, approximately 9%, approximately 10%, approximately 11%, approximately 12%, approximately 13%, approximately 14%, approximately 15%, approximately 16%, approximately 17%, approximately 18%, approximately 19%, approximately 20%, approximately 21%, approximately 22%, approximately 23%, approximately 24%, approximately 25%, approximately 26%, approximately 27%, approximately 28%, approximately 29%, approximately 30%, approximately 31%, approximately 32%, approximately 33%, approximately 34%, approximately 35%, approximately 36%, approximately 37%, approximately 38%, approximately 39%, approximately 40%, approximately 41%, approximately 42%, approximately 43%, approximately 44%, and approximately 45%. Approximately 46%, approximately 47%, approximately 48%, approximately 49%, approximately 50%, approximately 51%, approximately 52%, approximately 53%, approximately 54%, approximately 55%, approximately 56%, approximately 57%, approximately 58%, approximately 59%, approximately 60%, approximately 61%, approximately 62%, approximately 63%, approximately 64%, approximately 65%, approximately 66%, approximately 67%, approximately 68%, approximately 69%, approximately 70%, approximately 71%, approximately 72%, approximately 73%, approximately 74%, approximately 75 The GC content may be in the range of %, approximately 76%, approximately 77%, approximately 78%, approximately 79%, approximately 80%, approximately 81%, approximately 82%, approximately 83%, approximately 84%, approximately 85%, approximately 86%, approximately 87%, approximately 88%, approximately 89%, approximately 90%, approximately 91%, approximately 92%, approximately 93%, approximately 94%, approximately 95%, approximately 96%, approximately 97%, 98%, approximately 99%, or less than approximately 100%. In yet another embodiment, the coding nucleic acid sequence may have a GC content within the numerical range selected in the preceding sentence. For example, the coding nucleic acid sequence may have a GC content in the range of approximately 20% to approximately 50%. In yet another embodiment, the coding nucleic acid sequence may have a GC content less than the numerical value selected in the preceding sentence. For example, the coding nucleic acid sequence may have a GC content of less than approximately 25%.

[0348] Codon optimization of coding nucleic acid 2 - considerations for target cells for expression.

[0349] Codon optimization of coding nucleic acids may be achieved by considering which cells the coding nucleic acids should be injected into and expressed in. In one embodiment, codon optimization of coding nucleic acids may be achieved by considering codon use in prokaryotic or eukaryotic cells. In another embodiment, codon optimization of coding nucleic acids may be achieved by considering codon use in animal cells. In yet another embodiment, codon optimization of coding nucleic acids may be achieved by considering codon use in mammals. In yet another embodiment, codon optimization of coding nucleic acids may be achieved by considering codon use in humans. In yet another embodiment, the coding nucleic acids may be codon-optimized for E. coli. In yet another embodiment, the coding nucleic acids may be codon-optimized for mammals. In yet another embodiment, the coding nucleic acids may be codon-optimized for humans.

[0350] An embodiment of a coding nucleic acid sequence.

[0351] In one embodiment, the coding nucleic acid is 5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCTTTCCGTGGACTGATTTCCCGTTCCCAGGTTTATCTGTCC-3' (SEQ ID NO:248), 5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCTTTCCGTGGACTGATTTCCCGTTCCCAGGTTTATCTGTCC-3' (SEQ ID NO:249), 5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCTTTCCGTGGACTGATTTCCCGTTCCCAGGTTTATCTGTCC-3' (SEQ ID NO:249) NO:250)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNGGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAG-3'(SEQ ID NO:251)、5'-ACGTAATGTTCCTCCTATCTTCAATGATGTTATTGGATTGCATTCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNGGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAG-3'(SEQ ID NO:252)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNGGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAG-3'(SEQ IDNO:253)、5'-GGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAGNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNCGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTC-3'(SEQ ID NO:254)、5'-GGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAGNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNCGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTC-3'(SEQ ID NO:255)、5'-GGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAGNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNCGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTC-3'(SEQ ID NO:256)、5'-AAAACGACAAAGCAATCATTTGATTTAAGTGTAAAAGCTCAGTATNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:257)、5'-AAAACGACAAAGCAATCATTTGATTTAAGTGTAAAAGCTCAGTATNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:258)、5'-AAAACGACAAAGCAATCATTTGATTTAAGTGTAAAAGCTCAGTATNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ IDNO:259)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:260)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:261)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:262)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNCCTAAGTATGTGAAGCAGAATACACTGAAGCTGGCAACCNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:263)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:264)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:265)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ IDNO:266)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCA-3'(SEQ ID NO:267)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCA-3'(SEQ ID NO:268)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCA-3'(SEQ ID NO:269)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCACATCACCATCACCATCAC-3'(SEQ ID NO:270)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCACATCACCATCACCATCAC-3'(SEQ ID NO:271)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCACATCACCATCACCATCAC-3'(SEQ ID NO:272)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:273)、5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ IDNO:274), 5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:275), 5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGT-3'(SEQ ID It can be represented by a sequence selected from NO:277) and 5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGT-3' (SEQ ID NO:278).

[0352] In one embodiment, the coding nucleic acid can be represented by an RNA sequence equivalent to a sequence selected from SEQ ID NO:248 to SEQ ID NO:278.

[0353] In another embodiment, the coding nucleic acid may be such that, in a sequence selected from SEQ ID NO:248 to SEQ ID NO:278, at least one codon is replaced with a codon encoding the same amino acid. For example, the coding nucleic acid may be such that the first codon (the first to third nucleic acids at the 5' end) (i.e., CGT) in the sequence of SEQ ID NO:248 is replaced with CGC, CGG, CGA, AGA, or AGG.

[0354] In yet another embodiment, the coding nucleic acid can be represented by an RNA sequence equivalent to one in which one or more codons are replaced by codons encoding the same amino acid in a sequence selected from SEQ ID NO:248 to SEQ ID NO:278.

[0355] A pharmaceutical composition comprising peptide units and / or nucleic acids encoding peptides.

[0356] Pharmaceutical compositions containing coding nucleic acids - Overview.

[0357] This specification provides pharmaceutical compositions comprising peptide units and / or nucleic acids encoding peptides (i.e., coding nucleic acids). To deliver the coding nucleic acids to the target in order to exert the intended effect of inducing an immune response, the coding nucleic acids must be formulated by an appropriate method. The coding nucleic acid was determined by known methods, e.g., WKKIM (2019, mRNA vaccine - a new era in vaccinology, BRIC View 2019-R11), Zhang et al. (2019, Advances in mRNA Vaccines for Infectious Diseases, Frontiers in Immunology, Vol.10 Article 594), Reichmuth et al. (2016, mRNA vaccine delivery using lipid nanoparticles, Therapeutic Delivery, 7(5), 319-334), Miao et al. (2021, mRNA vaccine for cancer immunotherapy, Molecular Cancer, 20:41), Boen et al. (2021, Identification of T Cell Ligands in a Library of Peptides Covalently Attached to HLA-DR4, The Journal of Immunology, 165:2040-2047), Pardi et al. (2018, mRNA vaccines - a new era in vaccinology, Nature) It can be formulated by the methods disclosed in Reviews, Vol. 17, 261-279 and Korean Patent Application No. 10-2017-0054429, but the methods are not limited to these.

[0358] A pharmaceutical composition containing a coding nucleic acid may further include an adjuvant and / or additional components in addition to the formulated coding nucleic acid. In one embodiment, the pharmaceutical composition containing a coding nucleic acid comprises a formulated coding nucleic acid, optionally an adjuvant, and optionally additional components.

[0359] Formulated coding nucleic acids.

[0360] Formulated coding nucleic acids can be formulated by those skilled in the art by selecting an appropriate delivery means (vector) for the coding nucleic acid. Coding nucleic acids can be formulated using viral vectors and / or non-viral vectors. In one embodiment, the formulated coding nucleic acid may contain a viral vector. In another embodiment, the formulated coding nucleic acid may contain a non-viral vector. Specifically, the non-viral vector may include, but is not limited to, lipids, polymers, and inorganic nanoparticles.

[0361] In yet another embodiment, the formulated coding nucleic acid may include one or more selected from the following:

[0362] Naked nucleic acids; cationic peptide complex nucleic acids (protamine); positively charged oil-water cationic nanoemulsions (cationic nanoemulsions); nucleic acids bound to chemically modified dendrimers and complexed with polyethylene glycol and PEG-lipids (modified dendrimer nanoparticles); nucleic acids complexed with protamine in PEG-lipid nanoparticles (protamine liposomes); nucleic acids complexed with cationic polymers (e.g., polyethyleneimine (PEI)) (cationic polymers); nucleic acids complexed with cationic polymers such as PEI and lipid components (cationic polymer liposomes); nucleic acids complexed with polysaccharide polymers (e.g., chitosan) (polysaccharide particles); nucleic acids complexed with cationic lipid nanoparticle polymers (cationic lipid nanoparticles); nucleic acids complexed with cationic lipids and cholesterol (cationic lipid-cholesterol nanoparticles); and nucleic acids complexed with cationic lipids, cholesterol, and PEG-lipids (cationic lipid-cholesterol-PEG nanoparticles).

[0363] In yet another embodiment, the formulated coding nucleic acid may include lipid nanoparticles (LNPs). In the specific embodiments described above, the lipid nanoparticles may be ionizable cationic lipids, phospholipids, cholesterol, and / or lipid-anchored polyethylene glycol. Specifically, the ionizable cationic lipid may be one or more selected from DLin-DMA, DLin-KC2-DMA; DLin-MC3-DMA, C12-200, cKK-E12; DLin-MC3-DMA derivative L319 (Alnylam and AlCana ​​Technologies), C12-200 and cKK-E12 derivatives (Anderson Group), COVID-19 vaccine lipids ALC-0315 and SM-102, TT3 and biodegradable derivative FTT5 (Anderson Group), vitamin-derived lipids ssPalmE and VcLNP; A9 (Acuitas), L5 (Moderna), A18 lipid; ATX lipid (LUNAR® composition, Arcturus), and LP01 (Intellia Therapeutics). Specifically, the phospholipid may be one or more selected from 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).

[0364] In certain embodiments, the formulated coding nucleic acid may include a polymer-based delivery system. In certain embodiments, the polymer-based delivery system may include one or more selected from polyethyleneimine (PEI), polyamidoamine (PAMAM), polypropyleneimine, and polymer-based dendrimers.

[0365] In yet another embodiment, the formulated coding nucleic acid may include a peptide-based delivery system. In certain embodiments, the peptide-based delivery system may include protamine. Specifically, the formulated coding nucleic acid may be a protamine-mRNA complex.

[0366] In yet another embodiment, the formulated coding nucleic acid may include cationic lipids comprising liposomes, lipoplexes and / or cationic emulsions (CNEs). In certain embodiments, the cationic lipids may be 1,2-di-O-octadecenyl-3-trimethylammoniumpropane (DOTMA) and / or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP).

[0367] Adjuvant.

[0368] In one embodiment, a pharmaceutical composition containing coding nucleic acids may include, as an adjuvant, lipid nanoparticles (LNPs), aluminum salts, 1,2-dioleyl-3-trimethylammonium-propane chloride, MF59 (Novartis) adjuvant, CD70, CD40 ligand (CD40L), TriMix, protamine acting through TLR7 signaling, and / or bacterial monophosphoryl lipid A.

[0369] component.

[0370] In one embodiment, the pharmaceutical composition containing the coding nucleic acid may optionally contain a variety of additional components. In another embodiment, the additional components may be one or more selected from the following:

[0371] Lipids; salts to balance the body's acidity; sucrose to maintain stability between repeated freeze-thaw cycles; and vaccine stability enhancers.

[0372] Specifically, the lipids may be, but are not limited to, SM-102, PEG2000-DMG, DPSC, cholesterol, and / or ALC-0315. Specifically, the salts may be, but are not limited to, sodium acetate, potassium chloride, monobasic potassium phosphate, sodium chloride, and / or dibasic sodium phosphate anhydrous. Specifically, the vaccine stability enhancers may be, but are not limited to, acetic acid, an acid stabilizer (tromethamine), and / or ethanol.

[0373] Peptides - Overview.

[0374] The peptides provided herein comprise at least one peptide unit, which comprises at least one B cell epitope and at least one Th epitope, and may include an appropriate number of auxiliary parts. The peptide unit is a portion designed to uniformly induce only the intended antibody while exhibiting a certain level of immunogenicity in the target body. Furthermore, because the peptide unit is designed to be relatively short, it is easy to synthesize and has low manufacturing costs. Due to the characteristics of the peptide unit described above, the peptide is suitable for use as an immunotherapy. This specification discloses in detail the design principles of peptides and peptide units.

[0375] The names of the parts of the peptides disclosed herein (e.g., auxiliary parts) are given for explanatory purposes only. Accordingly, the scope and names of each part may vary depending on the perspective. For example, auxiliary parts may be called protective parts, dummy parts, and / or linkers, but are not limited to these. In another example, a B-cell epitope may be called a Th-epitope protective epitope, but are not limited to these.

[0376] Possible embodiments of the present invention.

[0377] The following are possible embodiments of the present invention provided herein. The following embodiments provided herein are merely corresponding to embodiments of the present invention. Therefore, the invention provided herein cannot be construed as being limited to the following embodiments.

[0378] Symbols used in each embodiment.

[0379] Below, we will explain the symbols used in the brief description of each embodiment, in addition to the numbers used to distinguish each embodiment.

[0380] "B" indicates a B cell epitope. "T" indicates a Th epitope. "A" indicates an auxiliary part. "U" indicates a peptide unit.

[0381] When components are linked by a hyphen ("-"), it means that the components on either side of the hyphen are either directly linked or linked via any other component. For example, when written as BT, it includes all peptides in which a B cell epitope and a Th epitope are directly linked, and peptides in which a B cell epitope and a Th epitope are linked via any other sequence.

[0382] If necessary, each component may be assigned a subscript number to indicate that the two components are different. For example, if represented as B1-B2-T, B1 and B2 represent different B cell epitopes.

[0383] The symbols above are for illustrative purposes only, and the examples should not be interpreted restrictively based on these symbols.

[0384] Peptide unit 1.

[0385] Example 1: A peptide unit capable of inducing humoral immunity.

[0386] A peptide unit that can induce humoral immunity by being recognized by CD4+ T cells, comprising at least one Th epitope and at least one B cell epitope, wherein the length of the Th epitope is 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, or 3 It is 0mer, and the length of the B cell epitope is 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, or 32mer, and the length of the peptide unit is 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 2 5mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, 33mer, 34mer, 35mer, 36mer, 37mer, 38mer, 39mer, 40mer, 41mer, 42mer, 43mer, 44mer, 45mer, 46mer, 47mer, 48mer, 49mer, 50mer, 51mer, 52mer, 53mer, 54mer, 55mer, 56mer, 57mer, 58mer, 59mer, 60mer, 61mer, 62mer, 63mer, 64mer A peptide unit characterized by being 65mer, 66mer, 67mer, 68mer, 69mer, 70mer, 71mer, 72mer, 73mer, 74mer, 75mer, 76mer, 77mer, 78mer, 79mer, 80mer, 81mer, 82mer, 83mer, 84mer, 85mer, 86mer, 87mer, 88mer, 89mer, 90mer, 91mer, 92mer, 93mer, 94mer, 95mer, 96mer, 97mer, 98mer, 99mer, or 100mer.

[0387] Example 2: A peptide unit that induces an antibody targeting apolipoprotein B-100.

[0388] A peptide unit that can induce humoral immunity by being recognized by CD4+ T cells, comprising at least one Th epitope and at least one B cell epitope, wherein the Th epitope has lengths of 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, and 25m. The B cell epitope is er, 26mer, 27mer, 28mer, 29mer, or 30mer, and the peptide unit length is 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, 33mer, 34mer, or 35mer. mer, 36mer, 37mer, 38mer, 39mer, 40mer, 41mer, 42mer, 43mer, 44mer, 45mer, 46mer, 47mer, 48mer, 49mer, 50mer, 51mer, 52mer r, 53mer, 54mer, 55mer, 56mer, 57mer, 58mer, 59mer, 60mer, 61mer, 62mer, 63mer, 64mer, 65mer, 66mer, 67mer, 68mer, 69mer, A peptide unit characterized by being 70mer, 71mer, 72mer, 73mer, 74mer, 75mer, 76mer, 77mer, 78mer, 79mer, 80mer, 81mer, 82mer, 83mer, 84mer, 85mer, 86mer, 87mer, 88mer, 89mer, 90mer, 91mer, 92mer, 93mer, 94mer, 95mer, 96mer, 97mer, 98mer, 99mer, or 100mer.

[0389] Example 3: A peptide unit that induces an antibody targeting apolipoprotein B-100 contained in LDL and / or VLDL.

[0390] The peptide unit according to Example 2, characterized in that the B cell epitope induces an antibody that targets a site selected from the externally exposed sites of apolipoprotein B-100 contained in low-density lipoprotein (LDL) and the externally exposed sites of apolipoprotein B-100 contained in very low-density lipoprotein (VLDL).

[0391] Limitations relating to Example 4, Type B.

[0392] The peptide unit according to Example 2, characterized in that the peptide unit's B cell epitope is a fragment of apolipoprotein B-100 and / or a mimotope of apolipoprotein B-100.

[0393] Example 5, limitations regarding the arrangement of B.

[0394] The peptide unit according to Example 4, characterized in that the B cell epitope is an epitope contained in a sequence selected from the group consisting of RNVPPIFNDVYWIAF (SEQ ID NO: 7), CRFRGLISLSQVYLS (SEQ ID NO: 7), KTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 8), RFRGLISLSQVYLDP (SEQ ID NO: 221), and SVCGCPVGHHDVVGL (SEQ ID NO: 222), or a sequence selected from SEQ ID NO: 6-8 and 221-222.

[0395] Example 6, Restrictions on the total sequence length of peptide units.

[0396] The peptide unit according to any one of Examples 1 to 5, characterized in that the peptide unit has a length of 23mer to 71mer or 26mer to 50mer.

[0397] Peptide unit 2-unit A.

[0398] Example 7, BT and TB.

[0399] The peptide unit according to any one of Examples 1 to 4, characterized in that the peptide unit comprises one B cell epitope and one Th epitope.

[0400] Example 8, restrictions on array B, restrictions on length T, and restrictions on length U

[0401] The peptide unit according to Example 7, characterized in that the peptide unit has a length of 26mer to 45mer, the B cell epitope is selected from RNVPPIFNDVYWIAF (SEQ ID NO: 6), NVPPIFNDVYWIAF (SEQ ID NO: 6), NVPPIFNDVYWIAF (SEQ ID NO: 6), RFRGLISLSQVYLDP (SEQ ID NO: 221), and SVCGCPVGHHDVVGL (SEQ ID NO: 222), and the Th epitope has a length of 11mer to 13mer.

[0402] Example 9, limitations regarding sequence T.

[0403] The epitope is K(Cha)VAAWTLKAA(SEQ ID NO:1);PKYVKQNTLKLAT(SEQ ID NO:2);ILMQYIKANSKFIGI(SEQ ID NO:3);QSIALSSLMVAQAIP(SEQ ID NO:4);ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5);PLGFFPDHQL(SEQ ID NO:162);WPEANQVGAGAFGPGF(SEQ ID NO:163);MQWNSTALHQALQDP(SEQ ID NO:164);MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165);FFLLTRILTI(SEQ ID NO:166);FFLLTRILTIPQSLD(SEQ ID NO:167);TSLNFLGGTTVCLGQ(SEQ ID NO:168);QSPTSNHSPTSCPPIC(SEQ ID NO:169);IIFLFILLLCLIFLLVLLD(SEQ ID NO:170);CTTPAQGNSMFPSC(SEQ ID NO:171);CTKPTDGN(SEQ ID NO:172);WASVRFSW(SEQ ID NO:173);LLPIFFCLW(SEQ ID NO:174);MDIDPYKEFGATVELLSFLP(SEQ ID NO:175);FLPSDFFPSV(SEQ ID NO:176);RDLLDTASALYREALESPEH(SEQ ID NO:177);PHHTALRQAILCWGELMTLA(SEQ ID NO:178);GRETVIEYLVSFGVW(SEQ ID NO:179);EYLVSFGVWIRTPPA(SEQ ID NO:180);VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181);TVVRRRGRSP(SEQ ID NO:182);VGPLTVNEKRRLKLI(SEQ ID NO:183);RHYLHTLWKAGILYK(SEQ ID NO:184);ESRLVVDFSQFSRGN(SEQ ID NO:185);LQSLTNLLSSNLSWL(SEQ ID NO:186);SSNLSWLSLDVSAAF(SEQ ID NO:187);A peptide unit according to either one of Examples 7 and 8, characterized by being selected from the group consisting of LHLYSHPIILGFRKI (SEQ ID NO: 188); KQCFRKLPVNRPIDW (SEQ ID NO: 189); LCQVFADATPTGWGL (SEQ ID NO: 190); AANWILRGTSFVYVP (SEQ ID NO: 191); and EIRLKVFVLGGCRHK (SEQ ID NO: 192) (where (Cha) represents L-cyclohexylalanine).

[0404] Example 10, BAT and TAB.

[0405] The peptide unit according to any one of Examples 7 and 8, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a B cell epitope and a Th epitope.

[0406] Example 11, Restrictions on A containing non-standard amino acids.

[0407] The peptide unit according to Example 10, characterized in that the peptide unit comprises one or more non-standard amino acids in its auxiliary portion.

[0408] Example 12, Restrictions on the sequence of A including non-standard amino acids.

[0409] The peptide unit according to Example 11, characterized in that the peptide unit is selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193), and aZGSHHHHHHGSDDDK (SEQ ID NO: 194) for its auxiliary portion.

[0410] Example 13, Restrictions on sequence A that does not contain non-standard amino acids.

[0411] The peptide unit according to Example 10, characterized in that the peptide unit's auxiliary portion is selected from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159).

[0412] Peptide unit 3-unit D.

[0413] Examples 14, B-T1-T2 and T2-T1-B.

[0414] The peptide unit according to any one of Examples 1 to 4, characterized in that the peptide unit comprises one B cell epitope and two Th epitopes called a first Th epitope and a second Th epitope, respectively, wherein the first Th epitope is linked between the B cell epitope and the second Th epitope.

[0415] Example 15, restrictions on sequence B, restrictions on length T, and restrictions on length U.

[0416] The peptide unit according to Example 14, characterized in that the peptide unit has a length of 37mer to 50mer, the B cell epitope is selected from RNVPPIFNDVYWIAF (SEQ ID NO: 6), CRFRGLISLSQVYLS (SEQ ID NO: 7), KTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 8), RFRGLISLSQVYLDP (SEQ ID NO: 221), and SVCGCPVGHHDVVGL (SEQ ID NO: 222), and the lengths of the first Th epitope and the second Th epitope are 11mer to 13mer, respectively.

[0417] Example 16, limitations regarding sequence T.

[0418] The epitope is K(Cha)VAAWTLKAA(SEQ ID NO:1);PKYVKQNTLKLAT(SEQ ID NO:2);ILMQYIKANSKFIGI(SEQ ID NO:3);QSIALSSLMVAQAIP(SEQ ID NO:4);ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5);PLGFFPDHQL(SEQ ID NO:162);WPEANQVGAGAFGPGF(SEQ ID NO:163);MQWNSTALHQALQDP(SEQ ID NO:164);MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165);FFLLTRILTI(SEQ ID NO:166);FFLLTRILTIPQSLD(SEQ ID NO:167);TSLNFLGGTTVCLGQ(SEQ ID NO:168);QSPTSNHSPTSCPPIC(SEQ ID NO:169);IIFLFILLLCLIFLLVLLD(SEQ ID NO:170);CTTPAQGNSMFPSC(SEQ ID NO:171);CTKPTDGN(SEQ ID NO:172);WASVRFSW(SEQ ID NO:173);LLPIFFCLW(SEQ ID NO:174);MDIDPYKEFGATVELLSFLP(SEQ ID NO:175);FLPSDFFPSV(SEQ ID NO:176);RDLLDTASALYREALESPEH(SEQ ID NO:177);PHHTALRQAILCWGELMTLA(SEQ ID NO:178);GRETVIEYLVSFGVW(SEQ ID NO:179);EYLVSFGVWIRTPPA(SEQ ID NO:180);VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181);TVVRRRGRSP(SEQ ID NO:182);VGPLTVNEKRRLKLI(SEQ ID NO:183);RHYLHTLWKAGILYK(SEQ ID NO:184);ESRLVVDFSQFSRGN(SEQ ID NO:185);LQSLTNLLSSNLSWL(SEQ ID NO:186);SSNLSWLSLDVSAAF(SEQ ID NO:187);A peptide unit according to either Example 14 or 15, characterized by being selected from the group consisting of LHLYSHPIILGFRKI (SEQ ID NO: 188); KQCFRKLPVNRPIDW (SEQ ID NO: 189); LCQVFADATPTGWGL (SEQ ID NO: 190); AANWILRGTSFVYVP (SEQ ID NO: 191); and EIRLKVFVLGGCRHK (SEQ ID NO: 192) (where a represents D-type alanine, (Cha) represents L-cyclohexyl alanine, and Z represents 6-aminohexanoic acid).

[0419] Example 17, BAT1-T2 and T2-T1AB.

[0420] The peptide unit according to either one of Examples 14 and 15, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a B cell epitope and a first Th epitope.

[0421] Example 18, B-T1AT2 and T2AT1-B.

[0422] The peptide unit according to either one of Examples 14 and 15, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a first Th epitope and a second Th epitope.

[0423] Example 19, Restrictions on A containing non-standard amino acids.

[0424] The peptide unit according to either one of Examples 17 and 18, characterized in that the peptide unit comprises one or more non-standard amino acids in its auxiliary portion.

[0425] Example 20, limitations regarding sequence A containing non-standard amino acids.

[0426] The peptide unit according to Example 19, characterized in that the peptide unit is selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193) and aZGSHHHHHHGSDDDK (SEQ ID NO: 194) for its auxiliary portion.

[0427] Example 21, Restrictions on sequence A that does not contain non-standard amino acids.

[0428] The peptide unit according to either Example 17 or 18, characterized in that the peptide unit's auxiliary portion is selected from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159).

[0429] Example 22, BAT1AT2 and T2AT1AB.

[0430] The peptide unit according to any one of Examples 14 and 15, characterized in that the peptide unit further comprises a first auxiliary portion and a second auxiliary portion, wherein the first auxiliary portion is linked between a B cell epitope and a Th epitope, and the second auxiliary portion is linked between the first Th epitope and the second Th epitope.

[0431] Example 23, Restrictions on A containing non-standard amino acids.

[0432] The peptide unit according to Example 22, characterized in that the peptide unit comprises one or more non-standard amino acids in a first auxiliary portion and / or a second auxiliary portion.

[0433] Example 24, Restrictions on the sequence of A including non-standard amino acids.

[0434] The peptide unit according to Example 23, characterized in that the peptide unit has an auxiliary portion containing one or more non-standard amino acids, which is independently selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193), and aZGSHHHHHHGSDDDK (SEQ ID NO: 194).

[0435] Example 25, Restrictions on sequence A that does not contain non-standard amino acids.

[0436] The peptide unit according to Example 22, characterized in that the peptide unit is selected independently from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159) for the first auxiliary part and / or the second auxiliary part.

[0437] Peptide unit 4-unit B.

[0438] Example 26, B1-B2-T and T-B2-B1.

[0439] The peptide unit according to any one of Examples 1 to 4, characterized in that the peptide unit comprises two B cell epitopes, each called a first B cell epitope and a second B cell epitope, wherein the second B cell epitope is linked between the first B cell epitope and a Th epitope.

[0440] Example 27, restrictions on sequence B, restrictions on length T, and restrictions on length U.

[0441] The peptide unit according to Example 26, characterized in that the peptide unit has a length of 45mer to 50mer, the first B cell epitope and the second B cell epitope are independently selected from RNVPPIFNDVYWIAF (SEQ ID NO: 6), CRFRGLISLSQVYLS (SEQ ID NO: 7), KTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 8), RFRGLISLSQVYLDP (SEQ ID NO: 221), and SVCGCPVGHHDVVGL (SEQ ID NO: 222), and the Th epitope has a length of 11mer to 13mer.

[0442] Example 28, limitations regarding sequence T.

[0443] The epitope is K(Cha)VAAWTLKAA(SEQ ID NO:1);PKYVKQNTLKLAT(SEQ ID NO:2);ILMQYIKANSKFIGI(SEQ ID NO:3);QSIALSSLMVAQAIP(SEQ ID NO:4);ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5);PLGFFPDHQL(SEQ ID NO:162);WPEANQVGAGAFGPGF(SEQ ID NO:163);MQWNSTALHQALQDP(SEQ ID NO:164);MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165);FFLLTRILTI(SEQ ID NO:166);FFLLTRILTIPQSLD(SEQ ID NO:167);TSLNFLGGTTVCLGQ(SEQ ID NO:168);QSPTSNHSPTSCPPIC(SEQ ID NO:169);IIFLFILLLCLIFLLVLLD(SEQ ID NO:170);CTTPAQGNSMFPSC(SEQ ID NO:171);CTKPTDGN(SEQ ID NO:172);WASVRFSW(SEQ ID NO:173);LLPIFFCLW(SEQ ID NO:174);MDIDPYKEFGATVELLSFLP(SEQ ID NO:175);FLPSDFFPSV(SEQ ID NO:176);RDLLDTASALYREALESPEH(SEQ ID NO:177);PHHTALRQAILCWGELMTLA(SEQ ID NO:178);GRETVIEYLVSFGVW(SEQ ID NO:179);EYLVSFGVWIRTPPA(SEQ ID NO:180);VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181);TVVRRRGRSP(SEQ ID NO:182);VGPLTVNEKRRLKLI(SEQ ID NO:183);RHYLHTLWKAGILYK(SEQ ID NO:184);ESRLVVDFSQFSRGN(SEQ ID NO:185);LQSLTNLLSSNLSWL(SEQ ID NO:186);SSNLSWLSLDVSAAF(SEQ ID NO:187);A peptide unit according to either Example 26 or 27, characterized by being selected from the group consisting of LHLYSHPIILGFRKI (SEQ ID NO: 188); KQCFRKLPVNRPIDW (SEQ ID NO: 189); LCQVFADATPTGWGL (SEQ ID NO: 190); AANWILRGTSFVYVP (SEQ ID NO: 191); and EIRLKVFVLGGCRHK (SEQ ID NO: 192) (where a represents D-type alanine, (Cha) represents L-cyclohexyl alanine, and Z represents 6-aminohexanoic acid).

[0444] Example 29, B1-B2AT and TAB2-B1.

[0445] The peptide unit according to either one of Examples 26 and 27, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a second B cell epitope and a Th epitope.

[0446] Examples 30, B1AB2-T and T-B2AB1.

[0447] The peptide unit according to either one of Examples 26 and 27, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a first B cell epitope and a second B cell epitope.

[0448] Example 31, Restrictions on A containing non-standard amino acids.

[0449] The peptide unit according to either one of Examples 29 and 30, characterized in that the peptide unit comprises one or more non-standard amino acids in its auxiliary portion.

[0450] Example 32, limitations regarding sequence A containing non-standard amino acids.

[0451] The peptide unit according to Example 31, characterized in that the peptide unit is selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193) and aZGSHHHHHHGSDDDK (SEQ ID NO: 194) for its auxiliary portion.

[0452] Example 33, A, Restrictions regarding sequences that do not contain non-standard amino acids.

[0453] The peptide unit according to either Example 29 or 30, characterized in that the peptide unit's auxiliary portion is selected from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159).

[0454] Examples 34, B1A1B2A2T and TA2B2A1B1.

[0455] The peptide unit according to either Example 26 or 27, characterized in that the peptide unit further comprises a first auxiliary portion and a second auxiliary portion, wherein the first auxiliary portion is linked between a first B cell epitope and a second B cell epitope, and the second auxiliary portion is linked between the second B cell epitope and a Th epitope.

[0456] Example 35, Restrictions on A containing non-standard amino acids.

[0457] The peptide unit according to Example 34, characterized in that the peptide unit comprises one or more non-standard amino acids in a first auxiliary portion and / or a second auxiliary portion.

[0458] Example 36, Restrictions on sequence A containing non-standard amino acids.

[0459] The peptide unit according to Example 35, characterized in that the peptide unit is independently selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193) and aZGSHHHHHHGSDDDK (SEQ ID NO: 194), each comprising an auxiliary portion containing one or more non-standard amino acids.

[0460] Example 37, Restrictions on sequence A that does not contain non-standard amino acids.

[0461] The peptide unit according to Example 34, characterized in that the peptide unit is selected independently from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159), respectively, for a first auxiliary part and / or a second auxiliary part.

[0462] Peptide unit 5-unit C.

[0463] Example 38, B1-T-B2.

[0464] The peptide unit according to any one of Examples 1 to 4, characterized in that the peptide unit comprises two B cell epitopes called a first B cell epitope and a second B cell epitope, and one Th epitope, wherein the Th epitope is linked between the first B cell epitope and the second B cell epitope.

[0465] Example 39, restrictions on array B, restrictions on length T, and restrictions on length U.

[0466] The peptide unit according to Example 38, characterized in that the peptide unit has a length of 45mer to 50mer, the first B cell epitope and the second B cell epitope are independently selected from RNVPPIFNDVYWIAF (SEQ ID NO: 6), CRFRGLISLSQVYLS (SEQ ID NO: 7), KTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 8), RFRGLISLSQVYLDP (SEQ ID NO: 221), and SVCGCPVGHHDVVGL (SEQ ID NO: 222), and the Th epitope has a length of 11mer to 13mer.

[0467] Example 40, limitations regarding sequence T.

[0468] The epitope is K(Cha)VAAWTLKAA(SEQ ID NO:1);PKYVKQNTLKLAT(SEQ ID NO:2);ILMQYIKANSKFIGI(SEQ ID NO:3);QSIALSSLMVAQAIP(SEQ ID NO:4);ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5);PLGFFPDHQL(SEQ ID NO:162);WPEANQVGAGAFGPGF(SEQ ID NO:163);MQWNSTALHQALQDP(SEQ ID NO:164);MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165);FFLLTRILTI(SEQ ID NO:166);FFLLTRILTIPQSLD(SEQ ID NO:167);TSLNFLGGTTVCLGQ(SEQ ID NO:168);QSPTSNHSPTSCPPIC(SEQ ID NO:169);IIFLFILLLCLIFLLVLLD(SEQ ID NO:170);CTTPAQGNSMFPSC(SEQ ID NO:171);CTKPTDGN(SEQ ID NO:172);WASVRFSW(SEQ ID NO:173);LLPIFFCLW(SEQ ID NO:174);MDIDPYKEFGATVELLSFLP(SEQ ID NO:175);FLPSDFFPSV(SEQ ID NO:176);RDLLDTASALYREALESPEH(SEQ ID NO:177);PHHTALRQAILCWGELMTLA(SEQ ID NO:178);GRETVIEYLVSFGVW(SEQ ID NO:179);EYLVSFGVWIRTPPA(SEQ ID NO:180);VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181);TVVRRRGRSP(SEQ ID NO:182);VGPLTVNEKRRLKLI(SEQ ID NO:183);RHYLHTLWKAGILYK(SEQ ID NO:184);ESRLVVDFSQFSRGN(SEQ ID NO:185);LQSLTNLLSSNLSWL(SEQ ID NO:186);SSNLSWLSLDVSAAF(SEQ ID NO:187);A peptide unit according to either Example 38 or 39, characterized by being selected from the group consisting of LHLYSHPIILGFRKI (SEQ ID NO: 188); KQCFRKLPVNRPIDW (SEQ ID NO: 189); LCQVFADATPTGWGL (SEQ ID NO: 190); AANWILRGTSFVYVP (SEQ ID NO: 191); and EIRLKVFVLGGCRHK (SEQ ID NO: 192) (where a represents D-type alanine, (Cha) represents L-cyclohexyl alanine, and Z represents 6-aminohexanoic acid).

[0469] Example 41, B1AT-B2 and B2-TAB1.

[0470] The peptide unit according to either one of Examples 38 and 39, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a first B cell epitope and a Th epitope.

[0471] Example 42, limitations on A containing non-standard amino acids.

[0472] The peptide unit according to Example 41, characterized in that the peptide unit comprises one or more non-standard amino acids in its auxiliary portion.

[0473] Example 43, limitations regarding sequence A containing non-standard amino acids.

[0474] The peptide unit according to Example 42, characterized in that the peptide unit is selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193) and aZGSHHHHHHGSDDDK (SEQ ID NO: 194) for its auxiliary portion.

[0475] Example 44, Restrictions on sequence A that does not contain non-standard amino acids.

[0476] The peptide unit according to Example 41, characterized in that the peptide unit's auxiliary portion is selected from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159).

[0477] Example 45, B1A1TA2B2.

[0478] The peptide unit according to any one of Examples 38 and 39, characterized in that the peptide unit further comprises a first auxiliary portion and a second auxiliary portion, wherein the first auxiliary portion is linked between a first B cell epitope and a Th epitope, and the second auxiliary portion is linked between a second B cell epitope and a Th epitope.

[0479] Example 46, limitations on A containing non-standard amino acids.

[0480] The peptide unit according to Example 45, characterized in that the peptide unit comprises one or more non-standard amino acids in a first auxiliary portion and / or a second auxiliary portion.

[0481] Example 47, limitations regarding sequence A containing non-standard amino acids.

[0482] The peptide unit according to Example 46, characterized in that the peptide unit is selected independently from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193) and aZGSHHHHHHGSDDDK (SEQ ID NO: 194), each comprising an auxiliary portion containing one or more non-standard amino acids.

[0483] Example 48, Restrictions on sequence A that does not contain non-standard amino acids.

[0484] The peptide unit according to Example 45, characterized in that the peptide unit is selected independently from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159), respectively, for a first auxiliary part and / or a second auxiliary part.

[0485] Peptide unit 6-unit E.

[0486] Example 49, B1-T1-T2-B2.

[0487] The peptide unit according to any one of Examples 1 to 4, characterized in that the peptide unit comprises two B cell epitopes, each called a first B cell epitope and a second B cell epitope, and two Th epitopes, each called a first Th epitope and a second Th epitope, wherein the first B cell epitope, the first Th epitope, the second Th epitope, and the second B cell epitope are sequentially linked from the N-terminus to the C-terminus.

[0488] Example 50, restrictions on sequence B, restrictions on length T, and restrictions on length U.

[0489] The peptide unit according to Example 49, characterized in that the peptide unit has a length of 52mer to 90mer, the first B cell epitope and the second B cell epitope are independently selected from RNVPPIFNDVYWIAF (SEQ ID NO: 6), CRFRGLISLSQVYLS (SEQ ID NO: 7), KTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 8), RFRGLISLSQVYLDP (SEQ ID NO: 221), and SVCGCPVGHHDVVGL (SEQ ID NO: 222), and the lengths of the first Th epitope and the second Th epitope are 11mer to 13mer, respectively.

[0490] Example 51, limitations regarding sequence T.

[0491] The first Th epitope and the second Th epitope are K(Cha)VAAWTLKAA(SEQ ID NO:1);PKYVKQNTLKLAT(SEQ ID NO:2);ILMQYIKANSKFIGI(SEQ ID NO:3);QSIALSSLMVAQAIP(SEQ ID NO:4);ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5);PLGFFPDHQL(SEQ ID NO:162);WPEANQVGAGAFGPGF(SEQ ID NO:163);MQWNSTALHQALQDP(SEQ ID NO:164);MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165);FFLLTRILTI(SEQ ID NO:166);FFLLTRILTIPQSLD(SEQ ID NO:167);TSLNFLGGTTVCLGQ(SEQ ID NO:168);QSPTSNHSPTSCPPIC(SEQ ID NO:169);IIFLFILLLCLIFLLVLLD(SEQ ID NO:170);CTTPAQGNSMFPSC(SEQ ID NO:171);CTKPTDGN(SEQ ID NO:172);WASVRFSW(SEQ ID NO:173);LLPIFFCLW(SEQ ID NO:174);MDIDPYKEFGATVELLSFLP(SEQ ID NO:175);FLPSDFFPSV(SEQ ID NO:176);RDLLDTASALYREALESPEH(SEQ ID NO:177);PHHTALRQAILCWGELMTLA(SEQ ID NO:178);GRETVIEYLVSFGVW(SEQ ID NO:179);EYLVSFGVWIRTPPA(SEQ ID NO:180);VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181);TVVRRRGRSP(SEQ ID NO:182);VGPLTVNEKRRLKLI(SEQ ID NO:183);RHYLHTLWKAGILYK(SEQ ID NO:184);ESRLVVDFSQFSRGN(SEQ ID NO:185);LQSLTNLLSSNLSWL(SEQ ID NO:186);SSNLSWLSLDVSAAF(SEQ ID NO:187);The peptide unit described in Example 50 is characterized by being independently selected from the group consisting of LHLYSHPIILGFRKI (SEQ ID NO: 188); KQCFRKLPVNRPIDW (SEQ ID NO: 189); LCQVFADATPTGWGL (SEQ ID NO: 190); AANWILRGTSFVYVP (SEQ ID NO: 191); and EIRLKVFVLGGCRHK (SEQ ID NO: 192) (where a represents D-type alanine, (Cha) represents L-cyclohexyl alanine, and Z represents 6-aminohexanoic acid).

[0492] Example 52, B1AT1-T2-B2 and B2-T2-T1AB1.

[0493] The peptide unit according to either one of Examples 49 and 50, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a first B cell epitope and a first Th epitope.

[0494] Example 53, B1-T1AT2-B2.

[0495] The peptide unit according to either one of Examples 49 and 50, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a first Th epitope and a second Th epitope.

[0496] Examples 54, B1-T1-T2AB2 and B2AT2-T1-B1.

[0497] The peptide unit according to either one of Examples 49 and 50, characterized in that the peptide unit further comprises an auxiliary portion, the auxiliary portion being linked between a second Th epitope and a second B cell epitope.

[0498] Example 55, Restrictions on A containing non-standard amino acids.

[0499] The peptide unit according to any one of Examples 52 to 54, characterized in that the peptide unit contains one or more non-standard amino acids in its auxiliary portion.

[0500] Example 56, Restrictions on A containing non-standard amino acids.

[0501] The peptide unit according to any one of Examples 52 to 54, characterized in that the peptide unit is selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193) and aZGSHHHHHHGSDDDK (SEQ ID NO: 194) for its auxiliary portion.

[0502] Example 57, limitations regarding sequence A that does not contain non-standard amino acids.

[0503] The peptide unit according to any one of Examples 52 to 54, characterized in that the peptide unit's auxiliary portion is selected from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159).

[0504] Examples 58, B1A1T1A2T2-B2 and B2-T2A2T1A1B1.

[0505] The peptide unit according to either one of Examples 49 and 50, characterized in that the peptide unit further comprises a first auxiliary portion and a second auxiliary portion, wherein the auxiliary portion is linked between a first B cell epitope and a first Th epitope, and the second auxiliary portion is linked between a first Th epitope and a second Th epitope.

[0506] Example 59, B1A1T1-T2A2B2.

[0507] A peptide unit according to any one of Examples 49 and 50, characterized in that the peptide unit further comprises a first auxiliary portion and a second auxiliary portion, wherein the auxiliary portion is linked between a first B cell epitope and a first Th epitope, and the second auxiliary portion is linked between a second Th epitope and a second B cell epitope.

[0508] Examples 60, B1-T1A1T2A2B2 and B2-T2A2T1A1B1.

[0509] The peptide unit according to any one of Examples 49 and 50, characterized in that the peptide unit further comprises a first auxiliary portion and a second auxiliary portion, wherein the auxiliary portion is linked between a first Th epitope and a second Th epitope, and the first Th epitope and the second Th epitope are linked between the second Th epitope and a second B cell epitope.

[0510] Example 61, Restrictions on A containing non-standard amino acids.

[0511] The peptide unit according to any one of Examples 58 to 60, characterized in that the peptide unit comprises one or more non-standard amino acids in a first auxiliary portion and / or a second auxiliary portion.

[0512] Example 62, limitations regarding sequence A containing non-standard amino acids.

[0513] The peptide unit according to any one of Examples 58 to 60, characterized in that the peptide unit is independently selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193), and aZGSHHHHHHGSDDDK (SEQ ID NO: 194), each comprising an auxiliary portion containing one or more non-standard amino acids.

[0514] Example 63, limitations regarding sequence A containing non-standard amino acids.

[0515] The peptide unit according to any one of Examples 58 to 60, characterized in that the peptide unit is selected independently from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159), respectively, for a first auxiliary part and / or a second auxiliary part.

[0516] Example 64, B1A1T1A2T2A3B2.

[0517] The peptide unit according to any one of Examples 49 and 50, wherein the peptide unit further comprises a first auxiliary portion, a second auxiliary portion, and a third auxiliary portion, wherein the first auxiliary portion is linked between a first B cell epitope and a first Th epitope, the second auxiliary portion is linked between a first Th epitope and a second Th epitope, and the third auxiliary portion is linked between a second Th epitope and a second B cell epitope.

[0518] Example 65, Restrictions on A containing non-standard amino acids.

[0519] The peptide unit according to Example 64, characterized in that the peptide unit comprises a first auxiliary portion, a second auxiliary portion, and / or a third auxiliary portion, each containing one or more non-standard amino acids.

[0520] Example 66, limitations regarding sequence A containing non-standard amino acids.

[0521] The peptide unit according to Example 65, characterized in that the peptide unit is independently selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193), and aZGSHHHHHHGSDDDK (SEQ ID NO: 194), each comprising an auxiliary portion containing one or more non-standard amino acids.

[0522] Example 67, limitations regarding sequence A that does not contain non-standard amino acids.

[0523] The peptide unit according to Example 64, characterized in that the peptide unit is selected independently from CR, HHHHHH (SEQ ID NO: 53), and RRRRRR (SEQ ID NO: 159) for the first auxiliary part, the second auxiliary part, and / or the third auxiliary part.

[0524] Peptide units: 7 units and additional auxiliary parts.

[0525] Examples 68, AU and UA.

[0526] A peptide unit comprising the peptide unit described in any one of Examples 1 to 67 and an additional auxiliary portion.

[0527] Example 69, limitations on A containing non-standard amino acids.

[0528] The peptide unit according to Example 67, characterized in that the peptide unit comprises an additional auxiliary portion containing one or more non-standard amino acids.

[0529] Example 70, limitations regarding sequence A containing non-standard amino acids.

[0530] The peptide unit according to Example 69, characterized in that the peptide unit is selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193) and aZGSHHHHHHGSDDDK (SEQ ID NO: 194).

[0531] Example 71, limitations regarding sequence A that does not contain non-standard amino acids.

[0532] The peptide unit according to Example 68, characterized in that the peptide unit is selected from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159) for the additional auxiliary portion.

[0533] Example 72, AUA.

[0534] A peptide unit comprising the peptide unit described in any one of Examples 1 to 67, a first additional auxiliary portion, and a second additional auxiliary portion. In particular, the peptide unit is linked between the first additional auxiliary portion and the second additional auxiliary portion.

[0535] Example 73, Restrictions on A containing non-standard amino acids.

[0536] The peptide unit according to Example 72, characterized in that the peptide unit comprises a first additional auxiliary portion and / or a second additional auxiliary portion comprising one or more non-standard amino acids.

[0537] Example 74, limitations regarding sequence A containing non-standard amino acids.

[0538] The peptide unit according to Example 73, characterized in that the peptide unit is independently selected from a, Z, aZ, Za, GSHHHHHHGSDDDKZa (SEQ ID NO: 193) and aZGSHHHHHHGSDDDK (SEQ ID NO: 194), each comprising an additional auxiliary portion containing one or more non-standard amino acids.

[0539] Example 75, Restrictions on sequence A that does not contain non-standard amino acids.

[0540] The peptide unit according to Example 72, characterized in that the peptide unit is selected independently from CR, HHHHHH (SEQ ID NO: 53) and RRRRRR (SEQ ID NO: 159), respectively, for a first additional auxiliary part and / or a second additional auxiliary part.

[0541] Restrictions on the sequence of 8-unit peptide units.

[0542] Example 76, limitations on the arrangement of unit A.

[0543] Material: RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:56);ZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:57); NO:58);ZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:59);KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAZ(SEQ ID NO:60);ZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:61);RNVPPIFNDVYWIAFK(Cha)VAOUT(SEQ ID NO:62);K(Cha)VAOUTVPPIFNDVYWIAF(SEQ ID NO:63);RNVPPIFNDVYK(Cha)VAOUT(SEQ ID NO:64); NO:65);PPIFNDVYWK(Cha)VAOTLKAA(SEQ ID NO:66);RNVPPIFNDVYWIAFK(Cha)VAOTLKAAHHHHHH(SEQ ID NO:67); NO:68);GSHHHHHHGSDDDDKZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:69); NO:70);GSHHHHHHGSDDDDKZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:71); NO:72);CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZGSHHHHHGGSDDDDK(SEQ ID NO:73);GSHHHHHHGSDDDDKZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:74);GSHHHHHHGSDDDDKKTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:75);KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZGSHHHHHHGSDDDDK(SEQ ID NO:76);MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:77);MRGSHHHHHHGSDDDDKIVDGSHHHHHHGSDDDDKRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:78);MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZGSHHHHHHGSDDDDK(SEQ ID NO:79);RNVPPIFNDVYWIAFILMQYIKANSKFIGI(SEQ ID NO:80);RNVPPIFNDVYWIAFILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:81);CRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZC(SEQ ID NO:82);RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAACR(SEQ ID NO:161);RNVPPIFNDVYWIAFXXKXVAAWTLKAAXXGSHHHHHHGSDDDDK(SEQ ID NO:199);GSHHHHHHGSDDDDKXXKXVAAWTLKAAXXRNVPPIFNDVYWIAF(SEQ ID NO:200);RNVPPIFNDVYWIAFXXKXVAAWTLKAAXX(SEQ ID NO:204);RNVPPIFNDVYWIAFKXVAAWTLKAA(SEQ ID NO:205);RNVPPIFNDVYWIAFKXVAAWTLKAAHHHHHH(SEQ ID NO:206);RNVPPIFNDVYWIAFXXKXVAAWTLKAACR(SEQ ID NO:208);RNVPPIFNDVYWIAFXXKFVAAWTLKAAXX(SEQ ID NO:210);RNVPPIFNDVYWIAFXXKFVAAWTLKAACR(SEQ ID NO:212);RNVPPIFNDVYWIAFCTKPTDGN(SEQ ID NO:213);RNVPPIFNDVYWIAFLLPIFFCLW(SEQ ID NO:214);RNVPPIFNDVYWIAFFLPSDFFPSV(SEQ ID NO:215);RNVPPIFNDVYWIAFILMQYIKANSKFIGIHHHHHH(SEQ ID NO:219);and RNVPPIFNDVYWIAFMDIDPYKEFGATVELLSFLPHHHHHH(SEQ ID A peptide unit as described in any one of Examples 1-8 and 68-75, selected from NO:220) (where a represents D-type alanine, Z represents 6-aminohexanoic acid, (Cha) represents L-cyclohexylalanine, and X represents any standard amino acid).

[0544] Example 77, restrictions on the arrangement of unit D.

[0545] SEQ ID NO:123; NO:124); NO:126);ILMQYIKANSKFIGIZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:127);ILMQYIKANSKFIGIZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:128);PIFNDVYWIAFK(Cha)VAAWTLKAAK(Cha)VAAWTLKAA(SEQ ID NO:129);PPIFNDVYWK(Cha)VAAWTLKAAK(Cha)VAAWTLKAA(SEQ ID NO:130);MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGI(SEQ ID NO:131);MRGSHHHHHHHGSDDDDKIVDILMQYIKANSKFIGIZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:132);MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGI(SEQ ID NO:133);MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSILMQYIKANSKFIGIPMGLPQSIALSSLMVAQGGGGSGGGGGGSSILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:134);RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZK(Cha)LAAFTIRAAaZ(SEQ ID NO:135);A peptide unit as described in any one of Examples 1-6, 14-15, and 68-75, selected from CRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIC(SEQ ID NO:136) (where a represents D-type alanine, Z represents 6-aminohexanoic acid, and (Cha) represents L-cyclohexylalanine).

[0546] Example 78, limitations regarding the arrangement of unit B.

[0547] Download RNVPPIFNDVYWIAFRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:83) NO:84)、CRFRGLISLSQVYLSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:85) NO:86)、CRFRGLISLSQVYLSCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:87)、CRFRGLISLSQVYLSKTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:88) KTTKQSFDLSVKAQYKKNKHCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:89). NO:90)、KTTKQSFDLSVKAQYKKNKHKTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:91)、RNVPPIFNDVYWIAFCRFRGLISLSQVYLSK(Cha)VAAWTLKAA(SEQ ID NO:92)、PIFNDVYWIAFGLISLSQVYLSK(Cha)VAAWTLKAA(SEQ ID NO:93)、RNVPPIFNDVYCRFRGLISLSQK(Cha)VAAWTLKAA(SEQ ID NO:94). NO:95) 、PPIFNDVYWRGLISLSQVK(CHA)VAUTLKAA(SEQ ID NO:96)、RNVPPIFNDVYWIAFCRFRGLISLSQVYLSK(Cha)VAUTLKAAHHHHHH(SEQ IDNO:97), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:98), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAA(SEQ ID NO:99), RNVPPIFDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAA(SEQ ID NO:100), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAA(SEQ ID NO:101), RNVPPIFNDVYWIAFGGGGSGGGGGGSSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAA(SEQ ID NO:102), RNVPPIFNDVYWIAFGGGGSGGGGGGSSRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZ(SEQ ID NO:103), RNVPPIFNDVYWIAFRNVPPIFNDVYWIAFILMQYIKANSKFIGI(SEQ ID NO:104), RNVPPIFNDVYWIAFRNVPPIFNDVYWIAFILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:105), CRNVPPIFNFDVYWIAFCRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZC(SEQ ID A peptide unit as described in any one of Examples 1-6, 26-27, and 68-75, selected from the group consisting of NO:106) and RNVPPIFNDVYWIAFCRFRGLISLSQVYLSXXK(Cha)VAAWTLKAAXX(SEQ ID NO:202) (where a represents D-type alanine, (Cha) represents L-cyclohexylalanine, Z represents 6-aminohexanoic acid, and X represents any standard amino acid).

[0548] Example 79, limitations regarding the arrangement of unit C.

[0549] Material: RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:107); NO:108);RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:109);CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:110);CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZCRFRGLISLSQVYLS(SEQ ID NO:111); NO:112);KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:113); NO:114);KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZKTTKQSFDLSVKAQYKKNKH(SEQ ID NO:115);PIFNDVYWIAFK(Cha)VAAWTLKAACRFRGLISLSQ(SEQ ID NO:116);PPIFNDVYWK(Cha)VAAWTLKAARGLISLSQV(SEQ ID NO:117);MRGSHHHHHHGSDDDDKIVD RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAF(SEQ ID NO:118); GGGGSGGGGGGSSCRFRGLISLSQVYLS(SEQ ID NO:119);RNVPPIFNDVYWIAFILMQYIKANSKFIGICRFRGLISLSQVYLS(SEQ ID NO:120);RNVPPIFNDVYWIAFZPKYVKQNTLKLATZCRFRGLISLSQVYLS(P5:SEQ ID NO:121);CRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZRNVPPIFNDVYWIAFC(SEQ ID NO:122);RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:160);RNVPPIFNDVYWIAFXXKXVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:198);KTTKQSFDLSVKAQYKKNKHXXKXVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:201);RNVPPIFNDVYWIAFXPKYVKQNTLKLATXCRFRGLISLSQVYLS(SEQ ID NO:203);RNVPPIFNDVYWIAFXXKXVAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:207);RNVPPIFNDVYWIAFXXKFVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:209);RNVPPIFNFDVYWIAFXXKFVAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:211);KTTKQSFDLSVKAQYKKNKHZaWPEANQVGAGAFGPGFaZCRFRGLISLSQVYLS(SEQ ID NO:216);KTTKQSFDLSVKAQYKKNKHZaMDIDPYKEFGATVELLSFLPaZCRFRGLISLSQVYLS(SEQ ID A peptide unit as described in any one of Examples 1-6, 38-39, and 68-75, selected from the group consisting of NO:217); and KTTKQSFDLSVKAQYKKNKHZaILMQYIKANSKFIGIPMGLPQSIALSSLMVAQaZCRFRGLISLSQVYLS(SEQ ID NO:218) (where a represents D-type alanine, (Cha) represents L-cyclohexyl alanine, Z represents 6-aminohexanoic acid, and X represents any standard amino acid).

[0550] Example 80, limitations regarding the arrangement of unit E.

[0551] The peptide unit is RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF (SEQ ID NO: 137), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGICRFRGLISLSQVYLS (SEQ ID NO: 138), RNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIKTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 139), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF (SEQ ID NO: 140), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGICRFRGLISLSQVYLS (SEQ ID NO: 141), CRFRGLISLSQVYLSZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIKTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 142), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF (SEQ ID NO: 143), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGICRFRGLISLSQVYLS (SEQ ID NO: 144), KTTKQSFDLSVKAQYKKNKHZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIKTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 145), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAF (SEQ IDNO:146), MRGSHHHHHHGSDDDDKIVDRNVPPIFNDVYWIAFGGGGSGGGGGGSSILMQYIKANSKFIGIPMGLPQSIALSSLMVAQILMQYIKANSKFIGIPMGLPQSIALSSLMVAQGGGGSGGGGGGSSCRFRGLISLSQVYLS(SEQ ID NO:147), PIFNDVYWIAFK(Cha)VAAWTLKAAK(Cha)VAAWTLKAACRFRGLISLSQ(SEQ ID NO:148), PPIFDVYWK(Cha)VAAWTLKAAK(Cha)VAAWTLKAARGLISLSQV(SEQ ID NO:149), and CRNVPPIFNDVYWIAFZaK(Cha)VAAWTLKAAaZILMQYIKANSKFIGIRNVPPIFNDVYWIAFC(SEQ ID A peptide unit as described in any one of Examples 1-6, 49-50, and 68-75, selected from the group consisting of NO:150) (where a represents D-type alanine, (Cha) represents L-cyclohexyl alanine, and Z represents 6-aminohexanoic acid).

[0552] Peptide unit 9-formula.

[0553] Example 81: A higher-order concept of unit A.

[0554] The peptide unit described in any one of Examples 1 to 2, wherein the peptide unit is represented by either [Formula A] or [Formula A'] below.

[0555] [Formula A]A1-B-A2-T-A3.

[0556] [Formula A']A1-T-A2-B-A3. In the formula, the peptide units are those that can induce humoral immunity by being recognized by CD4+ T cells, and their lengths are 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, 33mer, 34mer, 35mer, 36mer, 37mer, 38mer, 39mer, 40mer, 41mer, 42mer, 43mer, 44mer, 45mer, 46mer, 47mer, 48mer, 49mer, 50mer, 51mer, 52mer, 53mer, 54mer, 55mer, 56mer, 57mer, 58mer, 59mer, 60mer, 61mer, 62mer, 63mer, 64mer, 65mer, 66mer, 67mer, 68mer, 69mer, 70mer, and 71mer. In the formula, A1 is either a first auxiliary part or is absent, where the first auxiliary part has a linker function, a protective function, a cyclic structure formation function, a dummy function, and / or a solubility-enhancing function, and may optionally contain a non-standard amino acid. A2 is either a second auxiliary part or is absent, where the second auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A3 is either a third auxiliary part or is absent, where the third auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. B, a B cell epitope, is a fragment or mimotope of apolipoprotein B-100, and can induce antibodies that target apolipoprotein B-100. The Th epitope T can be recognized by CD4+ T cells and has lengths of 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, or 32mer.

[0557] Example 82, combination of arrangements of unit A.

[0558] In Example 81 A1, A2, and A3 are a, Z, aZ, Za, RN, AF, CR, LS, KT, KH, RF, DP, SV, GL, ZRNV(SEQ ID NO:36), aZRN(SEQ ID NO:37), IAFZ(SEQ ID NO:38), AFZa(SEQ ID NO:39), RNVP(SEQ ID NO:40), WIAF(SEQ ID NO:41), ZCRF(SEQ ID NO:42), aZCR(SEQ ID NO:43), YLSZ(SEQ ID NO:44), LSZa(SEQ ID NO:45), CRFR(SEQ ID NO:46), VYLS(SEQ ID NO:47), ZKTT(SEQ ID NO:48), aZKT(SEQ ID NO:49), NKHZ(SEQ ID NO:50), KHZa(SEQ ID The following groups may be independently selected from the group consisting of NO:51), GSHHHHHHGSDDDDK(SEQ ID NO:52), HHHHHH(SEQ ID NO:53), MRGSHHHHHHGSDDDDKIVD(SEQ ID NO:54), GGGGSGGGGGGSS(SEQ ID NO:55), RRRRRR(SEQ ID NO:159), GSHHHHHHGSDDDDKZa(SEQ ID NO:193), and aZGSHHHHHHGSDDDDK(SEQ ID NO:194), or they may not exist, where a represents D-type alanine and Z represents 6-aminohexanoic acid. B is RNVPPIFNDVYWIAF(SEQ ID NO:6), CRFRGLISLSQVYLS(SEQ ID NO:7), KTTKQSFDLSVKAQYKKNKH(SEQ ID NO:8), RNVPPIFNDVY(SEQ ID NO:9), CRFRGLISLSQ(SEQ ID NO:10), KTTKQSFDLSVK(SEQ ID NO:11), RNVPPIFNDVYW(SEQ ID NO:12), CRFRGLISLSQV(SEQ ID NO:13), KTTKQSFDLSVKAQYKK(SEQ ID NO:14), RNVPPIFNDVYWI(SEQ ID NO:15), CRFRGLISLSQVY(SEQ ID NO:16), KTTKQSFDLSVKAQYKKN(SEQ ID NO:17), PIFNDVYWIAF(SEQ ID NO:18), GLISLSQVYLS(SEQ ID NO:19), QSFDLSVKAQYKKNKH(SEQ ID NO:20), PPIFNDVYWIAF(SEQ ID NO:21), RGLISLSQVYLS(SEQ ID NO:22), KQSFDLSVKAQYKKNKH(SEQ ID NO:23), VPPIFNDVYWIAF(SEQ ID NO:24), FRGLISLSQVYLS(SEQ ID NO:25), TKQSFDLSVKAQYKKNKH(SEQ ID NO:26), NVPPIFNDVYWIA(SEQ ID NO:27), RFRGLISLSQVYL(SEQ ID NO:28), TKQSFDLSVKAQYKKN(SEQ ID NO:29), VPPIFNDVYWI(SEQ ID NO:30), FRGLISLSQVY(SEQ ID Selected from the group consisting of NO:31), TKQSFDLSVKAQYKKN (SEQ ID NO:32), PPIFNDVYW (SEQ ID NO:33), RGLISLSQV (SEQ ID NO:34), KQSFDLSVKAQYKK (SEQ ID NO:35), RFRGLISLSQVYLDP (SEQ ID NO:221), and SVCGCPVGHHDVVGL (SEQ ID NO:222); An epitope included in any one of SEQ ID NO:6~SEQ ID NO:35 and SEQ ID NO:221~SEQ ID NO:222; or A sequence that matches any one of SEQ ID NO:6~SEQ ID NO:35 and SEQ ID NO:221~SEQ ID NO:222 by more than 80%, more than 81%, more than 82%, more than 83%, more than 84%, more than 85%, more than 86%, more than 87%, more than 88%, more than 89%, more than 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than 95%, more than 96%, more than 97%, more than 98%, more than 99%, and more than 100%. (Here, a represents D-type alanine, and Z represents 6-aminohexanoic acid, T is selected from the following group: K(Cha)VAAWTLKAA(SEQ ID NO:1)、PKYVKQNTLKLAT(SEQ ID NO:2)、ILMQYIKANSKFIGI(SEQ ID NO:3)、QSIALSSLMVAQAIP(SEQ ID NO:4)、ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5)、PLGFFPDHQL(SEQ ID NO:162)、WPEANQVGAGAFGPGF(SEQ ID NO:163)、MQWNSTALHQALQDP(SEQ ID NO:164)、MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165)、FFLLTRILTI(SEQ ID NO:166)、FFLLTRILTIPQSLD(SEQ ID NO:167)、TSLNFLGGTTVCLGQ(SEQ ID NO:168)、QSPTSNHSPTSCPPIC(SEQ ID NO:169)、IIFLFILLLCLIFLLVLLD(SEQ ID NO:170)、CTTPAQGNSMFPSC(SEQ ID NO:171)、CTKPTDGN(SEQ ID NO:172)、WASVRFSW(SEQ ID NO:173)、LLPIFFCLW(SEQ ID NO:174)、MDIDPYKEFGATVELLSFLP(SEQ ID NO:175)、FLPSDFFPSV(SEQ ID NO:176)、RDLLDTASALYREALESPEH(SEQ ID NO:177)、PHHTALRQAILCWGELMTLA(SEQ ID NO:178)、GRETVIEYLVSFGVW(SEQ ID NO:179)、EYLVSFGVWIRTPPA(SEQ ID NO:180)、VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181)、TVVRRRGRSP(SEQ ID NO:182)、VGPLTVNEKRRLKLI(SEQ ID NO:183)、RHYLHTLWKAGILYK(SEQ ID NO:184)、ESRLVVDFSQFSRGN(SEQ ID NO:185)、LQSLTNLLSSNLSWL(SEQ ID NO:186)、SSNLSWLSLDVSAAF(SEQ ID NO:187)、LHLYSHPIILGFRKI(SEQ IDNO:188)、KQCFRKLPVNRPIDW(SEQ ID NO:189)、LCQVFADATPTGWGL(SEQ ID NO:190)、AANWILRGTSFVYVP(SEQ ID NO:191)、EIRLKVFVLGGCRHK(SEQ ID NO:192) NO:195)、KYVAAWTLKAA(SEQ ID NO:196)、DIEKKIAKMEKASSVFNVVNS(SEQ ID NO:223)、YSGPLKAEIAQRLEDV(SEQ ID NO:224)、K(Cha)VKANTLKAA(SEQ ID NO:225)、K(Cha)VKANTLKAA(SEQ ID NO:225) NO:226)、K(Cha)VKAWTLKAA(SEQ ID NO:227)、K(Cha)VKAWTLKAA(SEQ ID NO:228)、K(Cha)VWANTLKAA(SEQ ID NO:229)、K(Cha)VWANTLKAA(SEQ ID NO:229) NO:230)、K(Cha)VWAYTLKAA(SEQ ID NO:231)、K(Cha)VWAVTLKAA(SEQ ID NO:232)、K(Cha)VYAWTLKAA(SEQ ID NO:233)、K(Cha)VYAWTLKAA(SEQ ID NO:234)、K(Cha)VYAWTLKAA(SEQ ID NO:234) ID NO:235)、K(Cha)VKAHTLKAA(SEQ ID NO:236)、K(Cha)VKAHTLKAA(SEQ ID NO:237)、K(Cha)VAANTLKAA(SEQ ID NO:238)、K(Cha)VAANTLKAA(SEQ ID NO:239)、K(Cha)VAANTLKAA(SEQ ID NO:239) NO:240)、K(Cha)VAAYTLKAA(SEQ ID NO:241)、K(Cha)VAAWTLKAA(SEQ ID NO:242)、K(Cha)VAAKTLKAA(SEQ ID NO:243)、K(Cha)VAAHTLKAA(SEQ ID NO:244)、K(Cha)VAAHTLKAA(SEQ ID NO:244) NO:245)、K(Cha)VAAWTLKAA(SEQ ID NO:246)、K(Cha)VMAATLKAA(SEQ ID NO:247) The array represented by either [Formula I] or [Formula II] below; [Formula I](N)-Lys-X1-X2-Ala-Ala-X3-Thr-X4-X5-Ala-Ala-(C) In the formula, X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is a hydrophobic amino acid, or leucine (Leu) or isoleucine (Ile), X3 is an aromatic or cyclic amino acid, or phenylalanine (Phe), tyrosine (Tyr), or histidine (His). X4 is an aliphatic long-chain amino acid, or isoleucine (Ile) or valine (Val). X5 is a charged amino acid, or arginine (Arg), leucine (Leu), aspartic acid (Asp), glutamine (Gln), or glycine (Gly). [Formula II](N)-Lys-X1-Val-X2-Ala-X3-Thr-Leu-Lys-Ala-Ala-(C) In the formula, X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is lysine (Lys), tryptophan (Trp), tyrosine (Tyr), arginine (Arg), alanine (Ala), or methionine (Met). X3 is either asparagine (Asn), tryptophan (Trp), tyrosine (Tyr), valine (Val), histidine (His), lysine (Lys), or alanine (Ala); An array that matches any one of the sequences represented by SEQ ID NO:1~SEQ ID NO:5, SEQ ID NO:162~SEQ ID NO:192, SEQ ID NO:195~SEQ ID NO:196, SEQ ID NO:223~SEQ ID NO:247, and [Formula I] or [Formula II] with 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more; (Here, (Cha) represents L-cyclohexylalanine, and X represents any standard amino acid.) It holds.

[0559] Example 83: A higher-order concept of the formula for unit B.

[0560] The peptide unit according to either Example 1 or 2, wherein the peptide unit is represented by the following [Formula B] or [Formula B']:

[0561] [Formula B] A1-B1-A2-B2-A3-T-A4

[0562] [Formula B']A1-T-A2-B1-A3-B2-A4 In the formula, the peptide unit is characterized by being able to induce humoral immunity by being recognized by CD4+ T cells, and having a length of 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, 33mer, 34mer, 35mer, 36mer, 37mer, 38mer, 39mer, 40mer, 41mer, 42mer, 43mer, 44mer, 45mer, 46mer, 47mer, 48mer, 49mer, 50mer, 51mer, 52mer, 53mer, 54mer, 55mer, 56mer, 57mer, 58mer, 59mer, 60mer, 61mer, 62mer, 63mer, 64mer, 65mer, 66mer, 67mer, 68mer, 69mer, 70mer, or 71mer. A1 is either a first auxiliary part or is absent, where the first auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A2 is either a second auxiliary part or is absent, where the second auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A3 is either a third auxiliary part or is absent, where the third auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A4 is either a fourth auxiliary part or is absent, where the fourth auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. B1, a B cell epitope, is a fragment or mimotope of apolipoprotein B-100, and can induce antibodies that target apolipoprotein B-100. B2, a B cell epitope, is a fragment or mimotope of apolipoprotein B-100, and can induce antibodies that target apolipoprotein B-100. The Th epitope T can be recognized by CD4+ T cells and has lengths of 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, or 32mer.

[0563] Example 84, combination of arrangements of unit B.

[0564] In Example 83, A1, A2, and A3 are a, Z, aZ, Za, RN, AF, CR, LS, KT, KH, RF, DP, SV, GL, ZRNV(SEQ ID NO:36), aZRN(SEQ ID NO:37), IAFZ(SEQ ID NO:38), AFZa(SEQ ID NO:39), RNVP(SEQ ID NO:40), WIAF(SEQ ID NO:41), ZCRF(SEQ ID NO:42), aZCR(SEQ ID NO:43), YLSZ(SEQ ID NO:44), LSZa(SEQ ID NO:45), CRFR(SEQ ID NO:46), VYLS(SEQ ID NO:47), ZKTT(SEQ ID NO:48), aZKT(SEQ ID NO:49), NKHZ(SEQ ID NO:50), KHZa(SEQ ID A group consisting of NO:51), GSHHHHHHGSDDDDK(SEQ ID NO:52), HHHHHH(SEQ ID NO:53), MRGSHHHHHHGSDDDDKIVD(SEQ ID NO:54), GGGGSGGGGGGSS(SEQ ID NO:55), RRRRRR(SEQ ID NO:159), GSHHHHHHGSDDDDKZa(SEQ ID NO:193), and aZGSHHHHHHGSDDDDK(SEQ ID NO:194) is independently selected or absent, where a represents D-type alanine and Z represents 6-aminohexanoic acid. B1 and B2 are RNVPPIFNDVYWIAF(SEQ ID NO:6), CRFRGLISLSQVYLS(SEQ ID NO:7), KTTKQSFDLSVKAQYKKNKH(SEQ ID NO:8), RNVPPIFNDVY(SEQ ID NO:9), CRFRGLISLSQ(SEQ ID NO:10), KTTKQSFDLSVK(SEQ ID NO:11), RNVPPIFNDVYW(SEQ ID NO:12), CRFRGLISLSQV(SEQ ID NO:13), KTTKQSFDLSVKAQYKK(SEQ ID NO:14), RNVPPIFNDVYWI(SEQ ID NO:15), CRFRGLISLSQVY(SEQ ID NO:16), KTTKQSFDLSVKAQYKKN(SEQ ID NO:17), PIFNDVYWIAF(SEQ ID NO:18), GLISLSQVYLS(SEQ ID NO:19), QSFDLSVKAQYKKNKH(SEQ ID NO:20), PPIFNDVYWIAF(SEQ ID NO:21), RGLISLSQVYLS(SEQ ID NO:22), KQSFDLSVKAQYKKNKH(SEQ ID NO:23), VPPIFNDVYWIAF(SEQ ID NO:24), FRGLISLSQVYLS(SEQ ID NO:25), TKQSFDLSVKAQYKKNKH(SEQ ID NO:26), NVPPIFNDVYWIA(SEQ ID NO:27), RFRGLISLSQVYL(SEQ ID NO:28), TKQSFDLSVKAQYKKN(SEQ ID NO:29), VPPIFNDVYWI(SEQ ID NO:30), FRGLISLSQVY(SEQ ID Each of the following sequences is independently selected from the group consisting of NO:31), TKQSFDLSVKAQYKKN (SEQ ID NO:32), PPIFNDVYW (SEQ ID NO:33), RGLISLSQV (SEQ ID NO:34), KQSFDLSVKAQYKK (SEQ ID NO:35), RFRGLISLSQVYLDP (SEQ ID NO:221), and SVCGCPVGHHDVVGL (SEQ ID NO:222), An epitope included in any one of SEQ ID NO:6~SEQ ID NO:35 and SEQ ID NO:221~SEQ ID NO:222; or An array that matches any one of SEQ ID NO:6~SEQ ID NO:35 and SEQ ID NO:221~SEQ ID NO:222 with 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more; (Here, a represents D-type alanine, and Z represents 6-aminohexanoic acid, T is selected from the following group: K(Cha)VAAWTLKAA(SEQ ID NO:1)、PKYVKQNTLKLAT(SEQ ID NO:2)、ILMQYIKANSKFIGI(SEQ ID NO:3)、QSIALSSLMVAQAIP(SEQ ID NO:4)、ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5)、PLGFFPDHQL(SEQ ID NO:162)、WPEANQVGAGAFGPGF(SEQ ID NO:163)、MQWNSTALHQALQDP(SEQ ID NO:164)、MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165)、FFLLTRILTI(SEQ ID NO:166)、FFLLTRILTIPQSLD(SEQ ID NO:167)、TSLNFLGGTTVCLGQ(SEQ ID NO:168)、QSPTSNHSPTSCPPIC(SEQ ID NO:169)、IIFLFILLLCLIFLLVLLD(SEQ ID NO:170)、CTTPAQGNSMFPSC(SEQ ID NO:171)、CTKPTDGN(SEQ ID NO:172)、WASVRFSW(SEQ ID NO:173)、LLPIFFCLW(SEQ ID NO:174)、MDIDPYKEFGATVELLSFLP(SEQ ID NO:175)、FLPSDFFPSV(SEQ ID NO:176)、RDLLDTASALYREALESPEH(SEQ ID NO:177)、PHHTALRQAILCWGELMTLA(SEQ ID NO:178)、GRETVIEYLVSFGVW(SEQ ID NO:179)、EYLVSFGVWIRTPPA(SEQ ID NO:180)、VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181)、TVVRRRGRSP(SEQ ID NO:182)、VGPLTVNEKRRLKLI(SEQ ID NO:183)、RHYLHTLWKAGILYK(SEQ ID NO:184)、ESRLVVDFSQFSRGN(SEQ ID NO:185)、LQSLTNLLSSNLSWL(SEQ ID NO:186)、SSNLSWLSLDVSAAF(SEQ ID NO:187)、LHLYSHPIILGFRKI(SEQ IDNO:188)、KQCFRKLPVNRPIDW(SEQ ID NO:189)、LCQVFADATPTGWGL(SEQ ID NO:190)、AANWILRGTSFVYVP(SEQ ID NO:191)、EIRLKVFVLGGCRHK(SEQ ID NO:192) NO:195)、KYVAAWTLKAA(SEQ ID NO:196)、DIEKKIAKMEKASSVFNVVNS(SEQ ID NO:223)、YSGPLKAEIAQRLEDV(SEQ ID NO:224)、K(Cha)VKANTLKAA(SEQ ID NO:225)、K(Cha)VKANTLKAA(SEQ ID NO:225) NO:226)、K(Cha)VKAWTLKAA(SEQ ID NO:227)、K(Cha)VKAWTLKAA(SEQ ID NO:228)、K(Cha)VWANTLKAA(SEQ ID NO:229)、K(Cha)VWANTLKAA(SEQ ID NO:229) NO:230)、K(Cha)VWAYTLKAA(SEQ ID NO:231)、K(Cha)VWAVTLKAA(SEQ ID NO:232)、K(Cha)VYAWTLKAA(SEQ ID NO:233)、K(Cha)VYAWTLKAA(SEQ ID NO:234)、K(Cha)VYAWTLKAA(SEQ ID NO:234) ID NO:235)、K(Cha)VKAHTLKAA(SEQ ID NO:236)、K(Cha)VKAHTLKAA(SEQ ID NO:237)、K(Cha)VAANTLKAA(SEQ ID NO:238)、K(Cha)VAANTLKAA(SEQ ID NO:239)、K(Cha)VAANTLKAA(SEQ ID NO:239) NO:240)、K(Cha)VAAYTLKAA(SEQ ID NO:241)、K(Cha)VAAWTLKAA(SEQ ID NO:242)、K(Cha)VAAKTLKAA(SEQ ID NO:243)、K(Cha)VAAHTLKAA(SEQ ID NO:244)、K(Cha)VAAHTLKAA(SEQ ID NO:244) NO:245)、K(Cha)VAAWTLKAA(SEQ ID NO:246)、K(Cha)VMAATLKAA(SEQ ID NO:247) The array represented by either [Formula I] or [Formula II] below; [Formula I](N)-Lys-X1-X2-Ala-Ala-X3-Thr-X4-X5-Ala-Ala-(C) X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is a hydrophobic amino acid, or leucine (Leu) or isoleucine (Ile), X3 is an aromatic or cyclic amino acid, or phenylalanine (Phe), tyrosine (Tyr), or histidine (His). X4 is an aliphatic long-chain amino acid, or isoleucine (Ile) or valine (Val). X5 is a charged amino acid, or arginine (Arg), leucine (Leu), aspartic acid (Asp), glutamine (Gln), or glycine (Gly). [Formula II](N)-Lys-X1-Val-X2-Ala-X3-Thr-Leu-Lys-Ala-Ala-(C) X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is lysine (Lys), tryptophan (Trp), tyrosine (Tyr), arginine (Arg), alanine (Ala), or methionine (Met). X3 is either asparagine (Asn), tryptophan (Trp), tyrosine (Tyr), valine (Val), histidine (His), lysine (Lys), or alanine (Ala). An array that matches any one of the sequences represented by SEQ ID NO:1~SEQ ID NO:5, SEQ ID NO:162~SEQ ID NO:192, SEQ ID NO:195~SEQ ID NO:196, SEQ ID NO:223~SEQ ID NO:247, and [Formula I] or [Formula II] with 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more; (Here, (Cha) represents L-cyclohexylalanine, and X represents any standard amino acid.) It holds.

[0565] Example 85: A higher-order concept of the formula for unit C.

[0566] The peptide unit is represented by the following [Formula C], as described in either Example 1 or 2; [Formula C]A1-B1-A2-T-A3-B2-A4 In the formula, the peptide unit is characterized by being able to induce humoral immunity by being recognized by CD4+ T cells, and having a length of 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, 33mer, 34mer, 35mer, 36mer, 37mer, 38mer, 39mer, 40mer, 41mer, 42mer, 43mer, 44mer, 45mer, 46mer, 47mer, 48mer, 49mer, 50mer, 51mer, 52mer, 53mer, 54mer, 55mer, 56mer, 57mer, 58mer, 59mer, 60mer, 61mer, 62mer, 63mer, 64mer, 65mer, 66mer, 67mer, 68mer, 69mer, 70mer, or 71mer. A1 is either a first auxiliary part or is absent, where the first auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A2 is either a second auxiliary part or is absent, where the second auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A3 is either a third auxiliary part or is absent, where the third auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A4 is either a fourth auxiliary part or is absent, where the fourth auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. B1, a B cell epitope, is a fragment or mimotope of apolipoprotein B-100, and can induce antibodies that target apolipoprotein B-100. B2, a B cell epitope, is a fragment or mimotope of apolipoprotein B-100, and can induce antibodies that target apolipoprotein B-100. The Th epitope T can be recognized by CD4+ T cells and has lengths of 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, or 32mer.

[0567] Example 86, combination of arrangement of unit C.

[0568] In Example 85, A1, A2, A3, and A4 are a, Z, aZ, Za, RN, AF, CR, LS, KT, KH, RF, DP, SV, GL, ZRNV(SEQ ID NO:36), aZRN(SEQ ID NO:37), IAFZ(SEQ ID NO:38), AFZa(SEQ ID NO:39), RNVP(SEQ ID NO:40), WIAF(SEQ ID NO:41), ZCRF(SEQ ID NO:42), aZCR(SEQ ID NO:43), YLSZ(SEQ ID NO:44), LSZa(SEQ ID NO:45), CRFR(SEQ ID NO:46), VYLS(SEQ ID NO:47), ZKTT(SEQ ID NO:48), aZKT(SEQ ID NO:49), NKHZ(SEQ ID NO:50), KHZa(SEQ A group consisting of ID NO: 51), GSHHHHHHGSDDDDK (SEQ ID NO: 52), HHHHHH (SEQ ID NO: 53), MRGSHHHHHHHGSDDDDKIVD (SEQ ID NO: 54), GGGGSGGGGGGSS (SEQ ID NO: 55), RRRRRR (SEQ ID NO: 159), GSHHHHHHGSDDDDKZa (SEQ ID NO: 193), and aZGSHHHHHHGSDDDDK (SEQ ID NO: 194) is independently selected or absent, where a represents D-type alanine and Z represents 6-aminohexanoic acid. B1 and B2 each independently have one selected from the following group: RNVPPIFNDVYWIAF(SEQ ID NO:6), CRFRGLISLSQVYLS(SEQ ID NO:7), KTTKQSFDLSVKAQYKKNKH(SEQ ID NO:8), RNVPPIFNDVY(SEQ ID NO:9), CRFRGLISLSQ(SEQ ID NO:10), KTTKQSFDLSVK(SEQ ID NO:11), RNVPPIFNDVYW(SEQ ID NO:12), CRFRGLISLSQV(SEQ ID NO:13), KTTKQSFDLSVKAQYKK(SEQ ID NO:14), RNVPPIFNDVYWI(SEQ ID NO:15), CRFRGLISLSQVY(SEQ ID NO:16), KTTKQSFDLSVKAQYKKN(SEQ ID NO:17), PIFNDVYWIAF(SEQ ID NO:18), GLISLSQVYLS(SEQ ID NO:19), QSFDLSVKAQYKKNKH(SEQ ID NO:20), PPIFNDVYWIAF(SEQ ID NO:21), RGLISLSQVYLS(SEQ ID NO:22), KQSFDLSVKAQYKKNKH(SEQ ID NO:23), VPPIFNDVYWIAF(SEQ ID NO:24), FRGLISLSQVYLS(SEQ ID NO:25), TKQSFDLSVKAQYKKNKH(SEQ ID NO:26), NVPPIFNDVYWIA(SEQ ID NO:27), RFRGLISLSQVYL(SEQ ID NO:28), TKQSFDLSVKAQYKKN(SEQ ID NO:29), VPPIFNDVYWI(SEQ ID NO:30), FRGLISLSQVY(SEQ ID Selected from the group consisting of NO:31), TKQSFDLSVKAQYKKN (SEQ ID NO:32), PPIFNDVYW (SEQ ID NO:33), RGLISLSQV (SEQ ID NO:34), KQSFDLSVKAQYKK (SEQ ID NO:35), RFRGLISLSQVYLDP (SEQ ID NO:221), and SVCGCPVGHHDVVGL (SEQ ID NO:222); An epitope included in any one of SEQ ID NO:6 to SEQ ID NO:35, and SEQ ID NO:221 to SEQ ID NO:222; An array that matches any one of the arrays represented by SEQ ID NO:6~SEQ ID NO:35 and SEQ ID NO:221~SEQ ID NO:222 with an array that matches 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more; (Here, "a" represents D-type alanine, and "Z" represents 6-aminohexanoic acid.) T is selected from the following group: K(Cha)VAAWTLKAA(SEQ ID NO:1)、PKYVKQNTLKLAT(SEQ ID NO:2)、ILMQYIKANSKFIGI(SEQ ID NO:3)、QSIALSSLMVAQAIP(SEQ ID NO:4)、ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5)、PLGFFPDHQL(SEQ ID NO:162)、WPEANQVGAGAFGPGF(SEQ ID NO:163)、MQWNSTALHQALQDP(SEQ ID NO:164)、MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165)、FFLLTRILTI(SEQ ID NO:166)、FFLLTRILTIPQSLD(SEQ ID NO:167)、TSLNFLGGTTVCLGQ(SEQ ID NO:168)、QSPTSNHSPTSCPPIC(SEQ ID NO:169)、IIFLFILLLCLIFLLVLLD(SEQ ID NO:170)、CTTPAQGNSMFPSC(SEQ ID NO:171)、CTKPTDGN(SEQ ID NO:172)、WASVRFSW(SEQ ID NO:173)、LLPIFFCLW(SEQ ID NO:174)、MDIDPYKEFGATVELLSFLP(SEQ ID NO:175)、FLPSDFFPSV(SEQ ID NO:176)、RDLLDTASALYREALESPEH(SEQ ID NO:177)、PHHTALRQAILCWGELMTLA(SEQ ID NO:178)、GRETVIEYLVSFGVW(SEQ ID NO:179)、EYLVSFGVWIRTPPA(SEQ ID NO:180)、VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181)、TVVRRRGRSP(SEQ ID NO:182)、VGPLTVNEKRRLKLI(SEQ ID NO:183)、RHYLHTLWKAGILYK(SEQ ID NO:184)、ESRLVVDFSQFSRGN(SEQ ID NO:185)、LQSLTNLLSSNLSWL(SEQ ID NO:186)、SSNLSWLSLDVSAAF(SEQ ID NO:187)、LHLYSHPIILGFRKI(SEQ IDNO: 188), KQCFRKLPVNRPIDW (SEQ ID NO: 189), LCQVFADATPTGWGL (SEQ ID NO: 190), AANWILRGTSFVYVP (SEQ ID NO: 191), EIRLKVFVLGGCRHK (SEQ ID NO: 192), KFVAAWTLKAA (SEQ ID NO: 195), KYVAAWTLKAA (SEQ ID NO: 196), DIEKKIAKMEKASSVFNVVNS (SEQ ID NO: 223), YSGPLKAEIAQRLEDV (SEQ ID NO: 224), K(Cha)VKANTLKAA (SEQ ID NO: 225), K(Cha)VKANTLKAA (SEQ ID NO: 226), K(Cha)VKAWTLKAA (SEQ ID NO: 227), K(Cha)VKAWTLKAA (SEQ ID NO: 228), K(Cha)VWANTLKAA (SEQ ID NO: 229), K(Cha)VWANTLKAA (SEQ ID NO: 230), K(Cha)VWAYTLKAA (SEQ ID NO: 231), K(Cha)VWAVTLKAA (SEQ ID NO: 232), K(Cha)VYAWTLKAA (SEQ ID NO: 233), K(Cha)VYAWTLKAA (SEQ ID NO: 234), R(Cha)VRANTLKAA (SEQ ID NO: 235), K(Cha)VKAHTLKAA (SEQ ID NO: 236), K(Cha)VKAHTLKAA (SEQ ID NO: 237), K(Cha)VAANTLKAA (SEQ ID NO: 238), K(Cha)VAANTLKAA (SEQ ID NO: 239), K(Cha)VAAYTLKAA (SEQ ID NO: 240), K(Cha)VAAYTLKAA (SEQ ID NO: 241), K(Cha)VAAWTLKAA (SEQ ID NO: 242), K(Cha)VAAKTLKAA (SEQ ID NO: 243), K(Cha)VAAHTLKAA (SEQ ID NO: 244), K(Cha)VAAATLKAA (SEQ ID NO: 245), K(Cha)VAAWTLKAA (SEQ ID NO: 246), and K(Cha)VMAATLKAA (SEQ ID NO: 247); selected from the group consisting of; The array represented by either [Formula I] or [Formula II] below; [Formula I](N)-Lys-X1-X2-Ala-Ala-X3-Thr-X4-X5-Ala-Ala-(C) X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is a hydrophobic amino acid, or leucine (Leu) or isoleucine (Ile), X3 is an aromatic or cyclic amino acid, or phenylalanine (Phe), tyrosine (Tyr), or histidine (His). X4 is an aliphatic long-chain amino acid, or isoleucine (Ile) or valine (Val). X5 is a charged amino acid, or arginine (Arg), leucine (Leu), aspartic acid (Asp), glutamine (Gln), or glycine (Gly). [Formula II](N)-Lys-X1-Val-X2-Ala-X3-Thr-Leu-Lys-Ala-Ala-(C) X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is lysine (Lys), tryptophan (Trp), tyrosine (Tyr), arginine (Arg), alanine (Ala), or methionine (Met). X3 is either asparagine (Asn), tryptophan (Trp), tyrosine (Tyr), valine (Val), histidine (His), lysine (Lys), or alanine (Ala). A sequence that matches any one of the sequences represented by SEQ ID NO:1~SEQ ID NO:5, SEQ ID NO:162~SEQ ID NO:192, SEQ ID NO:195~SEQ ID NO:196, SEQ ID NO:223~SEQ ID NO:247, and [Formula I] or [Formula II] with 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more. (Here, (Cha) represents L-cyclohexylalanine, and X represents any standard amino acid.) It holds.

[0569] Example 87: A higher-order concept of the formula for unit D.

[0570] The peptide unit is represented by either [Formula I] or [Formula II] below, as described in either Example 1 or 2; [Formula D] A1-B-A2-T1-A3-T2-A4 [Formula D'] A1-T1-A2-T2-A3-B-A4 In the formula, the peptide unit is characterized by being able to induce humoral immunity by being recognized by CD4+ T cells, and having a length of 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, 33mer, 34mer, 35mer, 36mer, 37mer, 38mer, 39mer, 40mer, 41mer, 42mer, 43mer, 44mer, 45mer, 46mer, 47mer, 48mer, 49mer, 50mer, 51mer, 52mer, 53mer, 54mer, 55mer, 56mer, 57mer, 58mer, 59mer, 60mer, 61mer, 62mer, 63mer, 64mer, 65mer, 66mer, 67mer, 68mer, 69mer, 70mer, or 71mer. A1 is either a first auxiliary part or is absent, where the first auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A2 is either a second auxiliary part or is absent, where the second auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A3 is either a third auxiliary part or is absent, where the third auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A4 is either a fourth auxiliary part or is absent, where the fourth auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. B, a B cell epitope, is a fragment or mimotope of apolipoprotein B-100, and can induce antibodies that target apolipoprotein B-100. The Th epitope T1 can be recognized by CD4+ T cells, and its length is 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, or 32mer. The Th epitope T2 can be recognized by CD4+ T cells and has lengths of 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, or 32mer.

[0571] Example 88, combination of arrangements of unit D.

[0572] In Example 87, A1, A2, A3, and A4 are a, Z, aZ, Za, RN, AF, CR, LS, KT, KH, RF, DP, SV, GL, ZRNV(SEQ ID NO:36), aZRN(SEQ ID NO:37), IAFZ(SEQ ID NO:38), AFZa(SEQ ID NO:39), RNVP(SEQ ID NO:40), WIAF(SEQ ID NO:41), ZCRF(SEQ ID NO:42), aZCR(SEQ ID NO:43), YLSZ(SEQ ID NO:44), LSZa(SEQ ID NO:45), CRFR(SEQ ID NO:46), VYLS(SEQ ID NO:47), ZKTT(SEQ ID NO:48), aZKT(SEQ ID NO:49), NKHZ(SEQ ID NO:50), KHZa(SEQ A group consisting of ID NO: 51), GSHHHHHHGSDDDDK (SEQ ID NO: 52), HHHHHH (SEQ ID NO: 53), MRGSHHHHHHHGSDDDDKIVD (SEQ ID NO: 54), GGGGSGGGGGGSS (SEQ ID NO: 55), RRRRRR (SEQ ID NO: 159), GSHHHHHHGSDDDDKZa (SEQ ID NO: 193), and aZGSHHHHHHGSDDDDK (SEQ ID NO: 194) is independently selected or absent, where a represents D-type alanine and Z represents 6-aminohexanoic acid. B is RNVPPIFNDVYWIAF(SEQ ID NO:6), CRFRGLISLSQVYLS(SEQ ID NO:7), KTTKQSFDLSVKAQYKKNKH(SEQ ID NO:8), RNVPPIFNDVY(SEQ ID NO:9), CRFRGLISLSQ(SEQ ID NO:10), KTTKQSFDLSVK(SEQ ID NO:11), RNVPPIFNDVYW(SEQ ID NO:12), CRFRGLISLSQV(SEQ ID NO:13), KTTKQSFDLSVKAQYKK(SEQ ID NO:14), RNVPPIFNDVYWI(SEQ ID NO:15), CRFRGLISLSQVY(SEQ ID NO:16), KTTKQSFDLSVKAQYKKN(SEQ ID NO:17), PIFNDVYWIAF(SEQ ID NO:18), GLISLSQVYLS(SEQ ID NO:19), QSFDLSVKAQYKKNKH(SEQ ID NO:20), PPIFNDVYWIAF(SEQ ID NO:21), RGLISLSQVYLS(SEQ ID NO:22), KQSFDLSVKAQYKKNKH(SEQ ID NO:23), VPPIFNDVYWIAF(SEQ ID NO:24), FRGLISLSQVYLS(SEQ ID NO:25), TKQSFDLSVKAQYKKNKH(SEQ ID NO:26), NVPPIFNDVYWIA(SEQ ID NO:27), RFRGLISLSQVYL(SEQ ID NO:28), TKQSFDLSVKAQYKKN(SEQ ID NO:29), VPPIFNDVYWI(SEQ ID NO:30), FRGLISLSQVY(SEQ ID Selected from the group consisting of NO:31), TKQSFDLSVKAQYKKN (SEQ ID NO:32), PPIFNDVYW (SEQ ID NO:33), RGLISLSQV (SEQ ID NO:34), KQSFDLSVKAQYKK (SEQ ID NO:35), RFRGLISLSQVYLDP (SEQ ID NO:221), and SVCGCPVGHHDVVGL (SEQ ID NO:222); An epitope included in any one of SEQ ID NO:6 to SEQ ID NO:35, and SEQ ID NO:221 to SEQ ID NO:222; An array that matches any one of the sequences represented by SEQ ID NO:6~SEQ ID NO:35 and SEQ ID NO:221~SEQ ID NO:222 with an amount of 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more. (Here, "a" represents D-type alanine, and "Z" represents 6-aminohexanoic acid.) T1 and T2 are independently selected from the following groups: K(Cha)VAAWTLKAA(SEQ ID NO:1)、PKYVKQNTLKLAT(SEQ ID NO:2)、ILMQYIKANSKFIGI(SEQ ID NO:3)、QSIALSSLMVAQAIP(SEQ ID NO:4)、ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5)、PLGFFPDHQL(SEQ ID NO:162)、WPEANQVGAGAFGPGF(SEQ ID NO:163)、MQWNSTALHQALQDP(SEQ ID NO:164)、MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165)、FFLLTRILTI(SEQ ID NO:166)、FFLLTRILTIPQSLD(SEQ ID NO:167)、TSLNFLGGTTVCLGQ(SEQ ID NO:168)、QSPTSNHSPTSCPPIC(SEQ ID NO:169)、IIFLFILLLCLIFLLVLLD(SEQ ID NO:170)、CTTPAQGNSMFPSC(SEQ ID NO:171)、CTKPTDGN(SEQ ID NO:172)、WASVRFSW(SEQ ID NO:173)、LLPIFFCLW(SEQ ID NO:174)、MDIDPYKEFGATVELLSFLP(SEQ ID NO:175)、FLPSDFFPSV(SEQ ID NO:176)、RDLLDTASALYREALESPEH(SEQ ID NO:177)、PHHTALRQAILCWGELMTLA(SEQ ID NO:178)、GRETVIEYLVSFGVW(SEQ ID NO:179)、EYLVSFGVWIRTPPA(SEQ ID NO:180)、VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181)、TVVRRRGRSP(SEQ ID NO:182)、VGPLTVNEKRRLKLI(SEQ ID NO:183)、RHYLHTLWKAGILYK(SEQ ID NO:184)、ESRLVVDFSQFSRGN(SEQ ID NO:185)、LQSLTNLLSSNLSWL(SEQ ID NO:186)、SSNLSWLSLDVSAAF(SEQ ID NO:187)、LHLYSHPIILGFRKI(SEQ IDNO: 188), KQCFRKLPVNRPIDW (SEQ ID NO: 189), LCQVFADATPTGWGL (SEQ ID NO: 190), AANWILRGTSFVYVP (SEQ ID NO: 191), EIRLKVFVLGGCRHK (SEQ ID NO: 192), KFVAAWTLKAA (SEQ ID NO: 195), KYVAAWTLKAA (SEQ ID NO: 196), DIEKKIAKMEKASSVFNVVNS (SEQ ID NO: 223), YSGPLKAEIAQRLEDV (SEQ ID NO: 224), K(Cha)VKANTLKAA (SEQ ID NO: 225), K(Cha)VKANTLKAA (SEQ ID NO: 226), K(Cha)VKAWTLKAA (SEQ ID NO: 227), K(Cha)VKAWTLKAA (SEQ ID NO: 228), K(Cha)VWANTLKAA (SEQ ID NO: 229), K(Cha)VWANTLKAA (SEQ ID NO: 230), K(Cha)VWAYTLKAA (SEQ ID NO: 231), K(Cha)VWAVTLKAA (SEQ ID NO: 232), K(Cha)VYAWTLKAA (SEQ ID NO: 233), K(Cha)VYAWTLKAA (SEQ ID NO: 234), R(Cha)VRANTLKAA (SEQ ID NO: 235), K(Cha)VKAHTLKAA (SEQ ID NO: 236), K(Cha)VKAHTLKAA (SEQ ID NO: 237), K(Cha)VAANTLKAA (SEQ ID NO: 238), K(Cha)VAANTLKAA (SEQ ID NO: 239), K(Cha)VAAYTLKAA (SEQ ID NO: 240), K(Cha)VAAYTLKAA (SEQ ID NO: 241), K(Cha)VAAWTLKAA (SEQ ID NO: 242), K(Cha)VAAKTLKAA (SEQ ID NO: 243), K(Cha)VAAHTLKAA (SEQ ID NO: 244), K(Cha)VAAATLKAA (SEQ ID NO: 245), K(Cha)VAAWTLKAA (SEQ ID NO: 246), and K(Cha)VMAATLKAA (SEQ ID NO: 247); one selected from the group consisting of; The array represented by either [Formula I] or [Formula II] below; [Formula I](N)-Lys-X1-X2-Ala-Ala-X3-Thr-X4-X5-Ala-Ala-(C) X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is a hydrophobic amino acid, or leucine (Leu) or isoleucine (Ile), X3 is an aromatic or cyclic amino acid, or phenylalanine (Phe), tyrosine (Tyr), or histidine (His). X4 is an aliphatic long-chain amino acid, or isoleucine (Ile) or valine (Val). X5 is a charged amino acid, or arginine (Arg), leucine (Leu), aspartic acid (Asp), glutamine (Gln), or glycine (Gly). [Formula II](N)-Lys-X1-Val-X2-Ala-X3-Thr-Leu-Lys-Ala-Ala-(C): X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is either lysine (Lys), tryptophan (Trp), tyrosine (Tyr), arginine (Arg), alanine (Ala), or methionine (Met). X3 is asparagine (Asn), tryptophan (Trp), tyrosine (Tyr), valine (Val), histidine (His), lysine (Lys), or alanine (Ala). A sequence that matches any one of the sequences represented by SEQ ID NO:1~SEQ ID NO:5, SEQ ID NO:162~SEQ ID NO:192, SEQ ID NO:195~SEQ ID NO:196, SEQ ID NO:223~SEQ ID NO:247, and [Formula I] or [Formula II] with 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more. (Here, (Cha) represents L-cyclohexylalanine, and X represents any standard amino acid.) It holds.

[0573] Example 89: A higher-order concept of the formula for unit E.

[0574] The peptide unit is represented by the following [Formula E], as described in either Example 1 or 2: [Formula E]A1-B1-A2-T1-A3-T2-A4-B2-A5 In the formula, the peptide units are those that can induce humoral immunity by being recognized by CD4+ T cells, and their lengths are 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, 32mer, 33mer, 34mer, 35mer, 36mer, 37mer, 38mer, 39mer, 40mer, 41mer, 42mer, 43mer, 44mer, 45mer, 46mer, 47mer, 48mer, 49mer, 50mer, 51mer, 52mer, 53mer, 54mer, 55mer, 56mer, 57mer, 58mer, 59mer, 60mer, 61mer, 62mer, 63mer, 64mer, 65mer, 66mer, 67mer, 68mer, 69mer, 70mer, and 71mer. A1 is either a first auxiliary part or is absent, where the first auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A2 is either a second auxiliary part or is absent, where the second auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A3 is either a third auxiliary part or is absent, where the third auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. A4 is either a fourth auxiliary part or is absent, where the fourth auxiliary part has linker function, protective function, cyclic formation function, dummy function, and / or solubility-enhancing function, and may optionally contain non-standard amino acids. B1, a B cell epitope, is a fragment or mimotope of apolipoprotein B-100, and can induce antibodies that target apolipoprotein B-100. B2, a B cell epitope, is a fragment or mimotope of apolipoprotein B-100, and can induce antibodies that target apolipoprotein B-100. The Th epitope T1 can be recognized by CD4+ T cells and is characterized by having a length of 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, or 32mer. The Th epitope T2 can be recognized by CD4+ T cells and is characterized by having a length of 8mer, 9mer, 10mer, 11mer, 12mer, 13mer, 14mer, 15mer, 16mer, 17mer, 18mer, 19mer, 20mer, 21mer, 22mer, 23mer, 24mer, 25mer, 26mer, 27mer, 28mer, 29mer, 30mer, 31mer, or 32mer.

[0575] Example 90, combination of arrangements of unit E.

[0576] In Example 89, A1, A2, A3, and A4 are a, Z, aZ, Za, RN, AF, CR, LS, KT, KH, RF, DP, SV, GL, ZRNV(SEQ ID NO:36), aZRN(SEQ ID NO:37), IAFZ(SEQ ID NO:38), AFZa(SEQ ID NO:39), RNVP(SEQ ID NO:40), WIAF(SEQ ID NO:41), ZCRF(SEQ ID NO:42), aZCR(SEQ ID NO:43), YLSZ(SEQ ID NO:44), LSZa(SEQ ID NO:45), CRFR(SEQ ID NO:46), VYLS(SEQ ID NO:47), ZKTT(SEQ ID NO:48), aZKT(SEQ ID NO:49), NKHZ(SEQ ID NO:50), KHZa(SEQ A group consisting of ID NO: 51), GSHHHHHHGSDDDDK (SEQ ID NO: 52), HHHHHH (SEQ ID NO: 53), MRGSHHHHHHHGSDDDDKIVD (SEQ ID NO: 54), GGGGSGGGGGGSS (SEQ ID NO: 55), RRRRRR (SEQ ID NO: 159), GSHHHHHHGSDDDDKZa (SEQ ID NO: 193), and aZGSHHHHHHGSDDDDK (SEQ ID NO: 194) is independently selected or absent, where a represents D-type alanine and Z represents 6-aminohexanoic acid. B1 and B2 each independently have one selected from the following group: RNVPPIFNDVYWIAF(SEQ ID NO:6), CRFRGLISLSQVYLS(SEQ ID NO:7), KTTKQSFDLSVKAQYKKNKH(SEQ ID NO:8), RNVPPIFNDVY(SEQ ID NO:9), CRFRGLISLSQ(SEQ ID NO:10), KTTKQSFDLSVK(SEQ ID NO:11), RNVPPIFNDVYW(SEQ ID NO:12), CRFRGLISLSQV(SEQ ID NO:13), KTTKQSFDLSVKAQYKK(SEQ ID NO:14), RNVPPIFNDVYWI(SEQ ID NO:15), CRFRGLISLSQVY(SEQ ID NO:16), KTTKQSFDLSVKAQYKKN(SEQ ID NO:17), PIFNDVYWIAF(SEQ ID NO:18), GLISLSQVYLS(SEQ ID NO:19), QSFDLSVKAQYKKNKH(SEQ ID NO:20), PPIFNDVYWIAF(SEQ ID NO:21), RGLISLSQVYLS(SEQ ID NO:22), KQSFDLSVKAQYKKNKH(SEQ ID NO:23), VPPIFNDVYWIAF(SEQ ID NO:24), FRGLISLSQVYLS(SEQ ID NO:25), TKQSFDLSVKAQYKKNKH(SEQ ID NO:26), NVPPIFNDVYWIA(SEQ ID NO:27), RFRGLISLSQVYL(SEQ ID NO:28), TKQSFDLSVKAQYKKN(SEQ ID NO:29), VPPIFNDVYWI(SEQ ID NO:30), FRGLISLSQVY(SEQ ID Selected from the group consisting of NO:31), TKQSFDLSVKAQYKKN (SEQ ID NO:32), PPIFNDVYW (SEQ ID NO:33), RGLISLSQV (SEQ ID NO:34), KQSFDLSVKAQYKK (SEQ ID NO:35), RFRGLISLSQVYLDP (SEQ ID NO:221), and SVCGCPVGHHDVVGL (SEQ ID NO:222); An epitope included in any one of SEQ ID NO:6 to SEQ ID NO:35, and SEQ ID NO:221 to SEQ ID NO:222; An array that matches any one of the sequences represented by SEQ ID NO:6~SEQ ID NO:35 and SEQ ID NO:221~SEQ ID NO:222 with an amount of 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more. (Here, a represents D-type alanine, and Z represents 6-aminohexanoic acid, T1 and T2 are independently selected from the following groups: K(Cha)VAAWTLKAA(SEQ ID NO:1)、PKYVKQNTLKLAT(SEQ ID NO:2)、ILMQYIKANSKFIGI(SEQ ID NO:3)、QSIALSSLMVAQAIP(SEQ ID NO:4)、ILMQYIKANSKFIGIPMGLPQSIALSSLMVAQ(SEQ ID NO:5)、PLGFFPDHQL(SEQ ID NO:162)、WPEANQVGAGAFGPGF(SEQ ID NO:163)、MQWNSTALHQALQDP(SEQ ID NO:164)、MQWNSTTFHQTLQDPRVRGLYFPAGG(SEQ ID NO:165)、FFLLTRILTI(SEQ ID NO:166)、FFLLTRILTIPQSLD(SEQ ID NO:167)、TSLNFLGGTTVCLGQ(SEQ ID NO:168)、QSPTSNHSPTSCPPIC(SEQ ID NO:169)、IIFLFILLLCLIFLLVLLD(SEQ ID NO:170)、CTTPAQGNSMFPSC(SEQ ID NO:171)、CTKPTDGN(SEQ ID NO:172)、WASVRFSW(SEQ ID NO:173)、LLPIFFCLW(SEQ ID NO:174)、MDIDPYKEFGATVELLSFLP(SEQ ID NO:175)、FLPSDFFPSV(SEQ ID NO:176)、RDLLDTASALYREALESPEH(SEQ ID NO:177)、PHHTALRQAILCWGELMTLA(SEQ ID NO:178)、GRETVIEYLVSFGVW(SEQ ID NO:179)、EYLVSFGVWIRTPPA(SEQ ID NO:180)、VSFGVWIRTPPAYRPPNAPI(SEQ ID NO:181)、TVVRRRGRSP(SEQ ID NO:182)、VGPLTVNEKRRLKLI(SEQ ID NO:183)、RHYLHTLWKAGILYK(SEQ ID NO:184)、ESRLVVDFSQFSRGN(SEQ ID NO:185)、LQSLTNLLSSNLSWL(SEQ ID NO:186)、SSNLSWLSLDVSAAF(SEQ ID NO:187)、LHLYSHPIILGFRKI(SEQ IDNO: 188), KQCFRKLPVNRPIDW (SEQ ID NO: 189), LCQVFADATPTGWGL (SEQ ID NO: 190), AANWILRGTSFVYVP (SEQ ID NO: 191), EIRLKVFVLGGCRHK (SEQ ID NO: 192), KFVAAWTLKAA (SEQ ID NO: 195), KYVAAWTLKAA (SEQ ID NO: 196), DIEKKIAKMEKASSVFNVVNS (SEQ ID NO: 223), YSGPLKAEIAQRLEDV (SEQ ID NO: 224), K(Cha)VKANTLKAA (SEQ ID NO: 225), K(Cha)VKANTLKAA (SEQ ID NO: 226), K(Cha)VKAWTLKAA (SEQ ID NO: 227), K(Cha)VKAWTLKAA (SEQ ID NO: 228), K(Cha)VWANTLKAA (SEQ ID NO: 229), K(Cha)VWANTLKAA (SEQ ID NO: 230), K(Cha)VWAYTLKAA (SEQ ID NO: 231), K(Cha)VWAVTLKAA (SEQ ID NO: 232), K(Cha)VYAWTLKAA (SEQ ID NO: 233), K(Cha)VYAWTLKAA (SEQ ID NO: 234), R(Cha)VRANTLKAA (SEQ ID NO: 235), K(Cha)VKAHTLKAA (SEQ ID NO: 236), K(Cha)VKAHTLKAA (SEQ ID NO: 237), K(Cha)VAANTLKAA (SEQ ID NO: 238), K(Cha)VAANTLKAA (SEQ ID NO: 239), K(Cha)VAAYTLKAA (SEQ ID NO: 240), K(Cha)VAAYTLKAA (SEQ ID NO: 241), K(Cha)VAAWTLKAA (SEQ ID NO: 242), K(Cha)VAAKTLKAA (SEQ ID NO: 243), K(Cha)VAAHTLKAA (SEQ ID NO: 244), K(Cha)VAAATLKAA (SEQ ID NO: 245), K(Cha)VAAWTLKAA (SEQ ID NO: 246), and K(Cha)VMAATLKAA (SEQ ID NO: 247); one selected from the group consisting of; The array represented by either [Formula I] or [Formula II] below; [Formula I](N)-Lys-X1-X2-Ala-Ala-X3-Thr-X4-X5-Ala-Ala-(C) X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X1 is a hydrophobic amino acid, or leucine (Leu) or isoleucine (Ile), X3 is an aromatic or cyclic amino acid, or phenylalanine (Phe), tyrosine (Tyr), or histidine (His). X4 is an aliphatic long-chain amino acid, or isoleucine (Ile) or valine (Val). X5 is a charged amino acid, or arginine (Arg), leucine (Leu), aspartic acid (Asp), glutamine (Gln), or glycine (Gly). [Formula II](N)-Lys-X1-Val-X2-Ala-X3-Thr-Leu-Lys-Ala-Ala-(C): X1 is tyrosine (Tyr), phenylalanine (Phe), or L-cyclohexylalanine. X2 is lysine (Lys), tryptophan (Trp), tyrosine (Tyr), arginine (Arg), alanine (Ala), or methionine (Met). X3 is asparagine (Asn), tryptophan (Trp), tyrosine (Tyr), valine (Val), histidine (His), lysine (Lys), or alanine (Ala). An array that matches any one of the sequences represented by SEQ ID NO:1~SEQ ID NO:5, SEQ ID NO:162~SEQ ID NO:192, SEQ ID NO:195~SEQ ID NO:196, SEQ ID NO:223~SEQ ID NO:247, and [Formula I] or [Formula II] with 80% or more, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and 100% or more; (Here, (Cha) represents L-cyclohexylalanine, and X represents any standard amino acid.) It holds.

[0577] A peptide containing peptide units.

[0578] Example 91, a peptide containing two or more peptide units.

[0579] A peptide comprising two or more peptide units linked together, as described in any one of Examples 1 to 90.

[0580] Example 92: A peptide containing 2 to 8 peptide units.

[0581] A peptide comprising 2, 3, 4, 5, 6, 7, or 8 peptide units linked together, as described in any one of Examples 1 to 90.

[0582] Example 93, concatemer sequence.

[0583] The peptide according to Example 91, wherein each peptide unit has the same or equivalent sequence.

[0584] Example 94: A string of beads.

[0585] The peptide according to Example 91, wherein each peptide unit has a different sequence.

[0586] Example 95, cyclic body.

[0587] The peptide according to Example 91, further comprising auxiliary moieties having cyclic formation functions at the N-terminus and C-terminus, wherein the peptide forms a cyclic structure via the auxiliary moieties.

[0588] A nucleic acid that codes for a peptide unit and / or a peptide.

[0589] Example 96, Coating nucleic acid that does not contain non-standard amino acids.

[0590] A nucleic acid encoding a peptide unit described in any one of Examples 1 to 6 and / or a peptide described in any one of Examples 91 to 95, wherein the peptide unit and the peptide do not contain non-standard amino acids.

[0591] Example 97, a coding nucleic acid for each unit formula, free from non-standard amino acids.

[0592] A nucleic acid encoding a peptide unit described in any one of Examples 7 to 10, 14 to 18, 22, 26 to 30, 34, 38 to 41, 45, 49 to 54, 58 to 60, 64, 68, and 72, characterized in that the peptide unit does not contain non-standard amino acids.

[0593] Example 98, Restrictions on the sequence of the unit peptide.

[0594] The nucleic acid described in either one of Examples 96 and 97, wherein the nucleic acid is RNVPPIFNDVYWIAFXXKXVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:198);RNVPPIFNDVYWIAFXXKXVAAWTLKAAXXGSHHHHHHGSDDDDK(SEQ ID NO:199);GSHHHHHHGSDDDDKXXKXVAAWTLKAAXXRNVPPIFNDVYWIAF(SEQ ID NO:200);KTTKQSFDLSVKAQYKKNKHXXKXVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:201);RNVPPIFNDVYWIAFCRFRGLISLSQVYLSXXKXVAAWTLKAAXX(SEQ ID NO:202);RNVPPIFNDVYWIAFXPKYVKQNTLKLATXCRFRGLISLSQVYLS(SEQ ID NO:203);RNVPPIFNDVYWIAFXXKXVAAWTLKAAXX(SEQ ID NO:204);RNVPPIFNDVYWIAFKXVAAWTLKAA(SEQ ID NO:205);RNVPPIFNFDVYWIAFKXVAAWTLKAAHHHHHH(SEQ ID NO:206);RNVPPIFNDVYWIAFXXKXVAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:207);RNVPPIFNDVYWIAFXXKXVAAWTLKAACR(SEQ ID NO:208);RNVPPIFNDVYWIAFXXKFVAAWTLKAAXXCRFRGLISLSQVYLS(SEQ ID NO:209);RNVPPIFNFDVYWIAFXXKFVAAWTLKAAXX(SEQ ID Nucleic acids encoding peptide units selected from NO:210);RNVPPIFNDVYWIAFXXKFVAAWTLKAACRFRGLISLSQVYLS(SEQ ID NO:211); and RNVPPIFNDVYWIAFXXKFVAAWTLKAACR(SEQ ID NO:212) (where X represents any standard amino acid).

[0595] Example 99, limitations on the sequence of DNA-coding units.

[0596] The nucleic acid described in Example 98 is DNA represented by a sequence selected from the following: 5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:248);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:249);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:250);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNGGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAG-3'(SEQ ID NO:251);5'-ACGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNGGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAG-3'(SEQ ID NO:252);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNGGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAG-3'(SEQ ID NO:253);5'-GGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAGNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNCGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTC-3'(SEQ ID NO:254);5'-GGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAGNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNCGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTC-3'(SEQ ID NO:255);5'-GGATCGCATCACCATCACCATCACGGATCCGATGATGATGACAAGNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNCGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTC-3'(SEQ ID NO:256);5'-AAAACGACAAAGCAATCATTTGATTTAAGTGTAAAAGCTCAGTATNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:257);5'-AAAACGACAAAGCAATCATTTGATTTAAGTGTAAAAGCTCAGTATNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:258);5'-AAAACGACAAAGCAATCATTTGATTTAAGTGTAAAAGCTCAGTATNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:259);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:260);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:261);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:262);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNCCTAAGTATGTGAAGCAGAATACACTGAAGCTGGCAACCNNNTGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:263);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:264);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:265);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCANNNNNN-3'(SEQ ID NO:266);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCA-3'(SEQ ID NO:267);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCA-3'(SEQ ID NO:268);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCA-3'(SEQ ID NO:269);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCACATCACCATCACCATCAC-3'(SEQ ID NO:270);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCACATCACCATCACCATCAC-3'(SEQ ID NO:271);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCACATCACCATCACCATCAC-3'(SEQ ID NO:272);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:273);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTTCGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:274);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGTTTCCGTGGACTGATTTCCCTGTCCCAGGTTTATCTGTCC-3'(SEQ ID NO:275);5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGNNNGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGT-3'(SEQ ID and 5'-CGTAATGTTCCTCCTATCTTCAATGATGTTTATTGGATTGCATTCNNNNNNAAGTATGTGGCAGCTTGGACCCTGAAGGCAGCATGCCGT-3' (SEQ ID NO:278). ;

[0597] Example 100, limitations regarding the sequence of the unit encoding RNA.

[0598] RNA represented by a sequence selected from the following, which is the nucleic acid described in Example 98: 5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGNNNGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCC-3'(SEQ ID NO:279);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUUCGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCC-3'(SEQ ID NO:280);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCC-3'(SEQ ID NO:281);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGNNNGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNGGAUCGCAUCACCAUCACCAUCACGGAUCCGAUGAUGAUGACAAG-3'(SEQ ID NO:282);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUUCGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNGGAUCGCAUCACCAUCACCAUCACGGAUCCGAUGAUGAUGACAAG-3'(SEQ ID NO:283);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNGGAUCGCAUCACCAUCACCAUCACGGAUCCGAUGAUGAUGACAAG-3'(SEQ ID NO:284);5'-GGAUCGCAUCACCAUCACCAUCACGGAUCCGAUGAUGAUGACAAGNNNNNNAAGNNNGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNCGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUC-3'(SEQ ID NO:285);5'-GGAUCGCAUCACCAUCACCAUCACGGAUCCGAUGAUGAUGACAAGNNNNNNAAGUUCGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNCGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUC-3'(SEQ ID NO:286);5'-GGAUCGCAUCACCAUCACCAUCACGGAUCCGAUGAUGAUGACAAGNNNNNNAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNCGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUC-3'(SEQ ID NO:287);5'-AAAACGACAAAGCAAUCAUUUGAUUUAAGUGUAAAAGCUCAGUAUNNNNNNAAGNNNGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCC-3'(SEQ ID NO:288);5'-AAAACGACAAAGCAAUCAUUUGAUUUAAGUGUAAAAGCUCAGUAUNNNNNNAAGUUCGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCC-3'(SEQ ID NO:289);5'-AAAACGACAAAGCAAUCAUUUGAUUUAAGUGUAAAAGCUCAGUAUNNNNNNAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNNUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCC-3'(SEQ ID NO:290);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCCNNNNNNAAGNNNGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNN-3'(SEQ ID NO:291);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCCNNNNNNAAGUUCGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNN-3'(SEQ ID NO:292);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCCNNNNNNAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNN-3'(SEQ ID NO:293);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNCCUAAGUAUGUGAAGCAGAAUACACUGAAGCUGGCAACCNNNUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCC-3'(SEQ ID NO:294);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGNNNGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNN-3'(SEQ ID NO:295);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUUCGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNN-3'(SEQ ID NO:296);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCANNNNNN-3'(SEQ ID NO:297);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCAAGNNNNGUGGCAGCUUGGACCCUGAAGGCAGCA-3'(SEQ ID NO:298);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCAAGUAUCUGGAGCUUGGACCCUGAAGGCAGCA-3'(SEQ ID NO:299);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCAAGUAUGUUGGCAGCUUGGACCCUGAAGGCAGCA-3'(SEQ ID NO:300);5'-CGUAAUGUUCCUCCUAUCUCAAUGAUGUUUAUUGGAUUGCAUUCAAGNNNNGUGGCAGCUUGGACCCUGAAGGCAGCACAUCACCAUCACCAUCAC-3'(SEQ ID NO:301);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCAAGUUCGUGCAGCUUGGACCCUGAAGGCAGCACAUCACCAUCACCAUCAC-3'(SEQ ID NO:302) NO:302);5'-CGUAAUGUUCCUCCUAUCUCAAUGAUGUUUAUUGGAUUGCAUUCAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCACAUCACCAUCACCAUCAC-3'(SEQ ID NO:303);5'-CGUAAUGUUCCUCCUAUCUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNAAGNNNGUGGCAGCUUGGACCCUGAAGGCAGCAUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUCUCC-3'(SEQ ID NO:304);5'-CGUAAUGUUCCUCCUAUCUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUUCGUGGCAGCUUGGACCCUGAAGGCAGCAUGCCGUUUCCGUGGACUGAUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUCUCC-3'(SEQ ID NO:305);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCAUGCCGUUUCCGUGGACUGAUUUCCCUGUCCCAGGUUUAUCUGUCC-3'(SEQ ID NO:306);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGNNNGUGGCAGCUUGGACCCUGAAGGCAGCAUGCCGU-3'(SEQ ID NO:307);5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUUCGUGGCAGCUUGGACCCUGAAGGCAGCAUGCCGU-3'(SEQ ID and 5'-CGUAAUGUUCCUCCUAUCUUCAAUGAUGUUUAUUGGAUUGCAUUCNNNNNNAAGUAUGUGGCAGCUUGGACCCUGAAGGCAGCAUGCCGU-3' (SEQ ID NO:309). ;

[0599] Example 101, vector.

[0600] A vector containing the nucleic acid described in any one of Examples 96 to 100.

[0601] Example 102, limitations regarding the vector.

[0602] The vector according to Example 101, wherein the vector is selected from the group consisting of plasmids, retroviruses, lentiviruses, adenoviruses, adeno-associated viruses, vaccinia viruses, poxviruses, and herpes simplex viruses.

[0603] Example 103, Mammalian codon-optimized nucleic acid.

[0604] The nucleic acid according to any one of Examples 96-98, wherein the nucleic acid is codon-optimized for a species selected from mammals.

[0605] Example 104, Human codon-optimized nucleic acid.

[0606] The nucleic acid described in any one of Examples 96 to 98, wherein the nucleic acid is optimized for human codons.

[0607] Example 105, Prokaryotic codon-optimized nucleic acid.

[0608] The nucleic acid according to any one of Examples 96-98, wherein the nucleic acid is codon-optimized for a species selected from prokaryotes.

[0609] Example 106, Escherichia coli codon-optimized nucleic acid.

[0610] The nucleic acid described in any one of Examples 96 to 98, wherein the nucleic acid is optimized for E. coli codons.

[0611] A pharmaceutical composition containing peptides.

[0612] Example 107, Pharmaceutical composition for immunotherapy.

[0613] Immunotherapy pharmaceutical compositions including the following: A peptide unit as described in any one of Examples 1 to 90, and / or a peptide as described in any one of Examples 91 to 95; and

[0614] Adjuvant.

[0615] Example 108, Pharmaceutical composition for the treatment of obesity.

[0616] A pharmaceutical composition for the treatment of obesity, including the following: A peptide unit as described in any one of Examples 1 to 90, and / or a peptide as described in any one of Examples 91 to 95; and Adjuvant.

[0617] Example 109, limitations regarding the adjuvant.

[0618] In any one of Examples 107-108, the adjuvant is: water, physiological saline, dextrose, ethanol, glycerol, sodium chloride, dextrose, mannitol, sorbitol, lactose, gelatin, albumin, aluminum hydroxide, Freund's incomplete and complete adjuvants (Pifco Laboratories, Detroit, Michigan), Merck Antigen Adjuvant 65 (Merck and Company, Inc., Loway, New Jersey), ahydrogel (Al(OH)3), aluminum hydroxide gel (alum) or aluminum salt, e.g., aluminum phosphate, AS04 series, MF, squalene, MF59, QS21, calcium, iron or zinc salt, acylated tyrosine, insoluble suspension of acylated fructose, polysaccharides derived from cations or anions, polyphosphazene, biodegradable microspheres, Quil A, Toll-like receptor (TLR) agonists, PHAD [Avanti Polar Lipid, monophosphoryl lipid A (synthetic)], monophosphoryl lipid A (MPL, monophosphoryl lipid A), synthetic lipid A, lipid A mimics or analogues, aluminum salts, cytokines, saponins, prolactin, growth hormone deoxycholic acid, beta-glucan, polyribonucleotide, muramyl dipeptide (MDP) derivatives, CpG oligos, gram-negative bacterial lipopolysaccharide (LPS), polyphosphazenes, emulsions, virosomens, cocriates, poly(lactide-co-glycolide) (PLG) microparticles, poloxamer particles, microparticles, liposomes, or appropriate combinations thereof.

[0619] A pharmaceutical composition containing coding nucleic acid.

[0620] Example 110, formulated coding nucleic acid.

[0621] A formulated coding nucleic acid, characterized in that the nucleic acid described in any one of Examples 96 to 106 is formulated using a viral vector and / or a non-viral vector.

[0622] Example 111, limitations regarding viral vectors.

[0623] In Example 110, the coding nucleic acid is characterized by the selection of a viral vector from the following: Retroviruses; lentiviruses; adenoviruses; adeno-associated viruses; vaccinia viruses; poxviruses; and herpes simplex viruses.

[0624] Example 112, limitations on the form of formulated nucleic acids.

[0625] In Example 110, the coding nucleic acid is characterized in that the formulated nucleic acid is selected from the following: Naked nucleic acids; cationic peptide complex nucleic acids (protamine); positively charged oil-water cationic nanoemulsions containing nucleic acids (cationic nanoemulsions); nucleic acids bound to chemically modified dendrimers and complexed with polyethylene glycol and PEG-lipids (modified dendrimer nanoparticles); nucleic acids complexed with protamine in PEG-lipid nanoparticles (protamine liposomes); nucleic acids complexed with cationic polymers (e.g., polyethyleneimine (PEI)) (cationic polymers); nucleic acids complexed with cationic polymers such as PEI and lipid components (cationic polymer liposomes); nucleic acids complexed with polysaccharide polymers (e.g., chitosan) (polysaccharide particles); nucleic acids complexed with cationic lipid nanoparticle polymers (cationic lipid nanoparticles); nucleic acids complexed with cationic lipids and cholesterol (cationic lipid-cholesterol nanoparticles); and nucleic acids complexed with cationic lipids, cholesterol, and PEG-lipids (cationic lipid-cholesterol-PEG nanoparticles).

[0626] Example 113, a pharmaceutical composition for immunotherapy containing formulated nucleic acid.

[0627] Pharmaceutical compositions for immunotherapy that include the following: Formulated nucleic acids as described in any one of Examples 100 to 112; and Adjuvant.

[0628] Example 114, A pharmaceutical composition for the treatment of obesity containing formulated nucleic acid.

[0629] A pharmaceutical composition for the treatment of obesity, comprising the following:

[0630] Formulated nucleic acids as described in any one of Examples 100 to 112; and Adjuvant.

[0631] Example 115, limitations regarding the adjuvant.

[0632] The pharmaceutical composition according to either Example 113 or 114, characterized in that the adjuvant is one or more selected from the following. Lipid nanoparticles (LNPs), aluminum salts, 1,2-dioleyl-3-trimethylammonium-propane chloride, MF59 (Novartis) adjuvant, CD70, CD40 ligand (CD40L), TriMix, protamine acting through TLR7 signaling, and / or bacterial monophosphoryl lipid A.

[0633] Example 116, which includes additional components.

[0634] The pharmaceutical composition according to any one of Examples 113 to 114, wherein the pharmaceutical composition comprises one or more additional components selected from the following:

[0635] Lipids; salts to balance the body's acidity; sucrose to maintain stability between repeated freeze-thaw cycles; and vaccine stability enhancers.

[0636] Example 117, Restrictions on Additional Components

[0637] The pharmaceutical composition of Example 116, The pharmaceutical composition is characterized in that the lipid is one or more selected from SM-102, PEG2000-DMG, DPSC, cholesterol, and ALC-0315. The salt is one or more selected from sodium acetate, potassium chloride, monobasic potassium phosphate, sodium chloride, and dibasic sodium phosphate anhydrous. A pharmaceutical composition in which the vaccine stability-enhancing substance is one or more selected from acetic acid, an acid stabilizer (tromethamine), and / or ethanol.

[0638] Use of peptides.

[0639] Example 118, Use in immunotherapy (First medical use).

[0640] Use for immunotherapy of a peptide unit according to any one of Examples 1 to 90, a peptide according to any one of Examples 91 to 95, a nucleic acid according to any one of Examples 96 to 106, and / or a pharmaceutical composition according to any one of Examples 107 to 109 and Examples 113 to 117.

[0641] Example 119, Use for the treatment of obesity (First medical use).

[0642] Use of a peptide unit according to any one of Examples 1 to 90, a peptide according to any one of Examples 91 to 95, a nucleic acid according to any one of Examples 96 to 106, and / or a pharmaceutical composition according to any one of Examples 107 to 109 and Examples 113 to 117 for the treatment of obesity.

[0643] Example 120: Use in the preparation of immunotherapeutic drugs (second medical use).

[0644] Use of a peptide unit according to any one of Examples 1 to 90, a peptide according to any one of Examples 91 to 95, a nucleic acid according to any one of Examples 96 to 106, and / or a pharmaceutical composition according to any one of Examples 107 to 109 and Examples 113 to 117 for the preparation of an immunotherapy drug.

[0645] Example 121, Use in the preparation of therapeutic drugs for the treatment of obesity (second medical use).

[0646] Use of a peptide unit according to any one of Examples 1 to 90, a peptide according to any one of Examples 91 to 95, a nucleic acid according to any one of Examples 96 to 106, and / or a pharmaceutical composition according to any one of Examples 107 to 109 and Examples 113 to 117 for the preparation of therapeutic drugs for the treatment of obesity.

[0647] A treatment method using peptides.

[0648] Example 122: Immunotherapy using peptides.

[0649] Immunotherapy drugs including the following stages: A step of administering a peptide unit according to any one of Examples 1 to 90, a peptide according to any one of Examples 91 to 95, a nucleic acid according to any one of Examples 96 to 106, and / or a pharmaceutical composition according to any one of Examples 107 to 109 and Examples 113 to 117 into the body of a subject.

[0650] Example 123: A method for treating obesity using peptides.

[0651] Obesity treatment methods using the following stages: A step of administering a peptide unit according to any one of Examples 1 to 90, a peptide according to any one of Examples 91 to 95, a nucleic acid according to any one of Examples 96 to 106, and / or a pharmaceutical composition according to any one of Examples 107 to 109 and Examples 113 to 117 into the body of a subject.

[0652] Peptide units and / or sequences similar to peptides.

[0653] Example 124, a sequence similar to a peptide unit.

[0654] A peptide unit having a sequence that matches a peptide unit described in any one of Examples 1 to 90 by more than 80%, more than 81%, more than 82%, more than 83%, more than 84%, more than 85%, more than 86%, more than 87%, more than 88%, more than 89%, more than 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than 95%, more than 96%, more than 97%, more than 98%, more than 99%, or more than 100%.

[0655] Example 125, a sequence similar to a peptide.

[0656] A peptide having a sequence that matches the peptide unit described in any one of Examples 91 to 95 by more than 80%, more than 81%, more than 82%, more than 83%, more than 84%, more than 85%, more than 86%, more than 87%, more than 88%, more than 89%, more than 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than 95%, more than 96%, more than 97%, more than 98%, more than 99%, and more than 100%.

[0657] [Example of experiment]

[0658] The inventions provided herein will be described in more detail below through experimental examples and embodiments. It will be apparent to those skilled in the art that these embodiments are merely illustrative of the content disclosed herein and that the scope of the content disclosed herein should not be construed as limited by these embodiments.

[0659] Experimental Example 1, Experimental Method.

[0660] Experimental Example 1.1: Preparation of peptides.

[0661] The peptides were obtained by commissioning a peptide synthesis company (Anygen, Gwangju, South Korea). The peptides of the present invention can be synthesized using conventionally known techniques (e.g., liquid-phase peptide synthesis, solid-phase peptide synthesis, convergence of low-molecular-weight peptide fragments, etc.), and the synthesis method is not particularly limited. For example, the OTP3 peptide of the present invention can be synthesized using a convergence method of low-molecular-weight peptide fragments, in which a site where coupling of long-chain peptides can be easily performed is virtually cleaved, various parts are prepared based on this, and then they are combined to synthesize a peptide that is effectively desired. Since the above convergence method has the limitation that a specific amino acid must be present in the peptide sequence, the peptides can also be effectively synthesized by a combinatory peptide synthesis method that appropriately combines a solution-phase synthesis method and a solid-phase peptide synthesis method.

[0662] Experimental Example 1.2: Confirmation of prepared peptide 1 - purity analysis.

[0663] The purity of the peptides prepared in Experimental Example 1.1 was measured by HPLC analysis (Shimadzu HPLC LabSolutions) using a C-18 reversed-phase column (SHIMADZU C18 analytical column). For the analysis, the sample was separated and developed in aqueous solutions of 0.05% trifluoroacetic acid (TFA) and 0.05% TFA acetolyl solution at 60°C, and then the purity was confirmed by measuring the peak absorbance at a wavelength of 230 nm.

[0664] Experimental Example 1.3: Confirmation of prepared peptide 2 - analysis of molecular weight.

[0665] The molecular weight of the peptides prepared in Experimental Example 1.1 was analyzed using a mass spectrometer (AXIMA Assurance, MALDI-TOF, Shimadzu Corporation).

[0666] Experimental Example 1.4: Confirmation and Quantification Analysis of Prepared Peptide 2

[0667] The peptides prepared in Experimental Example 1.1 were quantified by measuring the ultraviolet extinction coefficient (Ultrospec 3000 Pro UV / VIS spectrophotometer, Pharmacia). Specifically, quantification was performed using the extinction coefficient at 280 nm.

[0668] Experimental Example 1.5: Preparation of a composition for in vivo administration.

[0669] The peptide prepared in Experimental Example 1.1 was mixed with an alhydrogel (Al(OH)3, manufactured by InvivoGe) and PHAD (manufactured by Avanti) to prepare a composition for in vivo administration. The specific process is as follows:

[0670] (1) The prepared peptide powder was dissolved in 100% dimethyl sulfoxide (DMSO) to obtain a concentration of 100 mg / L.

[0671] (2) PBS was added to the peptide-DMSO solution from (1) and mixed to prepare a peptide with a concentration of 50 mg / mL.

[0672] (3) PHAD was dissolved in 100% DMSO to a concentration of 10 mg / mL, and then diluted with distilled water to a concentration of 1 mg / mL.

[0673] (4) Alhydrogel adjuvant (Invivogen, USA) and PHAD solution were added to the mixture from (2). The concentration of the mixed composition was 50 g of peptide, 10 g of PHAD, and 10% (v / v) of alhydrogel adjuvant per 100 μL, which is a single dose.

[0674] (5) After thoroughly mixing the mixture from (4), the resulting product was reacted overnight in a low-temperature room (4°C) while being stirred with a rotor.

[0675] (6) For DSMO washing, the reaction mixture from (5) was centrifuged at 1,400 rpm for 15 minutes, and the supernatant was removed, with approximately 1 mL remaining on top of the pellet. Then, 10 mL of PBS was added and mixed.

[0676] The cleaning process in (7)(6) was repeated three times.

[0677] (8) After the final washing process, PBS was added to adjust the final concentration of the composition. Specifically, the peptide concentration was 50 μg / 100L (30 μg / 100L in Example 4), the PHAD concentration was 10 μg / 100L, and the hydrogel adjuvant concentration was 10% (v / v).

[0678] (9) The amount of peptide adsorbed onto the aluminum gel was measured according to the method described in Experimental Example 2.3. As a result, it was confirmed that the adsorption rate was 95% or higher, and the peptide was used in the experiment.

[0679] Experimental Example 1.6: Preparation of test subjects.

[0680] To verify the effects of the in vivo administration composition prepared in Experimental Example 1.5, C57BL / 6, Balbc, and / or ICR mice were used as experimental mice (purchased from Central Lab Animal Inc.). Although there were some species differences, the purchased mice were an average of 7 weeks old, acclimatized for one week, and used in the experiment at 8 weeks of age. The experimental mice were housed under constant temperature and humidity conditions within a temperature range of 23±1℃ and relative humidity of 50±5%, and under controlled conditions of 12 hours in a light room / 12 hours in a dark room. Drinking water and food were provided freely. The standard diet (purchased from Central Lab Animal Inc.) consisted of 20% protein, 70% carbohydrates, and 10% fat based on total calories, while the obesity-inducing diet (purchased from Research Diets) consisted of a high-fat diet containing 20% ​​protein, 20% carbohydrates, and 60% fat based on total calories. The experimental mice were divided into groups with different dietary and compositional administration conditions, and experiments were conducted with a statistically manageable number of individuals in each experimental group. Detailed conditions are disclosed in each specific experimental example.

[0681] Experimental Example 1.7: Administration of a peptide-containing composition to test subjects.

[0682] In Experimental Example 1.6, different compositions were administered to each experimental group of test subjects. All compositions were administered by intramuscular injection. After disinfecting the muscles of both thighs of each mouse with an alcohol swab, 50 μL of each composition, for a total of 100 μL, was injected.

[0683] Experimental Example 1.8: Confirmation of the effect of the in vivo administration composition 1 - Body weight measurement.

[0684] To confirm the weight-reducing effect of the orally administered composition according to Experimental Example 1.7 on test subjects, the body weight and organ weights of mice in each experimental group were measured. For each group of mice, measurements were taken three times at one-week intervals from arrival to the end of the experiment, and the average was calculated to determine the average body weight for each week. After the end of the experiment, each mouse was anesthetized, its organs were dissected, its body weight was measured, and the average for each experimental group was calculated.

[0685] Experimental Example 1.9: Confirmation of the effect of the in vivo administration composition 2 - Confirmation of antibody titer.

[0686] To determine whether the in vivo administration composition administered in Experimental Example 1.7 induced antibodies against the B cell epitope, the method for confirming antibody titers using the target antigen is as follows. In particular, the target antigens are RNVPPIFNDVYWIAF (SEQ ID NO: 6) or ApoB100. The time for checking antibody titers may be changed as needed, and this time is specifically described for each experimental example.

[0687] 1. The process of the antigen coating reaction.

[0688] 1-1) Each time the in vivo composition is injected into the test subject, approximately 200 liters of blood will be collected from the subject's tail vein one week after the injection.

[0689] 1-2) After the collected blood is left at 4°C for 1 hour, the blood sample is centrifuged at 14,000 rpm for 10 minutes to separate the supernatant serum.

[0690] 1-3) Dilute the target antigen to a concentration of 50 μg / 100 L with coating buffer (0.05 M, bicarbonate, pH 9.6), add the antigen to a 96-well plate at a rate of 50 μg / well, and allow to react overnight at 4°C so that the peptide coats the well walls.

[0691] 1-4) Wash the plates coated with the target antigen three times with 300 L of phosphate-buffered saline (PBS)-T (0.05% containing Tween®-20) per well.

[0692] 2. The blocking reaction process.

[0693] 2-1) Add 300 μL of 0.5% casein blocking solution to each well of the plate and allow to react overnight at 4°C.

[0694] 2-2) Wash the plate three times with 300 μL of PBS-T per well.

[0695] 3. The process of the primary antibody reaction.

[0696] 3-1) For the primary antibody reaction, the separated serum is diluted to an appropriate concentration and added in a volume of 100 L per well, and reacted at 37°C for 1 hour. In particular, after the first injection, the serum is subjected to serial dilution by diluting it to 1 / 20 to 1 / 1,000 during the experiment, and after the second and third injections, it is diluted to 1 / 500 to 1 / 10,000 during the experiment depending on the subject. A monoclonal antibody against the peptide of purified SEQ ID NO:41 is used as a positive control.

[0697] 3-2) After the reaction in 3-1, wash the plate three times with 300 μL of PBS-T per well.

[0698] 4. Secondary antibody reaction process.

[0699] 4-1) As a secondary antibody reaction, 100 μL of horseradish peroxidase (HRP) conjugated to an anti-mouse IgG antibody that recognizes mouse antibodies is added to each well, and the reaction is carried out at 37°C for 1 hour.

[0700] After the reaction in 4-2)4-1), wash the plate three times with 300 μL of PBS-T per well.

[0701] 5. The process of checking the color development and absorbance.

[0702] 5-1) Add 100 μL of o-phenylenediamine dihydrochloride (OPD) solution to each well, react at 37°C for 10 minutes, and then measure the absorbance at OD450 nm (Synergy HT microplate reader, BioTek).

[0703] The antibody titer in serum is determined by converting the extinction coefficient, measured using a monoclonal antibody concentration of 1 mg / mL as a reference against the target antibody used as a positive control.

[0704] Experimental Example 1.10: Confirmation of the effects of the in vivo administration composition 3 - Confirmation of blood lipid concentration.

[0705] The experimental method for confirming the effect of the in vivo composition administered in Experimental Example 1.7 on the blood lipid concentration of the test subject is as follows.

[0706] (1) One week after administration of each composition, approximately 200 μL of blood is collected from the tail vein of the subject.

[0707] (2) Measurement of blood triglyceride (TG) concentration: Triglyzyme-V (Shinyak Chemical Co., Ltd.) was used. i) 4 μL of blood sample and 300 μL of colorimetric reagent were mixed, and this mixture was reacted at 37°C for 5 minutes. ii) The absorbance of the generated red quinone was measured at 505 nm, and the concentration was calculated by comparing it with a standard solution.

[0708] (3) Measurement of total blood cholesterol concentration: Cholestezyme-V (Shinyak Chemical Co., Ltd.) was used. i) 4 μL of blood sample and 300 μL of chromogenic reagent were mixed, and this mixture was reacted at 37°C for 5 minutes. ii) The absorbance of the resulting red quinone was measured at 505 nm, and its concentration was calculated by comparing it with that of a standard solution.

[0709] (4) Measurement of blood high-density lipoprotein (HDL) concentration: HDL-C555 (Shinyak Chemical Co., Ltd.) was used. i) 10 μL of blood sample and 10 μL of precipitating reagent were mixed, and this mixture was reacted at room temperature for at least 10 minutes. ii) The reaction product was centrifuged at 300 rpm or higher, and the supernatant was separated. iii) 4 μL of the supernatant and 300 μL of colorimetric reagent were mixed, and this mixture was reacted at 37°C for 5 minutes. iv) For the above reaction, the absorbance at 555 nm was measured, and the concentration was calculated by comparison with a standard solution.

[0710] (5) Measurement of low-density lipoprotein (LDL) concentration in blood. i) The reaction was performed using a direct LDL cholesterol detection kit (Randox). ii) After the reaction in step 2, the absorbance of the produced quinone was measured at 600 nm, and the concentration was calculated by comparison with the absorbance of the standard solution.

[0711] Experimental Example 1.11, Confirmation of the effect of the composition for in vivo administration 4 - Confirmation of lipolytic ability and comparison of adipocyte size.

[0712] The method for confirming the effect of the composition for in vivo administration administered in Experimental Example 1.7 on the adipocyte lipolysis ability of the test subject by hormone-sensitive lipase (HSL) and adipocyte size is as follows.

[0713] 1. Isolation of adipocytes.

[0714] 1-1) Cut the epididymal fat pad with scissors, add 4 mL of KRB buffer containing 2% FBS, 2 mM glucose and 1 mg / mL collagenase per 1 g, and allow them to react while shaking at 37°C for 1 hour.

[0715] 1-2) After completion of the reaction, pass the resultant through a 300 µm nylon mesh to filter out adipose tissue residues and adipose tissue, then pass the filtrate through a 40 µm nylon mesh again to separate adipocytes and macrophages.

[0716] 1-3) Add DMEM containing 10% FBS and 1% AA to the adipocytes filtered in 1-2) for washing, remove the lower layer liquid with a syringe, and obtain collagenase-removed adipocytes.

[0717] 2. Comparison of lipolytic ability.

[0718] 2-1) The adipocytes obtained in 1-3) were placed in a 48-well plate at 1.0×10 5 seed at cells / well, add a total of 1 mL of DMEM (10% FBS, 1% AA) thereto, and culture for 2 hours at 37°C under 5% CO2.

[0719] 2-2) In the wells that induce HSL activity, norepinephrine was added to a final concentration of 10 -5 Add enough to make M

[0720] 2-3) After the reaction is complete, 100 μL of the supernatant from each well is reacted with 100 μL of free glycerol reagent, and the absorbance is measured at 540 nm.

[0721] 3. Observation of the size of fat cells.

[0722] 3-1)1-3) The adipocytes obtained in these steps were placed in a 48-well plate in a 1.0 × 10⁶ 5 Seed cells at a concentration of / mL / well, treated with 10 μM DAPI, allowed to react for 2 hours, and then observed under a microscope.

[0723] 3-2) To confirm whether cells stained with DAPI are adipocytes, stain the lipids and nuclei together and observe them. Specifically, treat the cells with 10 μM DAPI and HCS LipidTOX 1:1,000, allow them to react for 24 hours, and then observe them under a microscope.

[0724] Experimental example 2: Confirmation of peptide effect 1.

[0725] Experimental Example 2.1: Preparation of peptides and related experiments.

[0726] After preparing peptides according to [Table 1] in accordance with Experimental Example 1.1, the prepared peptides were verified according to Experimental Examples 1.2 to 1.4. In accordance with Experimental Example 1.5, a composition for in vivo administration containing the peptide shown in [Table 1] was prepared.

[0727] [Table 1] Peptides used in Experimental Example 2 and compositions for in vivo administration containing the same. [Table 1]

[0728] The test subjects shown in [Table 2] were prepared according to Experimental Example 1.6.

[0729] [Table 2] Test subjects used in Experimental Example 2. [Table 2]

[0730] The in vivo composition was administered to the test subjects according to Experimental Example 1.7. In particular, the administration cycles were as follows: 7 weeks, 9 weeks, 12 weeks, 15 weeks, and 18 weeks of age.

[0731] Experimental Example 2.2: Confirmation of experimental results.

[0732] To verify the experimental results of Experimental Example 2.1, the body weight of the test subjects was measured for each experimental group disclosed in [Table 2] according to Experimental Example 1.8.

[0733] The experimental results are shown in Figures 1-3.

[0734] Experimental example 3: Confirmation of peptide effect 2.

[0735] Experimental Example 3.1: Preparation of peptides and related experiments.

[0736] After preparing peptides according to [Table 3] in accordance with Experimental Example 1.1, the prepared peptides were verified according to Experimental Examples 1.2 to 1.4. A composition for in vivo administration containing the peptide shown in [Table 3] was prepared according to Experimental Example 1.5.

[0737] [Table 3] Peptides used in Experimental Example 3 and compositions for in vivo administration containing the same. [Table 3]

[0738] The test subjects shown in [Table 4] were prepared according to Experimental Example 1.6.

[0739] [Table 4] Test subjects used in Experimental Example 3. [Table 4]

[0740] Specifically, "underweight" represents the control group with a normal weight, "obese" represents the group with obesity induced by a high-fat diet, and "mock" represents the placebo group (the same applies hereafter).

[0741] The in vivo composition was administered to the test subjects according to Experimental Example 1.7. In particular, the administration cycles were as follows: 8 weeks, 10 weeks, 12 weeks, and 14 weeks of age.

[0742] Experimental Example 3.2: Confirmation of experimental results.

[0743] To verify the experimental results of Experimental Example 3.1, the following experiments were performed on the test subjects for each experimental group disclosed in [Table 4].

[0744] (1) The body weight of the test subjects in each experimental group was measured according to Experimental Example 1.8.

[0745] (2) The antibody titers observed in the test subjects of each experimental group were confirmed according to Experimental Example 1.9.

[0746] (3) The blood lipid concentrations of the test subjects in each experimental group were measured according to Experimental Example 1.10.

[0747] (4) Following Experimental Example 1.11, the lipolytic ability of the test subjects in each experimental group was confirmed and the size of the adipocytes was observed.

[0748] The experimental results are shown in Figures 4 to 9.

[0749] Experimental Example 4: Confirmation of Peptide Effect 3

[0750] Experimental Example 4.1: Preparation of Peptides and Their Experiments

[0751] After preparing the peptides according to [Table 5] in Experimental Example 1.1, the prepared peptides were verified according to Experimental Examples 1.2 to 1.4. A composition for in vivo administration containing the peptide shown in [Table 5] was prepared according to Experimental Example 1.5.

[0752] [Table 5] Peptides used in Experimental Example 4 and compositions for in vivo administration containing the same. [Table 5]

[0753] In particular, in Example 4, the final peptide concentration was 30 g / 100 L.

[0754] The test subjects shown in [Table 6] were prepared according to Experimental Example 1.6.

[0755] [Table 6] Test subjects used in Experimental Example 4 [Table 6]

[0756] The in vivo composition was administered to the test subjects according to Experimental Example 1.7. In particular, the administration cycle was as follows: 8 weeks of age, 11 weeks of age, 14 weeks of age, 17 weeks of age, and 20 weeks of age.

[0757] Experimental example 4.2, confirmation of experimental results.

[0758] To confirm the experimental results of Experimental Example 4.1, the following experiments were performed on the test subjects for each experimental group disclosed in [Table 6].

[0759] (1) The body weight of the test subjects in each experimental group was measured according to Experimental Example 1.8.

[0760] (2) The antibody titers observed in the test subjects of each experimental group were confirmed according to Experimental Example 1.9.

[0761] The experimental results are shown in Figures 10 and 11.

[0762] Experimental example 5: Confirmation of peptide effect 4.

[0763] Experimental Example 5.1: Preparation of peptides and related experiments.

[0764] After preparing peptides according to [Table 7] in accordance with Experimental Example 1.1, the prepared peptides were verified according to Experimental Examples 1.2 to 1.4. A composition for in vivo administration containing the peptides according to [Table 7] was prepared according to Experimental Example 1.5.

[0765] [Table 7] Peptides used in Experimental Example 5 and compositions for in vivo administration containing the same. [Table 7]

[0766] The test subjects shown in [Table 8] were prepared according to Experimental Example 1.6.

[0767] [Table 8] Test subjects used in Experimental Example 5. [Table 8]

[0768] The in vivo composition was administered to the test subjects according to Experimental Example 1.7. In particular, the administration cycles were as follows: 11 weeks, 13 weeks, 15 weeks, and 17 weeks of age.

[0769] Experimental Example 5.2: Confirmation of experimental results.

[0770] To verify the experimental results of Experimental Example 5.1, the body weight of the test subjects was measured for each experimental group disclosed in [Table 8] according to Experimental Example 1.8.

[0771] The experimental results are shown in Figure 12.

[0772] Experimental example 6: Confirmation of peptide effect 5.

[0773] Experimental Example 6.1: Preparation of peptides and related experiments.

[0774] After preparing peptides according to [Table 9] in accordance with Experimental Example 1.1, the prepared peptides were verified according to Experimental Examples 1.2 to 1.4. An in vivo composition containing the peptides according to [Table 9] was prepared according to Experimental Example 1.5.

[0775] [Table 9] Peptides used in Experimental Example 6 and compositions for in vivo administration containing the same. [Table 9]

[0776] The test subjects shown in [Table 10] were prepared according to Experimental Example 1.6.

[0777] [Table 10] Test subjects used in Experimental Example 6. [Table 10]

[0778] * The C57BL / 6J-Rag2em1hwl / Korl mouse is a mouse in which the Rag2 gene, which is involved in antibody production ability, has been knocked out in the C57BL / 6J mouse.

[0779] ** Wild-type (+ / +) refers to a wild-type mouse with no genetic mutations, heterozygous (+ / -) refers to a heterozygous mouse, and homozygous (- / -) refers to a homozygous mouse.

[0780] *** Homozygous (- / -) mice lack the ability to produce antibodies in their bodies.

[0781] The in vivo composition was administered to the test subjects according to Experimental Example 1.7. In particular, the administration cycles were as follows: 8 weeks, 10 weeks, 12 weeks, and 14 weeks of age.

[0782] Experimental Example 6.2: Confirmation of experimental results.

[0783] To verify the experimental results of Experimental Example 6.1, the body weight of the test subjects was measured for each experimental group disclosed in [Table 10] according to Experimental Example 1.8.

[0784] The experimental results are shown in Figure 13.

[0785] Experimental example 7, confirmation of peptide effect 6.

[0786] Experimental Example 7.1: Preparation of peptides and related experiments.

[0787] After preparing peptides according to [Table 11] in accordance with Experimental Example 1.1, the prepared peptides were verified according to Experimental Examples 1.2 to 1.4. An in vivo composition containing the peptides according to [Table 11] was prepared according to Experimental Example 1.5.

[0788] [Table 11] Peptides used in Experimental Example 7 and compositions for in vivo administration containing the same. [Table 11]

[0789] The test subjects shown in [Table 12] were prepared according to Experimental Example 1.6. [Table 12] Test subjects used in Experimental Example 7 [Table 12]

[0790] The in vivo composition was administered to the test subjects according to Experimental Example 1.7. In particular, the administration cycles were as follows: 8 weeks, 10 weeks, 12 weeks, and 14 weeks of age.

[0791] Experimental Example 7.2: Confirmation of experimental results.

[0792] To confirm the experimental results of Experimental Example 7.1, the following experiments were performed on the test subjects for each experimental group disclosed in [Table 12].

[0793] (1) The body weight of the test subjects in each experimental group was measured according to Experimental Example 1.8.

[0794] (2) In accordance with Experimental Example 1.9, antibody titers observed at weeks 11, 16, and 19 were confirmed in the test subjects of each experimental group. In particular, the target antigen was determined using RNVPPIFNDVYWIAF (SEQ ID NO: 6).

[0795] The experimental results are shown in Figures 14 to 25.

[0796] The experimental results showed a clear weight-loss effect in all experimental groups 6-1 (P1) to 6-9 (P9) compared to the control group (obese) that was given a high-fat diet.

[0797] The results of antibody titer tests, depending on the experimental group, can be interpreted as follows:

[0798] Antibody titers are not shown for the control group (i.e., the lean group and the obese group) because they were not administered the antigen.

[0799] Considering the experimental design, the antibody titer against SEQ ID NO:6 contained in the peptide used was primarily checked in the experimental group. Although antibody titers against sequences other than SEQ ID NO:6 contained in the peptide were not separately checked, the weight loss effect based on humoral immunity due to these other sequences was also checked.

[0800] The specific results will be explained below.

[0801] In experimental group 6-1 (P1), some individuals showed high antibody titers, while others showed no antibody titers. These results can be interpreted as follows: In some individuals of experimental group 6-1 (P1), humoral immunity to RNVPPIFNDVYWIAF (SEQ ID NO:6) contained in Example 6 was induced, and therefore weight loss and antibody titers were observed. In some individuals, humoral immunity to RNVPPIFNDVYWIAF (SEQ ID NO:6) contained in Example 6 was induced, resulting in weight loss. However, since the antigen used in the enzyme-linked immunosorbent assay (ELISA) consisted only of RNVPPIFNDVYWIAF (SEQ ID NO:6) and no other antigens (i.e., the antigen of SEQ ID NO:7) were present, antibody titers in the above experiment were not observed even in the presence of antibodies.

[0802] In experimental group 6-2 (P2), antibody titers against RNVPPIFNDVYWIAF (SEQ ID NO:6) contained in Example 7 were observed, and a weight loss effect was observed. Therefore, it can be interpreted that the B cell epitope contained in the peptide of Example 7 effectively induced humoral immunity against it.

[0803] In experimental group 6-3 (P3), antibody titers against RNVPPIFNDVYWIAF (SEQ ID NO:6) contained in Example 8 were observed, and a weight loss effect was observed. This can be interpreted as the B cell epitope contained in the peptide of Example 8 effectively inducing humoral immunity.

[0804] In the case of experimental group 6-4 (P4), it can be interpreted that humoral immunity to KTTKQSFDLSVKAQYKKNKH (SEQ ID NO: 8) and / or CRFRGLISLSQVYLS (SEQ ID NO: 7) included in Example 9 was induced. Therefore, although no weight loss effect was observed, antibody titers against RNVPPIFNDVYWIAF (SEQ ID NO: 6) were shown.

[0805] These results suggest that in some individuals of experimental group 6-5 (P5), humoral immunity was induced against RNVPPIFNDVYWIAF (SEQ ID NO:6) included in Example 10, resulting in both weight loss and antibody titers. In other individuals of experimental group 6-5 (P5), humoral immunity was induced against CRFRGLISLSQVYLS (SEQ ID NO:7) included in Example 10, resulting in weight loss, but antibody titers were not observed in the above experiment.

[0806] In experimental group 6-7 (P7), although there were individual differences, antibodies against RNVPPIFNDVYWIAF (SEQ ID NO:6) were observed, and a weight loss effect was observed. Therefore, it can be interpreted that the B cell epitope contained in the peptide of Example 11 effectively induced humoral immunity.

[0807] In the case of experimental group 6-8 (P8), antibody titers against RNVPPIFNDVYWIAF (SEQ ID NO:6) contained in Example 12 were observed, and a weight-loss effect was demonstrated. Therefore, it can be interpreted that the B cell epitope contained in the peptide of Example 12 effectively induced humoral immunity.

[0808] In experimental group 6-9 (P9), there was some individual variation. However, since antibodies against RNVPPIFNDVYWIAF (SEQ ID NO:6) were observed and a weight loss effect was observed, it can be interpreted that the B cell epitope contained in the peptide of Example 13 effectively induces humoral immunity.

[0809] Experimental example 8, confirmation of peptide effect 7.

[0810] Experimental Example 8.1: Preparation of peptides and related experiments.

[0811] After preparing the peptides according to [Table 13] in accordance with Experimental Example 1.1, the prepared peptides are verified according to Experimental Examples 1.2 to 1.4. An in vivo composition containing the peptides according to [Table 13] is prepared according to Experimental Example 1.5.

[0812] [Table 13] Peptides used in Experimental Example 8 and compositions for in vivo administration containing the same. [Table 13]

[0813] The test subjects shown in [Table 14] were prepared according to Experimental Example 1.6.

[0814] [Table 14] Test subjects used in Experimental Example 8 [Table 14]

[0815] The in vivo composition is administered to the test subjects according to Experimental Example 1.7. In particular, the administration cycle, timing, and frequency can be appropriately modified according to the experimental design. For example, the composition may be administered to 8-week-old test subjects four times at 2-week intervals, but is not limited to these.

[0816] The experimental method described above can be modified as needed.

[0817] Experimental E...

Claims

1. GSHHHHHHGSDDDDKZaK (Cha) VAAWTLKAAaZRNVPIFNDVYWIAF (SEQ ID NO: 69), RNVPPIFNDVYWIAFZaK (Cha) VAAWTLKAAaZGSHHHHHHGSDDDDK (SEQ ID NO: 68), RNVPPIFNDVYWIAFZaK (Cha) VAAWTLKAAaZ (SEQ ID NO: 56), RNVPPIFNDVYWIAFK(Cha)VAAWTLKAA(SEQ ID NO: 62), and, RNVPPIFNDVYWIAFK (Cha) VAAWTLKAAAHHHHHH (SEQ ID NO: 67) Having a peptide containing an amino acid sequence selected from the group consisting of, The above a represents D-type alanine, (Cha) represents L-cyclohexylalanine, and Z represents 6-aminohexanoic acid. A pharmaceutical composition for treating obesity.

2. The pharmaceutical composition according to claim 1, further comprising an adjuvant.

3. The pharmaceutical composition according to claim 2, wherein the adjuvant comprises an aluminum salt and monophosphoryl lipid A.

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