Title of Invention	ANTI-OBESE IMMUNOGENIC HYBRID POLYPEPTIDES AND ANTI-OBESE VACCINE COMPOSITION COMPRISING THE SAME
Abstract	Disclosed is an immungenci hybrid polypeptide comprising a mimetic peptide of a B cell epitope of apolipoprotein B -100 and a helper T cell epitope, the mimetic peptide being fused at its c-terminus to an N-terminus of the helper T cell epitope. Also disclosed is a vaccine composition for preventing or treating obesity comprising the polypeptide.

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FORM 2 THE PATENTS ACT, 1970 (39 of 1970) & THE PATENTS (AMENDMENT) RULES, 2006 COMPLETE SPECIFICATION (See section 10, rule 13) "ANTI-OBESE IMMUNOGENIC HYBRID POLYPEPTIDES AND ANTI-OBESE VACCINE COMPOSITION COMPRISING THE SAME SJ BIOMED INC, of 604 Business Incubator Center, Hanyang Univ., Sa l(il)-dong, Sangnok-gu, Ansan-si, Gyeonggi-do 426-791, Republic of Korea. The following specification particularly describes the invention and the manner in which it is to be performed. WO 2005/087800 PCT7KR2005/000784 ANTI-OBESE IMMUNOGENIC HYBRID POLYPEPTIDES AND ANTI-OBESE VACCINE COMPOSITION COMPRISING THE SAME Technical Field The present invention relates to an immunogenic 5 hybrid polypeptide, which comprises an amino acid sequence of a mimetic peptide of a B cell epitope of apolipoprotein B-100 and in which a C-terminus of the mimetic peptide is fused to an N-terminus of a helper T cell epitope, and a vaccine composition for preventing or treating obesity comprising 10 the same. Background Art Recently, arteriosclerosis and coronary atherosclerotic disease (CAD) have been gradually increasing in Korea due to a shift to Western dietary 15 habits, and are the leading cause of increased mortality. Serum lipids causing these diseases include cholesterol, triglycerides (TG), free fatty acids and phospholipids. They form lipoproteins with apolipoprotein and ere transported through the bloodstream. Among them, low 20 density lipoproteins (LDL) function to transport mainly TG and cholesterol, and changes in LDL-cholesterol levels are indications of the prognosis of the diseases. WO 2005/087800 PCT/KR2005/000784 LDL-cholesterol, which is a major factor of lipid metabolism-associated diseases of adult people, binds to LDL receptors on the plasma membrane of cells in each tissue and is stored and used in the tissue. Alternatively, 5 LDL-cholesterol is. taken up by scavenger cells and hydrolyzed, and free cholesterol is transferred to HDL along with apo E lipoprotein to be recycled in the liver, or is converted to bile salt to be discharged. During this process, the apolipoprotein performs very important 10 functions to maintain structural homeostasis of lipoproteins, serves as a cofactor of the enzyme lipoprotein lipase, and plays a critical role in binding to a specific receptor on the plasma membrane. Apolipoprotein B-100 (Apo B-100) is a major protein 15 component of LDL, and is also present in IDL and VLDL. Thus, when antibodies in the blood are induced to recognize apo B-100, LDL clearance by phagocytes will easily occur. In this regard, some recent studies have been focused on the employment of vaccines to decrease plasma LDL- 20 cholesterol levels and reduce the incidence of arteriosclerosis. Antibodies induced by such anti-cholesterol vaccine therapy are 1gM types which are considered to bind to VLDL, IDL and LDL, and such a strategy suggests the possibility of developing vaccines 25 for preventing and treating hypercholesterolemia and atherosclerosis (Bailey, et al., Cholesterol vaccines. WO 2005/087800 PCT/KR2005/000784 Science 264, 1067-1068, 1994; Palinski W et al., Proc Natl Acad Sci U.S.A. 92, 821-5, 1995; Wu R, de Faire U et al., Hypertension. 33, 53-9, 1999) . Also, apolipoprotein B-100 is a huge protein molecule, which consists of 4560 amino acid 5 residues, contains signal peptide of 24 amino acid residues and has a molecular weight of more than 500 kDa (Elovson J et al., Biochemistry, 24:1569-1578, 1985). Since apolipoprotein B-100 is secreted mainly by the liver and is an amphipathic molecule, it can interact with the lipid components of plasma 10 lipoproteins and an aqueous environment (Segrest J. P et al., Adv. Protein Chem., 45:303-369, 1994). Apolipoprotein B-100 stabilizes the size and structure of LDL particles and plays a critical xole in controlling the homeostasis of plasma LDL-cholesterol through binding to its receptor (Brown 15 MS et al., Science, 232:34-47, 1986). Korean Pat. Laid-open Publication No. 2002-0018971, which was filed by the present inventors, describes a mimetic peptide of an epitope of apo B-100 having an anti-obesity effect. However, this publication only discloses that the 20 mimetic peptide of the B cell epitope has an anti-obesity effect. Prior to the present invention, there is no report of enhancing the immuriogenicity of an apolipoprotein by fusing a B cell epitope of the apolipoprotein and a T cell 25 epitope, except for an attempt to enhance immune responses by employing a protein carrier or adjuvant. WO 2005/087800 PCT/KR2005/000784 As described in U.S. Pat. No. 5,843,446, when luteinizing hormone releasing hormone (LHRH) is conjugated with a different protein to enhance the immunogenicity of LHRH, the majority of immune responses are directed to the 5 carrier protein rather than to LHRH, leading to carrier-induced immune suppression. Thus, persistent effort is required for selecting additional materials and determining linkage patterns and linkage sites capable of enhancing the immunogenicity of B cell epitopes. 10 Many attempts to fuse a hapten with a carrier protein were made to enhance the immunogenicity of the hapten, but failed to obtain uniform enhancing effects. In particular, the linear linkage of a B cell epitope and a T cell epitope, like the present invention, resulted in loss of 15 immunogenicity according to the orientation of the epitopes, the type of each epitope, and the like (Francis, M. J. et al., Nature 330:168-170, 1987), and the presence of a linker brought about reduced antigenicity (Partidos, C. et al., Mol. Immunol. 29:651-658, 1992). That is, there is no 20 consistent rule applicable to design peptide vaccines, and the efficacy of designed vaccines is also not predictable. For the same reasons, when a highly hydrophobic PB1« peptide, which is an apo-B mimetic peptide, is fused with a T cell epitope, an antigenic region can be internalized into the 25 fusion protein, leading to a decrease in its ability to induce antibody responses. WO 2005/087800 PCT7KR2005/000784 Based on this background, the present inventors made various attempts to enhance the immunogenicity of PB14, which is a mimetic peptide of a B cell epitope of apolipoprotein B-100 having an anti-obesity effect. As a 5 result, a hybrid polypeptide, in which an N-terminus of a helper T cell epitope is fused to a C-terminus of the mimetic peptide, displayed an excellent immunoenhancing effect, indicating that it is effective for preventing or treating obesity. It was an unexpected result since hybrid 10 polypeptides displays excellent anti-obesity activity without inducing immune responses that neutralize beneficial activities or effects of the B cell epitope of apolipoprotein B-100 or without causing harmful side effects. 15 Disclosure of the Invention In one aspect, the present invention provides an immunogenic hybrid polypeptide, which comprises an amino acid sequence of a mimetic peptide of a B cell epitope of apolipoprotein B-100 and in which a C-terminus of the 20 mimetic peptide is fused to an N-terminus of a helper T cell epitope. In another aspect, the present invention provides a vaccine for preventing or treating obesity, comprising an immunogenic hybrid polypeptide, which comprises an amino WO 2005/087800 PCT/KK2005/000784 acid sequence of a mimetic peptide of a B cell epitope of apolipoprotein B-100 and in which a C-terminus of the mimetic peptide is fused to an N-terminus of a helper T cell epitope. 5 In a further aspect, the present invention provides a recombinant vector comprising a gene encoding the immunogenic hybrid polypeptide, a transformant comprising the recombinant vector, and a method of producing the hybrid polypeptide by culturing a host cell transformed 10 with the recombinant vector. Brief Description of the Drawings The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in 15 conjunction with the accompanying drawings, in which: FIG. 1 shows a process of constructing pBl4T; FIG. 2 shows the results of digestion of pBl4T with restriction enzymes; FIG. 3 shows a DNA sequence of PBI4T and an amino 20 acid sequence predicted therefrom; FIG. 4 shows the results of SDS-PAGE analysis for PBI4T expression in a transformed Escherichia coli strain, M15/pBl4T, which has been treated with IPTG to induce PB14T expression, wherein the expressed recombinant PB14T is WO 2005/087800 PCT/KR2005/000784 indicated by an arrow (M: prestained protein size marker; lane 1: E. coli M15 not induced with IPTG; and lanes 3 to 7: IPTG-induced E. coli M15/pBl4T, collected 1, 2, 3, 4 and 5 hrs, respectively, after IPTG induction); 5 FIG. 5 shows the results of SDS-PAGE analysis for PB18 expression in a transformed Escherichia coli strain, M15/pBl8, which has been treated with IPTG to induce PB18 expression, wherein the expressed recombinant PB18 is indicated by an arrow (M: prestained protein size marker; 10 lane 1: E. coli M15 not induced with IPTG; and lanes 3 to 7: IPTG-induced E. coli M15/pBl8, collected 1, 2, 3, 4 and 5 hrs,. respectively, after IPTG induction); FIG. 6 shows the results of SDS-PAGE analysis of the centrifugal supernatant (lane 1) and pellet (lane 2), of an 15 E. coli lysate, wherein expressed PB14T is indicated by an arrow and is found in the pellet; FIG. 7 shows the results of SDS-PAGE analysis of an E. coli lysate (lane 1: whole lysate; lane 2; centrifugal supernatant; lane 3: centrifugal pellet), wherein expressed 20 PB18 is indicated by an arrow and is found in the pellet; FIG. 8 shows the results of Western blotting for purified PB14T with a rabbit anti-PBl4 antibody (A) and an anti-preS2 monoclonal antibody (B) (lane 1: E. coli M15; lane 2: E. coli M15/pBl4T not induced with IPTG; lane 3: 25 IPTG-induced E. coli M15/pBl4T, collected 3 hrs after IPTG induction); WO 2005/087800 PCT7KR2005/000784 FIG. 9 shows the PB14 elution profile resulting from Ni-NTA affinity chromatography according to a linear imidazole gradient; FIG. 10 shows the PB14T elution profile resulting 5 from Ni-NTA affinity chromatography according to a linear imidazole gradient; FIG. 11 shows the PB18 elution profile resulting from Ni-NTA affinity chromatography according to a linear imidazole gradient; 10 FIG. 12 shows a process of constructing pTBl4; FIG. 13 shows the results of Western blotting for purified PBI4, PB14T and PTBI4 with a mouse anti-preS2 monoclonal antibody and 15 an HRP-conjugated goat anti-mouse IgG antibody (A) and with an anti-PBl4 anti-serum and an HRP-conjugated goat anti-rabbit IgG antibody (B) ; FIG. 14 shows a DNA sequence of TBl4/pQE30 and an amino acid sequence predicted therefrom; FIG. 15 is a graph showing the body weight increment of SD white rats of normal, mock and vaccinated groups, 20 wherein the normal group (■) was injected with PBS, the mock group (A) with ovalbumin, a vaccinated group (♦) with ovalbumin-conjugated PB14 (PBI4+OVA), and another vaccinated group (•) with PB14T peptide, each peptide being injected three times at 2-week intervals, the arrows indicating time 25 points at which vaccination was carried out; FIG. 16 is a graph showing the changes in titers of WO 2005/087800 PCT7KR2005/000784 anti-PB1 antibodies induced by immunization of PB14, PB14T and PTBI4, respectively; and FIG. 17 is a graph showing serum levels of triglyceride, HDL, LDL and total cholesterol. 5 Best Mode for Carrying Out the Invention In one aspect, the present invention relates to an immunogenic hybrid polypeptide, which comprises an amino acid sequence of a mimetic peptide of a B cell epitope of apolipoprotein B-100 and in which a C-terminus of the 10 mimetic peptide is fused to an N-terminus of a helper T cell epitope. In a strategy to enhance the immunogenicity of an apolipoprotein, the present invention intends to provide an immunogenic hybrid polypeptide in which a T cell epitope is 15 fused to a mimetic peptide of a B cell epitope of an apolipoprotein, especially apolipoprotein B-100 (apo B-100). When a T cell epitope was fused to a mimetic peptide of the B cell epitope of apo B-100, PB14 had improved ability to induce antibody responses and displayed vaccine 20 efficacy for an extended period of time, and so h.ad an excellent anti-obesity effect. The term "mimetic peptide of an epitope", as used herein refers to a peptide that mimics a minimal part of the epitope, which is an epitope that is sufficiently WO 2005/087800 PCT/KR2005/000784 similar to a native epitope so that it can be recognized by an antibody specific to the native epitope, or that is able to increase an antibody to crosslink with a native epitope. A mimetic peptide is also called a mimotope. Such a mimetic 5 peptide is advantageous because it is recognized as "non-self" in vivo and thus overcomes the problem of self-tolerance in immune responses. The mimetic peptide of a B cell epitope of apo B-100 is recognized by an antibody specifically binding to apo B-100. The antibody 10 specifically binding to apo B-10O includes polyclonal and monoclonal antibodies, which specifically recognize and bind to apo B-100, and fragments -thereof, for example, Fc, Fab and F(ab')2. The mimetic peptide of a B cell epitope of apo B-100 15 according to the present invention includes an amino acid sequence selected from SEQ ID Nos. 1, 2 and 3. Thus, in a preferred aspect, the present invention relates to an immunogenic hybrid polypeptide, which includes an amino acid sequence selected from SEQ ID Nos. 1, 2 and 3, and in 20 which a C-terminus of a peptide recognized by an antibody specifically binding to apo B-100 is fused to an N-terminus of a helper T cell epitope. The present inventors isolated mimetic peptides (SEQ ID Nos. 1, 2 and 3) that are recognizable by a monoclonal 25 antibody against apo B-100, Mab B or Mab B23, from a phage displayed peptide library by biopamning with the library. WO 2005/087800 PCT/KR2005/000784 The mimetic peptide of the epitope of apo B-100, which includes an amino acid sequence selected from SEQ ID Nos. 1, 2 and 3, may be in a monomeric form that is composed of a single copy of the amino acid sequence having 5 any one of the SEQ ID Nos., or, to further enhance the immunogenicity of the mimetic peptide, may be in a multimeric form in which two or more, preferably three to eight, and more preferably three to six copies of the amino acid sequence having any one of the SEQ ID Nos. are linked. 10 Most preferred is a tetramer (SEQ ID No. 4) in which four copies are linked. When the mimetic peptide is in a multimeric form, amino acid sequences each of which constitutes a monomer may be covalently linked directly or via a linker. When the amino acid sequences are linked via 15 a linker, the linker may consist of one to five amino acid residues, which are selected from, for example, glycine, alanine, valine, leucine, isoleucine, proline, serine, threonine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, lysine and arginine. Preferred amino acids 20 available in the linker may include valine, leucine, aspartic acid, glycine, alanine and proline. More preferably, taking the ease of gene manipulation into account, two amino acids selected from valine, leucine, aspartic acid, etc. may be linked and used as a linker. A 25 preferred mimetic peptide is prepared by linking two or more copies of an amino acid sequence selected from SEQ ID WO 2005/087800 PCT/KR2005/000784 Nos. 1, 2 and 3 via the linker. The term "T cell epitope", as used herein, refers to an amino acid sequence that is able to bind to MHC Class II molecules with a suitable efficiency and stimulate T cells 5 or bind to T cells in a complex with MHC Class II. In this case, the T cell epitope is recognized by a specific receptor present on T cells, and functions to provide a signal requiring the differentiation of B cells to antibody-producing cells and induce cytotoxic T lymphocytes 10 (CTL) to destroy target cells. The T cell epitope is not-specifically limited as long as it stimulates T cells and strengthens immune responses, and a variety of proteins, peptides, etc. suitable for the purpose are available. With respect to the objects of the present invention, the T cell 15 epitope is preferably a helper T cell epitope. Examples of the helper T cell epitope may include hepatitis B surface antigen helper T cell epitopes, Chlamydia trachomitis major outer membrane protein helper T cell epitopes, Plasmodium falciparum circumsporozoite helper T cell epitopes, 20 Escherichia coli TraT helper T cell epitopes, Tetanus toxoid helper T cell epitopes, diphtheria toxoid helper T cell epitopes, Schistosoma mansoni triose phosphate isomerase helper T cell epitopes, measles virus F protein helper T cell epitopes, T cell epitope sequences derived 25 from pertussis vaccines, BCG (Bacile Calmette-Guerin), polio vaccines, mumps vaccines, rubella vaccines, rabies WO 2005/087800 PCT/KR2005/000784 vaccines, purified protein derivatives of tuberculin, keyhole limpet hemocyanin, and fragments or combinations thereof. The T cell epitope may include an addition, deletion or substitution of a selected amino acid residue 5 according to the specific purpose, and may be provided in a multimeric form in which two or more different T cell epitopes are linked. In an embodiment of the present invention, a surface antigen of hepatitis B virus is used. The genome of hepatitis B virus (HBV) is 3.2 kb in length, 10 possesses the information for four important proteins and contains four open reading frames, S gene (surface antigen protein), C gene (core protein), P gene (DNA polymerase) and X gene. The S gene is divided into an S region encoding HBsAg and a preS region. The preS region is divided into 15 preSl encoding 108 or 119 amino acids according to HBV strains and preS2 encoding 55 amino acids regardless of subtype. The HBV preS2 protein activates helper T cells during in vivo immune responses, thereby stimulating the formation of an antibody against HBV. 20 The term "hybrid polypeptide", as used herein, generally indicates a peptide in which heterogenous peptides having different origins are linked, and in the present invention, refers to a peptide in which a B cell epitope and a T cell epitope are linked. This hybrid 25 polypeptide may be obtained by chemical synthesis or expression and purification through genetic recombination WO 2005/087800 PCT/KR2005/000784 after each partner is determined. Preferably, a hybrid gene, in which a gene sequence encoding a B cell epitope is linked to another gene sequence encoding a T cell epitope, is expressed in a cell expression system. In such a hybrid 5 polypeptide, the B cell epitope and the T cell epitope may be linked directly or by means of a connector, such as a linker. When a linker is used, it should not negatively affect the induction of immune responses by the hybrid polypeptide. 10 The term "polypeptide", as used herein, is a term including a full-length amino acid chain in which residues including two or more amino acids are conjugated by covalent peptide bonds, and includes dipeptides, tripeptides, oligopeptides and polypeptides. In particular, 15 in the present invention, the polypeptide means a hybrid polypeptide in which two or more peptides, in which several to several tens of amino acids are covalently bonded, are linked with each other. The hybrid polypeptide of the present invention is a polypeptide in which two or more 20 peptides, for example, a B cell epitope and a T cell epitope, are linked. Each peptide sequence comprising the polypeptide includes a sequence corresponding to the aforementioned epitope, and may further include a sequence adjacent to the epitope. These peptides may be made of L- 25 or D-amino acids, or may be in various combinations of amino acids in two different configurations. The hybrid WO 2005/087800 PCT7KR2005/000784 polypeptide of the present invention may be entirely composed of an antigenic region including the aforementioned B cell epitope, T cell epitope and a certain sequence adjacent thereto, and may further include an 5 additional sequence. However, this additional sequence preferably should not reduce the overall immunogenicity. Such an additional sequence is exemplified by a linker sequence. The term "immunogenicity", as used herein, refers to 10 the ability to induce both cellular and humoral immune responses to defend the body against impurities. A material inducing such immune responses is called an immunogen. The present invention employs a polypeptide having both a B cell epitope and a T cell epitope, which are immunogenic 15 materials. The present inventors linked a C-terminus of PB14/ which is a tetrameric apo B-100 mimetic peptide that is an anti-obesity functional peptide having a B cell epitope but deficient in a T cell epitope, to a portion (T fragment) of 20 HBV preS2 having a T cell epitope, thereby generating a gene fragment for the expression of PB14T (FIG. 1) . A PB14 fragment was obtained using BamHI and Xhol, and a T fragment was obtained using Sail and Hindlll. The PB14T gene fragment was inserted into a pQE30 vector and 25 transformed into E. coli JM109. An emerged colony was analyzed by restriction mapping (FIG. 2) and DNA sequencing WO 2005/087800 PCT/KR2005/000784 (FIG. 3), and was found to be a correct clone in which the B cell epitope is linked to the T cell epitope. This clone was designated "pBl4T". The pQE30 vector used for the expression of PBI4T and PBle initiates protein expression 5 from its internal start codon along with six histidine residues for the convenience of protein purification, followed by an enterokinase cleavage site. The thus expressed PB14T is 16.2 kDa, and PBls is 16.5 kDa. Protein expression was investigated by subjecting samples collected 10 at given time points to SDS-PAGE analysis (FIGS. 4 and 5). Thus, an immunogenic hybrid polypeptide of SEQ ID No. 9, in which a tetrameric apo B-100 mimetic peptide is linked to an HBV surface antigen preS2, may be provided in the practice of the present invention. 15 The immunogenic hybrid polypeptide of the present invention may be produced by chemical synthesis or genetic recombination. Preferably, the present hybrid polypeptide may be produced by transforming a host cell with a recombinant vector and isolating and purifying a 20 polypeptide expressed by the host cell. Thus, in another aspect, the present invention provides a recombinant vector comprising a gene encoding the immunogenic hybrid polypeptide, and a host cell transformed with the recombinant vector. 25 In a further aspect, the present invention provides a method of producing the immunogenic hybrid polypeptide by WO 2005/087800 PCT/KR2005/000784 culturing a host cell transformed with the recombinant vector. A process of producing the immunogenic hybrid polypeptide of the present invention by genetic 5 recombination comprises the following four steps. The first step is to insert a gene encoding the hybrid polypeptide into a vector to construct a recombinant vector. A vector into which foreign DNA is introduced may be a plasmid, a virus, a cosmid, or the like. The 10 recombinant vector includes a cloning vector and an expression vector. A cloning vector contains a replication origin, for example, a replication origin of a plasmid, pharge or cosmid, which is a "replicon" at which the replication of an exogenous DNA fragment attached thereto 15 is initiated. An expression vector was developed for use in protein synthesis. A recombinant vector serves as a carrier for a foreign DNA fragment inserted thereto, which typically means a double-stranded DNA fragment. The term "foreign DNA", as used herein, refers to DNA derived from a 20 heterogeneous species, or a substantially modified form of native DNA from a homogenous species. Also, the foreign DNA includes a non-modified DNA sequence that is not expressed in cells under normal conditions. In this case, a foreign gene is a specific target nucleic acid to be transcribed, 25 which encodes a polypeptide. The recombinant vector contains a target gene that • is operably linked to WO 2005/087800 PCT/KR200S/000784 transcription and translation expression regulatory sequences, which exert their functions in a selected host cell, in order to increase expression levels of the transfected gene in the host cell. The recombinant vector 5 is a genetic construct that contains essential regulatory elements to which a gene insert is operably linked to be expressed in cells of an individual. Such a genetic construct is prepared using a standard recombinant DNA technique. The type of the recombinant vector is not 10 specifically limited as long as the vector expresses a target gene in a variety of host cells including prokaryotes and eukaryotes and functions to produce a target protein. However, preferred is a vector which is capable of mass-producing a foreign protein in a form 15 similar to a native form while possessing a strong promoter to achieve strong expression of the target protein. The recombinant vector preferably contains at least a promoter, a start codon, a gene encoding a target protein, a stop codon and a terminator. The recombinant vector may further 20 suitably contain DNA coding a signal peptide, an enhancer sequence, 5'- and 3'-untranslational regions of a target gene, a selection marker region, a replication unit, or the like. The second step is to transform a host cell with the 25 recombinant vector and culture the host cell. The recombinant vector is introduced into a host cell to WO 2005/087800 PCT7KR2005/000784 generate a transformant by a method described by Sambrook, J. et al., Molecular Cloning, A Laboratory Manual (2nd Ed.), Cold Spring Harbor Laboratory, 1. 74, 1989, the method including a calcium phosphate or calcium 5 chloride/rubidium chloride method, electroporation, electro injection, chemical treatments such as PEG treatment, and gene gun. A useful protein can be produced and isolated on large scale by culturing a transformant expressing the recombinant vector in a nutrient medium. 10 Common media and culture conditions may be suitably selected according to host cells. Culture conditions, including temperature, pH of a medium and culture time, should be maintained suitable for cell growth and mass production of a protein of interest. Host cells capable of 15 being transformed with the recombinant vector according to the present invention include both prokaryotes and eukaryotes. Host cells having high introduction efficiency of DNA and having high expression levels of an introduced DNA may be typically used. Examples of host cells include 20 known prokaryotic and eukaryotic cells such as Escherichia sp., Pseudomonas sp., Bacillus sp., Steptomyces sp., fungi and yeast, insect cells such as Spodoptera frugiperda (Sf9), and animal cells such as CHO, COS 1, COS 7, BSC 1, BSC 40 and BMT 10. E. coli may be preferably used. 25 The third step is to induce the hybrid polypeptide to express and accumulate. In the present invention, the WO 2005/087800 PCT/KR2005/000784 inducer IPTG was used for the induction of peptide expression, and induction time was adjusted to obtain maxmimal protein yield. The final step is to isolate and purify the hybrid 5 polypeptide. Typically, a recombinantly produced peptide can be recovered from a medium or a cell lysate. When the peptide is in a membrane-bound form, it may be liberated from the membrane using a suitable surfactant solution (e.g., Triton-X 100) or by enzymatic cleavage. Cells used 10 in the expression of the hybrid peptide may be destroyed by a variety of physical or chemical means, such as repeated freezing and thawing, sonication, mechanical disruption or a cell disrupting agent, and the hybrid peptide may be isolated and purified by commonly used biochemical 15 isolation techniques (Sambrook et al., Molecular Cloning: A laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, 1989; Deuscher, M., Guide to Protein Purification Methods Enzymology, Vol. 182. Academic Press. Inc., San Diego, CA, 1990). Non-limiting examples of the biochemical 20 isolation techniques include electrophoresis, centrifugation, gel filtration, precipitation, dialysis, chromatography (ion-exchange chromatography, affinity chromatography, immunosorbent affinity chromatography, reverse phased HPLC, gel permeation HPLC), isoelectric 25 focusing, and variations and combinations thereof. In detail, in the present invention, the PB14T gene WO 2005/087800 PCT/KR2005/000784 fragment was ligated with a pQE30 vector and transformed into E. coli. The pQE30 vector is useful for mass-producing proteins in E. coli because it contains a promoter element consisting of the phage T5 promoter and a lac operator 5 system using IPTG as an inducer. The expression of PB14T was confirmed by Western blotting using two antibodies recognizing PB14T, a rabbit anti-PB14 polyclonal antibody and a mouse anti-preS2 monoclonal antibody, as primary antibodies, and expressed proteins were then purified. PB14 10 and PBI4T were denatured with 8 M urea because they are insoluble, and were purified by affinity chromatography using Ni-NTA resin for histidine-tagged proteins. Rats were immunized with the expressed and purified polypeptide, and were assessed for an increase in body 15 weight of rats, serum antibody titers and changes in serum lipid profiles. As a result, compared to a normal group or a group vaccinated with a non-fusion mimetic peptide, a group vaccinated with the hybrid polypeptide showed suppressed weight gain, high titers and extended retention 20 of an antibody against the mimetic peptide, and decreased serum levels of TG and LDL-cholesterol. There is no consistent rule applicable to peptide vaccine design, and the efficacy of designed vaccines is also unpredictable. For the same reasons, when a highly 25 hydrophobic PB14 peptide is fused with a T cell epitope that is a heterogeneous peptide, an antigenic region can be WO 2005/087800 PCT7KR2005/000784 internalized into the fusion protein, leading to a decrease in its ability to induce antibody responses. In this difficult situation to deduce the fusion results, the present inventors designed the hybrid polypeptide in which 5 a mimetic peptide of the apo B-100 epitope is linked to a T cell epitope, and demonstrated that the hybrid polypeptide has increased immunogenicity that results in increased anti-obesity effect. The immunogenicity of an artificially synthesized 10 hybrid polypeptide and a vaccine comprising the same is achieved when a B cell epitope and a helper T cell epitope are present at the same time. Also, the efficacy of the vaccine may be determined according to the orientation of the B cell epitope and the helper T cell epitope. That is, 15 the ability of the hybrid polypeptide to induce antibody responses may vary depending on the helper T cell epitope being located at an N-terminus or a C-terminus of the B cell epitope (Partidos, C, Stanley, C, and Steward, M, The effect of orientation of epitope on the immunogenicity of 20 chimeric synthetic peptides representing measles virus protein sequences, Molecular Immunology, 29(5), 651-658, 1992). In order to investigate the effect of the orientation of the B cell epitope and the helper T cell epitope on the 25 induction of immune responses, the present inventors prepared a TB14 gene fragment by linking an N-terminus of WO 2005/087800 PCT/KR2005/000784 PB14 to a T fragment (FIG. 12), unlike the preparation of the BI4T gene fragment involving linking a C-terminus of PBI4 to a T fragment. In detail, a pTBl4 vector was constructed according to a method described in Example 9, 5 transformed into E. coli M15, and expressed therein. The expressed hybrid polypeptide PTBI4, which has a His tag, was purified by affinity chromatography using Ni-NTA His-bound resin. In order to compare PTB14 and PB14T for their ability 10 to induce antibody responses and immunogenicity, SD rats were immunized with each of the polypeptides, and blood samples were collected. Compared to PB14, PTB14 had enhanced ability to induce antibody responses, and the retention period of the serum antibody against PTBI4 was 15 prolonged. However, these improvements upon immunization with PTBI4 were remarkably found to be about 50-60% lower than with PB14T (FIG. 16) . The same results were found in the suppression of body weight gain of the rats (Table 2) . These results indicate that the PB14T polypeptide, prepared 20 by linking a C-terminus of PBI4 to a T fragment, has much stronger immunogenicity and anti-obesity effects. Thus, in yet another aspect, the present invention relates to a vaccine for preventing or treating obesity, comprising an immunogenic hybrid polypeptide which includes 25 an amino acid sequence of a mimetic peptide of the apo B-100 epitope and in which a C-terminus of the mimetic WO 2005/087800 PCT/KR2005/000784 peptide is fused to an N-terminus of a helper T cell epitope. An iramunogen can be determined to be available as a vaccine having good efficacy by comparing the magnitude of 5 responses to the immunogen and the ratio of observed individuals. In the present invention, with respect to the present object to provide a vaccine for preventing and treating obesity, the effect of an antigen on the induction of immune responses was assessed by investigating (a) body 10 weight gain, (b) serum antibody titers and (c) changes in serum lipid profiles, thereby determining a highly efficient form of the antigen. In detail, 100 ug of each of purified PB14 and PB14T peptides were intraperitoneally injected into 7-week-old SD 15 white rats three times at 2-week intervals, and changes in body weight of the rats were observed and plotted ' on a graph (FIG. 15). From the primary injection to boosting (secondary injection), rats of each group showed similar body weight ranging from 292 g to 297 g. However, from one 20 week after the secondary injection, a difference in body weight of rats was observed between vaccinated groups and normal and mock groups. This indicates that the weak immune responses induced by the primary injection were enhanced after boosting by the secondary injection, and that the 25 enhanced immune responses lead to the suppression of body weight gain of rats. Compared to the normal and mock WO 2005/087800 PCT/KR2005/000784 groups, the vaccinated groups displayed a reduction in body weight increment. Also, the PB14T peptide had a stronger inhibitory effect on body weight increment than the PB14 peptide (Table 2). This difference in body weight increment 5 was maintained even after the third injection. In addition, the chimeric antigen PBI4T, which was homogenous, was found to more effectively induce immune responses than the PBI4 peptide conjugated with a carrier protein, ovalbumin. In vaccinated SD white rats, serum antibody titers were 10 measured at 10, 12, 14 and 16 weeks of age by ELISA (FIG. 16) . The PBl4T-immunized group showed increased antibody titers relative to the PB14-immunized group. At 14 weeks of age, the PBI4T-immunized group displayed 1.5-fold higher absorbancy (O.D.: optical density) values than the PB14- 15 immunized group. At 16 weeks of age, the PBl4-immunized group showed a reduction in antibody titer, whereas the PBl4T-immunized group maintained the increased antibody titers. With respect to serum lipids, the vaccinated groups displayed lower levels of TG and cholesterol than the 20 normal and mock groups. In particular, LDL-cholesterol levels were reduced to 60% of normal levels (FIG. 17) . These results demonstrate that a fusion form of PB14 with a T cell epitope has higher immunogenicity than PB14 itself, which has a B cell epitope, and thus can be used in 25 an effective vaccine composition. In addition, the present inventors conducted a WO 2005/087800 PCT/KR2005/000784 clinical test with pet dog subjects for the efficacy of ■PBI4T. PBI4T was mixed with alumina and injected into ten pet dogs twice at 2-week intervals, and changes in body weight were observed. As a result, no increment in body 5 weight was found in the pet dogs even when the dogs were allow to freely eat snacks and high-fat diets (Table 4). Also, when serum samples were collected from the immunized pet dogs after the secondary injection and serum antibody titers were measured by ELISA, high absorbance was found 10 even when the serum samples were diluted 5,000-50,000 times, indicating that the PBI4T peptide has an excellent effect on the induction of antibody responses. The anti-obesity vaccine of the present invention is composed of an antigen, a pharmaceutically acceptable 15 carrier, a suitable adjuvant and other common materials, and is administered in an immunologically effective amount. The term "immunologically effective amount", as used herein, refers to an amount that is sufficient to exert the therapeutic and preventive effect on obesity and does not 20 cause side effects or severe or excess immune responses. An accurate dosage may vary according to the specific immunogen to be administered, and may be determined by those skilled in the art using a known method for assaying the development of an immune response. Also, the dosage may 25 vary depending on administration forms and routes, the recipient's age, health state and weight, properties and WO 2005/087800 PCT/KR2005/000784 degree of symptoms, types of currently received therapy, and treatment frequency. The carriers are known in the art and include a stabilizer, a diluent and a buffer. Suitable stabilizers include carbohydrates, such as sorbitol, 5 lactose, mannitol, starch, sucrose, dextran and glucose, and proteins, such as albumin or casein. Suitable diluents include . saline, Hanks' Balanced Salts and Ringer's solution. Suitable buffers include an alkali metal phosphate, an alkali metal carbonate and an alkali earth 10 metal carbonate. The vaccine may also contain one or more adjuvants to enhance or strengthen immune responses. Suitable adjuvants include peptides; aluminum hydroxide; aluminum phosphate; aluminum oxide; and a composition that consists of a mineral oil, such as Marcol 52, or a 15 vegetable oil and one or more emulsifying agents, or surface active substances such as lysolecithin, polycations and polyanions. The vaccine composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and 20 may be co-administered either sequentially or simultaneously with a conventional therapeutic agent. The vaccine composition may be administered via known administration routes. Administration methods include, but are not limited to, oral, intradermal, intramuscular, 25 intraperitoneal, intravenous, subcutaneous, and intranasal routes. Also, a pharmaceutical composition may be WO 2005/087800 PCT/KR2005/000784 administered using a certain apparatus, which can deliver an active material to target cells. A better understanding of the present invention may be obtained through the following examples which are set 5 forth to illustrate, but are not to be construed as the limit of the present invention. EXAMPLES Test Materials A DNA miniprep kit and a kit used to extract DNA from 10 a gel were purchased from Nucleogen, Bacto trypton, Bacto yeast extract, agar, etc. from Difco (Detroti, MI), restriction enzymes from Takara, and T4 DNA ligase from NEB. pBluescript II SK (Stratagene), PCR 2.1 (Invitrogen, Carlsbad, CA) and pQE30 (Qiagen) vectors and E. coli JM109 15 and Ml5 strains (Qiagen) were used. IPTG used to induce protein production was purchased from Sigma, the Ni-NTA resin used to purify expressed proteins from Novagen, and the prestained marker used in SDS-PAGE, Western blotting, ECL, etc. from NEB. Urea used 20 to denature proteins was purchased from Duchefa, and immidazole used in protein purification from USB. The membrane used in dialysis was MWCO 3,500 purchased from Spectrum, and the reagent used to prevent protein WO 2005/087800 PCT/KR2005/000784 aggregation was CHAPS from Amresco. The antibody used in ELISA was HRP-conjugated anti-rat IgG" from Sigma. The substrate solution used in Western blotting and ECL was BCIP/NBT from Sigma, and the ECL Plus Western Blotting 5 Detection Reagent was purchased from Amersham. Adjuvants used were Freund's adjuvant (Sigma) and aluminum hydroxide (Reheis). Protein concentration was determined by Pierce's BCA protein assay and Biorad's Bradford assay. Tryglycerides, total cholesterol, HDL cholesterol and 10 LDL cholesterol in the serum were measured using triglyzyme-V, cholestezyme-V, HDL-C555 (Shinyang Diagnostics, Korea) and EZ LDL cholesterol (Sigma), respectively. An LDL calibrator (Randox) was used. 5-week-old male Sprague Dawley (SD) white rats were 15 purchased from Daehan Biolink Co. Ltd., Korea, and fed with a feedstuff from Samtako Inc., Korea, which contains more than 18% natural proteins, 5.3% crude fats, 4.5% crude fiber and 8.0% ash. The following buffers were used to purify recombinant 20 PB14T and PB14 peptides: sonication disruption buffer (5 mM imidazole, 0.5 M NaCl, 20 mM Tris-Cl, pH 7.9), binding buffer (5 mM imidazole, 0.5 M NaCl, 20 mM Tris-Cl, 8 M urea, pH 7.9), washing buffer (50 mM imidazole, 0.5 M NaCl, 20 mM Tris-Cl, 8 M urea, pH 7.9), and elution buffer (400 25 mM imidazole, 0.5 M NaCl, 20 mM Tris-Cl, 8 M urea, pH 7.9). WO 2005/087800 PCT/KR2005/000784 EXAMPLE 1: Preparation of an artificial gene for production of anti-obesity PB14T peptide A pBluescript II SK vector was digested with BamHI and Xhol to obtain a Bl4 fragment, and a PCR 2.1 vector was 5 digested with Sail and Hindi 11 to obtain a T fragment. Since Xhol and Sail have compatible cohesive ends, the Bl4 and T fragments, obtained from the two vectors, were ligated using T4 DNA ligase at 16°C for 12 hrs. Since the ligated site is not digested by Sail or Xhol, Sall/Hindlll 10 digestion was carried out again to obtain a B14T fragment. For protein expression, a pQE30 plasmid was selected as a vector system, which is designed to express a protein of interest in a form fused with six histidine residues to facilitate protein purification. The B14T gene fragment was 15 inserted into Sall/Hindlll sites of the pQE30 vector. The resulting expression vector was designated "pBl4T" (FIG. 1) . The expression vector was transformed into E. coli JM109. Plasmid DNA was isolated from the transformed cells and subjected to restriction mapping with Sail and Hindlll. As 20 a result, a 450 bp fragment was successfully inserted into the pQE30 vector (FIG. 2) . The recombinant vector' pBl4T was deposited in the form of being transformed into E. coli (E. coli M15/pBl4T) at the Korean Culture Center of Microorganisms (KCCM, 361- 25 221, Yurim B/D, Honje 1-dong, Sudaemum-gu, Seoul, Republic WO 2005/087800 PCT7KR2005/000784 of Korea) on March 4, 2004, and was assigned accession number KCCM-10562. EXAMPLB 2: Preparation of an artificial gene for production of antx-obesity PB18 peptide 5 A pBluescript II SK vector was digested with Sail and and Xhol to obtain a Bl4 fragment. A pBX4 vector (pQE30 vector having a Bl4 fragment insert, Korean Pat. Laid-open Publication No. 2002-0018971) was linearlized by Sail digestion, and ligated with the Bl4 fragment using T4 DNA 10 ligase at 16°C overnight. EXAMPLE! 3: Nucleotide sequence determination of gene In order to confirm whether the Bl4T gene fragment is correctly inserted in the pBl4T recombinant vector, the recombinant vector was prepared in a concentration of 300- 15 500 ng/jog and subjected to DNA sequencing, which was performed by Core Bio System Co. Ltd., Korea. As a result, the selected recombinant vector was found to be a correct clone (FIG. 3) . EXAMPLE! 4: Recombinant peptide PB14T expression 20 The PB14T and PBls peptides were expressed from the WO 2005/087800 PCT/KR2005/000784 pQE30 vector, which initiates protein expression from its internal start codon along with six histidine residues for convenience of protein purification, followed by an enterokinase cleavage site. E. coll M15 was used as a host 5 cell for peptide expression. The E. coll M15 strain was transformed with a recombinant vector and smeared onto LB plates containing ampicillin (Amp) and kanamycin (Kan). An emerged colony was cultured in 10 ml of LB medium containing Amp (100 ug/ml) and Kan (25 ug/ml) overnight. In 10 order to investigate protein expression according to culture time, 1 ml of the overnight-cultured culture was inoculated in 50 ml of fresh LB medium. Then, the cells were incubated with agitation at 37°C for 1 hr 30 min, where OD at 600 nm was 0.4 to 0.5. At this state, IPTG was added 15 to the medium at a final concentration of 1 mM, and the cells were further cultured for 5 hrs, during which 1 ml of the culture was collected every hour. Before IPTG addition, 1 ml of the culture was collected to be used as a non-induced control. The collected samples were centrifuged at 20 14,000 rpm for 1 min. The cell pellets were dissolved in 30 ul of 2xSDS sample buffer and subjected to SDS-PAGE. The results are given in FIGS. 4 and 5. The SDS-PAGE analysis revealed that PB14T is 16.2 kDa and PB18 is 16.5 kDa. EXAMPLE 5: Western blotting for the recombinant peptide 25 PB14T WO 2005/087800 PCT/KR2005/000784 The PBI4T peptide was identified by size analysis using SDS-PAGE, but in order to further confirm whether the expressed protein is PB14T, Western blotting was carried out using two antibodies capable of recognizing PBI4T. As a 5 control in Western blotting for PB14T, E. coli M15 was transformed with the pQE30 vector not containing the B14T ■ fragment. Samples were collected before IPTG induction and three hours after IPTG induction. A rabbit anti-PBl4 polyclonal antibody and a mouse anti-preS2 monoclonal 10 antibody were 1:10000 diluted in PBS and used as primary antibodies. As secondary antibodies capable of recognizing the primary antibodies, peroxidase-conjugated goat anti-rabbit IgG and goat anti-mouse IgG were used after being 1:10000 diluted in PBS. A resulting blot was developed 15 using an ECL Plus Western Blotting Kit. The blot was placed in a cassette, and a sheet of Fuji medical X~ray film was placed onto the blot. The blot was exposed to the film for 10 sec and developed. Since the rabbit anti-PBl4 polyclonal antibody recognizes a PB14 fragment of PBI4T and the mouse 20 anti-preS2 monoclonal antibody recognizes a T fragment of PB14T, bands should be observed on both blots, which were individually incubated with each of the primary antibodies, when the PBI4T protein is correctly expressed. As shown in FIG. 8, the primary antibodies individually recognized PBI4 25 and T of PB14T, indicating that PB14T is correctly WO 2005/087800 PCT/KR2005/000784 expressed. EXAMPLE 6: Evaluation of expression form of PB14T and PBle recombinant peptides in E. coll In order to determine whether PB14T and PBls were 5 expressed as soluble or insoluble proteins, the cells were harvested three hours after IPTG induction by centrifugation. The harvested cells were resuspended in sonication buffer and sonicated. The resulting pellet and supernatant were analyzed by SDS-PAGE. In detail, the cells 10 treated with IPTG to induce protein expression were centrifuged at 9,000 rpm at 4°C for 30 min. The pelleted cells was frozen at -20°C for a while, thawed on ice, and resuspended in sonication disruption buffer (5 ml per 1 g pellet). The cells were sonicated fifteen times for 30 sec 15 (each time with 1 min pause) . The cell lysate was then centrifuged at -9,000 rpm at 4°C for 30 min. The supernatant was recovered, thus yielding a crude extract A containing unprocessed soluble proteins. Also, the pellet was recovered, thus giving a crude extract B containing 20 unprocessed insoluble proteins. The crude extracts A and B were individually mixed with 2x SDS sample buffer, boiled at 95°C for 5 min, and electrophoresed on an SDS-PAGE gel. The SDS-PAGE analysis revealed that the target proteins were present mainly in the pellet rather than the WO 2005/087800 PCT7KR2005/000784 supernatant, indicating that the PB14T and PB18 proteins are expressed in an insoluble form (FIGS 6 and 7) . EXAMPLB 7: Purification of PB14, PB14T and PB18 recombinant peptides 5. Peptide purification was carried out using Ni-NTA resin for histidine-tagged proteins. This purification is an affinity chromatographic method using the interaction between Ni+ bound to the resin and the histidine hexamer at a terminal end of a fusion protein. After transformed E. 10 coli cells were pre~cultured in 10 ml of LB medium overnight, the 10-ml culture was inoculated in 500 ml of LB medium and cultured at 37°C until OD at 600 nm reached 0.4 to 0.5. Then, 1 mM IPTG was added to the medium, and the cells were further cultured for 4 hrs. The cells were 15 centrifuged at 9000 rpm for 30 min, and the cell pellet was placed at -20°C. After the frozen cells were thawed on ice, they were resuspended in sonication disruption buffer (5 ml/g of wet cells) and sonicated. The cell lysate was then centrifuged at 9000 rpm at 4°C for 30 min. The pellet was 20 resuspended in a volume of binding buffer equal to that of the supernatant, sonicated three times to remove cell debris, and centrifuged at 9000 rpm at 4°C for 30 min. The thus obtained supernatant was subjected to affinity chromatography using Ni-NTA resin. WO 2005/087800 PCT/KR2005/000784 A column was 1 cm in diameter and 15 cm in height and was packed with 2 ml of a resin, and all of the steps were carried out at a flow rate of 2 ml/min. After the resin was packed into the column, the resin was washed with a three 5 to five column volume of distilled water, and the resin was charged with Ni2+ using a five column volumn of lx charge buffer (50 mM NiS04) and equilibrated with the binding buffer, thereby generating a Ni-chelate affinity column. After a sample was loaded onto the column twice, the column 10 was washed with the binding buffer until the absorbance at 280 nm reached a baseline of 1.0 and then with washing buffer for 10 min. After the column was completely equilibrated, the column was eluted with elution buffer containing a higher concentration of imidazole than the 15 washing buffer, thereby forming an imidazole gradient, and the elution was run alone through the column for a futher 10 min to.completely elute proteins bound to the resin. A total of twenty 2-ml fractions were collected. Since the eluted peptide was dissolved in 8 M urea, it was dialyzed 20 in PBS overnight to remove urea. As described above, since each protein was highly insoluble, it was purified after being- denatured with a buffer containing 8 M urea, and proteins bound to the resin were eluted using an imidazole gradient of 50 mM to 400 mM. 25 The results are given in FIGS. 9, 10 and 11. Most proteins were eluted at about 300 mM of imidazole. Protein yields WO 2005/087800 PCT/KR2005/000784 per 1 L culture were 3-3.5 mg for PB1B and 4-4.5 mg for ,PB1«T._ EXAMPLE 8: Quantification of PB14, PB14T and PBla recombinant peptides 5 When the eluted PB14T, PB14 and PBls peptides were dialyzed in PBS, proteins were aggregated because urea was removed, thus forming precipitates. In this state, accurate protein concentrations could not be measured. The aggregation of the purified proteins was solved using 50 mM 10. CHAPS. Protein concentrations were determined by a BCA protein assay and a Bradford assay. 2 mg/ml of BSA was serially diluted to 1000, 500, 250, 125 and 62.5 ug/ml, and the serial BSA dilutions were used as standard. The BCA assay was performed according to the protocol provided by 15 Pierce. The BCA protein color reaction was carried out at 37°C for 30 min, and absorbance was then measured at 562 nm. Also, a sample was allowed to react with a Bradford reagent at room temperature for 10 min, and absorbance was then measured at 595 nm. Standard curves were obtained using the 20 absorbance of serial dilutions of BSA or Bradford protein color reactions, and protein concentrations of samples were determined using the standard curves. EXAMPLE 9: Construction of pXBl4 vector for PTB14 'expression -ar5 WO 2005/087800 PCT/KR2005/000784 The pQE30 vector, transformed into E. coli M15, was double-digested with Kpnl (Takara) and Sail (Takara) to excise a T cassette (preS2) . A pBluescript plasmid was also treated with the same restriction enzymes. The excised T 5 cassette and linearlized pBluescript were separated on a gel, purified, and ligated with each other using T4 DNA ligase. 4 ul of pBluescript, 4 fil of T cassette, 1 ul of T4 DNA ligase (MBI Fermentas, 1 Weiss u/ml) and 1 |jl of lOx buffer (MBI Fermentas) were mixed in a 1.5-ml tube, and the 10 ligation mixture was incubated at 16°C overnight. The recombined vector was then mixed with JM109 competent cells, heat-shocked at 42°C for 90 sec, and incubated in LB medium at 37°C for 1 hr. Then, the transformed cells were smeared onto LB/Amp plates and incubated at 37°C. Several 15 colonies were randomly selected from the emerged coloni es and cultured. Plasmid DNA was then isolated from the cultured cells, digested with restriction enzymes, and electrophoresed on an agarose gel to analyze the size of DNA fragments. An Xhol site in the T cassette was removed 20 to obtain a TB4 cassette. That is, since the T cassette (HBV preS2 gene, 183 bp) could not be used in cloning due to the Xhol site near its 3'-end (about 150 bp apart from the 5'-end of the T cassette), the T cassette was point-mutated at the internal Xhol site and thus had a new 25 sequence. A short DNA fragment (30 bp) was excised from WO 2005/087800 PCT/KR2005/000784 pBluescript-preS2 due to the internal Xhol site of the T cassette. Synthetic oligomers were inserted into this position. To prevent self-ligation, the vector was treated with alkaline phosphatase (Boehringer Mannheim, GmbH, 5 Germany) at 37°C for 30 min, dephosphorylated at 95°C for 5 min, and eluted from a gel. The oligomers were phosphorylated at their 5'-ends by treatment with polynucleotide kinase at 37°C for 30 min and 65°C for 20 min. Then, the vector and the oligomers were allowed to 10 stand at 95°C for 5 min, and were slowly cooled in a heat block to be annealed. The oligomers and pBluescript-T were then treated with ligase at 16°C overnight. The recombined pBluescript-T was transformed into JM109 cells and smeared onto LB/Amp plates. After plasmid DNA was Isolated from 15 emerged colonies and analyzed, a clone carrying a desired plasmid was obtained. The oligomers consisted of 28 nucleotides corresponding to preS2, in which the fifth nucleotide, G, at the 5'-end of a sense-strand, was replaced with A to remove Xhol site, thereby having a lysine 20 substitution for arginine. Sense and anti-sense strands, each of which was designed to be 28 mer, were annealed and inserted into the Xhol-treated pBluescript-preS2. After the pBluescript-T was double-digested with Sail and Xhol and pQE30-B4 was digested with Sail, they were purified from 25 gels. The. obtained T was inserted into the pQE30-B4 cleaved at its 5'-end, thereby generating pQE30-pTB4. The recombined WO 2005/087800 PCT7KR2005/000784 TB4 was confirmed by restriction mapping with Sail and Hindlll. The thus obtained vector was designated pTBl4 (FIG. 13) . EXAMPLE 10: Expression and purification of PTB14 5 The expression vector pTBl4 was introduced into E. coli M15, and the transformed cells were cultured in 2 L of LB medium containing Amp and Kan. The cultured cells were centrifuged at 7000 rpm for 10 min, thus yielding 9 g of wet cells. Since the recombinantly expressed hybrid 10 polypeptide PTB4 had a His-tag, it was subjected to affinity chromatography using an Ni-NTA His-bound resin. A column used was 4 ml in resin volume, 1.8 cm in diameter a.nd 8 cm in height. The absorbance range of an Econo system was 0.5, the paper speed of a recorder was 2 cm/hr, and the sample 15 loading rate was 2 ml/min. First, the wet cells were suspended in sonication buffer, sonicated and centrifuged at 10,000 rpm at 4°C for 30 min. The pellet was dissolved in binding buffer and subjected to affinity chromatography. A binding solution flowed through the column to settle a 20 resin. When a baseline was decided using a detector and a predetermined value was indicated, the sonicated sample was loaded onto the column. When the sample entered into the column and a predetermined value was indicated, a washing solution was run through the column. When a predetermined WO 2005/087800 PCT/KR2005/000784 value was indicated, an elution solution was run through the column, thereby isolating PTB14. The expressed and purified hybrid polypeptide was analyzed by SDS-PAGE and Western blotting. The PTBI4 separated on an SDS-PAGE gel 5 was transferred onto a membrane by semi-dry transfer. The blot was incubated in blocking buffer (0.5% casein-phosphate buffered saline-Tween, 0.02% NaN3) at 37°C for 2 hrs, and washed with Tris-buffeared saline-Tween (TBS-T, pH 7.6) twice for 2 min each washing. Then, the blot was 10 incubated in a primary antibody at 37°C for 1 hr and washed with TBS-T four times for 5 min each time. The blot was incubated in a secondary antibody for 1 hr and washed according to the same method, ro identify the T cassette, an anti-preS2 monoclonal antibody (1:10,000) and an HRP- 15 conjugated goat anti-mouse IgG- antibody (1:10,000) were used. A B cassette was detected using a rabbit anti-PBl4 anti-serum (1:10,000) and an HRP-conjugated goat anti-rabbit IgG antibody (1:10,000). After being dried, the blot was treated with ECL reagents fozr 5 min to detect bands. As 20 a result, in the B cassette, which was detected using the rabbit anti-PBl4 anti-serum and the HRP-conjugated goat anti-rabbit IgG antibody, an about 16-kDa band was found in PBI4T and PTBI4 samples. In -the T cassette, which was detected using the anti-preS2 monoclonal antibody and the 25 HRP-conj ugated goat anti-mouse IgG antibody, a band of about 8 kDa was found in the PBI4 sample, and a band of WO 2005/087800 PCT/KR2005/000784 about 16 kDa band was found in PBI4T and PTBI4 samples. These results indicate that each hybrid polypeptide was accurately expressed and purified (FIG. 13). EXAMPLE 11: Conjugation of PB14 and ovalbumin 5 PBI4 was conjugated with a carrier protein, ovalbumin. The carrier protein and PB14 were mixed at a molar ratio of about 1:10, and allowed to react with agitation at 4°C for about 1 hr in a reaction vial. After the reaction mixture was supplemented with 2% 10 glutaraldehyde, it was allowed to react for 3 hrs. The reaction mixture was then dialyzed using a dialysis membrane, MWCO 3,000, in PBS buffer overnight to remove remaining glutaraldehyde. EXAMPLE 12: Vaccination (Immunization) 15 7-week-old SD white rats were divided into six groups and vaccinated (Table 1) . As described in Table 1, 100 p.g of each peptide, purified and quantified in Examples 7 and 10, was mixed with each adjuvant to give a final volume of 100 ul, and intraperitoneally injected into the rats. 20 Injection was carried out three times at 2-week intervals, that is, at 7, 9 and 11 weeks of age. Freund's adjuvant and aluminum hydroxide were as adjuvants. The Freund's adjuvant WO 2005/087800 PCT/KR2005/000784 was used in the same amount as the peptide. Aluminum hydroxide of 5.8 mg/ml was adjusted to a final concentration of 0.2 mg/ml, mixed with each peptide, and incubated with agitation at room temperature. Blood samples 5 were collected five days after the first boosting and five days, two weeks and four weeks after the second boosting. TABLE 1 Vaccination with peptides Normal Mock Test groups A B C D E Antigen PBS OVA PBl«t4WA1 PBI4T PB1 Adjuvant Aluminum hydroxide Freund'sadjuvantoraluminumhydroxide Freund'sadjuvantoraluminumhydroxide Aluminum hydroxide Aluminum hydroxide Freund'sadjuvantoraluminumhydroxide Changes in body weight of SD rats after vaccination 10 were plotted on a graph (FIG. 15) . From the primary injection to boosting (secondary injection), rats of each group showed similar body weight ranging from 292 g to 297 g. However, from one week after the secondary injection, a difference in body weight of rats was observed between 15 vaccinated groups and normal and mock groups. At 18 weeks of age, compared to the mock groups, the PB14-vaccinated group showed a difference of 16 g in body weight, and the PBl4T-vaccinated group displayed a difference of 27 g in body weight (Table 2) . This indicates that the weak immune 20 responses induced by the primary injection were enhanced WO 2005/087800 PCI7KR2005/000784 after boosting by the secondary injection, that and the enhanced immune responses lead to the suppression of body weight increment of rats. This difference in body weight increment was maintained even after the third injection. 5 TABLE 2 Changes in body weight of SD rats after vaccination Age (wk) Normal Mock PBl^ PB14T PTB1 6 130±0 130±0 13010 130±0 130±0 7 (VI) 200±0 193±6 202±4 202±4 201+6 8 253±6 257±6 254±9 254+11 252±5 9(V2) 292+8 299±6 297±13 303+6 300±8 10 325±8 328±4 323±12 332±7 332±4 H(V3) 354±6 362±3 357±14 362±10 359±8 12 372±15 376±8 365±11 362±13 363±13 13 395±12 396±12 383±10 377±13 379±15 14 407±14 407±8 395±8 391112 396±10 15 413±16 414±9 403±11 397±10 401±10 16 422118 424±10 414±13 406±10 412+10 17 436±22 435±11 425±14 415±9 420±9 18 456±24 452±11 436±12 425±9 433111 In Table 2, all data are represented as mean+SD, wherein SD (standard deviation) was calculated for five SD white rats, and units are grams. 10 EXAMPLE 13: Measurement of antibody titers Antibody titers were measured using serum samples by indirect ELISA. 100 fil (100 ng) of PB14 was placed into each well of a microtiter plate. The plate was incubated at 4°C overnight, and incubated in a blocking solution (PBS, 15 0.5% casein, 0.02% NaN3) at 37°C for 1 hr. Each well was WO 2005/087800 PCT7KR2005/000784 washed with PBST three times. Serum samples collected from vaccinated SD rats were 1:500 to 1:8000 diluted in PBS. 100 jil of each diluted serum sample was added to each well, and incubated at 37°C for 1 hr. Each well was washed with PBST 5 three times and incubated with a 1:1000 dilution of goat anti-rat IgG as a secondary antibody. The plate was subjected to color development with OPD, and absorbance was measured at 450 nm. FIG. 16 shows the antibody titers of SD rats of 10 vaccinated groups at 10, 12, 14 and 16 weeks of age. Titers were determined by ELISA based on the absorbance value of 0.6 when each serum sample was 1:2000 diluted. When the serum sample was diluted at 1:500 to 1:8000, the groups injected with PB14, PB14T and PTB14 showed increased 15 antibody titers until 14 weeks of age. The PBl4T-immunized group displayed 1.5-fold higher O.D. values than the PB14-immunized group, and the PTBl4-immunized group showed a slight increase compared to the PB14 group. At 16 weeks of age, the PB14 group showed a reduction in antibody titer, 20 and the PB14T and PTB14 groups maintained the increase of antibody titers. However, PTB14 was found to have a remarkably weak effect in increasing antibody titers by about 50-60% compared to PB14T. EXAMPLE 14: Evaluation of serum lipid profiles WO 2005/087800 PCT7KR2005/000784 TG and cholesterol levels were measured as follows. 4 JJ.1 of a serum sample were mixed with 200 ul of a development reagent and incubated at 37°C ffor 5 min, and absorbance was then measured at 505 nm and 500nm. To 5 measure HDL levels, a serum sample was mixed with a precipitation reagent at a ratio of 1:1, allowed to stand at room temperature for 10 min, and centrifuged at over 3000 rpm for 10 min. 4 ul of the centrifugal supernatant was mixed with 200 ul of a development reagent and 10 incubated at 37°C for 5 min, and absorbance was then measured at 555 nm. LDL-cholesterol levels were measured using an EZ LDL cholesterol kit (Sigma) and an LDL calibrator (Randox) . According to the protocol supplied by the manufacturer, 4 ul of a serum sample was mixed with 15 1,150 ul of a reagent contained in the kit, incubated at 37°C for 5 min, supplemented with 250 pi o£ the reagent, and incubated again at 37°C for 5 min. Then, absorbance was measured at 600 nm.. Serum levels of each lipid were determined using measured absorbance and a standard curve 20 was obtained using standard solutions. The test results for lipid profiles in serum samples collected five weeks after the third injection into SD rats are given in Table 3, below. TABLE 3 25 Serum lipid profiles WO 2005/087800 PCT/KR200S/000784 TG HDL-cholesterol Total cholesterol LDL-cholesterol Normal 102.3±5.6 51.5±2.7 110.2±6.5 47.7±9.5 Mock 98.0+.5.9 54.6±7.8 104.1±3.9 42.9±9.1 PB1/°""| 92.5±4.5 41.7+4.3 94.6±7.1 34.8±4.0 PB1«T 90.3±6.2 43.0+2.5 97.6±2.3 33.0±4.3 In Table 3, all data are represented as mean±SD, wherein SD (standard deviation) was calculated for five SD white rats, and units are mg/dl. The normal and mock groups displayed levels of TG and 5 cholesterol about 10 mg/ml (10 mg/100 ml) higher than the vaccinated groups. When the vaccinated groups were compared with each other, higher levels of TG and LDL-cholesterol were found in the PBl4-vaccinated group but the difference was negligible (FIG. 17). 10 EXAMPLE 15: Clinical test with pet dog subjects PBI4T was mixed with alumina as an adjuvant. 0.5 ml of the mixture (2 mg/ml) was intramuscularly or subcutaneously injected into ten pet dogs (managed with an obesity treatment in an animal hospital in Ansan, Korea) 15 twice at 2-week intervals. Changes in body weight of the dogs were observed for a period of 1.5 to 3 months. As a result, an antibody was slowly reduced (half-life: three months), and no increase in body weight was found in the pet dogs even when the dogs were allow to freely eat snacks 20 and high-fat foods. In detail, the body weight increment WO 2005/087800 PCTYKR2005/000784 was suppressed in all of the ten pet dogs even whxen the dogs digested snacks and high calorie foods. In particular, Yorkshire Terriers did not increase body weight when injected with PB14T even in the situation in which thie body 5 weight of the dog was predicted to increase accorciing to the dog's sex and age. In addition, serum samples were collected frrom the immunized pet dogs to assess the induction degzree of antibody responses. One week after the secondary injection, 10 serum titers of an antibody to PB14T and PB14 were measured by ELISA. A high absorbance of 0.5 was found even wtien the serum samples were diluted 5,000-50,000 times, indicating that the PB14T peptide has an excellent effect on the induction of antibody responses. 15 TABLE 4 Changes in body weight after vaccination Species Sex Age (year) Body weight (kg) for the test period (wk) Diet 0 2 4 8 12 Shih Tzu F 4.4 5.5 5.2 5.5 5.3 5.3 Hig3n-calorrie Maltese F . 8 4.3 4.0 4.2 No:rmal Poodle F 7.4 4.7 4.7 4.6 Low— calorrie Poodle F 6.1 4.5 4.5 4.4 Low— caloirie Yorkshire Terrier F 4 5.9 5.6 5.6 Noarmal Yorkshire Terrier F 15 ■8.7 8.8 8.6 High.-calorrie Yorkshire Terrier F 3.7 3.8 3.8 3.7 High.-calorrie Yorkshire Terrier M 5.1 4.8 4.8 4.7 Noarmal WO 2005/087800 PCT7KR2005/000784 Yorkshire Terrier M 2.5 3.3 3.4 3.3 High-calories Miniature Pinsher M 5.1 3.6 3.5 3.5 High-calories Miniature Schunauzer F 1.4 7.2 7.0 7.0 Normal Industrial Applicability As described hereinbefore, the hybrid polypeptide of the present invention, in which a C-terminus of a mi_metic peptide of a B cell epitope of apo B-100 having an anti-5 obesity effect is fused to an N-terminus of a helper T7 cell epitope, displays an excellent anti-obesity activity without inducing immune responses that neutrralize beneficial activities or effects of the B cell epitope of apolipoprotein B-100 or without causing harmful side 10 effects. Therefore, the hybrid polypeptide is very useful in preventing or treating obesity. WO 2005/087800 PCT/KR2005/000784 BUDAPEST TREATY ON THE INTERNATIONAL raeoGNtnow OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE INTERNATIONAL FORM To. Hyo Joon Kim HBISty Hanyaag University Sa-1-toBt Sanerok-eu, Ansan Cyunggi-do, 423-791 L South Korea RECEIPT IN THE CASE OF AN ORIGINAL issued pursuant to Rule 7.1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of this ptiue I. IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR! MlbVpBUT Accession number given by the INTERNATIONAL DEPOSITARY AUTHORITY; KCCM-K552 fl. SCENTIBC DESCRIPTION AND/OR PROPOSED TAXQNOMC DESIGNATION The micraarijanism identified under I above was D s scientific description D A proceed taxcftttnic designation IMarlc with o cross where applicable! led by! 0. RECEIPT AND ACCEPTANCE This International Depositary Authoulty accepts (lie nifaoorgani^ identified under I above, which was received by it on Mar. 4.2p04. (rfat$ pf the orlflhtfl deposit)1 IV. INTERNATIONAL DEPOSITARY AUTHORITY I Where Ruk 6VHd) applies, sail dale is the date on which the status of tn&nraltitinar "depositary iutWty was acquired : where a deposit made outside the Budapest Treaty after the acquisition of the status of I ntemaSona] depositary authority is converted into s deposit tinder the Budajsest Treaty, such daw is die date en which tho microorganism was received by tSie international depositary authoulcy. Name: Korean Culture Center of Mtooorganlsm& Address: 351-221, Yurim B/D Hortgje-l-doag, Seodaemwi-su SEOUL 120-091 Republic of Korea Signatured) of peraonfe) having the power to represent the Inlemationul Dejxxiitary Autiiorily or of authora Date: Mar. 12. 2004. form BP/4 Sole page WO 2005/087800 PCT/KR2005/000784 Sequence Listing SJBIOMEDINC. 5 Anti-obese immunogenic hybrid polypeptides and anti-obese vaccine composition comprising the same 9 10 Kopatentln 1.71 1 15 PRT 15 Artificial Sequence mimetic peptide for apolipoprotein B-100 epitope 20 1 Arg Asn Val Pro Pro De Phe Asn Asp Val Tyr Trp De Ala Phe 15 10 15 25 2 15 PRT Artificial Sequence 3,0 WO 2005/087800 PCTYKR2005/000784 mimetic peptide for apolipoprotein B-100 epitope 5 2 Arg Phe Arg Gly Leu lie Ser Leu Ser Gin Val Tyr Leu Asp Pro 15 10 15 10 3 15 PRT Artificial Sequence 15 mimetic peptide for apolipoprotein B-100 epitope 3 20 Ser Val Cys Gly Cys Pro Val Gly His His Asp Val Val Gly Leu 1 5 ' • 10 15 4 25 204 DNA Artificial Sequence 30 DNA sequence for terameric mimetic peptide WO 2005/087800 PCT/KR2005/000784 CDS 5 (D..C204) 4 gtc gac cgt aat gtt cct cct ate ttc aat gat gtt tat tgg att gca 48 Val Asp Arg Asn Val Pro Pro lie Phe Asn Asp Val Tyr Trp lie Ala 10 1 5 10 15 ttc etc gac cgt aat gtt cct cct ate ttc aat gat gtt tat tgg att 96 Phe Leu Asp Arg Asn Val Pro Pro lie Phe Asn Asp Val Tyr Trp lie 20 25 30 15 gca ttc etc gac cgt aat gtt cct cct ate ttc aat gat gtt tat tgg 144 Ala Phe Leu Asp Arg Asn Val Pro Pro He Phe Asn Asp Val Tyr Trp 35 40 45 20 att gca ttc etc gac cgt aat gtt cct cct ate ttc aat gat gtt tat 192 lie Ala Phe Leu Asp Arg Asn Val Pro Pro De Phe Asn Asp Val Tyr 50 55 60 tgg att gca ttc 204 25 Trp De Ala Phe 65 5 30 68 WO 2005/087800 PCT/KR2005/000784 PPT Artificial Sequence 5 5 Val Asp Arg Asn Val Pro Pro He Phe Asn Asp Val Tyr Trp He Ala 15 10 15 Phe Leu Asp Arg Asn Val Pro Pro Be Phe Asn Asp Val Tyr Trp He 10 20 25 30 Ala Phe Leu Asp Arg Asn Val Pro Pro He Phe Asn Asp Val Tyr Trp 35 40 45 15 He Ala Phe Leu Asp Arg Asn Val Pro Pro He Phe Asn Asp Val Tyr 50 55 60 Trp He Ala Phe 65 6 180 DNA 25 Hepatitis B virus CDS (D..C177) 30 Hepatitis B virus preS2 WO 2005/087800 PCT7KR2005/000784 terminator (178),(180) 5 6 atg cag tgg aac tec ace aca ttc cac caa get ctg eta gat ccc aga 48 Met Gin Trp Asn Ser Thr Thr Phe His Gin Ala Leu Leu Asp Pro Arg 15 10 15 10 gtg agg ggc eta tat ttt cct get ggt ggc tec agt tec gga aca gta 96 Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly Ser Ser Ser Gly Thr Val 20 25 30 15 aac cct gtt ccg act act gee tea ccc ata teg tea ate ttc teg agg 144 Asn Pro Val Pro Thr Thr Ala Ser Pro He Ser Ser lie Phe Ser Arg 35 40 45 act ggg gac cct gca ccg aac etc gag egg tea taa 180 20 Thr Gly Asp Pro Ala Pro Asn Leu Glu Arg Ser 50 55 7 25 59 PRT Hepatitis B virus 7 3 0 Met Gin Trp Asn Ser Thr Thr Phe His Gin Ala Leu Leu Asp Pro Arg WO 2005/087800 PCT/KR2005/000784 1 5 10 15 Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly Ser Ser Ser Gly Thr Val 20 25 30 5 • Asn Pro Val Pro Thr Thr Ala Ser Pro fle Ser Ser lie Phe Ser Arg 35 40 45 Thr Gly Asp Pro Ala Pro Asn Leu Glu Arg Ser 10 50 55 8 444 15 DNA Artificial Sequence DNA sequence for hybride polypeptide 20 CDS (1)..(441) 25 terminator (441)..(444) 30 8 WO 2005/087800 PCT7KR2005/000784 atg aga gga teg cat cac cat cac cat cac gga tec gat gat gat gac 48 Met Arg Gly Ser His His His His His His Gly Ser Asp Asp Asp Asp 1 5 10 15 5 aag ate gtc gac cgt aat gtt cct cct ate ttc aat gat gtt tat tgg 96 Lys lie Val Asp Arg Asn Val Pro Pro De Phe Asn Asp Val Tyr Trp 20 25 30 att gca ttc etc gac cgt aat gtt cct cct ate ttc aat gat gtt tat 144 10 lie Ala Phe Leu Asp Arg Asn Val Pro Pro lie Phe Asn Asp Val Tyr 35 40 45 tgg att gca ttc etc gac cgt aat gtt cct cct ate ttc aat gat gtt 192 Trp lie Ala Phe Leu Asp Arg Asn Val Pro Pro lie Phe Asn Asp Val 15 50 55 60 tat tgg att gca ttc etc gac cgt aat gtt cct cct ate ttc aat gat 240 Tyr Trp Be Ala Phe Leu Asp Arg Asn Val Pro Pro De Phe Asn Asp 65 70 75 80 .20 gtt tat tgg att gca ttc etc gac atg cag tgg aac tec ace aca ttc 288 Val Tyr Trp lie Ala Phe Leu Asp Met Gin Trp Asn Ser Thr Thr Phe 85 90 95 2 5 cac caa get ctg eta gat ccc aga gtg agg ggc eta tat ttt cct get 336 His Gin Ala Leu Leu Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala 100 105 110 ggt ggc tec agt tec gga aca gta aac cct gtt ccg act act gee tea 384 30 Gly Gly Ser Ser Ser Gly Thr Val Asn Pro Val Pro Thr Thr Ala Ser WO 2005/087800 PCT/KR2005/000784 115 120 125 ccc ata teg tea ate ttc teg agg act ggg gac cct gca ccg aac etc 432 Pro lie Ser Ser De Phe Ser Arg Thr Gly Asp Pro Ala Pro Asn Leu 5 • 130 135 140 gag egg tea taa GluArgSer 145 10 9 147 PRT 15 Artificial Sequence 444 20 9 Met Arg Gly Ser His His His His His His Gly Ser Asp Asp Asp Asp 1 5 10 15 Lys De Val Asp Arg Asn Val Pro Pro De Phe Asn Asp Val Tyr Trp 20 25 30 De Ala Phe Leu Asp Arg Asn Val Pro Pro De Phe Asn Asp Val Tyr 25 35 40 45 Trp De Ala Phe Leu Asp Arg Asn Val Pro Pro De Phe Asn Asp Val 50 55 60 30 Tyr Trp lie Ala Phe Leu Asp Arg Asn Val Pro Pro De Phe Asn Asp WO 2005/087800 PCT/KR2005/000784 65 70 75 80 Val Tyr Trp He Ala Phe Leu Asp Met Gin Trp Asn Ser Thr Thr Phe 85 90 95 5 His Gin Ala Leu Leu Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala 100- 105 110 Gly Gly Ser Ser Ser Gly Thr Val Asn Pro Val Pro Thr Thr Ala Ser 10 115 120 125 Pro lie Ser Ser lie Phe Ser Arg Thr Gly Asp Pro Ala Pro Asn Leu 130 135 140 15 Glu Arg Ser 145 10 20 432 DNA Artificial Sequence 25 DNA sequence for PTB14 CDS 30 (1)..(429) WO 2005/087800 PCT/KR2005/000784 10 atg aga gga teg cat cac cat cac cat cac gga tec gat gat gat gac 48 Met Arg Gly Ser His His His His His His Gly Ser Asp Asp Asp Asp 5 1 5 10 15 aag ate gtc gac atg cag tgg aac tec ace aca ttc cac caa get ctg 96 Lys He Val Asp Met Gin Trp Asn Ser Thr Thr Phe His Gin Ala Leu 20 25 30 10 eta gat ccc aga gtg agg ggc eta tat ttt cct get ggt ggc tec agt 144 Leu Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly Ser Ser 35 40 45 15 tec gga aca gta aac cct gtt ccg act act gec tea ccc ata teg tea 192 Ser Gly Thr Val Asn Pro Val Pro Thr Thr Ala Ser Pro He Ser Ser 50 55 60 ate ttc teg aag act ggg gac cct gca ccg aac etc gac cgt aat gtt 240 20 lie Phe Ser Lys Thr Gly Asp Pro Ala Pro Asn Leu Asp Arg Asn VEII 65 70 75 80 cct cct ate ttc aat gat gtt tat tgg att gca ttc etc gac cgt aat 288 Pro Pro De Phe Asn Asp Val Tyr Trp Be Ala Phe Leu Asp Arg Asn 25 85 90 95 gtt cct cct ate ttc aat gat gtt tat tgg att gca ttc etc gac cgt 336 Val Pro Pro lie Phe Asn Asp Val Tyr Trp De Ala Phe Leu Asp Arg 100 105 110 WO 2005/087800 PCT/KR2005/000784 aat gtt cct cct ate ttc aat gat gtt tat tgg att gca ttc etc gac 384 - Asn Val Pro Pro lie Phe Asn Asp Val Tyr Trp lie Ala Phe Leu Asp 115 120 125 5 cgt aat gtt cct cct ate ttc aat gat gtt tat tgg att gca ttc t 430 Arg Asn Val Pro Pro lie Phe Asn Asp Val Tyr Trp He Ala Phe 130 135 140 aa 432 10 11 143 PRT 15 Artificial Sequence 11 Met Arg Gly Ser His His His His His His Gly Ser Asp Asp Asp Asp 15 10 15 20 Lys lie Val Asp Met Gin Trp Asn Ser Thr Thr Phe His Gin Ala Leu 20 25 30 Leu Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly Ser Ser 25 35 40 45 Ser Gly Thr Val Asn Pro Val Pro Thr Thr Ala Ser Pro lie Ser Ser 50 55 60 30 lie Phe Ser Lys Thr Gly Asp Pro Ala Pro Asn Leu Asp Arg Asn Val WO 2005/087800 PC17KR2005/000784 65 70 75 80 Pro Pro lie Phe Asn Asp Val Tyr Trp lie Ala Phe Leu Asp Arg Asn , 85 90 95 5 Val Pro Pro De Phe Asn Asp Val Tyr Trp De Ala Phe Leu Asp Arg 100 105 110 Asn Val Pro Pro De Phe Asn Asp Val Tyr Trp De Ala Phe Leu Asp 10 115 120 125 Arg Asn Val Pro Pro De Phe Asn Asp Val Tyr Trp De Ala Phe 130 135 140 15 WO 2005/087800 PCT/KR2005/000784 Claims 1. An immunogenic hybrid polypeptide, in which a C- terminus of a peptide comprising an amino acid sequence selected from SEQ ID Nos. 1, 2 and 3 is fused to an N- 5 . terminus of a helper T cell epitope. 2. The polypeptide according to claim 1, wherein the peptide is prepared by linking two to eight copies of the amino acid sequence selected from SEQ ID Nos. 1, 2 and 3. 3. The polypeptide according to claim 2, wherein the 10 peptide is prepared by linking four copies of the amino acid sequence selected from SEQ ID Nos. 1, 2 and 3. 4. The polypeptide according to claim 3, wherein the peptide is prepared by linking four copies of the amino acid sequence of SEQ ID No. 1. 15 5. The polypeptide according to claim 4, wherein the peptide is a polypeptide having an amino acid sequence of SEQ ID No. 5.. 6. The polypeptide according to claim 1, wherein the helper T cell epitope is selected from the group consisting 20 of hepatitis B surface antigen helper T cell epitopes, WO 2005/087800 PCT7KR2005/000784 Chlamydia trachomitis major outer membrane protein helper T cell epitopes, Plasmodium falciparum circumsporozoite helper T cell epitopes, Escherichia coli TraT helper T cell epitopes, Tetanus toxoid helper T cell epitopes, diphtheria toxoid helper T cell epitopes, Schistosoma mansoni triose phosphate isomerase helper T cell epitopes, measles virus F protein helper T cell epitopes, and rabies virus helper T cell epitopes. 7. The polypeptide according to claim 6, wherein the T cell epitope is a helper T cell epitope of the hepatitis B surface antigen. 8. The polypeptide according to claim 7, wherein the T cell epitope is a preS2 helper T cell epitope of the hepatitis B surface antigen. 9. The polypeptide according to claim 8, wherein the T cell epitope has an amino acid sequence of SEQ ID No. 7. 10. The polypeptide according to claim 1, which has an amino acid sequence of SEQ ID No. 9. 11. A vaccine for preventing or treating obesity, comprising the polypeptide of any one of claims 1 to 10. WO 2005/087800 PCT/KR2005/000784 12. A recombinant vector comprising a gene encoding the polypeptide of any one of claims 1 to 10. 13. The recombinant vector according to claim 12, which is pBl4T (KCCM-10562). 14. A host cell transformed with the recombinant vector of claim 12. 15. A method of preparing the polypeptide of claim 1 by culturing the host transformed with the recombinant vector cell of claim 12. 16. An immunogenic hybrid polypeptide and/or a vaccine for preventing and/or a recombinant vector and/or a host cell and/or a method of preparing substantially as herein described with reference to the given examples and accompanying drawings. Dated this the 25th day m^ of September, 2006. [VIBHASHUKLA] OF K & S PARTNERS AGENT FOR THE APPLICANT(S) ABSTRACT Disclosed is an immunogenic hybrid polypeptide comprising a mimetic peptide of a B cell epitope of apolipoprotein B-100 and a helper T cell epitope, the mimetic .peptide being fused at its C-terminus to an N-terminus of the helper T cell epitope. Also disclosed is a vaccine composition for preventing or treating obesity comprising the polypeptide.

Documents:

1147-MUMNP-2006-ABSTRACT 12-6-2008.pdf

1147-mumnp-2006-abstract(12-6-2008).doc

1147-MUMNP-2006-ABSTRACT(26-9-2006).pdf

1147-MUMNP-2006-ABSTRACT(AMENDED)-(12-6-2008).pdf

1147-MUMNP-2006-ABSTRACT(GRANTED)-(22-12-2008).pdf

1147-mumnp-2006-abstract.doc

1147-mumnp-2006-abstract.pdf

1147-MUMNP-2006-CALIMS(AMENDED)-(12-6-2008).pdf

1147-MUMNP-2006-CANCELLED PAGES 12-6-2008.pdf

1147-MUMNP-2006-CANCELLED PAGES(12-6-2008).pdf

1147-MUMNP-2006-CLAIMS 12-6-2008.pdf

1147-MUMNP-2006-CLAIMS(26-9-2006).pdf

1147-mumnp-2006-claims(granted)-(12-6-2008).doc

1147-MUMNP-2006-CLAIMS(GRANTED)-(22-12-2008).pdf

1147-mumnp-2006-claims.doc

1147-mumnp-2006-claims.pdf

1147-mumnp-2006-correspondance-received.pdf

1147-MUMNP-2006-CORRESPONDENCE 12-6-2008.pdf

1147-MUMNP-2006-CORRESPONDENCE 13-6-2008.pdf

1147-MUMNP-2006-CORRESPONDENCE(12-6-2008).pdf

1147-MUMNP-2006-CORRESPONDENCE(IPO)-(25-2-2009).pdf

1147-mumnp-2006-description (complete).pdf

1147-MUMNP-2006-DESCRIPTION(COMPLETE) 12-6-2008.pdf

1147-MUMNP-2006-DESCRIPTION(COMPLETE)-(26-9-2006).pdf

1147-MUMNP-2006-DESCRIPTION(GRANTED)-(22-12-2008).pdf

1147-MUMNP-2006-DRAWING 12-6-2008.pdf

1147-MUMNP-2006-DRAWING(26-9-2006).pdf

1147-MUMNP-2006-DRAWING(AMENDED)-(12-6-2008).pdf

1147-MUMNP-2006-DRAWING(GRANTED)-(22-12-2008).pdf

1147-mumnp-2006-drawings.pdf

1147-MUMNP-2006-FORM 2(GRANTED)-(22-12-2008).pdf

1147-MUMNP-2006-FORM 1 12-6-2008.pdf

1147-MUMNP-2006-FORM 1(12-6-2008).pdf

1147-MUMNP-2006-FORM 13(26-6-2008).pdf

1147-MUMNP-2006-FORM 18(26-9-2006).pdf

1147-mumnp-2006-form 2 12-6-2008.pdf

1147-MUMNP-2006-FORM 2(COMPLETE)-(26-9-2006).pdf

1147-mumnp-2006-form 2(granted)-(12-6-2008).doc

1147-MUMNP-2006-FORM 2(GRANTED)-(22-12-2008).pdf

1147-MUMNP-2006-FORM 2(TITLE PAGE) 12-6-2008.pdf

1147-MUMNP-2006-FORM 2(TITLE PAGE)-(COMPLETE)-(26-9-2006).pdf

1147-MUMNP-2006-FORM 2(TITLE PAGE)-(GRANTED)-(22-12-2008).pdf

1147-MUMNP-2006-FORM 26(15-12-2006).pdf

1147-MUMNP-2006-FORM 3 12-6-2008.pdf

1147-MUMNP-2006-FORM 3 13-6-2008.pdf

1147-MUMNP-2006-FORM 3(12-6-2008).pdf

1147-MUMNP-2006-FORM 3(26-9-2006).pdf

1147-mumnp-2006-form-1.pdf

1147-mumnp-2006-form-2.doc

1147-mumnp-2006-form-2.pdf

1147-mumnp-2006-form-3.pdf

1147-mumnp-2006-form-5.pdf

1147-mumnp-2006-form-pct-ib-304.pdf

1147-mumnp-2006-form-pct-ib-311.pdf

1147-mumnp-2006-form-pct-isa-210.pdf

1147-mumnp-2006-form-pct-isa-237.pdf

1147-MUMNP-2006-PCT OTHER DOCUMENT 12-6-2008.pdf

1147-MUMNP-2006-PETITION UNDER RULE 137 12-6-2008.pdf

1147-MUMNP-2006-POWER OF ATTORNEY 12-6-2008.pdf

1147-MUMNP-2006-SPECIFICATION(AMENDED)-(12-6-2008).pdf

1147-MUMNP-2006-WO INTERNATIONAL PUBLICATION REPORT(26-9-2006).pdf

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