RU2830870C1 - Stable vaccine preparation from virus-like particles of human papillomavirus - Google Patents

Abstract

FIELD: biotechnology; medicine.

SUBSTANCE: invention relates to medical biotechnology. Presented is a stable preparation of a polyvalent vaccine of human papillomavirus virus-like particles for preventing diseases or infections associated with HPV. Stable preparation contains: (a) a plurality of virus-like particles of human papillomavirus, where the concentration of virus-like particles of papillomavirus of any particular type included in the polyvalent virus-like particles of papillomavirus is from 40 mcg/ml to 120 mcg/ml; (b) an aluminium phosphate adjuvant; (c) a histidine buffer with concentration of 10 mM to 26 mM; (d) an osmotic pressure regulator, which is sodium chloride with concentration of 150 mM to 320 mM; and, optionally, (e) surfactant, which is polysorbate 80 with concentration of not more than 0.3 mg/ml, wherein said virus-like particles of human papillomavirus are selected from virus-like particles of HPV formed by HPV type L1 proteins 6, 11, 16, 18, 31, 33, 45, 52 and 58; and one or more HPV virus-like particles formed by L1 proteins of other HPV pathogen types selected from HPV types 35, 39, 51, 56 and 59, wherein said virus-like human papillomavirus particles are adsorbed on an adjuvant. Disclosed is a method for preventing an HPV-associated disease or infection, comprising administering to a subject a polyvalent vaccine of human papillomavirus virus-like particles, as well as use of said preparation for preparing a vaccine for preventing an HPV-associated disease or infection.

EFFECT: preparation can increase the stability of the vaccine and prolonging the action of the vaccine in an aqueous preparation.

17 cl, 17 tbl, 8 dwg, 6 ex

Description

CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] This application claims the benefit of Chinese Patent Application No. 202110049777.7, filed on January 14, 2021, the entire contents of which are incorporated herein by reference.

AREA OF TECHNOLOGY

[0002] The present invention relates to the field of biological pharmaceutical preparations, in particular to a stable vaccine preparation from virus-like particles of human papillomavirus.

LEVEL OF TECHNOLOGY

[0003] Cervical cancer is one of the most common malignancies in women, with approximately 500,000 new patients worldwide each year, and the incidence rate is the second highest among tumors in women. More than 95% of cervical cancer cases are associated with human papillomavirus (HPV). In addition to being the direct cause of cervical cancer, HPV is also strongly associated with bronchogenic cancer, rectal cancer, oral cancer, and skin cancer. In addition, HPV is also the main pathogenic factor causing warts on the skin and mucous membranes.

[0004] At present, more than 100 types of HPV have been discovered, and different types of HPV can cause different diseases. According to its close relationship with cervical cancer, HPV can be divided into high-risk type, suspected carcinogenic type, and low-risk type. High-risk type and suspected carcinogenic type can cause cancer such as cervical cancer; High-risk types include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Types with suspected carcinogenicity include types 26, 53, 66, 68, 73, and 82. Low-risk types are mainly associated with genital warts, genital condylomata, and other diseases and include types 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89. HPV types 6, 11, and 16 were the subtypes with the highest detection rates in patients with genital lesions.

[0005] The HPV vaccine is an effective way to stop human papillomavirus infection. The virus-like particle (VLP) vaccine is the preferred form of vaccine among many vaccine forms. However, the HPV-based HPV vaccine is type-specific, meaning it only provides strong protection against the HPV types present in the HPV vaccine. Multivalent HPV vaccines need to be developed to provide broad protection.

[0006] However, prior to administration, the human papillomavirus vaccine formulation undergoes a storage and transportation process during which the antigen undergoes physical and chemical degradation, and these instabilities may reduce the immunogenicity and/or safety of the antigen, and thus there is a need for a stable formulation to ensure that the antigen still retains immunogenicity and safety immediately prior to administration while still meeting prophylactic purposes.

BRIEF DESCRIPTION OF THE PRESENT INVENTION

[0007] In one aspect, the present invention provides a stable formulation of a multivalent human papillomavirus virus-like particle vaccine for the prevention of HPV-associated diseases or infections, comprising a plurality of human papillomavirus virus-like particles adsorbed onto an adjuvant; as well as physiologically acceptable concentrations of a buffer, an osmotic pressure regulator, and optionally a surfactant.

[0008] In this case, the virus-like particles of human papillomavirus are selected from virus-like particles of HPV assembled from L1 proteins of HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58, respectively; and one or more virus-like particles of HPV assembled from L1 proteins of other pathogenic types of HPV.

[0009] In one embodiment,

the buffer is selected from one or more of a citric acid buffer, an acetic acid buffer, or a histidine buffer;

the osmotic pressure regulator is selected from one or more of sodium chloride, sodium phosphate or sodium sulfate;

the surfactant is a polyethoxyether, preferably polysorbate 80;

the adjuvant is selected from one or more of aluminum hydroxyphosphate (AlPO ₄ ), amorphous aluminum hydroxyphosphate sulfate (AAHS) or aluminum hydroxide (Al(OH) ₃ ), preferably aluminum hydroxyphosphate (AlPO ₄ ).

[0010] In one embodiment,

(a) the total concentration of virus-like particles of papillomaviruses of all types ranges from 40 μg/ml to 740 μg/ml;

(b) the buffer concentration is from 10 mM to 26 mM, preferably 10 mM, 18 mM or 26 mM;

(c) the concentration of the osmotic pressure regulator is from 150 mM to 320 mM, preferably 150 mM or 320 mM;

(d) the concentration of surfactant is from 0 to 0.02% by weight;

(d) the concentration of adjuvant is about 1.0 mg/ml;

(e) the pH of the composition is 5.9-6.5, preferably 5.9, 6.2 or 6.5.

[0011] In one embodiment, the concentration of any individual type of papillomavirus virus-like particles included in the polyvalent papillomavirus virus-like particles is from 40 μg/ml to 120 μg/ml.

[0012] In one embodiment, the preparation contains a total of 0.74 mg/ml of virus-like particles of papillomaviruses of all types, 1.0 mg/ml of aluminum phosphate adjuvant, 18 mM histidine buffer, 320 mM sodium chloride, the pH of the preparation solution is 6.2; optionally, polysorbate 80 at a concentration of no more than 0.3 mg/ml.

[0013] In one embodiment, one or more other pathogenic HPV types are selected from HPV types 35, 39, 51, 56, and 59.

[0014] In one embodiment, at least one of the HPV virus-like particles is a chimeric HPV virus-like particle comprising a chimeric HPV L1 protein; wherein said chimeric HPV L1 protein comprises, from its N-terminus to its C-terminus:

a. An N-terminal fragment obtained from the L1 protein of human papillomavirus type 1, wherein the N-terminal fragment retains the immunogenicity of the L1 protein of that type, wherein the human papillomavirus type 1 is selected from HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58, and one or more other pathogenic HPV types; and

b. A C-terminal fragment derived from the L1 protein of human papillomavirus type 2, which has better expression and solubility characteristics compared to L1 proteins of other types,

Moreover, such a chimeric HPV L1 protein has the immunogenicity of the L1 protein of the first papillomavirus.

[0015] In one embodiment, said N-terminal fragment is a fragment obtained by truncating the C-terminus of the natural sequence of said human papillomavirus type I L1 protein at any amino acid position within its α5 region, and a fragment having at least 98% identity thereto; and said C-terminal fragment is a fragment obtained by truncating the N-terminus of the natural sequence of said human papillomavirus type II L1 protein at any amino acid position within its α5 region and functional variants resulting from further mutations, deletions and/or additions to this fragment.

[0016] In one embodiment, the C-terminal fragment comprises one or more nuclear localization sequences.

[0017] In one embodiment, wherein the L1 protein of the first papillomavirus type is selected from HPV types 6, 11, 16, 18, 31, 35, 39, 45, 51, 52, 56 or 58; preferably, its natural sequence is an amino acid sequence encoded by the coding gene set forth in SEQ ID No: 30, SEQ ID No: 31, SEQ ID No: 32, SEQ ID No: 33, SEQ ID No: 34, SEQ ID No: 35, SEQ ID No: 36, SEQ ID No: 37, SEQ ID No: 38, SEQ ID No: 39, SEQ ID No: 40, or SEQ ID No: 41, respectively;

the L1 protein of human papillomavirus type 2 is selected from the L1 protein of HPV types 16, 28, 33, 59 or 68;

more preferably, the L1 protein of the human papillomavirus type 2 is selected from the L1 protein of HPV type 33 or PVR type 59.

[0018] In one embodiment, said C-terminal fragment is SEQ ID No: 1; or a fragment thereof having a length of m1 amino acids, preferably a fragment encompassing amino acids 1-m1 of SEQ ID No: 1; wherein m1 is an integer from 8 to 26; or said C-terminal fragment is SEQ ID No: 2; or a fragment thereof having a length of m2 amino acids, preferably a fragment encompassing amino acids 1-m2 of SEQ ID No: 2; wherein m2 is an integer from 13 to 31.

[0019] In one embodiment, said C-terminal fragment is SEQ ID No: 3; or a fragment thereof having a length of n amino acids, preferably a fragment spanning amino acids 1-n of SEQ ID No: 3; wherein n is an integer from 16 to 38.

[0020] In one embodiment, said N-terminal fragment of the HPV type 6 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to a fragment obtained by truncating the C-terminus of the sequence presented in SEQ ID No: 4, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 11 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 5, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 16 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 6, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 18 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 7, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 31 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 8, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 35 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 9, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 39 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 10, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 45 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 11, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 51 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 12, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 52 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 13, at any amino acid position within its α5 region;

said N-terminal fragment of the HPV type 56 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to a fragment obtained by truncating the C-terminus of the sequence presented in SEQ ID No: 14, at any amino acid position within its α5 region; and

said N-terminal fragment of the HPV type 58 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 15, at any amino acid position within its α5 region.

[0021] In one embodiment, the C-terminus of the N-terminal fragment is connected directly to the N-terminus of the C-terminal fragment or connected via a linker.

[0022] In one embodiment, when the C-terminus of said N-terminal fragment is connected to the N-terminus of said C-terminal fragment, the contiguous amino acid sequence RKFL is present within a range of plus or minus 4 amino acid positions of the splice site,

preferably, the contiguous amino acid sequence LGRKFL is present within a range of plus or minus 6 amino acid positions of the splice site.

[0023] In one embodiment, the chimeric HPV L1 proteins of types 6, 11, 16, 18, 31, 35, 39, 45, 51, 52, 56, and 58 have 98%, 98.5%, 99%, 99.5%, or 100% identity to SEQ ID No: 16, SEQ ID No: 17, SEQ ID No: 18, SEQ ID No: 19, SEQ ID No: 20, SEQ ID No: 21, SEQ ID No: 22, SEQ ID No: 23, SEQ ID No: 24, SEQ ID No: 25, SEQ ID No: 26, and SEQ ID No: 27, respectively; and the HPV type 33 L1 protein and the HPV type 59 L1 protein have 98%, 98.5%, 99%, 99.5%, or 100% identity to SEQ ID No:28 and SEQ ID No:29, respectively.

[0024] In one embodiment, said preparation comprises chimeric HPV L1 proteins of types 6, 11, 16, 18, 31, 35, 39, 45, 51, 52, 56 and 58 having the amino acid sequences shown in SEQ ID No:16, SEQ ID No:17, SEQ ID No:18, SEQ ID No:19, SEQ ID No:20, SEQ ID No:21, SEQ ID No:22, SEQ ID No:23, SEQ ID No:24, SEQ ID No:25, SEQ ID No:26 and SEQ ID No:27, respectively; and

and the HPV type 33 L1 protein and the HPV type 59 L1 protein have the amino acid sequences shown in SEQ ID No: 28 and SEQ ID No: 29, respectively.

[0025] In one aspect, the present invention relates to a method for preventing a disease or infection associated with HPV, comprising administering to a subject a stable preparation of a multivalent vaccine of human papillomavirus virus-like particles. Prevention can be considered as treatment, and the two terms are used interchangeably. In one embodiment, the subject is a human.

[0026] In one aspect, the formulation is stable at 2 to 8 °C for at least 24 months and at 25 °C for at least 16 weeks.

[0027] In one aspect, the present invention provides the use of a vaccine preparation of human papillomavirus virus-like particles for the preparation of a vaccine for the prevention of HPV-associated diseases or infections.

BRIEF DESCRIPTION OF DRAWINGS

[0028] Fig. 1 shows the results of the adsorption degree test of each drug sample in Example 1.

[0029] Fig. 2 shows the result of the analysis of the antigen content in each sample of the preparation in Example 1. T0:37 °C, week 0; 37 °C_1W: 37 °C, week 1; 37 °C_2 W: 37 °C, week 2; 37 °C_4 W: 37 °C week 4.

[0030] Fig. 3 shows the results of the adsorption degree test of each drug sample in Example 2.

[0031] Fig. 4 shows the result of the analysis of the antigen content in each sample of the preparation in Example 2. T0:37 °C, week 0; 37 °C_1W: 37 °C, week 1; 37 °C_2 W: 37 °C, week 2; 37 °C_4 W: 37 °C week 4.

[0032] Fig. 5 shows the results of the adsorption degree test of each drug sample in Example 3.

[0033] Fig. 6 shows the result of the analysis of the antigen content in each sample of the preparation in Example 3. T0:37 °C, week 0; 37 °C_1W: 37 °C, week 1; 37 °C_2 W: 37 °C, week 2; 37 °C_4 W: 37 °C week 4.

[0034] Fig. 7 shows the results of the adsorption degree test of each drug sample in Example 4.

[0035] Fig. 8 shows the result of the analysis of the antigen content in each sample of the preparation in Example 4. T0:37 °C, week 0; 37 °C_1W: 37 °C, week 1; 37 °C_2 W: 37 °C, week 2; 37 °C_4 W: 37 °C week 4.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

[0036] The present invention provides a stable preparation of a human papillomavirus vaccine, solves the problem of antibody stability during storage and transportation processes, and ensures that the pre-dosed antigen still has immunogenicity and safety that satisfy the purposes of prevention.

[0037] The term "preparation" refers to a composition that maintains the biological activity of the active component in an effective manner and does not contain other components that are unacceptably toxic to the subject. Such preparations are sterile. The term "sterile" refers to the absence of living bacteria or the absence or absence of substantially all living microorganisms and their spores.

[0038] As used herein, the term "stable" in relation to a preparation refers to a preparation in which the active ingredient substantially retains its physical and/or chemical stability and/or biological activity after storage. Preferably, the preparation substantially retains its physical and chemical stability, as well as its biological activity after storage.

[0039] The terms "patient" or "subject" are used interchangeably and refer to any mammal suffering from a condition or disease in accordance with the present invention. Preferably, it is a human.

[0040] As used herein, the term "physiologically acceptable" means a concentration or ionic strength of a buffer, excipient, or salt that renders the preparation biocompatible with an immunized target host, such as a human.

[0041] The stable preparation according to the present invention contains human papillomavirus virus-like particles, a buffer, an osmotic pressure regulator and an aluminum-based adjuvant.

[0042] The term "comprising" means that in addition to the components mentioned, additional components may be included.

[0043] As used in this description and in the appended claims, the singular forms "said" also include plural forms unless the context clearly dictates otherwise.

[0044] As used herein, the term "buffer" refers to a buffer solution that resists a change in pH due to its conjugate acid-base pair. In one embodiment of the present invention, a histidine buffer is used, and the pH of the drug solution is preferably from about 5.9 to 6.5, more preferably 6.2.

[0045] As used herein, the term "surfactant" refers to a surface-active agent, and in one embodiment, the surfactant herein is polysorbate 80.

[0046] The term "osmotic pressure regulator" means a pharmaceutically acceptable osmotic pressure regulator. Suitable osmotic pressure regulators include, but are not limited to, salts, and in one embodiment of the present invention are sodium chloride (NaCl) at a concentration of about 150 mM to 320 mM.

[0047] The term "adjuvant" refers to a compound or mixture that enhances an immune response. In particular, the vaccine of the present invention may comprise an adjuvant. Adjuvants used in the present invention are selected from one or more of aluminum hydroxyphosphate (AlPO ₄ ), amorphous aluminum hydroxyphosphate sulfate (AAHS) or aluminum hydroxide (Al(OH) ₃ ), preferably aluminum hydroxyphosphate (AlPO ₄ ).

[0048] The "stability" of a protein after storage at a selected temperature for a selected period of time can be assessed qualitatively and/or quantitatively in several different ways. In an embodiment of the present invention, an enzyme-linked immunosorbent assay (ELISA) was used to measure the content of active antigen binding to the recombinant human papillomavirus neutralizing antibody, and the ratio of the content of active antigen at each time point to T0 was used to compare the stability of the corresponding preparation; the content of antigen not adsorbed to the aluminum phosphate adjuvant was determined by enzyme-linked immunosorbent assay (ELISA) after centrifugation and then the degree of absorption was calculated; the EC ₅₀ of the human papillomavirus vaccine preparation and the positive control to the recombinant human papillomavirus neutralizing antibody was determined, respectively, the ratio of the EC ₅₀ of the vaccine preparation to the positive control was calculated, thereby determining the relative activity of the vaccine in vitro .

[0049] The term "immunogenicity" refers to the ability of a substance, such as a protein or polypeptide, to stimulate an immune response, i.e., to stimulate the production of antibodies, particularly responses that elicit humoral or stimulated cell-mediated responses.

[0050] The term "HPV" or "HPV virus" refers to papillomaviruses of the Papillomaviridae family, which is a naked DNA virus with a double-stranded closed-loop DNA genome of approximately 8 kbp, which can be generally divided into three regions: ① an early region (E) containing six open reading frames encoding nonstructural proteins related to E1, viral replication, transcription and transformation proteins E2, E4-E7, as well as open reading frames E3 and E8; ② a late region (L) containing a reading frame encoding the major capsid protein L1 and the minor capsid protein L2; ③ a long regulatory region (LCR) does not encode any protein, but has an origin of replication and multiple transcription factor binding sites.

[0051] The terms "HPV L1 protein" and "HPV L2 protein" refer to proteins encoded by the late region (L) of the HPV genome and synthesized during the mid to late period of the HPV infection cycle. The L1 protein is the major capsid protein and has a molecular weight of 55-60 kDa. The L2 protein is a minor capsid protein. Seventy-two L1 pentamers form the envelope of the icosahedral HPV virus particle, enveloping the closed double-stranded DNA microchromosome. The L2 protein is located on the inner envelope of the L1 protein.

[0052] The term "virus-like particle" is a hollow particle containing one or more structural proteins of a virus without viral nucleic acid.

[0053] The term "the concentration of virus-like particles of any single type of human papillomavirus" refers to the content of virus-like particles of any single type of human papillomavirus in the preparation, and the term "the total concentration of virus-like particles of all types of human papillomavirus" is the sum of the concentrations of virus-like particles of each single type of human papillomavirus included in the preparation.

[0054] In one embodiment of the present invention, a multivalent immunogenic composition of human papillomavirus is used, as described in patent application PCT/CN2020/102601, filed July 17, 2020, wherein the application PCT/CN2020/102601 is incorporated by reference into the present description and claims in its entirety.

[0055] In the most preferred embodiment of the present invention, the preparation contains 0.74 mg/ml of papillomavirus virus-like particles, 1.0 mg/ml of aluminum phosphate adjuvant, 18 mM histidine buffer, 320 mM sodium chloride, and pH 6.2. The vaccine contains polysorbate 80 at a concentration of no more than 0.3 mg/ml due to residues formed during preparation. The preparation has good stability and can be stably stored at a temperature of 2 to 8 °C for at least 24 months and at 25 °C for at least 16 weeks.

[0056] The preparations according to the present invention may be provided in liquid form or may be provided in lyophilized form. The lyophilized preparation may be reconstituted prior to administration.

EXAMPLES

[0057] The present invention will be more fully understood with reference to the following examples. However, they should not be construed as limiting the scope of the present invention. All cited documents, patents and patent applications are incorporated herein by reference in their entirety.

[0058] In the examples below, the preparation, characterization, and identification of the efficacy of the various types of human papillomavirus virus-like particles used are described in patent application PCT/CN2020/102601, filed July 17, 2020.

[0059] In the following examples, the following detection method was used:

[0060] 1) Antigen content analysis (enzyme-linked immunosorbent assay (ELISA)

[0061] The positive control (human papillomavirus virus-like particle, standard, source: SinoCellTech Ltd., chimeric HPV types 6, 16, 18, 31, 35, 30, 45, 51, 52 and 56, chimeric HPV L1 protein and HPV L1 protein type 33 and HPV L1 protein type 59, corresponding to the amino acid sequences of SEQ ID NOs: 16 to 29, respectively, the same as below) and the test sample were completely dissolved using the desorption buffer serving as a positive control and the test sample.

[0062] A recombinant human papillomavirus neutralizing antibody (source: Sino Biological, Inc., as follows) was combined with a solid-phase carrier to form a solid-phase antibody. A positive control and a detection sample were diluted with a sample diluent and then combined with the solid-phase antibody to form a solid-phase antigen-antibody complex; then, an enzyme-labeled antibody and a development substrate were added, and the color of the product was read at a wavelength of 450 nm. A linear regression was constructed for the concentration of a series of positive controls and the corresponding absorbance, the absorbance values of the analyzed sample were substituted into the linear regression equation, and the antigen content of the detected sample was obtained (M. Shank-Retzlaff, F. Wang, T. Morley et al. Correlation between Mouse Potency and In Vitro Relative Potency for Human Papillomavirus Type 16 Virus-Like Particles and Gardasil Vaccine Samples. Human Vaccines, 1:5, 191-197).

[0063] 2) Analysis of the degree of adsorption (enzyme-linked immunosorbent assay (ELISA)

[0064] The recombinant antibody neutralizing human papillomavirus was combined with a solid-phase carrier to form a solid-phase antibody. The detection sample was centrifuged, and the supernatant was taken as the test sample. The positive control and test sample were diluted with sample diluent, respectively, and then combined with the solid-phase antibody to form a solid-phase antigen-antibody complex; then, the enzyme-labeled antibody and the development substrate were added, and the color of the product was read at 450 nm. A linear regression was performed for the concentration of a series of positive controls and the corresponding absorbance, the absorbance values measured with the test sample were substituted into the linear regression equation to obtain the concentration of antigen in the supernatant, and the adsorption rates of the detection sample were calculated according to the following equation (Michael J. Caulfield, Li Shi, Su Wang, et al. Effect of Alternative Aluminum Adjuvants on the Absorption and Immunogenicity of HPV16 L1 VLPs in Mice. Human Vaccines 3:4, 139-146).

[0065] Degree of adsorption (%) = (1 - concentration of antigen in supernatant / concentration of antigen in analyzed sample) %.

[0066] 3) Determination of in vitro relative activity, IVRP (IVRP)

[0067] The positive control (14-valent human papillomavirus vaccine (types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) control product obtained from SinoCellTech Ltd., with the same sequence as the protein sequence in the test sample) and the test sample were completely dissolved using desorption buffer and used as the positive control and test sample. The recombinant human papillomavirus neutralizing antibody was diluted to a final concentration of 2 μg/mL, added to 96-well plates at 100 μL/well, the plates were tapped to mix the samples, and the samples were coated overnight at 4 °C; The plates were washed once with 200 μl/well of wash solution and the ELISA plate was dried. Then, the ELISA plate was blocked with 300 μl/well of blocking solution for one hour at room temperature. The samples were washed twice with 300 μl/well of wash solution and 100 μl of treated control (buffer solution matching the sample to be tested), positive control and sample to be tested were added to each well and incubated for 1 hour at room temperature. After the plates were washed three times with 200 μl/well of wash solution, diluted enzyme-labeled recombinant human papillomavirus neutralizing antibody was added at 100 μl/well. After incubation at room temperature for 1 h, the plates were washed with 200 μl of washing solution per well three times, 200 μl of developing solution per well were added and the plates were placed at room temperature for 20±5 min. The reaction was stopped by adding 50 μl of stop solution per well; the absorbance at 450 nm was determined with a microplate reader. The data were processed using the Origin software or a four-parameter fitting method, taking the concentration of the positive control or test sample as the abscissa and the mean absorbance as the ordinate to obtain the _EC50 of the test sample and positive control, and dividing the _EC50 of the test sample by the _EC50 of the positive control to obtain the relative potency of the test sample in vitro (M. Shank-Retzlaff, F. Wang, T. Morley, et al. Correlation between Mouse Potency and In Vitro Relative Potency for Human Papillomavirus Type 16 Virus-Like Particles and Gardasil Vaccine Samples. Human Vaccines, 1:5, 191-197).

[0068] Example 1: Screening test for surfactant concentration

[0069] The composition of the papillomavirus virus-like particle vaccine preparation according to the present Example is indicated in the following table:

Table 1. Preparations of different concentrations of surfactant Composition number Virus-like particle of papillomavirus Aluminum Phosphate Adjuvant Histidine buffer NaCl Polysorbate 80 pH F1 0.74 mg/ml 1.0 mg/ml 18 mM 320 mm 0.00 wt.% 6.5 F2 0.74 mg/ml 1.0 mg/ml 18 mM 320 mm 0.02 wt.% 6.5

[0070] Method for preparing a vaccine preparation of virus-like particles of papillomavirus:

[0071] A certain amount of HPV type 18 virus-like particles corresponding to the preparation was taken, and then mixed with aluminum phosphate adjuvant and adsorbed overnight at 4 °C so that the pH, the corresponding concentrations of human papillomavirus virus-like particles, aluminum phosphate adjuvant, histidine, sodium chloride and polysorbate 80 in the human papillomavirus virus-like particle vaccine preparation, respectively, met the requirements of Table 1, and dosed it in aliquots. Labeled with corresponding numbers, placed the samples in an incubator at 37 °C and taken out for adsorption rate and antigen content analysis at week 0 and for antigen content analysis at weeks 1, 2 and 4.

[0072] Analytical research method:

[0073] Adsorption rate analysis: The detection principle is that antigens not adsorbed on the aluminum phosphate adjuvant are separated by centrifugation and their content is analyzed to calculate the adsorption rate.

[0074] Antigen content assay: The detection principle is that the content of active antigen capable of binding to the recombinant antibody neutralizing human papillomavirus is measured by ELISA, and the stability of each preparation is compared by comparing the ratio of the content of active antigen at each time point with the T0 point. The higher the ratio, the higher the content of active antigen in the preparation and the better its activity is preserved.

[0075] The test results are shown in Tables 2-3 and Figs. 1-2.

Table 2. Degree of adsorption of the preparation of virus-like particles of HPV18 Number %HPV18 bound to aluminum-based adjuvant F1 99.8 F2 99.9

Table 3. Antigen content in the HPV18 virus-like particle preparation Moment in time Content of HPV HPV18, as a percentage of T0, % F1 F2 T ₀ 100 100 37 °C_1W 87.9 88.2 37 °C_2W 84.8 85.3 37 °C_4W 54.5 55.9

[0076] The test results showed that the adsorption rate of both HPV-like particle vaccine preparations was greater than 99%, and there was no significant difference in the changes in antigen content between F1 and F2, that is, the stabilities of F1 and F2 were comparable.

[0077] Example 2: pH Screening Study

[0078] The composition of the papillomavirus virus-like particle vaccine preparation according to the present example is shown in the following Table:

Table 4. Preparations with different pH Composition number Virus-like particle of papillomavirus Aluminum Phosphate Adjuvant Histidine buffer NaCl Polysorbate 80 pH F1 0.74 mg/ml 1.0 mg/ml 18 mm 320 mm 0.00 wt.% 5.9 F2 0.74 mg/ml 1.0 mg/ml 18 mm 320 mm 0.00 wt.% 6.2 F3 0.74 mg/ml 1.0 mg/ml 18 mm 320 mm 0.00 wt.% 6.5

[0079] Method for preparing a vaccine preparation of virus-like particles of papillomavirus:

[0080] A certain amount of HPV 18 virus-like particles corresponding to the preparation was taken, and then mixed with aluminum phosphate adjuvant and adsorbed overnight at 4 °C so that the pH, the corresponding concentrations of human papillomavirus virus-like particles, aluminum phosphate adjuvant, histidine, sodium chloride and polysorbate 80 in the human papillomavirus virus-like particle vaccine preparation met the requirements of Table 4, dosed it in aliquots. Labeled it with corresponding numbers, placed the samples in an incubator at 37 °C and taken out for adsorption rate and antigen content analysis at week 0, and for antigen content analysis at weeks 1, 2 and 4.

[0081] Analytical research method:

[0082] Adsorption rate analysis: The detection principle is that antigens not adsorbed on the aluminum phosphate adjuvant are obtained by centrifugation and their content is analyzed to calculate the adsorption rate.

[0083] Antigen content assay: The detection principle is that the content of active antigen capable of binding to the recombinant antibody neutralizing human papillomavirus is measured by ELISA, and the stability of each preparation is compared by comparing the ratio of the content of active antigen at each time point with the T0 point. The higher the ratio, the higher the content of active antigen in the preparation and the better the activity is preserved.

[0084] The test results are shown in Tables 5-6 and Figs. 3-4.

Table 5. Degree of adsorption of the preparation of virus-like particles of HPV18 Number %HPV18 bound to aluminum-based adjuvant F1 99.4 F2 99.4 F3 99.8

Table 6. Antigen content in the preparation of HPV18 virus-like particles Moment in time Content of HPV HPV18, as a percentage of T0, % F1 F2 F3 T ₀ 100 100 100 37 °C_1W 93.5 100 87.9 37 °C_2W 87.1 96.6 84.8 37 °C_4W 90.3 82.8 54.5

[0085] The test results showed that the adsorption rate of the three human papillomavirus virus-like particle vaccine preparations was higher than 99%, and the change trends of the antigen content of human papillomavirus virus-like particle vaccines in F1 and F2 were better than that of F3, that is, the stability of F1 and F2 was better than that of F3.

[0086] Example 3: Screening study of osmotic pressure regulator concentration

[0087] The composition of the vaccine preparation of virus-like particles of papillomavirus according to the present example is given in the following Table:

Table 7. Preparations with different concentrations of osmotic pressure regulators Composition number Virus-like particle of papillomavirus Aluminum Phosphate Adjuvant Histidine buffer NaCl Polysorbate 80 pH F1 0.74 mg/ml 1.0 mg/ml 18 mM 320 mM 0.00 wt.% 6.2 F2 0.74 mg/ml 1.0 mg/ml 18 mM 150 mM 0.00 wt.% 6.2

[0088] Method for preparing a vaccine preparation of virus-like particles of papillomavirus:

[0089] A certain amount of HPV 18 virus-like particles corresponding to the preparation was taken, and then mixed with aluminum phosphate adjuvant and adsorbed overnight at 4 °C so that the pH, corresponding concentrations of papillomavirus virus-like particles, aluminum phosphate adjuvant, histidine, sodium chloride and polysorbate 80 in the papillomavirus virus-like particle vaccine preparation met the requirements of Table 7, dosed it in aliquots. Labeled it with corresponding numbers, placed the samples in an incubator at 37 °C and taken out for adsorption rate and antigen content analysis at week 0, and for antigen content analysis at weeks 1, 2 and 4.

[0090] Analytical research method:

[0091] Adsorption rate analysis: The detection principle is that antigens not adsorbed on the aluminum phosphate adjuvant are separated by centrifugation and their content is analyzed to calculate the adsorption rate.

[0092] Antigen content assay: The detection principle is that the content of active antigen capable of binding to the recombinant human papillomavirus neutralizing antibody is measured by ELISA, and the stability of each preparation is compared by comparing the ratio of the content of active antigen at each time point with the T0 time point. The higher the ratio, the higher the content of active antigen in the preparation and the better the activity is preserved.

[0093] The test results are shown in Tables 8-9 and Figs. 5-6.

Table 8. Degree of adsorption of the preparation of virus-like particles of HPV18 Number %HPV18 bound to aluminum-based adjuvant F1 99.4 F2 99.6

Table 9. Antigen content in the preparation of HPV18 virus-like particles Moment in time Content of HPV HPV18, as a percentage of T0, % F1 F2 T ₀ 100 100 37 °C_1W 87.9 88.2 37 °C_2W 84.8 85.3 37 °C_4W 54.5 55.9

[0094] The test results showed that the adsorption rate of the two HPV-like particle vaccine preparations exceeded 99%. There was no significant difference in the change in the active antigen content of the F1 and F2 preparations after 4 weeks at 37 °C, i.e., the stability of F1 and F2 was comparable.

[0095] Example 4: Screening Study of Buffer Concentration

[0096] The composition of the preparation of the papillomavirus virus-like particle vaccine according to the present example is given in the following Table:

Table 10. Preparations with different buffer concentrations Composition number Virus-like particle of papillomavirus Aluminum Phosphate Adjuvant Histidine buffer NaCl Polysorbate 80 pH F1 0.74 mg/ml 1.0 mg/ml 10 mM 320 mM 0.00 wt.% 6.2 F2 0.74 mg/ml 1.0 mg/ml 18 mM 320 mM 0.00 wt.% 6.2 F3 0.74 mg/ml 1.0 mg/ml 26 mM 320 mM 0.00 wt.% 6.2

[0097] Method for preparing a vaccine preparation of virus-like particles of papillomavirus:

[0098] A certain amount of HPV 18 virus-like particles corresponding to the preparation was taken, and then mixed with aluminum phosphate adjuvant and adsorbed overnight at 4 °C so that the pH, the corresponding concentrations of papillomavirus virus-like particles, aluminum phosphate adjuvant, histidine, sodium chloride and polysorbate 80 in the papillomavirus virus-like particles vaccine preparation met the requirements of Table 10, dosed it in aliquots. Labeled it with corresponding numbers, placed the samples in an incubator at 37 °C and taken out for analysis of the adsorption rate and antigen content at week 0, and for analysis of the antigen content at weeks 1, 2 and 4.

[0099] Analytical research method:

[00100] Adsorption rate analysis: The detection principle is that antigens not adsorbed on the aluminum phosphate adjuvant are separated by centrifugation, and their content is analyzed to calculate the adsorption rate.

[00101] Antigen content assay: The detection principle is that the content of active antigen capable of binding to the recombinant antibody neutralizing human papillomavirus is measured by ELISA, and the stability of each preparation is compared by comparing the ratio of the content of active antigen at each time point with the T0 point. The higher the ratio, the higher the content of active antigen in the preparation and the better the activity is preserved.

[00102] The test results are shown in Tables 11-12 and Figs. 7-8.

Table 11. Degree of adsorption of the preparation of virus-like particles of HPV18 Number %HPV18 bound to aluminum-based adjuvant F1 99.6 F2 99.4 F3 99.6

Table 12 Antigen content in the preparation of HPV18 virus-like particles Moment in time Content of HPV HPV18, as a percentage of T0, % F1 F2 F3 T ₀ 100 100 100 37°C_1W 96.6 100 76.5 37 °C_2W 96.6 96.6 70.6 37 °C_4W 89.7 82.8 70.6

[00103] The test results showed that the adsorption rate of the three human papillomavirus virus-like particle vaccine preparations was higher than 99%, and the change trends of the antigen content of the human papillomavirus virus-like particle vaccines in F1 and F2 were better than that of F3, that is, the stability of F1 and F2 was better than that of F3.

[00104] Example 5: Study to confirm the composition of each individual type (type 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) of virus-like particles of the papillomavirus vaccine

[00105] Each individual type (type 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) of human papillomavirus virus-like particle vaccine preparations (preparation: 0.74 mg/mL human papillomavirus virus-like particle + 1.0 mg/mL aluminum phosphate adjuvant + 18 mM histidine buffer + 320 mM sodium chloride at pH 6.2) were subjected to stability monitoring at 2-8 °C, respectively. In this case, the vaccine contained polysorbate 80 at a concentration of no more than 0.3 mg/mL due to residues formed during the preparation process. The monitoring time points were 3 m (3 months), 6 m (6 months), 9 m (9 months) and 12 m (12 months), while the degree of adsorption and relative activity in vitro were monitored.

[00106] Analytical research method:

[00107] Adsorption rate analysis: The detection principle is that antigens not adsorbed on the aluminum phosphate adjuvant are separated by centrifugation, and their content is analyzed to calculate the adsorption rate.

[00108] Relative in vitro potency: The detection principle of this method is to determine the EC ₅₀ of the test sample and the positive control using a recombinant human papillomavirus neutralizing antibody, respectively, and then calculate its EC ₅₀ percentage. The higher the value, the higher the relative in vitro potency and the higher the quality of the test sample.

[00109] The experimental results are shown in Table 13.

[00110] The experimental results demonstrate that each individual type of the papillomavirus virus-like particle vaccine preparations disclosed in the present invention has good stability and can be stably stored for at least 12 months at a temperature of 2-8 °C.

Table 13. Stability data for all 14 individual types (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) of human papillomavirus virus-like particles in a liquid formulation with adsorption on an adjuvant.

A type of human papillomavirus virus-like particle Degree of adsorption, % Relative activity
in vitro,% T0 4℃-3m 4℃-6 m 4℃-9m 4℃-12m T0 4℃-3m 4℃-6 m 4℃-9m 4℃-12m 6 98 99 99 100 >99 101 117 99 116 113 11 99 100 100 >99 >99 96 113 108 143 113 16 >99 >99 >99 >99 >99 92 116 100 130 97 18 >99 >99 >99 >99 >99 86 110 106 97 109 31 >99 >99 >99 >99 >99 109 108 98 113 92 33 >99 >99 >99 >99 >99 96 113 107 108 103 35 >99 >99 >99 >99 >99 85 86 91 88 97 39 >99 >99 >99 >99 >99 101 110 109 105 102 45 99 >99 >99 >99 >99 88 119 115 107 120 51 >99 >99 >99 >99 >99 94 118 98 110 117 52 >99 >99 >99 >99 >99 90 120 104 103 106 56 >99 >99 >99 >99 >99 90 108 99 92 101 58 >99 >99 >99 >99 >99 97 98 106 113 108 59 >99 >99 >99 >99 >99 96 104 106 114 115

[00111] Example 6. Obtaining and confirming the composition of a 14-valent vaccine against human papillomavirus (types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59)

[00112] A method for producing a 14-valent vaccine against human papillomavirus (types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59):

[00113] Each individual type (types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) of the human papillomavirus virus-like particle vaccine preparation (composition: 0.74 mg/ml human papillomavirus virus-like particle + 1.0 mg/ml aluminum phosphate adjuvant + 18 mM histidine buffer + 320 mM sodium chloride, pH value: 6.2) were respectively taken and mixed in a certain volume ratio (types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 = 1.5:2:3:2:1:1:1:1:1:1:1:1:1:1) to obtain a semi-finished product of 14-valent vaccine against human papillomavirus (types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) with the corresponding concentrations of 0.06 mg/ml, 0.08 mg/ml, 0.12 mg/ml, 0.08 mg/ml, 0.04 mg/ml, 0.04 mg/ml, 0.04 mg/ml, 0.04 mg/ml, 0.04 mg/ml, 0.04 mg/ml, 0.04 mg/ml, 0.04 mg/ml, 0.04 mg/mL of each type of virus-like particles, respectively; then dispensed into vials with penicillin, which were then stoppered, capped and labeled to prepare recombinant 14-valent human papillomavirus (types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) vaccine containing polysorbate 80 at a concentration of not more than 0.3 mg/mL due to the preparation process. Stability was then monitored at 2-8 °C (time points 3, 6, 9, 12, 18 and 24 months) and 25 ± 2 °C (time points 2 weeks, 4 weeks, 8 weeks and 16 weeks), and the relative potency and the degree of adsorption in vitro were monitored.

[00114] Analytical research method:

[00115] Adsorption rate analysis: The detection principle is that antigens not adsorbed on the aluminum phosphate adjuvant are separated by centrifugation, and their content is analyzed to calculate the adsorption rate.

[00116] Antigen content assay: The detection principle is that the content of active antigen capable of binding to the recombinant antibody neutralizing human papillomavirus is measured by ELISA, and the stability of each preparation is compared by comparing the ratio of the content of active antigen at each time point with the T0 point. The higher the ratio, the higher the content of active antigen in the preparation and the better the activity is preserved.

[00117] The results of the experiment are shown in Tables 14-17.

[00118]

[00119] The experimental results show that the 14-valent human papillomavirus (types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) vaccine disclosed in the present invention has good stability and can be stably stored for at least 24 months at a temperature of 2 - 8 °C and at least 16 weeks at a temperature of 25 °C.

SEQUENCE LIST

SEQ ID NO Description of the sequence Sequence of amino acids or nucleic acids SEQ ID No: 1 Amino acid sequence 474-499 of HPV type 33 L1 protein KAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 2 Amino acid sequence 469-499 of HPV type 33 L1 protein LQAGLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 3 Amino acid sequence 471-508 of HPV type 59 L1 protein LQLGARPKPTIGPRKRAAPAPTSTPSPKRVKRRKSSRK SEQ ID No: 4 Amino acid sequence 1-469 of HPV type 6 L1 protein MWRPSDSTVYVPPPNPVSKVVATDAYVTRTNIFYHASSSRLLAVGHPYFSIKRANKTVVPKVSGYQYRVFKVVLPDPNKFALPDSSLFDPTTQRLVWACTGLEVGRGQPLGVGVSGH PFLNKYDDVENSGSGGNPGQDNRVNVGMDYKQTQLCMVGCAPPLGEHWGKGKQCTNTPVQAGDCPPLELITSVIQDGDMVDTGFGAMNFADLQTNKSDVPIDICGTTCKYPDYLQMA ADPYGDRLFFFLRKEQMFARHFFNRAGEVGEPVPDTLIIKGSGNRTSVGSSIYVNTPSGSLVSSEAQLFNKPYWLQKAQGHNNGICWGNQLFVTVVDTTRSTNMTLCASVTTSSTYT NSDYKEYMRHVEEYDLQFIFQLCSITLSAEVMAYIHTMNPSVLEDWNFGLSPPPNGTLEDTYRYVQSQAITCQKPTPEKEKPDPYKNLSFWEVNLKEKFSSELDQYPLGRKFLLQSGY SEQ ID No: 5 Amino acid sequence 1-470 of HPV type 11 L1 protein MWRPSDSTVYVPPPNPVSKVVATDAYVKRTNIFYHASSSRLLAVGHPYYSIKKVNKTVVPKVSGYQYRVFKVVLPDPNKFALPDSSLFDPTTQRLVWACTGLEVGRGQPLGVGVSGH PLLNKYDDVENSGGYGGNPGQDNRVNVGMDYKQTQLCMVGCAPPLGEHWGKGTQCSNTSVQNGDCPPLELITSVIQDGDMVDTGFGAMNFADLQTNKSDVPLDICGTVCKYPDYLQMA ADPYGDRLFYLRKEQMFARHFFNRAGTVGEPVPDDLLVKGGNNRSSVASSIYVHTPSGSLVSSEAQLFNKPYWLQKAQGHNNGICWGNHLFVTVVDTTRSTNMTLCASVSKSATYT NSDYKEYMRHVEEFDLQFIFQLCSITLSAEVMAYIHTMNPSVLEDWNFGLSPPPNGTLEDTYRYVQSQAITCQKPTPEKEKQDPYKDMSFWEVNLKEKFSSELDQFPLGRKFLLQSGY SEQ ID No: 6 Amino acid sequence 1-474 of HPV type 16 L1 protein MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNNNKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLGVGIS GHPLLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIGCKPPIGEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSICKYPDYIKM VSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTANLASSNYFPPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMSLCAAISTSETTY KNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTILEDWNFGLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLKKYTFWEVNLKEKFSADLDQFPLGRKFLLQAGL SEQ ID No: 7 Amino acid sequence 1-470 of HPV type 18 L1 protein MALWRPSDNTVYLPPPSVARVVNTDDYVTRTSIFYHAGSSRLLTVGNPYFRVPAGGGNKQDIPKVSAYQYRVFRVQLPDPNKFGLPDTSIYNPETQRLVWACAGVEIGRGQPLGVGL SGHPFYNKLDDTESSHAATSNVSEDVRDNVSVDYKQTQLCILGCAPAIGEHWAKGTACKSRPLSQGDCPPLELKNTVLEDGDMVDTGYGAMDFSTLQDTKCEVPLDICQSICKYPDYL QMSADPYGDSMFFCLRREQLFARHFWNRAGTMGDTVPQSLYIKGTGMRASPGSCVYSPSPSGSIVTSDSQLFNKPYWLHKAQGHNNGVCWHNQLFVTVVDTTRSTNLTICASTQSPV PGQYDATKFKQYSRHVEEYDLQFIFQLCTITLTADVMSYIHSMNSSILEDWNFGVPPPPTTSLVDTYRFVQSVAITCQKDAAPAENKDPYDKLKFWNVDLKEKFSLDLDQYPLGRKFL SEQ ID No: 8 Amino acid sequence 1-475 of HPV type 31 L1 protein MSLWRPSEATVYLPPVPVSKVVSTDEYVTRTNIYYHAGSARLLTVGHPYYSIPKSDNPKKIVVPKVSGLQYRVFRVRLPDPNKFGFPDTSFYNPETQRLVWACVGLEVGRGQPLGVGI SGHPLLNKFDDTENSNRYAGGPGTDNRECISMDYKQTQLCLLGCKPPIGEHWGKGSPCSNNAITPGDCPPLELKNSVIQDGDMVDTGFGAMDFTALQDTKSNVPLDICNSICKYPDYLK MVAEPYGDTLFFYLRREQMFVRHFFNRSGTVGESVPTDLYIKGSGSTATLANSTYFPPTPSGSMVTSDAQIFNKPYWMQRAQGHNNGICWGNQLFVTVVDTTRSTNMSVCAAIANSDTTF KSSNFKEYLRHGEEFDLQFIFQLCKITLSADIMTYIHSMNPAILEDWNFGLTTPPSGSLEDTYRFVTSQAITCQKSAPQKPKEDPFKDYVFWEVNLKEKFSADLDQFPLGRKFLLQAGY SEQ ID No: 9 Amino acid sequence 1-472 of HPV type 35 L1 protein MSLWRSNEATVYLPPVSVSKVVSTDEYVTRTNIYYHAGSSRLLAVGHPYYAIKKQDSNKIAVPKVSGLQYRVFRVKLPDPNKFGFPDTSFYDPASQRLVWACTGVEVGRGQPLGVGIS GHPLLNKLDDTENSNKYVGNSGTDNRECISMDYKQTQLCLIGCRPPIGEHWGKGTPCNANQVKAGECPPLELLNTVLQDGDMVDTGFGAMDFTTLQANKSDVPLDICSSICKYPDYLK MVSEPYGDMLFFYLRREQMFVRHLFNRAGTVGETVPADLYIKGTTGTLPSTSYFPPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWSNQLFVTVVDTTRSTNMSVCSAVSSSDSTYK NDNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNPSILEDWNFGLTPPPSGTLEDTYRYVTSQAVTCQKPSAPKPKDDPLKNYTFWEVDLKEKFSADLDQFPLGRKFLLQAGL SEQ ID No: 10 Amino acid sequence 1-469 of HPV type 39 L1 protein MAMWRSSDSMVYLPPPSVAKVVNTDDYVTRTGIYYYAGSSRLLTVGHPYFKVGMNGGRKQDIPKVSAYQYRVFRVTLPDPNKFSIPDASLYNPETQRLVWACVGVEVGRGQPLGVGI SGHPLYNRQDDTENSPFSSTTNKDSRDNVSVDYKQTQLCIIGCVPAIGEHWGKGKACKPNNVSTGDCPPLELVNTPIEDGDMIDTGYGAMDFGALQETKSEVPLDICQSICKYPDYL QMSADVYGDSMFFCLRREQLFARHFWNRGGMVGDAIPAQLYIKGTDIRANPGSSVYCPSPSGSMVTSDSQLFNKPYWLHKAQGHNNGICWHNQLFLTVVDTTRSTNFTLSTSIESSI PSTYDPSKFKEYTRHVEEYDLQFIFQLCTVTLTTDVMSYIHTMNSSILDNWNFAVAPPPSASLVDTYRYLQSAAITCQKDAPAPEKKDPYDGLKFWNVDLREKFSLELDQFPLGRKFL SEQ ID No: 11 Amino acid sequence 1-478 of HPV type 45 L1 protein MALWRPSDSTVYLPPPSVARVVNTDDYVSRTSIFYHAGSSRLLTVGNPYFRVVPSGAGNKQAVPKVSAYQYRVFRVALPDPNKFGLPDSTIYNPETQRLVWACVGMEIGRGQPLGIGLS GHPFYNKLDDTESAHAATAVITQDVRDNVSVDYKQTQLCILGCVPAIGEHWAKGTLCKPAQLQPGDCPPLELKNTIIEDGDMVDTGYGAMDFSTLQDTKCEVPLDICQSICKYPDYLQMS ADPYGDSMFFCLRREQLFARHFWNRAGVMGDTVPTDLYIKGTSANMRETPGSCVYSPSPSGSITTSDSQLFNKPYWLHKAQGHNNGICWHNQLFVTVVDTTRSTNLTLCASTQNPVPNT YDPTKFKHYSRHVEEYDLQFIFQLCTITLTAEVMSYIHSMNSSILENWNFGVPPPPTTSLVDTYRFVQSVAVTCQKDTTPPEKQDPYDKLKFWTVDLKEKFSSDLDQYPLGRKFLVQAGL SEQ ID No: 12 Amino acid sequence 1-474 of HPV type 51 L1 protein MALWRTNDSKVYLPPAPVSRIVNTEEYITRTGIYYYAGSSRLITLGHPYFPIPKTSTRAAIPKVSAFQYRVFRVQLPDPNKFGLPDPNLYNPDTDRLVWGCVGVEVGRGQPLGVGLSG HPLFNKYDDTENSRIANGNAQQDVRDNTSVDNKQTQLCIIGCAPPIGEHWGIGTTCKNTPVPPGDCPPLELVSSVIQDGDMIDTGFGAMDFAALQATKSDVPLDISQSVCKYPDYLKMS ADTYGNSMFFHLRREQIFARHYYNKLVGVGEDIPNDYYIKGSGNGRDPIESYIYSATPSGSMITSDSQIFNKPYWLHRAQGHNNGICWNNQLFITCVDTTRSTNLTISTATAAVSPTF TPSNFKQYIRHGEEYELQFIFQLCKITLTTEVMAYLHTMDPTILEQWNFGLTLPPSASLEDAYRFVRNAATSCQKDTPPQAKPDPLAKYKFWDVDLKERFSLDLDQFALGRKFLLQVGV SEQ ID No: 13 Amino acid sequence 1-478 of HPV type 52 L1 protein MSVWRPSEATVYLPPVPVSKVVSTDEYVSRTSIYYYAGSSRLLTVGHPYFSIKNTSSGNGKKVLVPKVSGLQYRVFRIKLPDPNKFGFPDTSFYNPETQRLVWACTGLEIGRGQPLGVG ISGHPLLNKFDDTETSNKYAGKPGIDNRECLSMDYKQTQLCILGCKPPIGEHWGKGTPCNNNSGNPGDCPPLQLINSVIQDGDMVDTGFGCMDFNTLQASKSDVPIDICSSVCKYPDYLQ MASEPYGDSLFFFLRREQMFVRHFFNRAGTLGDPVPGDLYIQGSNSGNTATVQSSAFFPTPSGSMVTSESQLFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMTLCAEVKKEST YKNENFKEYLRHGEEFDLQFIFQLCKITLTADVMTYIHKMDATILEDWQFGLTPPPSASLEDTYRFVTSTAITCQKNTPPKGKEDPLKDYMFWEVDLKEKFSADLDQFPLGRKFLLQAGL SEQ ID No: 14 Amino acid sequence 1-467 of HPV type 56 L1 protein MATWRPSENKVYLPPTPVSKVVATDSYVKRTSIFYHAGSSRLLAVGHPYYSVTKDNTKTNIPKVSAYQYRVFRVRLPDPNKFGLPDTNIYNPDQERLVWACVGLEVGRGQPLGAGL SGHPLFNRLDDTESSNLANNNVIEDSRDNISVDGKQTQLCIVGCTPAMGEHWTKGAVCKSTQVTTGDCPPLALINTPIEDGDMIDTGFGAMDFKVLQESKAEVPLDIVQSTCKYPDY LKMSADAYGDSMWFYLRREQLFARHYFNRAGKVGETIPAELYLKGSNGREPPPSSVYVATPSGSMITSEAQLFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMTISTATEQL SKYDARKINQYLRHVEEYELQFVFQLCKITLSAEVMAYLHNMNANLLEDWNIGLSPPVATSLEDKYRYVRSTAITCQREQPPTEKQDPLAKYKFWDVNLQDSFSTDLDQFPLGRKFL SEQ ID No: 15 Amino acid sequence 1-473 of HPV type 58 L1 protein MSVWRPSEATVYLPPVPVSKVVSTDEYVSRTSIYYYAGSSRLLAVGNPYFSIKSPNNNKKVLVPKVSGLQYRVFRVRLPDPNKFGFPDTSFYNPDTQRLVWACVGLEIGRGQPLGVGV SGHPYLNKFDDTETSNRYPAQPGSDNRECLSMDYKQTQLCLIGCKPPTGEHWGKGVACNNNAAATDCPPLELFNSIIEDGDMVDTGFGCMDFGTLQANKSDVPIDICNSTCKYPDYLK MASEPYGDSLFFFLRREQMFVRHFFNRAGKLGEAVPDDLYIKGSGNTAVIQSSAFFPTPSGSIVTSESQLFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMTLCTEVTKEGTY KNDNFKEYVRHVEEYDLQFVFQLCKITLTAEIMTYIHTMDSNILEDWQFGLTPPPSASLQDTYRFVTSQAITCQKTAPPKEKEDPLNKYTFWEVNLKEKFSADLDQFPLGRKFLLQSGL SEQ ID No: 16 Amino acid sequence of chimeric protein L1 of HPV type 6 MWRPSDSTVYVPPPNPVSKVVATDAYVTRTNIFYHASSSRLLAVGHPYFSIKRANKTVVPKVSGYQYRVFKVVLPDPNKFALPDSSLFDPTTQRLVWACTGLEVGRGQPLGVGVSGHPFLNKY DDVENSGSGGNPGQDNRVNVGMDYKQTQLCMVGCAPPLGEHWGKGKQCTNTPVQAGDCPPLELITSVIQDGDMVDTGFGAMNFADLQTNKSDVPIDICGTTCKYPDYLQMAADPYGDRLFFFLR KEQMFARHFFNRAGEVGEPVPDTLIIKGSGNRTSVGSSIYVNTPSGSLVSSEAQLFNKPYWLQKAQGHNNGICWGNQLFVTVVDTTRSTNMTLCASVTTSSTYTNSDYKEYMRHVEEYDLQFIF QLCSITLSAEVMAYIHTMNPSVLEDWNFGLSPPPNGTLEDTYRYVQSQAITCQKPTPEKEKPDPYKNLSFWEVNLKEKFSSELDQYPLGRKFLLQSGYKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 17 Amino acid sequence of chimeric protein L1 of HPV type 11 MWRPSDSTVYVPPPNPVSKVVATDAYVKRTNIFYHASSSRLLAVGHPYYSIKKVNKTVVPKVSGYQYRVFKVVLPDPNKFALPDSSLFDPTTQRLVWACTGLEVGRGQPLGVGVSGHPLLNKYD DVENSGGYGGNPGQDNRVNVGMDYKQTQLCMVGCAPPLGEHWGKGTQCSNTSVQNGDCPPLELITSVIQDGDMVDTGFGAMNFADLQTNKSDVPLDICGTVCKYPDYLQMAADPYGDRLFFYLR KEQMFARHFFNRAGTVGEPVPDDLLVKGGNNRSSVASSIYVHTPSGSLVSSEAQLFNKPYWLQKAQGHNNGICWGNHLFVTVVDTTRSTNMTLCASVSKSATYTNSDYKEYMRHVEEFDLQFIF QLCSITLSAEVMAYIHTMNPSVLEDWNFGLSPPPNGTLEDTYRYVQSQAITCQKPTPEKEKQDPYKDMSFWEVNLKEKFSSELDQFPLGRKFLLQSGYKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 18 Amino acid sequence of chimeric protein L1 of HPV type 16 MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNNNKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLGVGISGHPLLNK LDDTENASAYAANAGVDNRECISMDYKQTQLCLIGCKPPIGEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSEVPLDICTSICKYPDYIKMVSEPYGDSLFFYL RREQMFVRHLFNRAGAVGENVPDDLYIKGSGSTANLASSNYFPPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFI FQLCKITLTADVMTYIHSMNSTILEDWNFGLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLKKYTFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 19 Amino acid sequence of chimeric protein L1 of HPV type 18 MALWRPSDNTVYLPPPSVARVVNTDDYVTRTSIFYHAGSSRLLTVGNPYFRVPAGGGNKQDIPKVSAYQYRVFRVQLPDPNKFGLPDTSIYNPETQRLVWACAGVEIGRGQPLGVGLSGHPFYN KLDDTESSHAATSNVSEDVRDNVSVDYKQTQLCILGCAPAIGEHWAKGTACKSRPLSQGDCPPLELKNTVLEDGDMVDTGYGAMDFSTLQDTKCEVPLDICQSICKYPDYLQMSADPYGDSMFF CLRREQLFARHFWNRAGTMGDTVPQSLYIKGTGMRASPGSCVYSPSPSGSIVTSDSQLFNKPYWLHKAQGHNNGVCWHNQLFVTVVDTTRSTNLTICASTQSPVPGQYDATKFKQYSRHVEEYD LQFIFQLCTITLTADVMSYIHSMNSSILEDWNFGVPPPPTTSLVDTYRFVQSVAITCQKDAAPAENKDPYDKLKFWNVDLKEKFSLDLDQYPLGRKFLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 20 Amino acid sequence of chimeric protein L1 of HPV type 31 MSLWRPSEATVYLPPVPVSKVVSTDEYVTRTNIYYHAGSARLLTVGHPYYSIPKSDNPKKIVVPKVSGLQYRVFRVRLPDPNKFGFPDTSFYNPETQRLVWACVGLEVGRGQPLGVGISGHPLLN KFDDTENSNRYAGGPGTDNRECISMDYKQTQLCLLGCKPPIGEHWGKGSPCSNNAITPGDCPPLELKNSVIQDGDMVDTGFGAMDFTALQDTKSNVPLDICNSICKYPDYLKMVAEPYGDTLFFY LRREQMFVRHFFNRSGTVGESVPTDLYIKGSGSTATLANSTYFPPTPSGSMVTSDAQIFNKPYWMQRAQGHNNGICWGNQLFVTVVDTTRSTNMSVCAAIANSDTTFKSSNFKEYLRHGEEFDLQF IFQLCKITLSADIMTYIHSMNPAILEDWNFGLTTPPSGSLEDTYRFVTSQAITCQKSAPQKPKEDPFKDYVFWEVNLKEKFSADLDQFPLGRKFLLQAGYKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 21 Amino acid sequence of chimeric protein L1 of HPV type 35 MSLWRSNEATVYLPPVSVSKVVSTDEYVTRTNIYYHAGSSRLLAVGHPYYAIKKQDSNKIAVPKVSGLQYRVFRVKLPDPNKFGFPDTSFYDPASQRLVWACTGVEVGRGQPLGVGISGHPLLN KLDDTENSNKYVGNSGTDNRECISMDYKQTQLCLIGCRPPIGEHWGKGTPCNANQVKAGECPPLELLNTVLQDGDMVDTGFGAMDFTTLQANKSDVPLDICSSICKYPDYLKMVSEPYGDMLFFY LRREQMFVRHLFNRAGTVGETVPADLYIKGTTGTLPSTSYFPPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWSNQLFVTVVDTTRSTNMSVCSAVSSSDSTYKNDNFKEYLRHGEEYDLQFI FQLCKITLTADVMTYIHSMNPSILEDWNFGLTPPPSGTLEDTYRYVTSQAVTCQKPSAPKPKDDPLKNYTFWEVDLKEKFSADLDQFPLGRKFLLQAGLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 22 Amino acid sequence of chimeric HPV type 39 Protein L1 MAMWRSSDSMVYLPPPSVAKVVNTDDYVTRTGIYYYAGSSRLLTVGHPYFKVGMNGGRKQDIPKVSAYQYRVFRVTLPDPNKFSIPDASLYNPETQRLVWACVGVEVGRGQPLGVGISGHPLYNRQ DDTENSPFSSTTNKDSRDNVSVDYKQTQLCIIGCVPAIGEHWGKGKACKPNNVSTGDCPPLELVNTPIEDGDMIDTGYGAMDFGALQETKSEVPLDICQSICKYPDYLQMSADVYGDSMFFCLRREQ LFARHFWNRGGMVGDAIPAQLYIKGTDIRANPGSSVYCPSPSGSMVTSDSQLFNKPYWLHKAQGHNNGICWHNQLFLTVVDTTRSTNFTLSTSIESSIPSTYDPSKFKEYTRHVEEYDLQFIFQLCT VTLTTDVMSYIHTMNSSILDNWNFAVAPPPSASLVDTYRYLQSAAITCQKDAPAPEKKDPYDGLKFWNVDLREKFSLELDQFPLGRKFLLQLGARPKPTIGPRKRAAPAPTSTPSPKRVKRRKSSRK SEQ ID No: 23 Amino acid sequence of chimeric protein L1 of HPV type 45 MALWRPSDSTVYLPPPSVARVVNTDDYVSRTSIFYHAGSSRLLTVGNPYFRVVPSGAGNKQAVPKVSAYQYRVFRVALPDPNKFGLPDSTIYNPETQRLVWACVGMEIGRGQPLGIGLSGHPFYNK LDDTESAHAATAVITQDVRDNVSVDYKQTQLCILGCVPAIGEHWAKGTLCKPAQLQPGDCPPLELKNTIIEDGDMVDTGYGAMDFSTLQDTKCEVPLDICQSICKYPDYLQMSADPYGDSMFFCLR REQLFARHFWNRAGVMGDTVPTDLYIKGTSANMRETPGSCVYSPSPSGSITTSDSQLFNKPYWLHKAQGHNNGICWHNQLFVTVVDTTRSTNLTLCASTQNPVPNTYDPTKFKHYSRHVEEYDLQF IFQLCTITLTAEVMSYIHSMNSSILENWNFGVPPPPTTSLVDTYRFVQSVAVTCQKDTTPPEKQDPYDKLKFWTVDLKEKFSSDLDQYPLGRKFLVQAGLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 24 Amino acid sequence of chimeric protein L1 of HPV type 51 MALWRTNDSKVYLPPAPVSRIVNTEEYITRTGIYYYAGSSRLITLGHPYFPIPKTSTRAAIPKVSAFQYRVFRVQLPDPNKFGLPDPNLYNPDTDRLVWGCVGVEVGRGQPLGVGLSGHPLFNKY DDTENSRIANGNAQQDVRDNTSVDNKQTQLCIIGCAPPIGEHWGIGTTCKNTPVPPGDCPPLELVSSVIQDGDMIDTGFGAMDFAALQATKSDVPLDISQSVCKYPDYLKMSADTYGNSMFFHLR REQIFARHYYNKLVGVGEDIPNDYYIKGSGNGRDPIESYIYSATPSGSMITSDSQIFNKPYWLHRAQGHNNGICWNNQLFITCVDTTRSTNLTISTATAAVSPTFTPSNFKQYIRHGEEYELQFI FQLCKITLTTEVMAYLHTMDPTILEQWNFGLTLPPSASLEDAYRFVRNAATSCQKDTPPQAKPDPLAKYKFWDVDLKERFSLDLDQFALGRKFLLQVGVKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No:25 Amino acid sequence of chimeric protein L1 of HPV type 52 MSVWRPSEATVYLPPVPVSKVVSTDEYVSRTSIYYYAGSSRLLTVGHPYFSIKNTSSGNGKKVLVPKVSGLQYRVFRIKLPDPNKFGFPDTSFYNPETQRLVWACTGLEIGRGQPLGVGISGHPLL NKFDDTETSNKYAGKPGIDNRECLSMDYKQTQLCILGCKPPIGEHWGKGTPCNNNSGNPGDCPPLQLINSVIQDGDMVDTGFGCMDFNTLQASKSDVPIDICSSVCKYPDYLQMASEPYGDSLFFF LRREQMFVRHFFNRAGTLGDPVPGDLYIQGSNSGNTATVQSSAFFPTPSGSMVTSESQLFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMTLCAEVKKESTYKNENFKEYLRHGEEFDLQF IFQLCKITLTADVMTYIHKMDATILEDWQFGLTPPPSASLEDTYRFVTSTAITCQKNTPPKGKEDPLKDYMFWEVDLKEKFSADLDQFPLGRKFLLQAGLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 26 Amino acid sequence of chimeric protein L1 of HPV type 56 MATWRPSENKVYLPPTPVSKVVATDSYVKRTSIFYHAGSSRLLAVGHPYYSVTKDNTKTNIPKVSAYQYRVFRVRLPDPNKFGLPDTNIYNPDQERLVWACVGLEVGRGQPLGAGLSGHPLFNR LDDTESSNLANNNVIEDSRDNISVDGKQTQLCIVGCTPAMGEHWTKGAVCKSTQVTTGDCPPLALINTPIEDGDMIDTGFGAMDFKVLQESKAEVPLDIVQSTCKYPDYLKMSADAYGDSMWFYL RREQLFARHYFNRAGKVGETIPAELYLKGSNGREPPPSSVYVATPSGSMITSEAQLFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMTISTATEQLSKYDARKINQYLRHVEEYELQFV FQLCKITLSAEVMAYLHNMNANLLEDWNIGLSPPVATSLEDKYRYVRSTAITCQREQPPTEKQDPLAKYKFWDVNLQDSFSTDLDQFPLGRKFLLQAGLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 27 Amino acid sequence of chimeric protein L1 of HPV type 58 MSVWRPSEATVYLPPVPVSKVVSTDEYVSRTSIYYYAGSSRLLAVGNPYFSIKSPNNNKKVLVPKVSGLQYRVFRVRLPDPNKFGFPDTSFYNPDTQRLVWACVGLEIGRGQPLGVGVSGHPYL NKFDDTETSNRYPAQPGSDNRECLSMDYKQTQLCLIGCKPPTGEHWGKGVACNNNAAATDCPPLELFNSIIEDGDMVDTGFGCMDFGTLQANKSDVPIDICNSTCKYPDYLKMASEPYGDSLFFF LRREQMFVRHFFNRAGKLGEAVPDDLYIKGSGNTAVIQSSAFFPTPSGSIVTSESQLFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMTLCTEVTKEGTYKNDNFKEYVRHVEEYDLQFV FQLCKITLTAEIMTYIHTMDSNILEDWQFGLTPPPSASLQDTYRFVTSQAITCQKTAPPKEKEDPLNKYTFWEVNLKEKFSADLDQFPLGRKFLLQSGLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 28 Amino acid sequence of the L1 protein of HPV type 33 MSVWRPSEATVYLPPVPVSKVVSTDEYVSRTSIYYYAGSSRLLAVGHPYFSIKNPTNAKKLLVPKVSGLQYRVFRVRLPDPNKFGFPDTSFYNPDTQRLVWACVGLEIGRGQPLGVGISGHPLL NKFDDTETGNKYPGQPGADNRECLSMDYKQTQLCLLGCKPPTGEHWGKGVACTNAAPANDCPPLELINTIIEDGDMVDTGFGCMDFKTLQANKSDVPIDICGSTCKYPDYLKMTSEPYGDSLFFF LRREQMFVRHFFNRAGTLGEAVPDDLYIKGSGTTASIQSSAFFPTPSGSMVTSESQLFNKPYWLQRAQGHNNGICWGNQVFVTVVDTTRSTNMTLCTQVTSDSTYKNENFKEYIRHVEEYDLQFV FQLCKVTLTAEVMTYIHAMNPDILEDWQFGLTPPPSASLQDTYRFVTSQAITCQKTVPPKEKEDPLGKYTFWEVDLKEKFSADLDQFPLGRKFLLQAGLKAKPKLKRAAPTSTRTSSAKRKKVKK SEQ ID No: 29 Amino acid sequence of the L1 protein of HPV type 59 MALWRSSDNKVYLPPPSVAKVVSTDEYVTRTTSIFYHAGSSRLLTVGHPYFKVPKGGNGRQDVPKVSAYQYRVFRVKLPDPNKFGLPDNTVYDPNSQRLVWACVGVEIGRGQPLGVGLSGHPLYNKLD DTENSHVASAVDTKDTRDNVSVDYKQTQLCIIGCVPAIGEHWTKGTACKPTTVVQGDCPPLELINTPIEDGDMVDTGYGAMDFKLLQDNKSEVPLDICQSICKYPDYLQMSADAYGDSMFFCLRREQ VFARHFWNRSGTMGDQLPESLYIKGTDIRANPGSYLYSPSPSGSVVTSDSQLFNKPYWLHKAQGLNNGICWHNQLFLTVVDTTRSTNLSVCASTTSSIPNVYTPTSFKEYARHVEEFDLQFIFQLCK ITLTTEVMSYIHNMNTTILEDWNFGVTPPPTASLVDTYRFVQSAAVTCQKDTAPPVKQDPYDKLKFWPVDLKERFSADLDQFPLGRKFLLQLGARPKPTIGPRKRAAPAPTSTPSPKRVKRRKSSRK SEQ ID No: 30 Synthetic gene HPV6 L1 ctgggtaccATGTGGAGACCATCTGACAGCACAGTCTATGTGCCTCCTCCAAACCCTGTGAGCAAGGTGGTGGCTACAGATGCCTATGTGACCAGGACCAACATCTTCTACCATGCCTCCTCCAGCAGACTGCTGGCTGTGGGACACCCATACTTCAGCATCAAGAGGGCTAACAAGACAGTGGTGCCAA AGGTGTCTGGCTACCAATACAGGGTGTTCAAGGTGGTGCTGCCTGACCCAAACAAGTTTGCCCTGCCTGACTCCTCCCTGTTTGACCCAACCACCCAGAGACTGGTGTGGGCTTGTACTGGATTGGAGGTGGGCAGGGGACAACCACTGGGAGTGGGAGTGTCTGGACACCCATTCCTGAACAAATATGA TGATGTGGAGAACTCTGGCTCTGGAGGCAACCCTGGACAAGACAACAGGGTGAATGTGGGGATGGACTACAAGCAGACCCAACTTTGTATGGTGGGCTGTGCCCCTCCACTGGGAGAACACTGGGGCAAGGGCAAGCAGTGTACCAACACACCTGTCCAGGCTGGAGACTGTCCTCCATTGGAACTGATT ACCTCTGTGATTCAGGATGGAGATATGGTGGACACAGGCTTTGGAGCTATGAACTTTGCTGACCTCCAAACCAACAAGTCTGATGTGCCAATTGACATCTGTGGCACCACTTGTAAATACCCTGACTACCTCCAAATGGCTGCTGACCCATATGGAGACAGACTGTTCTTCTTCCTGAGGAAGGAACAGAT GTTTGCCAGACACTTCTTCAACAGGGCTGGAGAGGTGGGAGAACCTGTGCCTGACACCCTGATTATCAAGGGCTCTGGCAACAGGACCTCTGTGGGCTCCAGCATCTATGTGAACACACCATCTGGCTCCCTGGTGTCCTCTGAGGCTCAACTTTTCAACAAGCCATACTGGCTCCAAAAGGCTCAAGGA CACAACAATGGCATCTGTTGGGGCAACCAACTTTTTGTGACAGTGGTGGACACCACCAGGAGCACCAATATGACCCTGTGTGCCTCTGTGACCACCTCCAGCACCTACACCAACTCTGACTACAAGGAATATATGAGGCATGTGGAGGAATATGACCTCCAATTCATCTTCCAACTTTGTAGCATCACCC TGTCTGCTGAGGTGATGGCTTACATCCACACAATGAACCCATCTGTGTTGGAGGACTGGAACTTTGGACTGAGCCCTCCTCCAAATGGCACCTTGGAGGACACCTACAGATATGTCCAGAGCCAGGCTATCACTTGTCAGAAGCCAACACCTGAGAAGGAGAAGCCTGACCCATACAAGAACCTGTCCTT CTGGGAGGTGAACCTGAAAGAGAAGTTCTCCTCTGAACTGGACCAATACCCACTGGGCAGGAAGTTCCTGCTCCAATCTGGCTACAGGGGCAGGTCCAGCATCAGGACAGGAGTGAAGAGACCTGCTGTGAGCAAGGCATCTGCTGCCCCAAAGAGGAAGAGGGCTAAGACCAAGAGGTAAActcgagctc SEQ ID No: 31 Synthetic gene HPV11 L1 ctgggtaccATGTGGAGACCATCTGACAGCACAGTCTATGTGCCTCCTCCAAACCCTGTGAGCAAGGTGGTGGCTACAGATGCCTATGTGAAGAGGACCAACATCTTCTACCATGCCTCCTCCAGCAGACTGCTGGCTGTGGGACACCCATACTACAGCATCAAGAAGGTGAACAAGACAGTGGTGCCAA AGGTGTCTGGCTACCAATACAGGGTGTTCAAGGTGGTGCTGCCTGACCCAAACAAGTTTGCCCTGCCTGACTCCTCCCTGTTTGACCCAACCACCCAGAGACTGGTGTGGGCTTGTACTGGATTGGAGGTGGGCAGGGGACAACCACTGGGAGTGGGAGTGTCTGGACACCCACTGCTGAACAAATATGAT GATGTGGAGAACTCTGGAGGCTATGGAGGCAACCCTGGACAAGACAACAGGGTGAATGTGGGGATGGACTACAAGCAGACCCAACTTTGTATGGTGGGCTGTGCCCCTCCACTGGGAGAACACTGGGGCAAGGGCACCCAGTGTAGCAACACCTCTGTCCAGAATGGAGACTGTCCTCCATTGGAACTGA TTACCTCTGTGATTCAGGATGGAGATATGGTGGACACAGGCTTTGGAGCTATGAACTTTGCTGACCTCCAAACCAACAAGTCTGATGTGCCACTGGACATCTGTGGCACAGTGTGTAAATACCCTGACTACCTCCAAATGGCTGCTGACCCATATGGAGACAGACTGTTCTTCTACCTGAGGAAGGAACAG ATGTTTGCCAGACACTTCTTCAACAGGGCTGGCACAGTGGGAGAACCTGTGCCTGATGACCTGCTGGTGAAGGGAGGCAACAACAGGTCCTCTGTGGCATCCAGCATCTATGTGCATACACCATCTGGCTCCCTGGTGTCCTCTGAGGCTCAACTTTTCAACAAGCCATACTGGCTCCAAAAGGCTCAAG GACACAAACAATGGCATCTGTTGGGGCAACCACCTGTTTGTGACAGTGGTGGACACCACCAGGAGCACCAATATGACCCTGTGTGCCTCTGTGAGCAAGTCTGCCACCTACACCAACTCTGACTACAAGGAATATATGAGGCATGTGGAGGAGTTTGACCTCCAATTCATCTTCCAACTTTGTAGCATCACC CTGTCTGCTGAGGTGATGGCTTACATCCACACAATGAACCCATCTGTGTTGGAGGACTGGAACTTTGGACTGAGCCCTCCTCCAAATGGCACCTTGGAGGACACCTACAGATATGTCCAGAGCCAGGCTATCACTTGTCAGAAGCCAACACCTGAGAAGGAGAAGCAGGACCCATACAAGGATATGAGTTT CTGGGAGGTGAACCTGAAAGAGAAGTTCTCCTCTGAACTGGACCAGTTTCCACTGGGCAGGAAGTTCCTGCTCCAATCTGGCTACAGGGGCAGGACCTCTGCCAGGACAGGCATCAAGAGACCTGCTGTGAGCAAGCCAAGCACAGCCCCAAAGAGGAAGAGGACCAAGACCAAGAAGTAAActcgagctc SEQ ID No: 32 Synthetic HPV16 L1 gene ctgggtaccATGAGTCTGTGGCTGCCATCTGAGGCTACAGTCTACCTGCCTCCTGTGCCTGTGAGCAAGGTGGTGAGCACAGATGAATATGTGGCAAGGACCAACATCTACTACCATGCTGGCACCAGCAGACTGCTGGCTGTGGGACACCCATACTTTCCAATCAAGAAGCCAAACAACAACAAGATTCTG GTGCCAAAGGTGTCTGGACTCCAATACAGGGTGTTCAGGATTCACCTGCCTGACCCAAAACAAGTTTGGCTTTCCTGACACCTCCTTCTACAACCCTGACACCCAGAGACTGGTGTGGGCTTGTGTGGGAGTGGAGGTGGGCAGGGGACAACCACTGGGAGTGGGCATCTCTGGACACCCACTGCTGAACAAA CTGGATGACACAGAGAATGCCTCTGCCTATGCTGCCAATGCTGGAGTGGACAACAGGGAGTGTATCAGTATGGACTACAAGCAGACCCAACTTTGTCTGATTGGCTGTAAGCCTCCAATTGGAGAACACTGGGGCAAGGGCAGCCCATGTACCAATGTGGCTGTGAACCCTGGAGACTGTCCTCCATTGGAA CTGATAAACACAGTGATTCAGGATGGAGATATGGTGGACACAGGCTTTGGAGCTATGGACTTCACCACCTCCAAGCCAACAAGTCTGAGGTGCCACTGGACATCTGTACCAGCATCTGTAAATACCCTGACTACATCAAGATGGTGTCTGAACCATATGGAGACTCCCTGTTCTTCTACCTGAGGAGGGAA CAGATGTTTGTGAGACACCTGTTCAACAGGGCTGGAGCAGTGGGAGAGAATGTGCCTGATGACCTCTACATCAAGGGCTCTGGCAGCACAGCCAACCTGGCATCCAGCAACTACTTTCCAACACCATCTGGCAGTATGGTGACCTCTGATGCCCAGATTTTCAACAAGCCATACTGGCTCCAAAGGGCTCAA GGACACAACAATGGCATCTGTTGGGGCAACCAACTTTTTGTGACAGTGGTGGACACCACCAGGAGCACCAATATGAGTCTGTGTGCTGCCATCAGCACCTCTGAGACCACCTACAAGAACACCAACTTCAAGGAATACCTGAGACATGGAGAGGAATATGACCTCCAATTCATCTTCCAACTTTGTAAGATT ACCCTGACAGCAGATGTGATGACCTACATCCACAGTATGAACAGCACCATCTTGGAGGACTGGAACTTTGGACTCCAACCTCCTCCTGGAGGCACCTTGGAGGACACCTACAGGTTTGTGACCAGCCAGGCTATTGCCTGTCAGAAACACACACCTCCTGCCCCAAAGGGAGGACCCACTGAAAAAATACACC TTCTGGGAGGTGAACCTGAAAGAGAAGTTCTCTGCTGACCTGGACCAGTTTCCACTGGGCAGGAAGTTCCTGCTCCAAGCAGGACTGAAAGCCAAGCCAAAGTTCACCCTGGGCAAGAGGAAGGCTACACCAACCACCTCCAGCACCAGCACCACAGCCAAGAGGAAGAAGAGGAAACTGTAAActcgagctc SEQ ID No: 33 Synthetic gene HPV18 L1 ctgggtaccATGGCCCTCTGGAGACCATCCGATAACACAGTGTACTTGCCCCCACCCAGCGTCGCCCGGGTGGTGAACACAGACGACTACGTCACCAGAACCTCAATCTTCTACCACGCCGGGTCCAGCCGGCTGCTGACCGTGGGCAACCCCTACTTCCGCGTGCCCGCCGGCGGCGGAAACAAACAAGAC ATCCCCAAAGTCAGCGCCTATCAGTACCGGGTGTTCCGCGTCCAACTGCCCGATCCCAACAAGTTCGGCCTGCCCGACACCTCCATCTACAACCCCGAGACCCAGAGGCTGGTCTGGGCTTGCGCCGGCGTCGAGATCGGGAGGGGCCAACCCCTGGGCGTGGGGTTGTCCGGCCACCCTTCTACAACAAGC TGGACGATACCGAGTCCAGCCACGCAGCAACCAGCAACGTCTCCGAAGATGTGCGCGATAACGTCAGCGTGGACTACAAACAAACCCAACTGTGCATCCTGGGATGCGCACCCGCCATCGGCGAGCATTGGGCCAAGGGGACCGCCTGCAAGAGCAGGCCCCTGAGCCAAGGGGACTGTCCACCCCTGGAGTT GAAGAATACCGTGCTCGAGGACGGCGACATGGTGGACACCGGCTACGGCGCTATGGATTTCTCCACCCTCCAGGACACCAAGTGCGAAGTGCCCCTCGACATCTGCCAAAGCATCTGCAAGTACCCCGACTACCTCCAGATGAGCGCCGACCCCTACGGCGACAGCATGTTCTTCTGTCTCAGAAGGGAACAA TTGTTCGCCCGCCACTTCTGGAACCGGGCCGGCACAATGGGAGATACAGTCCCCCAGAGCCTGTACATCAAGGGGACCGGAATGAGGGCCAGCCCCGGGTCCTGCGTCTACAGCCCAAGCCCCTCCGGGAGCATCGTCACAAGCGATAGCCAACTCTTCAACAAGCCCTACTGGCTCCACAAAGCCCAAGGCC ACAATAACGGGGTGTGTTGGCACAACCAGCTGTTCGTGACCGTCGTGGACACAACCAGGTCCACAAACCTGACCATCTGCGCCAGCACCCAAAGCCCCGTGCCCGGCCAGTACGACGCCAAAAGTTCAAACAATACTCTCGGCACGTGGAAGAGTACGACCTCCAATTCATCTTCCAACTCTGCACCATCAC CCTCACCGCCGACGTGATGAGCTACATCCACTCCATGAACTCCTCCATCCTGGAAGACTGGAATTTCGGCGTGCCACCACCCCCTACCACCTCCCTCGTCGACACCTACAGATTCGTGCAGAGCGTGGCCATCACATGCCAGAAAGACGCCGCCCCCGCCGAGAACAAAGACCCATACGACAAACTGAAATTC TGGAACGTCGACCTGAAAGAGAAATTCAGCCTGGATCTGGACCAGTACCCATTGGGCAGGAAGTTCCTCGTGCAAGCCGGCCTCAGGAGAAAACCAACAATCGGGCCCAGGAAGAGGAGCGCCCCCAGCGCAACCACCAGCAGCAAGCCCGCAAAAAGGGTCAGAGTGAGGGCACGCAAATAAActcgagctc SEQ ID No: 34 Synthetic gene HPV31 L1 ctgggtaccATGAGCCTGTGGAGGCCCAGCGAGGCCACCGTGTACCTGCCCCCCGTGCCCGTGAGCAAGGTGGTGAGCACCGACGAGTACGTGACCAGGACCAACATCTACTACCACGCCGGCAGCGCCAGGCTGCTGACCGTGGGCCACCCCTACTACAGCATCCCCAAGAGCGACAACCCCAAGAAGAT CGTGGTGCCCAAGGTGAGCGGCCTGCAGTACAGGGTGTTCAGGGTGAGGCTGCCCGACCCCAACAAGTTCGGCTTCCCCGACACCAGCTTCTACAACCCCGAGACCCAGAGGCTGGTGTGGGCCTGCGTGGGCCTGGAGGTGGGCAGGGGCCAGCCCCTGGGCGTGGGCATCAGCGGCCACCCCCTGCTGAA CAAGTTCGACGACACCGAGAACAGCAACAGGTACGCCGGCGGCCCCGGCACCGACAACAGGGAGTGCATCAGCATGGACTACAAGCAGACCCAGCTGTGCCTGCTGGGCTGCAAGCCCCCCATCGGCGAGCACTGGGGCAAGGGCAGCCCCTGCAGCAACAACGCCATCACCCCCGGCGACTGCCCCCCCCT GGAGCTGAAGAACAGCGTGATCCAGGACGGCGACATGGTGGACACCGGCTTCGGCGCCATGGACTTCACCGCCCTGCAGGACACCAAGAGCAACGTGCCCCTGGACATCTGCAACAGCATCTGCAAGTACCCCGACTACCTGAAGATGGTGGCCGAGCCCTACGGCGACACCCTGTTCTTCTACCTGAGGAG GGAGCAGATGTTCGTGAGGCACTTCTTCAACAGGAGCGGCACCGTGGGCGAGAGCGTGCCCACCGACCTGTACATCAAGGGCAGCGGCAGCACCGCCACCCTGGCCAACAGCACCTACTTCCCCACCCCCAGCGGCAGCATGGTGACCAGCGACGCCCAGATCTTCAACAAGCCCTACTGGATGCAGAGGG CCCAGGGCCACAACAACGGCATCTGCTGGGGCAACCAGCTGTTCGTGACCGTGGTGGACACCACCAGGAGCACCAACATGAGCGTGTGCGCCGCCATCGCCAACAGCGACACCACCTTCAAGAGCAGCAACTTCAAGGAGTACCTGAGGCACGGCGAGGAGTTCGACCTGCAGTTCATCTTCCAGCTGTGCA AGATCACCCTGAGCGCCGACATCATGACCTACATCCACAGCATGAACCCCGCCATCCTGGAGGACTGGAACTTCGGCCTGACCACCCCCCCCAGCGGCAGCCTGGAGGACACCTACAGGTTCGTGACCAGCCAGGCCATCACCTGCCAGAAGTCCGCCCCCCAGAAGCCCAAGGAGGACCCCTTCAAGGACT ACGTGTTCTGGGAGGTGAACCTGAAGGAGAAGTTCAGCGCCGACCTGGACCAGTTCCCCCTGGGCAGGAAGTTCCTGCTGCAGGCCGGCTACAGGGCCAGGCCCAAGTTCAAGGCCGGCAAGAGGAGCGCCCCCAGCGCCAGCACCACCACCCCCGCCAAGAGGAAGAAGACCAAGAAGTAAActcgagctc SEQ ID No: 35 Synthetic gene HPV35 L1 ctgggtaccATGAGTCTGTGGAGGAGCAATGAGGCTACAGTCTACCTGCCTCCTGTGTCTGTGAGCAAGGTGGTGAGCACAGATGAATATGTGACCAGGACCAACATCTACTACCATGCTGGCTCCAGCAGACTGCTGGCTGTGGGACACCCATACTATGCCATCAAGAAGCAGGACAGCAACAAGATTGC TGTGCCAAAGGTGTCTGGACTCCAATACAGGGTGTTCAGGGTGAAACTGCCTGACCAAACAAGTTTGGCTTTCCTGACACCTCCTTCTATGACCCTGCCAGCCAGAGACTGGTGTGGGCTTGTACTGGAGTGGAGGTGGGCAGGGGACAACCACTGGGAGTGGGCATCTCTGGACACCCACTGCTGAACA AACTGGATGACACAGAGAACAGCAACAAATATGTGGGCAACTCTGGCACAGACAACAGGGAGTGTATCAGTATGGACTACAAGCAGACCCAACTTTGTCTGATTGGCTGTAGACCTCCAATTGGAGAACACTGGGGCAAGGGCACACCATGTAATGCCAACCAGGTGAAGGCTGGAGAGTGTCCTCCATTG GAACTGCTGAACACAGTGCTCCAAGATGGAGATATGGTGGACACAGGCTTTGGAGCTATGGACTTCACCACCTCCAAGCCAACAAGTCTGATGTGCCACTGGACATCTGTTCCAGCATCTGTAAATACCCTGACTACCTGAAAATGGTGTCTGAACCATATGGAGATATGCTGTTCTTCTACCTGAGGAG GGAACAGATGTTTGTGAGACACCTGTTCAACAGGGCTGGCACAGTGGGAGAGACAGTGCCTGCTGACCTCTACATCAAGGGCACCACAGGCACCCTGCCAAGCACCTCCTACTTTCCAACACCATCTGGCAGTATGGTGACCTCTGATGCCCAGATTTTCAACAAGCCATACTGGCTCCAAAGGGCTCAAG GACACAAACAATGGCATCTGTTGGAGCAACCAACTTTTTGTGACAGTGGTGGACACCACCAGGAGCACCAATATGAGTGTGTGTTCTGCTGTGTCCTCCTCTGACAGCACCTACAAGAATGACAACTTCAAGGAATACCTGAGACATGGAGAGGAATATGACCTCCAATTCATCTTCCAACTTTGTAAGATT ACCCTGACAGCAGATGTGATGACCTACATCCACAGTATGAACCCAAGCATCTTGGAGGACTGGAACTTTGGACTGACACCTCCTCCATCTGGCACCTTGGAGGACACCTACAGATATGTGACCAGCCAGGCTGTGACTTGTCAGAAGCCATCTGCCCCAAAGCCAAAGGATGACCCACTGAAAAACTACAC CTTCTGGGAGGTGGACCTGAAAGAGAAGTTCTCTGCTGACCTGGACCAGTTTCCACTGGGCAGGAAGTTCCTGCTCCAAGCAGGACTGAAAGCCAGACCAAACTTCAGACTGGGCAAGAGGGCTGCCCCTGCCAGCACCAGCAAGAAGTCCAGCACCAAGAGGAGGAAGGTGAAGAGCTAAActcgagctc SEQ ID No: 36 Synthetic gene HPV39 L1 ctgggtaccATGGCTATGTGGAGGTCCTCTGACAGTATGGTCTACCTGCCTCCTCCATCTGTGGCTAAGGTGGTGAACACAGATGACTATGTGACCAGGACAGGCATCTACTACTATGCTGGCTCCAGCAGACTGCTGACAGTGGGACACCCATACTTCAAGGTGGGGATGAATGGAGGCAGGAAGCAGGAC ATCCCAAAGGTGTCTGCCTACCAATACAGGGTGTTCAGGGTGACCCTGCCTGACCCAAACAAGTTCAGCATCCCTGATGCCTCCCTCTACAACCCTGAGACCCAGAGACTGGTGTGGGCTTGTGTGGGAGTGGAGGTGGGCAGGGGACAACCACTGGGAGTGGGCATCTCTGGACACCCACTCTACAACAGA CAGGATGACACAGAGAACAGCCCATTCTCCAGCACCACCAACAAGGACAGCAGGGACAATGTGTCTGTGGACTACAAGCAGACCCAACTTTGTATCATTGGCTGTGTGCCTGCCATTGGAGAACACTGGGGCAAGGGCAAGGCTTGTAAGCCAAACAATGTGAGCACAGGAGACTGTCCTCCATTGGAACTG GTGAACACACCAATTGAGGATGGAGATATGATTGACACAGGCTATGGAGCTATGGACTTTGGAGCCCTCCAAGAGACCAAGTCTGAGGTGCCACTGGACATCTGTCAGAGCATCTGTAAATACCCTGACTACCTCCAAATGAGTGCTGATGTCTATGGAGACAGTATGTTCTTCTGTCTGAGGAGGGAACAA CTTTTTGCCAGACACTTCTGGAACAGGGGAGGGATGGTGGGAGATGCCATCCCTGCCCAACTCTACATCAAGGGCACAGACATCAGGGCTAACCCTGGCTCCTCTGTCTACTGTCCAAGCCCATCTGGCAGTATGGTGACCTCTGACAGCCAACTTTTCAACAAGCCATACTGGCTGCACAAGGCTCAAGGA CACAACAATGGCATCTGTTGGCACAACCAACTTTTCCTGACAGTGGTGGACACCACCAGGAGCACCAACTTCACCCTGAGCACCAGCATTGAGTCCAGCATCCCAAGCACCTAGCCCAAGCAAGTTCAAGGAATACACCAGGCATGTGGAGGAATATGACCTCCAATTCATCTTCCAACTTTGTACTGTG ACCCTGACCACAGATGTGATGAGTTACATCCACACAATGAACTCCAGCATCCTGGACAACTGGAACTTTGCTGTGGCTCCTCCTCCATCTGCCTCCCTGGTGGACACCTACAGATACCTCCAATCTGCTGCCATCACTTGTCAGAAGGATGCCCCTGCCCCTGAGAAGAAGGACCCATATGATGGACTGAAG TTCTGGAATGTGGACCTGAGGGAGAAGTTCTCCTTGGAACTGGACCAGTTTCCACTGGGCAGGAAGTTCCTGCTCCAAGCCAGGGTGAGGAGGAGACCAACCATTGGACCAAGGAAGAGACCTGCTGCCAGCACCTCCTCCTCCTCTGCCACCAAACACAAGAGGAAGAGGGTGAGCAAGTAAActcgagctc SEQ ID No: 37 Synthetic gene HPV45 L1 ctgggtaccATGGCTCTGTGGAGACCATCTGACAGCACAGTCTACCTGCCTCCTCCATCTGTGGCAAGGGTGGTGAACACAGATGACTATGTGAGCAGGACCAGCATCTTCTACCATGCTGGCTCCAGCAGACTGCTGACAGTGGGCAACCCATACTTCAGGGTGGTGCCAAGTGGAGCAGGCAACAAGCAG GCTGTGCCAAAGGTGTCTGCCTACCAATACAGGGTGTTCAGGGTGGCTCTGCCTGACCCAAACAAGTTTGGACTGCCTGACAGCACCATCTACAACCCTGAGACCCAGAGACTGGTGTGGGCTTGTGTGGGGATGGAGATTGGCAGGGGACAACCACTGGGCATTGGACTGTCTGGACACCCATTCTACAACA AACTGGATGACACAGAGTCTGCCCATGCTGCCACAGCAGTGATTACCCAGGATGTGAGGGACAATGTGTCTGTGGACTACAAGCAGACCCAACTTTGTATCCTGGGCTGTGTGCCTGCCATTGGAGAACACTGGGCTAAGGGCACCCTGTGTAAGCCTGCCCAACTCCAACCTGGAGACTGTCCTCCATTGGA ACTGAAAAACACCATCATTGAGGATGGAGATATGGTGGACACAGGCTATGGAGCTATGGACTTCAGCACCTCTCCAAGACACCAAGTGTGAGGTGCCACTGGACATCTGTCAGAGCATCTGTAAATACCCTGACTACCTCCAAATGAGTGCTGACCCATATGGAGACAGTATGTTCTTCTGTCTGAGGAGGGAA CAACTTTTTGCCAGACACTTCTGGAACAGGGCTGGAGTGATGGGAGACACAGTGCCAACAGACCTCTACATCAAGGGCACCTCTGCCAATATGAGGGAGACACCTGGCTCCTGTGTCTACAGCCCAAGCCCATCTGGCAGCATCACCACCTCTGACAGCCAACTTTTCAACAAGCCATACTGGCTGCACAAGG CTCAAGGACACAACAATGGCATCTGTTGGCACAACCAACTTTTTGTGACAGTGGTGGACACCACCAGGAGCACCAACCTGACCCTGTGTGCCAGCACCCAGAACCCTGTGCCAAACACCTATGACCCAACCAAGTTCAAGCACTACAGCAGGCATGTGGAGGAATATGACCTCCAATTCATCTTCCAACTTTG TACCATCACCCTGACAGCAGAGGTGATGAGTTACATCCACAGTATGAACTCCAGCATCTTGGAGAACTGGAACTTTGGAGTGCCTCCTCCTCCAACCACCTCCCTGGTGGACACCTACAGGTTTGTCCAGTCTGTGGCTGTGACTTGTCAGAAGGACACCACACCTCCTGAGAAGCAGGACCCATATGACAAA CTGAAGTTCTGGACAGTGGACCTGAAAGAGAAGTTCTCCTCTGACCTGGACCAATACCCACTGGGCAGGAAGTTCCTGGTCCAGGCTGGACTGAGGAGGAGACCAACCATTGGACCAAGGAAGAGACCTGCTGCCAGCACCAGCACAGCCAGCAGACCTGCCAAGAGGGTGAGGATTAGGAGCAAGAAGTAAA ctcgagctc SEQ ID No: 38 Synthetic gene HPV51 L1 ctgggtaccATGGCTCTGTGGAGGACCAATGACAGCAAGGTCTACCTGCCTCCTGCCCCTGTGAGCAGGATTGTGAACACAGAGGAATACATCACCAGGACAGGCATCTACTATGCTGGCTCCAGCAGACTGATTACCCTGGGACACCCATACTTTCCAATCCCAAAGACCAGCACCAGGGCTGCCAT CCCAAAGGTGTCTGCCTTCCAATACAGGGTGTTCAGGGTCCAACTTCCTGACCCAAACAAGTTTGGACTGCCTGACCCAAACCTCTACAACCCTGACACAGACAGACTGGTGTGGGGCTGTGTGGGAGTGGAGGTGGGCAGGGGACAACCACTGGGAGTGGGACTGTCTGGACACCCACTGTTCAACAAATA TGATGACACAGAGAACAGCAGGATTGCCAATGGCAATGCCCAACAGGATGTGAGGGACAACACCTCTGTGGACAACAAGCAGACCCAACTTTGTATCATTGGCTGTGCCCCTCCAATTGGAGAACACTGGGGCATTGGCACCACTTGTAAGAACACACCTGTGCCTCCTGGAGACTGTCCTCCATTGGAACT GGTGTCCTCTGTGATTCAGGATGGAGATATGATTGACACAGGCTTTGGAGCTATGGACTTTGCTGCCCTCCAAGCCACCAAGTCTGATGTGCCACTGGACATCAGCCAGTCTGTGTGTAAATACCCTGACTACCTGAAAATGAGTGCTGACACCTATGGCAACAGTATGTTCTTCCACCTGAGGAGGGAACA GATTTTTGCCAGACACTACTACAACAAACTGGTGGGAGTGGGAGAGGACATCCCAAATGACTACTACATCAAGGGCTCTGGCAATGGCAGGGACCCAATTGAGTCCTACATCTACTCTGCCACACCATCTGGCAGTATGATTACCCTGACAGCCAGATTTTCAACAAGCCATACTGGCTGCACAGGGCTC AAGGACACAACAATGGCATCTGTTGGAACAACCAACTTTTCATCACTTGTGTGGACACCACCAGGAGCACCAACCTGACCATCAGCACAGCCACAGCAGCAGTGAGCCCAACCTTCACACCAAGCAACTTCAAGCAATACATCAGACATGGAGAGGAATATGAACTCCAATTCATCTTCCAACTTTGTAAGA TTACCCTGACCACAGAGGTGATGGCTTACCTGCACACAATGGACCCAACCATCTTGGAACAGTGGAACTTTGGACTGACCCTGCCTCCATCTGCCTCCTTGGAGGATGCCTACAGGTTTGTGAGGAATGCTGCCACCTCCTGTCAGAAGGACACACCTCCACAGGCTAAGCCTGACCCACTGGCTAAATACA AGTTCTGGGATGTGGACCTGAAAGAGAGGTTCTCCCTGGACCTGGACCAGTTTGCCCTGGGCAGGAAGTTCCTGCTCCAAGTGGGAGTCCAGAGGAAGCCAAGACCTGGACTGAAAAGACCTGCCTCCTCTGCCTCCTCCTCCTCCTCCTCCTCTGCCAAGAGGAAGAGGGTGAAGAAGTAAActcgagctc SEQ ID No: 39 Synthetic gene HPV52 L1 ctgggtaccATGAGCGTGTGGAGGCCCAGCGAGGCCACCGTGTACCTGCCCCCCGTGCCCGTGAGCAAGGTGGTGAGCACCGACGAGTACGTGAGCAGGACCAGCATCTACTACTACGCCGGCAGCAGCAGGCTGCTGACCGTGGGCCACCCCTACTTCAGCATCAAGAACACCAGCAGCGGCAACGGCAA GAAGGTGCTGGTGCCCAAGGTGAGCGGCCTGCAGTACAGGGTGTTCAGGATCAAGCTGCCCGACCCCAACAAGTTCGGCTTCCCCGACACCAGCTTCTACAACCCCGAGACCCAGAGGCTGGTGTGGGCCTGCACCGGCCTGGAGATCGGCAGGGGCCAGCCCCTGGGCGTGGGCATCAGCGGCCACCCCC TGCTGAACAAGTTCGACGACACCGAGACCAGCAACAAGTACGCCGGCAAGCCCGGCATCGACAACAGGGAGTGCCTGAGCATGGACTACAAGCAGACCCAGCTGTGCATCCTGGGCTGCAAGCCCCCCATCGGCGAGCACTGGGGCAAGGGCACCCCCTGCAACAACAACAGCGGCAACCCCGGCGACTGC CCCCCCCTGCAGCTGATCAACAGCGTGATCCAGGACGGCGACATGGTGGACACCGGCTTCGGCTGCATGGACTTCAACACCCTGCAGGCCAGCAAGAGCGACGTGCCCATCGACATCTGCAGCAGCGTGTGCAAGTACCCCGACTACCTGCAGATGGCCAGCGAGCCCTACGGCGACAGCCTGTTCTTCTTC CTGAGGAGGGAGCAGATGTTCGTGAGGCACTTCTTCAACAGGGCCGGCACCCTGGGCGACCCCGTGCCCGGCGACCTGTACATCCAGGGCAGCAACAGCGGCAACACCGCCACCGTGCAGAGCAGCGCCTTCTTCCCCACCCCCAGCGGCAGCATGGTGACCAGCGAGAGCCAGCTGTTCAACAAGCCCTA CTGGCTGCAGAGGGCCCAGGGCCACAACAACGGCATCTGCTGGGGCAACCAGCTGTTCGTGACCGTGGTGGACACCACCAGGAGCACCAACATGACCCTGTGCGCCGAGGTGAAGAAGGAGAGCACCTACAAGAACGAGAACTTCAAGGAGTACCTGAGGCACGGCGAGGAGTTCGACCTGCAGTTCATCTT CCAGCTGTGCAAGATCACCCTGACCGCCGACGTGATGACCTACATCCACAAGATGGACGCCACCATCCTGGAGGACTGGCAGTTCGGCCTGACCCCCCCCCCCAGCGCCAGCCTGGAGGACACCTACAGGTTCGTGACCAGCACCGCCATCACCTGCCAGAAGAACACCCCCCCCAAGGGCAAGGAGGACC CCCTGAAGGACTACATGTTCTGGGAGGTGGAACCTGAAGGAGAAGTTCAGCGCCGACCTGGACCAGTTCCCCCTGGGCAGGAAGTTCCTGCTGCAGGCCGGCCTGCAGGCCAGGCCCAAGCTGAAGAGGCCCGCCAGCAGCGCCCCCAGGACCAGCACCAAGAAGAAGAAGGTGAAGAGGTAAActcgagctc SEQ ID No: 40 Synthetic gene HPV56 L1 ctgggtaccATGGCTACCTGGAGACCATCTGAGAACAAGGTCTACCTGCCTCCAACACCTGTGAGCAAGGTGGTGGCTACAGACTCCTATGTGAAGAGGACCAGCATCTTCTACCATGCTGGCTCCAGCAGACTGCTGGCTGTGGGACACCCATACTACTCTGTGACCAAGGACAACACCAAGACCAAC ATCCCAAAGGTGTCTGCCTACCAATACAGGGTGTTCAGGGTGAGACTGCCTGACCAAACAAGTTTGGACTGCCTGACACCAACATCTACAACCCTGACCAGGAGAGACTGGTGTGGGCTTGTGTGGGATTGGAGGTGGGCAGGGGACAACCACTGGGAGCAGGACTGTCTGGACACCCACTGTTCAACA GACTGGATGACACAGAGTCCAGCAACCTGGCTAACAACAATGTGATTGAGGACAGCAGGGACAACATCTCTGTGGATGGCAAGCAGACCCAACTTTGTATTGTGGGCTGTACTCCTGCTATGGGAGAACACTGGACCAAGGGAGCAGTGTGTAAGAGCACCCAGGTGACCACAGGAGACTGTCCTCCACT GGCTCTGATAAACACACCAATTGAGGATGGAGATATGATTGACACAGGCTTTGGAGCTATGGACTTCAAGGTGCTCCAAGAGAGCAAGGCTGAGGTGCCACTGGACATTGTCCAGAGCACTTGTAAATACCCTGACTACCTGAAAATGAGTGCTGATGCCTATGGAGACAGTATGTGGTTCTACCTGAGG AGGGAACAACTTTTTGCCAGACACTACTTCAACAGGGCTGGCAAGGTGGGAGAGACCATCCCTGCTGAACTCTACCTGAAAGGCAGCAATGGCAGGGAACCTCCTCCATCCTCTGTCTATGTGGCTACACCATCTGGCAGTATGATTACCCTGAGGCTCAACTTTTCAACAAGCCATACTGGCTCCAAA GGGCTCAAGGACACAACAATGGCATCTGTTGGGGCAACCAACTTTTTGTGACAGTGGTGGACACCACCAGGAGCACCAATATGACCATCAGCACAGCCACAGAACAACTTAGCAAATATGATGCCAGGAAGATAAACCAATACCTGAGGCATGTGGAGGAATATGAACTCCAATTTGTGTTCCAACTTTG TAAGATTACCCTGTCTGCTGAGGTGATGGCTTACCTGCACAATATGAATGCCAACCTGTTGGAGGACTGGAACATTGGACTGAGCCCTCCTGTGGCTACCTCCTTGGAGGACAAATACAGATATGTGAGGAGCACAGCCATCACTTGTCAGAGGGAACAACCTCCAACAGAGAAGCAGGACCCACTGGCT AAATACAAGTTCTGGGATGTGAACCTCCAAGACTCCTTCAGCACAGACCTGGACCAGTTTCCACTGGGCAGGAAGTTCCTGATGCAACTTGGCACCAGGAGCAAGCCTGCTGTGGCTACCAGCAAGAAGAGGTCTGCCCCAACCAGCACCAGCACACCTGCCAAGAGGAAGAGGAGGTAAActcgagctc SEQ ID No: 41 Synthetic gene HPV58 L1 ctgggtaccATGAGCGTGTGGAGGCCCAGCGAGGCCACCGTGTACCTGCCCCCCGTGCCCGTGAGCAAGGTGGTGAGCACCGACGAGTACGTGAGCAGGACCAGCATCTACTACTACGCCGGCAGCAGCAGGCTGCTGGCCGTGGGCAACCCCTACTTCAGCATCAAGAGCCCCAACAACAACAAGAA GGTGCTGGTGCCCAAGGTGAGCGGCCTGCAGTACAGGGTGTTCAGGGTGAGGCTGCCCGACCCCAACAAGTTCGGCTTCCCCGACACCAGCTTCTACAACCCCGACACCCAGAGGCTGGTGTGGGCCTGCGTGGGCCTGGAGATCGGCAGGGGCCAGCCCCTGGGCGTGGGCGTGAGCGGCCACCCCT ACCTGAACAAGTTCGACGACACCGAGACCAGCAACAGGTACCCCGCCCAGCCCGGCAGCGACAACAGGGAGTGCCTGAGCATGGACTACAAGCAGACCCAGCTGTGCCTGATCGGCTGCAAGCCCCCCACCGGCGAGCACTGGGGCAAGGGCGTGGCCTGCAACAACAACGCCGCCGCCACCGACTGC CCCCCCCTGGAGCTGTTCAACAGCATCATCGAGGACGGCGACATGGTGGACACCGGCTTCGGCTGCATGGACTTCGGCACCCTGCAGGCCAACAAGAGCGACGTGCCCATCGACATCTGCAACAGCACCTGCAAGTACCCCGACTACCTGAAGATGGCCAGCGAGCCCTACGGCGACAGCCTGTTCTTC TTCCTGAGGAGGGAGCAGATGTTCGTGAGGCACTTCTTCAACAGGGCCGGCAAGCTGGGCGAGGCCGTGCCCGACGACCTGTACATCAAGGGCAGCGGCAACACCGCCGTGATCCAGAGCAGCGCCTTCTTCCCCACCCCCAGCGGCAGCATCGTGACCAGCGAGAGCCAGCTGTTCAACAAGCCCTA CTGGCTGCAGAGGGCCCAGGGCCACAACAACGGCATCTGCTGGGGCAACCAGCTGTTCGTGACCGTGGTGGACACCACCAGGAGCACCAACATGACCCTGTGCACCGAGGTGACCAAGGAGGGCACCTACAAGAACGACAACTTCAAGGAGTACGTGAGGCACGTGGAGGAGTACGACCTGCAGTTCGT GTTCCAGCTGTGCAAGATCACCCTGACCGCCGAGATCATGACCTACATCCACACCATGGACAGCAACATCCTGGAGGACTGGCAGTTCGGCCTGACCCCCCCCCCCAGCGCCAGCCTGCAGGACACCTACAGGTTCGTGACCAGCCAGGCCATCACCTGCCAGAAGACCGCCCCCCCCAAGGAGAAGG AGGACCCCCTGAACAAGTACACCTTCTGGGAGGTGAACCTGAAGGAGAAGTTCAGCGCCGACCTGGACCAGTTCCCCCTGGGCAGGAAGTTCCTGCTGCAGAGCGGCCTGAAGGCCAAGCCCAGGCTGAAGAGGAGCGCCCCCACCACCAGGGCCCCCAGCACCAAGAGGAAGAAGGTGAAGAAGTAAA ctcgagctc

--->

SEQUENCE LIST

<110> SINOCELLTECH

<120> STABLE VACCINE PREPARATION FROM VIRUS-LIKE PARTICLES OF PAPILLOMAVIRUS

HUMAN

<130> PCT74213SXB

<160> 41

<170> PatentIn version 3.3

<210> 1

<211> 26

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 1

Lys Ala Lys Pro Lys Leu Lys Arg Ala Ala Pro Thr Ser Thr Arg Thr

1 5 10 15

Ser Ser Ala Lys Arg Lys Lys Val Lys Lys

20 25

<210> 2

<211> 31

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 2

Leu Gln Ala Gly Leu Lys Ala Lys Pro Lys Leu Lys Arg Ala Ala Pro

1 5 10 15

Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys Lys Val Lys Lys

20 25 30

<210> 3

<211> 38

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 3

Leu Gln Leu Gly Ala Arg Pro Lys Pro Thr Ile Gly Pro Arg Lys Arg

1 5 10 15

Ala Ala Pro Ala Pro Thr Ser Thr Pro Ser Pro Lys Arg Val Lys Arg

20 25 30

Arg Lys Ser Ser Arg Lys

35

<210> 4

<211> 469

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 4

Met Trp Arg Pro Ser Asp Ser Thr Val Tyr Val Pro Pro Pro Asn Pro

1 5 10 15

Val Ser Lys Val Val Ala Thr Asp Ala Tyr Val Thr Arg Thr Asn Ile

20 25 30

Phe Tyr His Ala Ser Ser Ser Arg Leu Leu Ala Val Gly His Pro Tyr

35 40 45

Phe Ser Ile Lys Arg Ala Asn Lys Thr Val Val Pro Lys Val Ser Gly

50 55 60

Tyr Gln Tyr Arg Val Phe Lys Val Val Leu Pro Asp Pro Asn Lys Phe

65 70 75 80

Ala Leu Pro Asp Ser Ser Leu Phe Asp Pro Thr Thr Gln Arg Leu Val

85 90 95

Trp Ala Cys Thr Gly Leu Glu Val Gly Arg Gly Gln Pro Leu Gly Val

100 105 110

Gly Val Ser Gly His Pro Phe Leu Asn Lys Tyr Asp Asp Val Glu Asn

115 120 125

Ser Gly Ser Gly Gly Asn Pro Gly Gln Asp Asn Arg Val Asn Val Gly

130 135 140

Met Asp Tyr Lys Gln Thr Gln Leu Cys Met Val Gly Cys Ala Pro Pro

145 150 155 160

Leu Gly Glu His Trp Gly Lys Gly Lys Gln Cys Thr Asn Thr Pro Val

165 170 175

Gln Ala Gly Asp Cys Pro Pro Leu Glu Leu Ile Thr Ser Val Ile Gln

180 185 190

Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala Met Asn Phe Ala Asp

195 200 205

Leu Gln Thr Asn Lys Ser Asp Val Pro Ile Asp Ile Cys Gly Thr Thr

210 215 220

Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ala Ala Asp Pro Tyr Gly Asp

225 230 235 240

Arg Leu Phe Phe Phe Leu Arg Lys Glu Gln Met Phe Ala Arg His Phe

245 250 255

Phe Asn Arg Ala Gly Glu Val Gly Glu Pro Val Pro Asp Thr Leu Ile

260 265 270

Ile Lys Gly Ser Gly Asn Arg Thr Ser Val Gly Ser Ser Ile Tyr Val

275 280 285

Asn Thr Pro Ser Gly Ser Leu Val Ser Ser Glu Ala Gln Leu Phe Asn

290 295 300

Lys Pro Tyr Trp Leu Gln Lys Ala Gln Gly His Asn Asn Gly Ile Cys

305 310 315 320

Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp Thr Thr Arg Ser Thr

325 330 335

Asn Met Thr Leu Cys Ala Ser Val Thr Thr Ser Ser Thr Tyr Thr Asn

340 345 350

Ser Asp Tyr Lys Glu Tyr Met Arg His Val Glu Glu Tyr Asp Leu Gln

355 360 365

Phe Ile Phe Gln Leu Cys Ser Ile Thr Leu Ser Ala Glu Val Met Ala

370 375 380

Tyr Ile His Thr Met Asn Pro Ser Val Leu Glu Asp Trp Asn Phe Gly

385 390 395 400

Leu Ser Pro Pro Pro Asn Gly Thr Leu Glu Asp Thr Tyr Arg Tyr Val

405 410 415

Gln Ser Gln Ala Ile Thr Cys Gln Lys Pro Thr Pro Glu Lys Glu Lys

420 425 430

Pro Asp Pro Tyr Lys Asn Leu Ser Phe Trp Glu Val Asn Leu Lys Glu

435 440 445

Lys Phe Ser Ser Glu Leu Asp Gln Tyr Pro Leu Gly Arg Lys Phe Leu

450 455 460

Leu Gln Ser Gly Tyr

465

<210> 5

<211> 470

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 5

Met Trp Arg Pro Ser Asp Ser Thr Val Tyr Val Pro Pro Pro Asn Pro

1 5 10 15

Val Ser Lys Val Val Ala Thr Asp Ala Tyr Val Lys Arg Thr Asn Ile

20 25 30

Phe Tyr His Ala Ser Ser Ser Arg Leu Leu Ala Val Gly His Pro Tyr

35 40 45

Tyr Ser Ile Lys Lys Val Asn Lys Thr Val Val Pro Lys Val Ser Gly

50 55 60

Tyr Gln Tyr Arg Val Phe Lys Val Val Leu Pro Asp Pro Asn Lys Phe

65 70 75 80

Ala Leu Pro Asp Ser Ser Leu Phe Asp Pro Thr Thr Gln Arg Leu Val

85 90 95

Trp Ala Cys Thr Gly Leu Glu Val Gly Arg Gly Gln Pro Leu Gly Val

100 105 110

Gly Val Ser Gly His Pro Leu Leu Asn Lys Tyr Asp Asp Val Glu Asn

115 120 125

Ser Gly Gly Tyr Gly Gly Asn Pro Gly Gln Asp Asn Arg Val Asn Val

130 135 140

Gly Met Asp Tyr Lys Gln Thr Gln Leu Cys Met Val Gly Cys Ala Pro

145 150 155 160

Pro Leu Gly Glu His Trp Gly Lys Gly Thr Gln Cys Ser Asn Thr Ser

165 170 175

Val Gln Asn Gly Asp Cys Pro Pro Leu Glu Leu Ile Thr Ser Val Ile

180 185 190

Gln Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala Met Asn Phe Ala

195 200 205

Asp Leu Gln Thr Asn Lys Ser Asp Val Pro Leu Asp Ile Cys Gly Thr

210 215 220

Val Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ala Ala Asp Pro Tyr Gly

225 230 235 240

Asp Arg Leu Phe Phe Tyr Leu Arg Lys Glu Gln Met Phe Ala Arg His

245 250 255

Phe Phe Asn Arg Ala Gly Thr Val Gly Glu Pro Val Pro Asp Asp Leu

260 265 270

Leu Val Lys Gly Gly Asn Asn Arg Ser Ser Val Ala Ser Ser Ile Tyr

275 280 285

Val His Thr Pro Ser Gly Ser Leu Val Ser Ser Glu Ala Gln Leu Phe

290 295 300

Asn Lys Pro Tyr Trp Leu Gln Lys Ala Gln Gly His Asn Asn Gly Ile

305 310 315 320

Cys Trp Gly Asn His Leu Phe Val Thr Val Val Asp Thr Thr Arg Ser

325 330 335

Thr Asn Met Thr Leu Cys Ala Ser Val Ser Lys Ser Ala Thr Tyr Thr

340 345 350

Asn Ser Asp Tyr Lys Glu Tyr Met Arg His Val Glu Glu Phe Asp Leu

355 360 365

Gln Phe Ile Phe Gln Leu Cys Ser Ile Thr Leu Ser Ala Glu Val Met

370 375 380

Ala Tyr Ile His Thr Met Asn Pro Ser Val Leu Glu Asp Trp Asn Phe

385 390 395 400

Gly Leu Ser Pro Pro Pro Asn Gly Thr Leu Glu Asp Thr Tyr Arg Tyr

405 410 415

Val Gln Ser Gln Ala Ile Thr Cys Gln Lys Pro Thr Pro Glu Lys Glu

420 425 430

Lys Gln Asp Pro Tyr Lys Asp Met Ser Phe Trp Glu Val Asn Leu Lys

435 440 445

Glu Lys Phe Ser Ser Glu Leu Asp Gln Phe Pro Leu Gly Arg Lys Phe

450 455 460

Leu Leu Gln Ser Gly Tyr

465 470

<210> 6

<211> 474

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 6

Met Ser Leu Trp Leu Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Ala Arg Thr Asn

20 25 30

Ile Tyr Tyr His Ala Gly Thr Ser Arg Leu Leu Ala Val Gly His Pro

35 40 45

Tyr Phe Pro Ile Lys Lys Pro Asn Asn Asn Lys Ile Leu Val Pro Lys

50 55 60

Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Ile His Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro Asp Thr Gln

85 90 95

Arg Leu Val Trp Ala Cys Val Gly Val Glu Val Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys Leu Asp Asp

115 120 125

Thr Glu Asn Ala Ser Ala Tyr Ala Ala Asn Ala Gly Val Asp Asn Arg

130 135 140

Glu Cys Ile Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Ile Gly

145 150 155 160

Cys Lys Pro Pro Ile Gly Glu His Trp Gly Lys Gly Ser Pro Cys Thr

165 170 175

Asn Val Ala Val Asn Pro Gly Asp Cys Pro Pro Leu Glu Leu Ile Asn

180 185 190

Thr Val Ile Gln Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala Met

195 200 205

Asp Phe Thr Thr Leu Gln Ala Asn Lys Ser Glu Val Pro Leu Asp Ile

210 215 220

Cys Thr Ser Ile Cys Lys Tyr Pro Asp Tyr Ile Lys Met Val Ser Glu

225 230 235 240

Pro Tyr Gly Asp Ser Leu Phe Phe Tyr Leu Arg Arg Glu Gln Met Phe

245 250 255

Val Arg His Leu Phe Asn Arg Ala Gly Ala Val Gly Glu Asn Val Pro

260 265 270

Asp Asp Leu Tyr Ile Lys Gly Ser Gly Ser Thr Ala Asn Leu Ala Ser

275 280 285

Ser Asn Tyr Phe Pro Thr Pro Ser Gly Ser Met Val Thr Ser Asp Ala

290 295 300

Gln Ile Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn

305 310 315 320

Asn Gly Ile Cys Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Met Ser Leu Cys Ala Ala Ile Ser Thr Ser Glu

340 345 350

Thr Thr Tyr Lys Asn Thr Asn Phe Lys Glu Tyr Leu Arg His Gly Glu

355 360 365

Glu Tyr Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu Thr

370 375 380

Ala Asp Val Met Thr Tyr Ile His Ser Met Asn Ser Thr Ile Leu Glu

385 390 395 400

Asp Trp Asn Phe Gly Leu Gln Pro Pro Pro Gly Gly Thr Leu Glu Asp

405 410 415

Thr Tyr Arg Phe Val Thr Ser Gln Ala Ile Ala Cys Gln Lys His Thr

420 425 430

Pro Pro Ala Pro Lys Glu Asp Pro Leu Lys Lys Tyr Thr Phe Trp Glu

435 440 445

Val Asn Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro Leu

450 455 460

Gly Arg Lys Phe Leu Leu Gln Ala Gly Leu

465 470

<210> 7

<211> 470

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 7

Met Ala Leu Trp Arg Pro Ser Asp Asn Thr Val Tyr Leu Pro Pro Pro

1 5 10 15

Ser Val Ala Arg Val Val Asn Thr Asp Asp Tyr Val Thr Arg Thr Ser

20 25 30

Ile Phe Tyr His Ala Gly Ser Ser Arg Leu Leu Thr Val Gly Asn Pro

35 40 45

Tyr Phe Arg Val Pro Ala Gly Gly Gly Asn Lys Gln Asp Ile Pro Lys

50 55 60

Val Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Gln Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Gly Leu Pro Asp Thr Ser Ile Tyr Asn Pro Glu Thr Gln

85 90 95

Arg Leu Val Trp Ala Cys Ala Gly Val Glu Ile Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Leu Ser Gly His Pro Phe Tyr Asn Lys Leu Asp Asp

115 120 125

Thr Glu Ser Ser His Ala Ala Thr Ser Asn Val Ser Glu Asp Val Arg

130 135 140

Asp Asn Val Ser Val Asp Tyr Lys Gln Thr Gln Leu Cys Ile Leu Gly

145 150 155 160

Cys Ala Pro Ala Ile Gly Glu His Trp Ala Lys Gly Thr Ala Cys Lys

165 170 175

Ser Arg Pro Leu Ser Gln Gly Asp Cys Pro Pro Leu Glu Leu Lys Asn

180 185 190

Thr Val Leu Glu Asp Gly Asp Met Val Asp Thr Gly Tyr Gly Ala Met

195 200 205

Asp Phe Ser Thr Leu Gln Asp Thr Lys Cys Glu Val Pro Leu Asp Ile

210 215 220

Cys Gln Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala Asp

225 230 235 240

Pro Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Arg Glu Gln Leu Phe

245 250 255

Ala Arg His Phe Trp Asn Arg Ala Gly Thr Met Gly Asp Thr Val Pro

260 265 270

Gln Ser Leu Tyr Ile Lys Gly Thr Gly Met Arg Ala Ser Pro Gly Ser

275 280 285

Cys Val Tyr Ser Pro Ser Pro Ser Gly Ser Ile Val Thr Ser Asp Ser

290 295 300

Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln Gly His Asn

305 310 315 320

Asn Gly Val Cys Trp His Asn Gln Leu Phe Val Thr Val Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Leu Thr Ile Cys Ala Ser Thr Gln Ser Pro Val

340 345 350

Pro Gly Gln Tyr Asp Ala Thr Lys Phe Lys Gln Tyr Ser Arg His Val

355 360 365

Glu Glu Tyr Asp Leu Gln Phe Ile Phe Gln Leu Cys Thr Ile Thr Leu

370 375 380

Thr Ala Asp Val Met Ser Tyr Ile His Ser Met Asn Ser Ser Ile Leu

385 390 395 400

Glu Asp Trp Asn Phe Gly Val Pro Pro Pro Pro Thr Thr Ser Leu Val

405 410 415

Asp Thr Tyr Arg Phe Val Gln Ser Val Ala Ile Thr Cys Gln Lys Asp

420 425 430

Ala Ala Pro Ala Glu Asn Lys Asp Pro Tyr Asp Lys Leu Lys Phe Trp

435 440 445

Asn Val Asp Leu Lys Glu Lys Phe Ser Leu Asp Leu Asp Gln Tyr Pro

450 455 460

Leu Gly Arg Lys Phe Leu

465 470

<210> 8

<211> 475

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 8

Met Ser Leu Trp Arg Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Thr Arg Thr Asn

20 25 30

Ile Tyr Tyr His Ala Gly Ser Ala Arg Leu Leu Thr Val Gly His Pro

35 40 45

Tyr Tyr Ser Ile Pro Lys Ser Asp Asn Pro Lys Lys Ile Val Val Pro

50 55 60

Lys Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Val Arg Leu Pro Asp

65 70 75 80

Pro Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro Glu Thr

85 90 95

Gln Arg Leu Val Trp Ala Cys Val Gly Leu Glu Val Gly Arg Gly Gln

100 105 110

Pro Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys Phe Asp

115 120 125

Asp Thr Glu Asn Ser Asn Arg Tyr Ala Gly Gly Pro Gly Thr Asp Asn

130 135 140

Arg Glu Cys Ile Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Leu

145 150 155 160

Gly Cys Lys Pro Pro Ile Gly Glu His Trp Gly Lys Gly Ser Pro Cys

165 170 175

Ser Asn Asn Ala Ile Thr Pro Gly Asp Cys Pro Pro Leu Glu Leu Lys

180 185 190

Asn Ser Val Ile Gln Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala

195 200 205

Met Asp Phe Thr Ala Leu Gln Asp Thr Lys Ser Asn Val Pro Leu Asp

210 215 220

Ile Cys Asn Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Lys Met Val Ala

225 230 235 240

Glu Pro Tyr Gly Asp Thr Leu Phe Phe Tyr Leu Arg Arg Glu Gln Met

245 250 255

Phe Val Arg His Phe Phe Asn Arg Ser Gly Thr Val Gly Glu Ser Val

260 265 270

Pro Thr Asp Leu Tyr Ile Lys Gly Ser Gly Ser Thr Ala Thr Leu Ala

275 280 285

Asn Ser Thr Tyr Phe Pro Thr Pro Ser Gly Ser Met Val Thr Ser Asp

290 295 300

Ala Gln Ile Phe Asn Lys Pro Tyr Trp Met Gln Arg Ala Gln Gly His

305 310 315 320

Asn Asn Gly Ile Cys Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp

325 330 335

Thr Thr Arg Ser Thr Asn Met Ser Val Cys Ala Ala Ile Ala Asn Ser

340 345 350

Asp Thr Thr Phe Lys Ser Ser Asn Phe Lys Glu Tyr Leu Arg His Gly

355 360 365

Glu Glu Phe Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu

370 375 380

Ser Ala Asp Ile Met Thr Tyr Ile His Ser Met Asn Pro Ala Ile Leu

385 390 395 400

Glu Asp Trp Asn Phe Gly Leu Thr Thr Pro Pro Ser Gly Ser Leu Glu

405 410 415

Asp Thr Tyr Arg Phe Val Thr Ser Gln Ala Ile Thr Cys Gln Lys Ser

420 425 430

Ala Pro Gln Lys Pro Lys Glu Asp Pro Phe Lys Asp Tyr Val Phe Trp

435 440 445

Glu Val Asn Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro

450 455 460

Leu Gly Arg Lys Phe Leu Leu Gln Ala Gly Tyr

465 470 475

<210> 9

<211> 472

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 9

Met Ser Leu Trp Arg Ser Asn Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Ser Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Thr Arg Thr Asn

20 25 30

Ile Tyr Tyr His Ala Gly Ser Ser Arg Leu Leu Ala Val Gly His Pro

35 40 45

Tyr Tyr Ala Ile Lys Lys Gln Asp Ser Asn Lys Ile Ala Val Pro Lys

50 55 60

Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Val Lys Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asp Pro Ala Ser Gln

85 90 95

Arg Leu Val Trp Ala Cys Thr Gly Val Glu Val Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys Leu Asp Asp

115 120 125

Thr Glu Asn Ser Asn Lys Tyr Val Gly Asn Ser Gly Thr Asp Asn Arg

130 135 140

Glu Cys Ile Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Ile Gly

145 150 155 160

Cys Arg Pro Pro Ile Gly Glu His Trp Gly Lys Gly Thr Pro Cys Asn

165 170 175

Ala Asn Gln Val Lys Ala Gly Glu Cys Pro Pro Leu Glu Leu Leu Asn

180 185 190

Thr Val Leu Gln Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala Met

195 200 205

Asp Phe Thr Thr Leu Gln Ala Asn Lys Ser Asp Val Pro Leu Asp Ile

210 215 220

Cys Ser Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Lys Met Val Ser Glu

225 230 235 240

Pro Tyr Gly Asp Met Leu Phe Phe Tyr Leu Arg Arg Glu Gln Met Phe

245 250 255

Val Arg His Leu Phe Asn Arg Ala Gly Thr Val Gly Glu Thr Val Pro

260 265 270

Ala Asp Leu Tyr Ile Lys Gly Thr Thr Gly Thr Leu Pro Ser Thr Ser

275 280 285

Tyr Phe Pro Thr Pro Ser Gly Ser Met Val Thr Ser Asp Ala Gln Ile

290 295 300

Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn Asn Gly

305 310 315 320

Ile Cys Trp Ser Asn Gln Leu Phe Val Thr Val Val Asp Thr Thr Arg

325 330 335

Ser Thr Asn Met Ser Val Cys Ser Ala Val Ser Ser Ser Asp Ser Thr

340 345 350

Tyr Lys Asn Asp Asn Phe Lys Glu Tyr Leu Arg His Gly Glu Glu Tyr

355 360 365

Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu Thr Ala Asp

370 375 380

Val Met Thr Tyr Ile His Ser Met Asn Pro Ser Ile Leu Glu Asp Trp

385 390 395 400

Asn Phe Gly Leu Thr Pro Pro Pro Ser Gly Thr Leu Glu Asp Thr Tyr

405 410 415

Arg Tyr Val Thr Ser Gln Ala Val Thr Cys Gln Lys Pro Ser Ala Pro

420 425 430

Lys Pro Lys Asp Asp Pro Leu Lys Asn Tyr Thr Phe Trp Glu Val Asp

435 440 445

Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro Leu Gly Arg

450 455 460

Lys Phe Leu Leu Gln Ala Gly Leu

465 470

<210> 10

<211> 469

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 10

Met Ala Met Trp Arg Ser Ser Asp Ser Met Val Tyr Leu Pro Pro Pro

1 5 10 15

Ser Val Ala Lys Val Val Asn Thr Asp Asp Tyr Val Thr Arg Thr Gly

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Leu Thr Val Gly His Pro

35 40 45

Tyr Phe Lys Val Gly Met Asn Gly Gly Arg Lys Gln Asp Ile Pro Lys

50 55 60

Val Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Thr Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Ser Ile Pro Asp Ala Ser Leu Tyr Asn Pro Glu Thr Gln

85 90 95

Arg Leu Val Trp Ala Cys Val Gly Val Glu Val Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Ile Ser Gly His Pro Leu Tyr Asn Arg Gln Asp Asp

115 120 125

Thr Glu Asn Ser Pro Phe Ser Ser Thr Thr Asn Lys Asp Ser Arg Asp

130 135 140

Asn Val Ser Val Asp Tyr Lys Gln Thr Gln Leu Cys Ile Ile Gly Cys

145 150 155 160

Val Pro Ala Ile Gly Glu His Trp Gly Lys Gly Lys Ala Cys Lys Pro

165 170 175

Asn Asn Val Ser Thr Gly Asp Cys Pro Pro Leu Glu Leu Val Asn Thr

180 185 190

Pro Ile Glu Asp Gly Asp Met Ile Asp Thr Gly Tyr Gly Ala Met Asp

195 200 205

Phe Gly Ala Leu Gln Glu Thr Lys Ser Glu Val Pro Leu Asp Ile Cys

210 215 220

Gln Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala Asp Val

225 230 235 240

Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Arg Glu Gln Leu Phe Ala

245 250 255

Arg His Phe Trp Asn Arg Gly Gly Met Val Gly Asp Ala Ile Pro Ala

260 265 270

Gln Leu Tyr Ile Lys Gly Thr Asp Ile Arg Ala Asn Pro Gly Ser Ser

275 280 285

Val Tyr Cys Pro Ser Pro Ser Gly Ser Met Val Thr Ser Asp Ser Gln

290 295 300

Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln Gly His Asn Asn

305 310 315 320

Gly Ile Cys Trp His Asn Gln Leu Phe Leu Thr Val Val Asp Thr Thr

325 330 335

Arg Ser Thr Asn Phe Thr Leu Ser Thr Ser Ile Glu Ser Ser Ile Pro

340 345 350

Ser Thr Tyr Asp Pro Ser Lys Phe Lys Glu Tyr Thr Arg His Val Glu

355 360 365

Glu Tyr Asp Leu Gln Phe Ile Phe Gln Leu Cys Thr Val Thr Leu Thr

370 375 380

Thr Asp Val Met Ser Tyr Ile His Thr Met Asn Ser Ser Ile Leu Asp

385 390 395 400

Asn Trp Asn Phe Ala Val Ala Pro Pro Pro Ser Ala Ser Leu Val Asp

405 410 415

Thr Tyr Arg Tyr Leu Gln Ser Ala Ala Ile Thr Cys Gln Lys Asp Ala

420 425 430

Pro Ala Pro Glu Lys Lys Asp Pro Tyr Asp Gly Leu Lys Phe Trp Asn

435 440 445

Val Asp Leu Arg Glu Lys Phe Ser Leu Glu Leu Asp Gln Phe Pro Leu

450 455 460

Gly Arg Lys Phe Leu

465

<210> 11

<211> 478

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 11

Met Ala Leu Trp Arg Pro Ser Asp Ser Thr Val Tyr Leu Pro Pro Pro

1 5 10 15

Ser Val Ala Arg Val Val Asn Thr Asp Asp Tyr Val Ser Arg Thr Ser

20 25 30

Ile Phe Tyr His Ala Gly Ser Ser Arg Leu Leu Thr Val Gly Asn Pro

35 40 45

Tyr Phe Arg Val Val Pro Ser Gly Ala Gly Asn Lys Gln Ala Val Pro

50 55 60

Lys Val Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Ala Leu Pro Asp

65 70 75 80

Pro Asn Lys Phe Gly Leu Pro Asp Ser Thr Ile Tyr Asn Pro Glu Thr

85 90 95

Gln Arg Leu Val Trp Ala Cys Val Gly Met Glu Ile Gly Arg Gly Gln

100 105 110

Pro Leu Gly Ile Gly Leu Ser Gly His Pro Phe Tyr Asn Lys Leu Asp

115 120 125

Asp Thr Glu Ser Ala His Ala Ala Thr Ala Val Ile Thr Gln Asp Val

130 135 140

Arg Asp Asn Val Ser Val Asp Tyr Lys Gln Thr Gln Leu Cys Ile Leu

145 150 155 160

Gly Cys Val Pro Ala Ile Gly Glu His Trp Ala Lys Gly Thr Leu Cys

165 170 175

Lys Pro Ala Gln Leu Gln Pro Gly Asp Cys Pro Pro Leu Glu Leu Lys

180 185 190

Asn Thr Ile Ile Glu Asp Gly Asp Met Val Asp Thr Gly Tyr Gly Ala

195 200 205

Met Asp Phe Ser Thr Leu Gln Asp Thr Lys Cys Glu Val Pro Leu Asp

210 215 220

Ile Cys Gln Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala

225 230 235 240

Asp Pro Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Arg Glu Gln Leu

245 250 255

Phe Ala Arg His Phe Trp Asn Arg Ala Gly Val Met Gly Asp Thr Val

260 265 270

Pro Thr Asp Leu Tyr Ile Lys Gly Thr Ser Ala Asn Met Arg Glu Thr

275 280 285

Pro Gly Ser Cys Val Tyr Ser Pro Ser Pro Ser Gly Ser Ile Thr Thr

290 295 300

Ser Asp Ser Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln

305 310 315 320

Gly His Asn Asn Gly Ile Cys Trp His Asn Gln Leu Phe Val Thr Val

325 330 335

Val Asp Thr Thr Arg Ser Thr Asn Leu Thr Leu Cys Ala Ser Thr Gln

340 345 350

Asn Pro Val Pro Asn Thr Tyr Asp Pro Thr Lys Phe Lys His Tyr Ser

355 360 365

Arg His Val Glu Glu Tyr Asp Leu Gln Phe Ile Phe Gln Leu Cys Thr

370 375 380

Ile Thr Leu Thr Ala Glu Val Met Ser Tyr Ile His Ser Met Asn Ser

385 390 395 400

Ser Ile Leu Glu Asn Trp Asn Phe Gly Val Pro Pro Pro Pro Thr Thr

405 410 415

Ser Leu Val Asp Thr Tyr Arg Phe Val Gln Ser Val Ala Val Thr Cys

420 425 430

Gln Lys Asp Thr Thr Pro Pro Glu Lys Gln Asp Pro Tyr Asp Lys Leu

435 440 445

Lys Phe Trp Thr Val Asp Leu Lys Glu Lys Phe Ser Ser Asp Leu Asp

450 455 460

Gln Tyr Pro Leu Gly Arg Lys Phe Leu Val Gln Ala Gly Leu

465 470 475

<210> 12

<211> 474

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 12

Met Ala Leu Trp Arg Thr Asn Asp Ser Lys Val Tyr Leu Pro Pro Ala

1 5 10 15

Pro Val Ser Arg Ile Val Asn Thr Glu Glu Tyr Ile Thr Arg Thr Gly

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Ile Thr Leu Gly His Pro

35 40 45

Tyr Phe Pro Ile Pro Lys Thr Ser Thr Arg Ala Ala Ile Pro Lys Val

50 55 60

Ser Ala Phe Gln Tyr Arg Val Phe Arg Val Gln Leu Pro Asp Pro Asn

65 70 75 80

Lys Phe Gly Leu Pro Asp Pro Asn Leu Tyr Asn Pro Asp Thr Asp Arg

85 90 95

Leu Val Trp Gly Cys Val Gly Val Glu Val Gly Arg Gly Gln Pro Leu

100 105 110

Gly Val Gly Leu Ser Gly His Pro Leu Phe Asn Lys Tyr Asp Asp Thr

115 120 125

Glu Asn Ser Arg Ile Ala Asn Gly Asn Ala Gln Gln Asp Val Arg Asp

130 135 140

Asn Thr Ser Val Asp Asn Lys Gln Thr Gln Leu Cys Ile Ile Gly Cys

145 150 155 160

Ala Pro Pro Ile Gly Glu His Trp Gly Ile Gly Thr Thr Cys Lys Asn

165 170 175

Thr Pro Val Pro Pro Gly Asp Cys Pro Pro Leu Glu Leu Val Ser Ser

180 185 190

Val Ile Gln Asp Gly Asp Met Ile Asp Thr Gly Phe Gly Ala Met Asp

195 200 205

Phe Ala Ala Leu Gln Ala Thr Lys Ser Asp Val Pro Leu Asp Ile Ser

210 215 220

Gln Ser Val Cys Lys Tyr Pro Asp Tyr Leu Lys Met Ser Ala Asp Thr

225 230 235 240

Tyr Gly Asn Ser Met Phe Phe His Leu Arg Arg Glu Gln Ile Phe Ala

245 250 255

Arg His Tyr Tyr Asn Lys Leu Val Gly Val Gly Glu Asp Ile Pro Asn

260 265 270

Asp Tyr Tyr Ile Lys Gly Ser Gly Asn Gly Arg Asp Pro Ile Glu Ser

275 280 285

Tyr Ile Tyr Ser Ala Thr Pro Ser Gly Ser Met Ile Thr Ser Asp Ser

290 295 300

Gln Ile Phe Asn Lys Pro Tyr Trp Leu His Arg Ala Gln Gly His Asn

305 310 315 320

Asn Gly Ile Cys Trp Asn Asn Gln Leu Phe Ile Thr Cys Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Leu Thr Ile Ser Thr Ala Thr Ala Ala Val Ser

340 345 350

Pro Thr Phe Thr Pro Ser Asn Phe Lys Gln Tyr Ile Arg His Gly Glu

355 360 365

Glu Tyr Glu Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu Thr

370 375 380

Thr Glu Val Met Ala Tyr Leu His Thr Met Asp Pro Thr Ile Leu Glu

385 390 395 400

Gln Trp Asn Phe Gly Leu Thr Leu Pro Pro Ser Ala Ser Leu Glu Asp

405 410 415

Ala Tyr Arg Phe Val Arg Asn Ala Ala Thr Ser Cys Gln Lys Asp Thr

420 425 430

Pro Pro Gln Ala Lys Pro Asp Pro Leu Ala Lys Tyr Lys Phe Trp Asp

435 440 445

Val Asp Leu Lys Glu Arg Phe Ser Leu Asp Leu Asp Gln Phe Ala Leu

450 455 460

Gly Arg Lys Phe Leu Leu Gln Val Gly Val

465 470

<210> 13

<211> 478

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 13

Met Ser Val Trp Arg Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Ser Arg Thr Ser

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Leu Thr Val Gly His Pro

35 40 45

Tyr Phe Ser Ile Lys Asn Thr Ser Ser Gly Asn Gly Lys Lys Val Leu

50 55 60

Val Pro Lys Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Ile Lys Leu

65 70 75 80

Pro Asp Pro Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro

85 90 95

Glu Thr Gln Arg Leu Val Trp Ala Cys Thr Gly Leu Glu Ile Gly Arg

100 105 110

Gly Gln Pro Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys

115 120 125

Phe Asp Asp Thr Glu Thr Ser Asn Lys Tyr Ala Gly Lys Pro Gly Ile

130 135 140

Asp Asn Arg Glu Cys Leu Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys

145 150 155 160

Ile Leu Gly Cys Lys Pro Pro Ile Gly Glu His Trp Gly Lys Gly Thr

165 170 175

Pro Cys Asn Asn Asn Ser Gly Asn Pro Gly Asp Cys Pro Pro Leu Gln

180 185 190

Leu Ile Asn Ser Val Ile Gln Asp Gly Asp Met Val Asp Thr Gly Phe

195 200 205

Gly Cys Met Asp Phe Asn Thr Leu Gln Ala Ser Lys Ser Asp Val Pro

210 215 220

Ile Asp Ile Cys Ser Ser Val Cys Lys Tyr Pro Asp Tyr Leu Gln Met

225 230 235 240

Ala Ser Glu Pro Tyr Gly Asp Ser Leu Phe Phe Phe Leu Arg Arg Glu

245 250 255

Gln Met Phe Val Arg His Phe Phe Asn Arg Ala Gly Thr Leu Gly Asp

260 265 270

Pro Val Pro Gly Asp Leu Tyr Ile Gln Gly Ser Asn Ser Gly Asn Thr

275 280 285

Ala Thr Val Gln Ser Ser Ala Phe Phe Pro Thr Pro Ser Gly Ser Met

290 295 300

Val Thr Ser Glu Ser Gln Leu Phe Asn Lys Pro Tyr Trp Leu Gln Arg

305 310 315 320

Ala Gln Gly His Asn Asn Gly Ile Cys Trp Gly Asn Gln Leu Phe Val

325 330 335

Thr Val Val Asp Thr Thr Arg Ser Thr Asn Met Thr Leu Cys Ala Glu

340 345 350

Val Lys Lys Glu Ser Thr Tyr Lys Asn Glu Asn Phe Lys Glu Tyr Leu

355 360 365

Arg His Gly Glu Glu Phe Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys

370 375 380

Ile Thr Leu Thr Ala Asp Val Met Thr Tyr Ile His Lys Met Asp Ala

385 390 395 400

Thr Ile Leu Glu Asp Trp Gln Phe Gly Leu Thr Pro Pro Pro Ser Ala

405 410 415

Ser Leu Glu Asp Thr Tyr Arg Phe Val Thr Ser Thr Ala Ile Thr Cys

420 425 430

Gln Lys Asn Thr Pro Pro Lys Gly Lys Glu Asp Pro Leu Lys Asp Tyr

435 440 445

Met Phe Trp Glu Val Asp Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp

450 455 460

Gln Phe Pro Leu Gly Arg Lys Phe Leu Leu Gln Ala Gly Leu

465 470 475

<210> 14

<211> 467

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 14

Met Ala Thr Trp Arg Pro Ser Glu Asn Lys Val Tyr Leu Pro Pro Thr

1 5 10 15

Pro Val Ser Lys Val Val Ala Thr Asp Ser Tyr Val Lys Arg Thr Ser

20 25 30

Ile Phe Tyr His Ala Gly Ser Ser Arg Leu Leu Ala Val Gly His Pro

35 40 45

Tyr Tyr Ser Val Thr Lys Asp Asn Thr Lys Thr Asn Ile Pro Lys Val

50 55 60

Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Arg Leu Pro Asp Pro Asn

65 70 75 80

Lys Phe Gly Leu Pro Asp Thr Asn Ile Tyr Asn Pro Asp Gln Glu Arg

85 90 95

Leu Val Trp Ala Cys Val Gly Leu Glu Val Gly Arg Gly Gln Pro Leu

100 105 110

Gly Ala Gly Leu Ser Gly His Pro Leu Phe Asn Arg Leu Asp Asp Thr

115 120 125

Glu Ser Ser Asn Leu Ala Asn Asn Asn Val Ile Glu Asp Ser Arg Asp

130 135 140

Asn Ile Ser Val Asp Gly Lys Gln Thr Gln Leu Cys Ile Val Gly Cys

145 150 155 160

Thr Pro Ala Met Gly Glu His Trp Thr Lys Gly Ala Val Cys Lys Ser

165 170 175

Thr Gln Val Thr Thr Gly Asp Cys Pro Pro Leu Ala Leu Ile Asn Thr

180 185 190

Pro Ile Glu Asp Gly Asp Met Ile Asp Thr Gly Phe Gly Ala Met Asp

195 200 205

Phe Lys Val Leu Gln Glu Ser Lys Ala Glu Val Pro Leu Asp Ile Val

210 215 220

Gln Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Lys Met Ser Ala Asp Ala

225 230 235 240

Tyr Gly Asp Ser Met Trp Phe Tyr Leu Arg Arg Glu Gln Leu Phe Ala

245 250 255

Arg His Tyr Phe Asn Arg Ala Gly Lys Val Gly Glu Thr Ile Pro Ala

260 265 270

Glu Leu Tyr Leu Lys Gly Ser Asn Gly Arg Glu Pro Pro Pro Ser Ser

275 280 285

Val Tyr Val Ala Thr Pro Ser Gly Ser Met Ile Thr Ser Glu Ala Gln

290 295 300

Leu Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn Asn

305 310 315 320

Gly Ile Cys Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp Thr Thr

325 330 335

Arg Ser Thr Asn Met Thr Ile Ser Thr Ala Thr Glu Gln Leu Ser Lys

340 345 350

Tyr Asp Ala Arg Lys Ile Asn Gln Tyr Leu Arg His Val Glu Glu Tyr

355 360 365

Glu Leu Gln Phe Val Phe Gln Leu Cys Lys Ile Thr Leu Ser Ala Glu

370 375 380

Val Met Ala Tyr Leu His Asn Met Asn Ala Asn Leu Leu Glu Asp Trp

385 390 395 400

Asn Ile Gly Leu Ser Pro Pro Val Ala Thr Ser Leu Glu Asp Lys Tyr

405 410 415

Arg Tyr Val Arg Ser Thr Ala Ile Thr Cys Gln Arg Glu Gln Pro Pro

420 425 430

Thr Glu Lys Gln Asp Pro Leu Ala Lys Tyr Lys Phe Trp Asp Val Asn

435 440 445

Leu Gln Asp Ser Phe Ser Thr Asp Leu Asp Gln Phe Pro Leu Gly Arg

450 455 460

Lys Phe Leu

465

<210> 15

<211> 473

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 15

Met Ser Val Trp Arg Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Ser Arg Thr Ser

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Leu Ala Val Gly Asn Pro

35 40 45

Tyr Phe Ser Ile Lys Ser Pro Asn Asn Asn Lys Lys Val Leu Val Pro

50 55 60

Lys Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Val Arg Leu Pro Asp

65 70 75 80

Pro Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro Asp Thr

85 90 95

Gln Arg Leu Val Trp Ala Cys Val Gly Leu Glu Ile Gly Arg Gly Gln

100 105 110

Pro Leu Gly Val Gly Val Ser Gly His Pro Tyr Leu Asn Lys Phe Asp

115 120 125

Asp Thr Glu Thr Ser Asn Arg Tyr Pro Ala Gln Pro Gly Ser Asp Asn

130 135 140

Arg Glu Cys Leu Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Ile

145 150 155 160

Gly Cys Lys Pro Pro Thr Gly Glu His Trp Gly Lys Gly Val Ala Cys

165 170 175

Asn Asn Asn Ala Ala Ala Thr Asp Cys Pro Pro Leu Glu Leu Phe Asn

180 185 190

Ser Ile Ile Glu Asp Gly Asp Met Val Asp Thr Gly Phe Gly Cys Met

195 200 205

Asp Phe Gly Thr Leu Gln Ala Asn Lys Ser Asp Val Pro Ile Asp Ile

210 215 220

Cys Asn Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Lys Met Ala Ser Glu

225 230 235 240

Pro Tyr Gly Asp Ser Leu Phe Phe Phe Leu Arg Arg Glu Gln Met Phe

245 250 255

Val Arg His Phe Phe Asn Arg Ala Gly Lys Leu Gly Glu Ala Val Pro

260 265 270

Asp Asp Leu Tyr Ile Lys Gly Ser Gly Asn Thr Ala Val Ile Gln Ser

275 280 285

Ser Ala Phe Phe Pro Thr Pro Ser Gly Ser Ile Val Thr Ser Glu Ser

290 295 300

Gln Leu Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn

305 310 315 320

Asn Gly Ile Cys Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Met Thr Leu Cys Thr Glu Val Thr Lys Glu Gly

340 345 350

Thr Tyr Lys Asn Asp Asn Phe Lys Glu Tyr Val Arg His Val Glu Glu

355 360 365

Tyr Asp Leu Gln Phe Val Phe Gln Leu Cys Lys Ile Thr Leu Thr Ala

370 375 380

Glu Ile Met Thr Tyr Ile His Thr Met Asp Ser Asn Ile Leu Glu Asp

385 390 395 400

Trp Gln Phe Gly Leu Thr Pro Pro Pro Ser Ala Ser Leu Gln Asp Thr

405 410 415

Tyr Arg Phe Val Thr Ser Gln Ala Ile Thr Cys Gln Lys Thr Ala Pro

420 425 430

Pro Lys Glu Lys Glu Asp Pro Leu Asn Lys Tyr Thr Phe Trp Glu Val

435 440 445

Asn Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro Leu Gly

450 455 460

Arg Lys Phe Leu Leu Gln Ser Gly Leu

465 470

<210> 16

<211> 495

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 16

Met Trp Arg Pro Ser Asp Ser Thr Val Tyr Val Pro Pro Pro Asn Pro

1 5 10 15

Val Ser Lys Val Val Ala Thr Asp Ala Tyr Val Thr Arg Thr Asn Ile

20 25 30

Phe Tyr His Ala Ser Ser Ser Arg Leu Leu Ala Val Gly His Pro Tyr

35 40 45

Phe Ser Ile Lys Arg Ala Asn Lys Thr Val Val Pro Lys Val Ser Gly

50 55 60

Tyr Gln Tyr Arg Val Phe Lys Val Val Leu Pro Asp Pro Asn Lys Phe

65 70 75 80

Ala Leu Pro Asp Ser Ser Leu Phe Asp Pro Thr Thr Gln Arg Leu Val

85 90 95

Trp Ala Cys Thr Gly Leu Glu Val Gly Arg Gly Gln Pro Leu Gly Val

100 105 110

Gly Val Ser Gly His Pro Phe Leu Asn Lys Tyr Asp Asp Val Glu Asn

115 120 125

Ser Gly Ser Gly Gly Asn Pro Gly Gln Asp Asn Arg Val Asn Val Gly

130 135 140

Met Asp Tyr Lys Gln Thr Gln Leu Cys Met Val Gly Cys Ala Pro Pro

145 150 155 160

Leu Gly Glu His Trp Gly Lys Gly Lys Gln Cys Thr Asn Thr Pro Val

165 170 175

Gln Ala Gly Asp Cys Pro Pro Leu Glu Leu Ile Thr Ser Val Ile Gln

180 185 190

Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala Met Asn Phe Ala Asp

195 200 205

Leu Gln Thr Asn Lys Ser Asp Val Pro Ile Asp Ile Cys Gly Thr Thr

210 215 220

Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ala Ala Asp Pro Tyr Gly Asp

225 230 235 240

Arg Leu Phe Phe Phe Leu Arg Lys Glu Gln Met Phe Ala Arg His Phe

245 250 255

Phe Asn Arg Ala Gly Glu Val Gly Glu Pro Val Pro Asp Thr Leu Ile

260 265 270

Ile Lys Gly Ser Gly Asn Arg Thr Ser Val Gly Ser Ser Ile Tyr Val

275 280 285

Asn Thr Pro Ser Gly Ser Leu Val Ser Ser Glu Ala Gln Leu Phe Asn

290 295 300

Lys Pro Tyr Trp Leu Gln Lys Ala Gln Gly His Asn Asn Gly Ile Cys

305 310 315 320

Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp Thr Thr Arg Ser Thr

325 330 335

Asn Met Thr Leu Cys Ala Ser Val Thr Thr Ser Ser Thr Tyr Thr Asn

340 345 350

Ser Asp Tyr Lys Glu Tyr Met Arg His Val Glu Glu Tyr Asp Leu Gln

355 360 365

Phe Ile Phe Gln Leu Cys Ser Ile Thr Leu Ser Ala Glu Val Met Ala

370 375 380

Tyr Ile His Thr Met Asn Pro Ser Val Leu Glu Asp Trp Asn Phe Gly

385 390 395 400

Leu Ser Pro Pro Pro Asn Gly Thr Leu Glu Asp Thr Tyr Arg Tyr Val

405 410 415

Gln Ser Gln Ala Ile Thr Cys Gln Lys Pro Thr Pro Glu Lys Glu Lys

420 425 430

Pro Asp Pro Tyr Lys Asn Leu Ser Phe Trp Glu Val Asn Leu Lys Glu

435 440 445

Lys Phe Ser Ser Glu Leu Asp Gln Tyr Pro Leu Gly Arg Lys Phe Leu

450 455 460

Leu Gln Ser Gly Tyr Lys Ala Lys Pro Lys Leu Lys Arg Ala Ala Pro

465 470 475 480

Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys Lys Val Lys Lys

485 490 495

<210> 17

<211> 496

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 17

Met Trp Arg Pro Ser Asp Ser Thr Val Tyr Val Pro Pro Pro Asn Pro

1 5 10 15

Val Ser Lys Val Val Ala Thr Asp Ala Tyr Val Lys Arg Thr Asn Ile

20 25 30

Phe Tyr His Ala Ser Ser Ser Arg Leu Leu Ala Val Gly His Pro Tyr

35 40 45

Tyr Ser Ile Lys Lys Val Asn Lys Thr Val Val Pro Lys Val Ser Gly

50 55 60

Tyr Gln Tyr Arg Val Phe Lys Val Val Leu Pro Asp Pro Asn Lys Phe

65 70 75 80

Ala Leu Pro Asp Ser Ser Leu Phe Asp Pro Thr Thr Gln Arg Leu Val

85 90 95

Trp Ala Cys Thr Gly Leu Glu Val Gly Arg Gly Gln Pro Leu Gly Val

100 105 110

Gly Val Ser Gly His Pro Leu Leu Asn Lys Tyr Asp Asp Val Glu Asn

115 120 125

Ser Gly Gly Tyr Gly Gly Asn Pro Gly Gln Asp Asn Arg Val Asn Val

130 135 140

Gly Met Asp Tyr Lys Gln Thr Gln Leu Cys Met Val Gly Cys Ala Pro

145 150 155 160

Pro Leu Gly Glu His Trp Gly Lys Gly Thr Gln Cys Ser Asn Thr Ser

165 170 175

Val Gln Asn Gly Asp Cys Pro Pro Leu Glu Leu Ile Thr Ser Val Ile

180 185 190

Gln Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala Met Asn Phe Ala

195 200 205

Asp Leu Gln Thr Asn Lys Ser Asp Val Pro Leu Asp Ile Cys Gly Thr

210 215 220

Val Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ala Ala Asp Pro Tyr Gly

225 230 235 240

Asp Arg Leu Phe Phe Tyr Leu Arg Lys Glu Gln Met Phe Ala Arg His

245 250 255

Phe Phe Asn Arg Ala Gly Thr Val Gly Glu Pro Val Pro Asp Asp Leu

260 265 270

Leu Val Lys Gly Gly Asn Asn Arg Ser Ser Val Ala Ser Ser Ile Tyr

275 280 285

Val His Thr Pro Ser Gly Ser Leu Val Ser Ser Glu Ala Gln Leu Phe

290 295 300

Asn Lys Pro Tyr Trp Leu Gln Lys Ala Gln Gly His Asn Asn Gly Ile

305 310 315 320

Cys Trp Gly Asn His Leu Phe Val Thr Val Val Asp Thr Thr Arg Ser

325 330 335

Thr Asn Met Thr Leu Cys Ala Ser Val Ser Lys Ser Ala Thr Tyr Thr

340 345 350

Asn Ser Asp Tyr Lys Glu Tyr Met Arg His Val Glu Glu Phe Asp Leu

355 360 365

Gln Phe Ile Phe Gln Leu Cys Ser Ile Thr Leu Ser Ala Glu Val Met

370 375 380

Ala Tyr Ile His Thr Met Asn Pro Ser Val Leu Glu Asp Trp Asn Phe

385 390 395 400

Gly Leu Ser Pro Pro Pro Asn Gly Thr Leu Glu Asp Thr Tyr Arg Tyr

405 410 415

Val Gln Ser Gln Ala Ile Thr Cys Gln Lys Pro Thr Pro Glu Lys Glu

420 425 430

Lys Gln Asp Pro Tyr Lys Asp Met Ser Phe Trp Glu Val Asn Leu Lys

435 440 445

Glu Lys Phe Ser Ser Glu Leu Asp Gln Phe Pro Leu Gly Arg Lys Phe

450 455 460

Leu Leu Gln Ser Gly Tyr Lys Ala Lys Pro Lys Leu Lys Arg Ala Ala

465 470 475 480

Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys Lys Val Lys Lys

485 490 495

<210> 18

<211> 500

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 18

Met Ser Leu Trp Leu Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Ala Arg Thr Asn

20 25 30

Ile Tyr Tyr His Ala Gly Thr Ser Arg Leu Leu Ala Val Gly His Pro

35 40 45

Tyr Phe Pro Ile Lys Lys Pro Asn Asn Asn Lys Ile Leu Val Pro Lys

50 55 60

Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Ile His Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro Asp Thr Gln

85 90 95

Arg Leu Val Trp Ala Cys Val Gly Val Glu Val Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys Leu Asp Asp

115 120 125

Thr Glu Asn Ala Ser Ala Tyr Ala Ala Asn Ala Gly Val Asp Asn Arg

130 135 140

Glu Cys Ile Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Ile Gly

145 150 155 160

Cys Lys Pro Pro Ile Gly Glu His Trp Gly Lys Gly Ser Pro Cys Thr

165 170 175

Asn Val Ala Val Asn Pro Gly Asp Cys Pro Pro Leu Glu Leu Ile Asn

180 185 190

Thr Val Ile Gln Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala Met

195 200 205

Asp Phe Thr Thr Leu Gln Ala Asn Lys Ser Glu Val Pro Leu Asp Ile

210 215 220

Cys Thr Ser Ile Cys Lys Tyr Pro Asp Tyr Ile Lys Met Val Ser Glu

225 230 235 240

Pro Tyr Gly Asp Ser Leu Phe Phe Tyr Leu Arg Arg Glu Gln Met Phe

245 250 255

Val Arg His Leu Phe Asn Arg Ala Gly Ala Val Gly Glu Asn Val Pro

260 265 270

Asp Asp Leu Tyr Ile Lys Gly Ser Gly Ser Thr Ala Asn Leu Ala Ser

275 280 285

Ser Asn Tyr Phe Pro Thr Pro Ser Gly Ser Met Val Thr Ser Asp Ala

290 295 300

Gln Ile Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn

305 310 315 320

Asn Gly Ile Cys Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Met Ser Leu Cys Ala Ala Ile Ser Thr Ser Glu

340 345 350

Thr Thr Tyr Lys Asn Thr Asn Phe Lys Glu Tyr Leu Arg His Gly Glu

355 360 365

Glu Tyr Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu Thr

370 375 380

Ala Asp Val Met Thr Tyr Ile His Ser Met Asn Ser Thr Ile Leu Glu

385 390 395 400

Asp Trp Asn Phe Gly Leu Gln Pro Pro Pro Gly Gly Thr Leu Glu Asp

405 410 415

Thr Tyr Arg Phe Val Thr Ser Gln Ala Ile Ala Cys Gln Lys His Thr

420 425 430

Pro Pro Ala Pro Lys Glu Asp Pro Leu Lys Lys Tyr Thr Phe Trp Glu

435 440 445

Val Asn Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro Leu

450 455 460

Gly Arg Lys Phe Leu Leu Gln Ala Gly Leu Lys Ala Lys Pro Lys Leu

465 470 475 480

Lys Arg Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys

485 490 495

Lys Val Lys Lys

500

<210> 19

<211> 496

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 19

Met Ala Leu Trp Arg Pro Ser Asp Asn Thr Val Tyr Leu Pro Pro Pro

1 5 10 15

Ser Val Ala Arg Val Val Asn Thr Asp Asp Tyr Val Thr Arg Thr Ser

20 25 30

Ile Phe Tyr His Ala Gly Ser Ser Arg Leu Leu Thr Val Gly Asn Pro

35 40 45

Tyr Phe Arg Val Pro Ala Gly Gly Gly Asn Lys Gln Asp Ile Pro Lys

50 55 60

Val Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Gln Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Gly Leu Pro Asp Thr Ser Ile Tyr Asn Pro Glu Thr Gln

85 90 95

Arg Leu Val Trp Ala Cys Ala Gly Val Glu Ile Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Leu Ser Gly His Pro Phe Tyr Asn Lys Leu Asp Asp

115 120 125

Thr Glu Ser Ser His Ala Ala Thr Ser Asn Val Ser Glu Asp Val Arg

130 135 140

Asp Asn Val Ser Val Asp Tyr Lys Gln Thr Gln Leu Cys Ile Leu Gly

145 150 155 160

Cys Ala Pro Ala Ile Gly Glu His Trp Ala Lys Gly Thr Ala Cys Lys

165 170 175

Ser Arg Pro Leu Ser Gln Gly Asp Cys Pro Pro Leu Glu Leu Lys Asn

180 185 190

Thr Val Leu Glu Asp Gly Asp Met Val Asp Thr Gly Tyr Gly Ala Met

195 200 205

Asp Phe Ser Thr Leu Gln Asp Thr Lys Cys Glu Val Pro Leu Asp Ile

210 215 220

Cys Gln Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala Asp

225 230 235 240

Pro Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Arg Glu Gln Leu Phe

245 250 255

Ala Arg His Phe Trp Asn Arg Ala Gly Thr Met Gly Asp Thr Val Pro

260 265 270

Gln Ser Leu Tyr Ile Lys Gly Thr Gly Met Arg Ala Ser Pro Gly Ser

275 280 285

Cys Val Tyr Ser Pro Ser Pro Ser Gly Ser Ile Val Thr Ser Asp Ser

290 295 300

Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln Gly His Asn

305 310 315 320

Asn Gly Val Cys Trp His Asn Gln Leu Phe Val Thr Val Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Leu Thr Ile Cys Ala Ser Thr Gln Ser Pro Val

340 345 350

Pro Gly Gln Tyr Asp Ala Thr Lys Phe Lys Gln Tyr Ser Arg His Val

355 360 365

Glu Glu Tyr Asp Leu Gln Phe Ile Phe Gln Leu Cys Thr Ile Thr Leu

370 375 380

Thr Ala Asp Val Met Ser Tyr Ile His Ser Met Asn Ser Ser Ile Leu

385 390 395 400

Glu Asp Trp Asn Phe Gly Val Pro Pro Pro Pro Thr Thr Ser Leu Val

405 410 415

Asp Thr Tyr Arg Phe Val Gln Ser Val Ala Ile Thr Cys Gln Lys Asp

420 425 430

Ala Ala Pro Ala Glu Asn Lys Asp Pro Tyr Asp Lys Leu Lys Phe Trp

435 440 445

Asn Val Asp Leu Lys Glu Lys Phe Ser Leu Asp Leu Asp Gln Tyr Pro

450 455 460

Leu Gly Arg Lys Phe Leu Lys Ala Lys Pro Lys Leu Lys Arg Ala Ala

465 470 475 480

Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys Lys Val Lys Lys

485 490 495

<210> 20

<211> 501

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 20

Met Ser Leu Trp Arg Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Thr Arg Thr Asn

20 25 30

Ile Tyr Tyr His Ala Gly Ser Ala Arg Leu Leu Thr Val Gly His Pro

35 40 45

Tyr Tyr Ser Ile Pro Lys Ser Asp Asn Pro Lys Lys Ile Val Val Pro

50 55 60

Lys Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Val Arg Leu Pro Asp

65 70 75 80

Pro Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro Glu Thr

85 90 95

Gln Arg Leu Val Trp Ala Cys Val Gly Leu Glu Val Gly Arg Gly Gln

100 105 110

Pro Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys Phe Asp

115 120 125

Asp Thr Glu Asn Ser Asn Arg Tyr Ala Gly Gly Pro Gly Thr Asp Asn

130 135 140

Arg Glu Cys Ile Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Leu

145 150 155 160

Gly Cys Lys Pro Pro Ile Gly Glu His Trp Gly Lys Gly Ser Pro Cys

165 170 175

Ser Asn Asn Ala Ile Thr Pro Gly Asp Cys Pro Pro Leu Glu Leu Lys

180 185 190

Asn Ser Val Ile Gln Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala

195 200 205

Met Asp Phe Thr Ala Leu Gln Asp Thr Lys Ser Asn Val Pro Leu Asp

210 215 220

Ile Cys Asn Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Lys Met Val Ala

225 230 235 240

Glu Pro Tyr Gly Asp Thr Leu Phe Phe Tyr Leu Arg Arg Glu Gln Met

245 250 255

Phe Val Arg His Phe Phe Asn Arg Ser Gly Thr Val Gly Glu Ser Val

260 265 270

Pro Thr Asp Leu Tyr Ile Lys Gly Ser Gly Ser Thr Ala Thr Leu Ala

275 280 285

Asn Ser Thr Tyr Phe Pro Thr Pro Ser Gly Ser Met Val Thr Ser Asp

290 295 300

Ala Gln Ile Phe Asn Lys Pro Tyr Trp Met Gln Arg Ala Gln Gly His

305 310 315 320

Asn Asn Gly Ile Cys Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp

325 330 335

Thr Thr Arg Ser Thr Asn Met Ser Val Cys Ala Ala Ile Ala Asn Ser

340 345 350

Asp Thr Thr Phe Lys Ser Ser Asn Phe Lys Glu Tyr Leu Arg His Gly

355 360 365

Glu Glu Phe Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu

370 375 380

Ser Ala Asp Ile Met Thr Tyr Ile His Ser Met Asn Pro Ala Ile Leu

385 390 395 400

Glu Asp Trp Asn Phe Gly Leu Thr Thr Pro Pro Ser Gly Ser Leu Glu

405 410 415

Asp Thr Tyr Arg Phe Val Thr Ser Gln Ala Ile Thr Cys Gln Lys Ser

420 425 430

Ala Pro Gln Lys Pro Lys Glu Asp Pro Phe Lys Asp Tyr Val Phe Trp

435 440 445

Glu Val Asn Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro

450 455 460

Leu Gly Arg Lys Phe Leu Leu Gln Ala Gly Tyr Lys Ala Lys Pro Lys

465 470 475 480

Leu Lys Arg Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg

485 490 495

Lys Lys Val Lys Lys

500

<210> 21

<211> 498

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 21

Met Ser Leu Trp Arg Ser Asn Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Ser Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Thr Arg Thr Asn

20 25 30

Ile Tyr Tyr His Ala Gly Ser Ser Arg Leu Leu Ala Val Gly His Pro

35 40 45

Tyr Tyr Ala Ile Lys Lys Gln Asp Ser Asn Lys Ile Ala Val Pro Lys

50 55 60

Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Val Lys Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asp Pro Ala Ser Gln

85 90 95

Arg Leu Val Trp Ala Cys Thr Gly Val Glu Val Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys Leu Asp Asp

115 120 125

Thr Glu Asn Ser Asn Lys Tyr Val Gly Asn Ser Gly Thr Asp Asn Arg

130 135 140

Glu Cys Ile Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Ile Gly

145 150 155 160

Cys Arg Pro Pro Ile Gly Glu His Trp Gly Lys Gly Thr Pro Cys Asn

165 170 175

Ala Asn Gln Val Lys Ala Gly Glu Cys Pro Pro Leu Glu Leu Leu Asn

180 185 190

Thr Val Leu Gln Asp Gly Asp Met Val Asp Thr Gly Phe Gly Ala Met

195 200 205

Asp Phe Thr Thr Leu Gln Ala Asn Lys Ser Asp Val Pro Leu Asp Ile

210 215 220

Cys Ser Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Lys Met Val Ser Glu

225 230 235 240

Pro Tyr Gly Asp Met Leu Phe Phe Tyr Leu Arg Arg Glu Gln Met Phe

245 250 255

Val Arg His Leu Phe Asn Arg Ala Gly Thr Val Gly Glu Thr Val Pro

260 265 270

Ala Asp Leu Tyr Ile Lys Gly Thr Thr Gly Thr Leu Pro Ser Thr Ser

275 280 285

Tyr Phe Pro Thr Pro Ser Gly Ser Met Val Thr Ser Asp Ala Gln Ile

290 295 300

Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn Asn Gly

305 310 315 320

Ile Cys Trp Ser Asn Gln Leu Phe Val Thr Val Val Asp Thr Thr Arg

325 330 335

Ser Thr Asn Met Ser Val Cys Ser Ala Val Ser Ser Ser Asp Ser Thr

340 345 350

Tyr Lys Asn Asp Asn Phe Lys Glu Tyr Leu Arg His Gly Glu Glu Tyr

355 360 365

Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu Thr Ala Asp

370 375 380

Val Met Thr Tyr Ile His Ser Met Asn Pro Ser Ile Leu Glu Asp Trp

385 390 395 400

Asn Phe Gly Leu Thr Pro Pro Pro Ser Gly Thr Leu Glu Asp Thr Tyr

405 410 415

Arg Tyr Val Thr Ser Gln Ala Val Thr Cys Gln Lys Pro Ser Ala Pro

420 425 430

Lys Pro Lys Asp Asp Pro Leu Lys Asn Tyr Thr Phe Trp Glu Val Asp

435 440 445

Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro Leu Gly Arg

450 455 460

Lys Phe Leu Leu Gln Ala Gly Leu Lys Ala Lys Pro Lys Leu Lys Arg

465 470 475 480

Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys Lys Val

485 490 495

Lys Lys

<210> 22

<211> 507

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 22

Met Ala Met Trp Arg Ser Ser Asp Ser Met Val Tyr Leu Pro Pro Pro

1 5 10 15

Ser Val Ala Lys Val Val Asn Thr Asp Asp Tyr Val Thr Arg Thr Gly

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Leu Thr Val Gly His Pro

35 40 45

Tyr Phe Lys Val Gly Met Asn Gly Gly Arg Lys Gln Asp Ile Pro Lys

50 55 60

Val Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Thr Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Ser Ile Pro Asp Ala Ser Leu Tyr Asn Pro Glu Thr Gln

85 90 95

Arg Leu Val Trp Ala Cys Val Gly Val Glu Val Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Ile Ser Gly His Pro Leu Tyr Asn Arg Gln Asp Asp

115 120 125

Thr Glu Asn Ser Pro Phe Ser Ser Thr Thr Asn Lys Asp Ser Arg Asp

130 135 140

Asn Val Ser Val Asp Tyr Lys Gln Thr Gln Leu Cys Ile Ile Gly Cys

145 150 155 160

Val Pro Ala Ile Gly Glu His Trp Gly Lys Gly Lys Ala Cys Lys Pro

165 170 175

Asn Asn Val Ser Thr Gly Asp Cys Pro Pro Leu Glu Leu Val Asn Thr

180 185 190

Pro Ile Glu Asp Gly Asp Met Ile Asp Thr Gly Tyr Gly Ala Met Asp

195 200 205

Phe Gly Ala Leu Gln Glu Thr Lys Ser Glu Val Pro Leu Asp Ile Cys

210 215 220

Gln Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala Asp Val

225 230 235 240

Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Arg Glu Gln Leu Phe Ala

245 250 255

Arg His Phe Trp Asn Arg Gly Gly Met Val Gly Asp Ala Ile Pro Ala

260 265 270

Gln Leu Tyr Ile Lys Gly Thr Asp Ile Arg Ala Asn Pro Gly Ser Ser

275 280 285

Val Tyr Cys Pro Ser Pro Ser Gly Ser Met Val Thr Ser Asp Ser Gln

290 295 300

Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln Gly His Asn Asn

305 310 315 320

Gly Ile Cys Trp His Asn Gln Leu Phe Leu Thr Val Val Asp Thr Thr

325 330 335

Arg Ser Thr Asn Phe Thr Leu Ser Thr Ser Ile Glu Ser Ser Ile Pro

340 345 350

Ser Thr Tyr Asp Pro Ser Lys Phe Lys Glu Tyr Thr Arg His Val Glu

355 360 365

Glu Tyr Asp Leu Gln Phe Ile Phe Gln Leu Cys Thr Val Thr Leu Thr

370 375 380

Thr Asp Val Met Ser Tyr Ile His Thr Met Asn Ser Ser Ile Leu Asp

385 390 395 400

Asn Trp Asn Phe Ala Val Ala Pro Pro Pro Ser Ala Ser Leu Val Asp

405 410 415

Thr Tyr Arg Tyr Leu Gln Ser Ala Ala Ile Thr Cys Gln Lys Asp Ala

420 425 430

Pro Ala Pro Glu Lys Lys Asp Pro Tyr Asp Gly Leu Lys Phe Trp Asn

435 440 445

Val Asp Leu Arg Glu Lys Phe Ser Leu Glu Leu Asp Gln Phe Pro Leu

450 455 460

Gly Arg Lys Phe Leu Leu Gln Leu Gly Ala Arg Pro Lys Pro Thr Ile

465 470 475 480

Gly Pro Arg Lys Arg Ala Ala Pro Ala Pro Thr Ser Thr Pro Ser Pro

485 490 495

Lys Arg Val Lys Arg Arg Lys Ser Ser Arg Lys

500 505

<210> 23

<211> 504

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 23

Met Ala Leu Trp Arg Pro Ser Asp Ser Thr Val Tyr Leu Pro Pro Pro

1 5 10 15

Ser Val Ala Arg Val Val Asn Thr Asp Asp Tyr Val Ser Arg Thr Ser

20 25 30

Ile Phe Tyr His Ala Gly Ser Ser Arg Leu Leu Thr Val Gly Asn Pro

35 40 45

Tyr Phe Arg Val Val Pro Ser Gly Ala Gly Asn Lys Gln Ala Val Pro

50 55 60

Lys Val Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Ala Leu Pro Asp

65 70 75 80

Pro Asn Lys Phe Gly Leu Pro Asp Ser Thr Ile Tyr Asn Pro Glu Thr

85 90 95

Gln Arg Leu Val Trp Ala Cys Val Gly Met Glu Ile Gly Arg Gly Gln

100 105 110

Pro Leu Gly Ile Gly Leu Ser Gly His Pro Phe Tyr Asn Lys Leu Asp

115 120 125

Asp Thr Glu Ser Ala His Ala Ala Thr Ala Val Ile Thr Gln Asp Val

130 135 140

Arg Asp Asn Val Ser Val Asp Tyr Lys Gln Thr Gln Leu Cys Ile Leu

145 150 155 160

Gly Cys Val Pro Ala Ile Gly Glu His Trp Ala Lys Gly Thr Leu Cys

165 170 175

Lys Pro Ala Gln Leu Gln Pro Gly Asp Cys Pro Pro Leu Glu Leu Lys

180 185 190

Asn Thr Ile Ile Glu Asp Gly Asp Met Val Asp Thr Gly Tyr Gly Ala

195 200 205

Met Asp Phe Ser Thr Leu Gln Asp Thr Lys Cys Glu Val Pro Leu Asp

210 215 220

Ile Cys Gln Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala

225 230 235 240

Asp Pro Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Arg Glu Gln Leu

245 250 255

Phe Ala Arg His Phe Trp Asn Arg Ala Gly Val Met Gly Asp Thr Val

260 265 270

Pro Thr Asp Leu Tyr Ile Lys Gly Thr Ser Ala Asn Met Arg Glu Thr

275 280 285

Pro Gly Ser Cys Val Tyr Ser Pro Ser Pro Ser Gly Ser Ile Thr Thr

290 295 300

Ser Asp Ser Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln

305 310 315 320

Gly His Asn Asn Gly Ile Cys Trp His Asn Gln Leu Phe Val Thr Val

325 330 335

Val Asp Thr Thr Arg Ser Thr Asn Leu Thr Leu Cys Ala Ser Thr Gln

340 345 350

Asn Pro Val Pro Asn Thr Tyr Asp Pro Thr Lys Phe Lys His Tyr Ser

355 360 365

Arg His Val Glu Glu Tyr Asp Leu Gln Phe Ile Phe Gln Leu Cys Thr

370 375 380

Ile Thr Leu Thr Ala Glu Val Met Ser Tyr Ile His Ser Met Asn Ser

385 390 395 400

Ser Ile Leu Glu Asn Trp Asn Phe Gly Val Pro Pro Pro Pro Thr Thr

405 410 415

Ser Leu Val Asp Thr Tyr Arg Phe Val Gln Ser Val Ala Val Thr Cys

420 425 430

Gln Lys Asp Thr Thr Pro Pro Glu Lys Gln Asp Pro Tyr Asp Lys Leu

435 440 445

Lys Phe Trp Thr Val Asp Leu Lys Glu Lys Phe Ser Ser Asp Leu Asp

450 455 460

Gln Tyr Pro Leu Gly Arg Lys Phe Leu Val Gln Ala Gly Leu Lys Ala

465 470 475 480

Lys Pro Lys Leu Lys Arg Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser

485 490 495

Ala Lys Arg Lys Lys Val Lys Lys

500

<210> 24

<211> 500

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 24

Met Ala Leu Trp Arg Thr Asn Asp Ser Lys Val Tyr Leu Pro Pro Ala

1 5 10 15

Pro Val Ser Arg Ile Val Asn Thr Glu Glu Tyr Ile Thr Arg Thr Gly

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Ile Thr Leu Gly His Pro

35 40 45

Tyr Phe Pro Ile Pro Lys Thr Ser Thr Arg Ala Ala Ile Pro Lys Val

50 55 60

Ser Ala Phe Gln Tyr Arg Val Phe Arg Val Gln Leu Pro Asp Pro Asn

65 70 75 80

Lys Phe Gly Leu Pro Asp Pro Asn Leu Tyr Asn Pro Asp Thr Asp Arg

85 90 95

Leu Val Trp Gly Cys Val Gly Val Glu Val Gly Arg Gly Gln Pro Leu

100 105 110

Gly Val Gly Leu Ser Gly His Pro Leu Phe Asn Lys Tyr Asp Asp Thr

115 120 125

Glu Asn Ser Arg Ile Ala Asn Gly Asn Ala Gln Gln Asp Val Arg Asp

130 135 140

Asn Thr Ser Val Asp Asn Lys Gln Thr Gln Leu Cys Ile Ile Gly Cys

145 150 155 160

Ala Pro Pro Ile Gly Glu His Trp Gly Ile Gly Thr Thr Cys Lys Asn

165 170 175

Thr Pro Val Pro Pro Gly Asp Cys Pro Pro Leu Glu Leu Val Ser Ser

180 185 190

Val Ile Gln Asp Gly Asp Met Ile Asp Thr Gly Phe Gly Ala Met Asp

195 200 205

Phe Ala Ala Leu Gln Ala Thr Lys Ser Asp Val Pro Leu Asp Ile Ser

210 215 220

Gln Ser Val Cys Lys Tyr Pro Asp Tyr Leu Lys Met Ser Ala Asp Thr

225 230 235 240

Tyr Gly Asn Ser Met Phe Phe His Leu Arg Arg Glu Gln Ile Phe Ala

245 250 255

Arg His Tyr Tyr Asn Lys Leu Val Gly Val Gly Glu Asp Ile Pro Asn

260 265 270

Asp Tyr Tyr Ile Lys Gly Ser Gly Asn Gly Arg Asp Pro Ile Glu Ser

275 280 285

Tyr Ile Tyr Ser Ala Thr Pro Ser Gly Ser Met Ile Thr Ser Asp Ser

290 295 300

Gln Ile Phe Asn Lys Pro Tyr Trp Leu His Arg Ala Gln Gly His Asn

305 310 315 320

Asn Gly Ile Cys Trp Asn Asn Gln Leu Phe Ile Thr Cys Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Leu Thr Ile Ser Thr Ala Thr Ala Ala Val Ser

340 345 350

Pro Thr Phe Thr Pro Ser Asn Phe Lys Gln Tyr Ile Arg His Gly Glu

355 360 365

Glu Tyr Glu Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu Thr

370 375 380

Thr Glu Val Met Ala Tyr Leu His Thr Met Asp Pro Thr Ile Leu Glu

385 390 395 400

Gln Trp Asn Phe Gly Leu Thr Leu Pro Pro Ser Ala Ser Leu Glu Asp

405 410 415

Ala Tyr Arg Phe Val Arg Asn Ala Ala Thr Ser Cys Gln Lys Asp Thr

420 425 430

Pro Pro Gln Ala Lys Pro Asp Pro Leu Ala Lys Tyr Lys Phe Trp Asp

435 440 445

Val Asp Leu Lys Glu Arg Phe Ser Leu Asp Leu Asp Gln Phe Ala Leu

450 455 460

Gly Arg Lys Phe Leu Leu Gln Val Gly Val Lys Ala Lys Pro Lys Leu

465 470 475 480

Lys Arg Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys

485 490 495

Lys Val Lys Lys

500

<210> 25

<211> 504

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 25

Met Ser Val Trp Arg Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Ser Arg Thr Ser

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Leu Thr Val Gly His Pro

35 40 45

Tyr Phe Ser Ile Lys Asn Thr Ser Ser Gly Asn Gly Lys Lys Val Leu

50 55 60

Val Pro Lys Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Ile Lys Leu

65 70 75 80

Pro Asp Pro Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro

85 90 95

Glu Thr Gln Arg Leu Val Trp Ala Cys Thr Gly Leu Glu Ile Gly Arg

100 105 110

Gly Gln Pro Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys

115 120 125

Phe Asp Asp Thr Glu Thr Ser Asn Lys Tyr Ala Gly Lys Pro Gly Ile

130 135 140

Asp Asn Arg Glu Cys Leu Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys

145 150 155 160

Ile Leu Gly Cys Lys Pro Pro Ile Gly Glu His Trp Gly Lys Gly Thr

165 170 175

Pro Cys Asn Asn Asn Ser Gly Asn Pro Gly Asp Cys Pro Pro Leu Gln

180 185 190

Leu Ile Asn Ser Val Ile Gln Asp Gly Asp Met Val Asp Thr Gly Phe

195 200 205

Gly Cys Met Asp Phe Asn Thr Leu Gln Ala Ser Lys Ser Asp Val Pro

210 215 220

Ile Asp Ile Cys Ser Ser Val Cys Lys Tyr Pro Asp Tyr Leu Gln Met

225 230 235 240

Ala Ser Glu Pro Tyr Gly Asp Ser Leu Phe Phe Phe Leu Arg Arg Glu

245 250 255

Gln Met Phe Val Arg His Phe Phe Asn Arg Ala Gly Thr Leu Gly Asp

260 265 270

Pro Val Pro Gly Asp Leu Tyr Ile Gln Gly Ser Asn Ser Gly Asn Thr

275 280 285

Ala Thr Val Gln Ser Ser Ala Phe Phe Pro Thr Pro Ser Gly Ser Met

290 295 300

Val Thr Ser Glu Ser Gln Leu Phe Asn Lys Pro Tyr Trp Leu Gln Arg

305 310 315 320

Ala Gln Gly His Asn Asn Gly Ile Cys Trp Gly Asn Gln Leu Phe Val

325 330 335

Thr Val Val Asp Thr Thr Arg Ser Thr Asn Met Thr Leu Cys Ala Glu

340 345 350

Val Lys Lys Glu Ser Thr Tyr Lys Asn Glu Asn Phe Lys Glu Tyr Leu

355 360 365

Arg His Gly Glu Glu Phe Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys

370 375 380

Ile Thr Leu Thr Ala Asp Val Met Thr Tyr Ile His Lys Met Asp Ala

385 390 395 400

Thr Ile Leu Glu Asp Trp Gln Phe Gly Leu Thr Pro Pro Pro Ser Ala

405 410 415

Ser Leu Glu Asp Thr Tyr Arg Phe Val Thr Ser Thr Ala Ile Thr Cys

420 425 430

Gln Lys Asn Thr Pro Pro Lys Gly Lys Glu Asp Pro Leu Lys Asp Tyr

435 440 445

Met Phe Trp Glu Val Asp Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp

450 455 460

Gln Phe Pro Leu Gly Arg Lys Phe Leu Leu Gln Ala Gly Leu Lys Ala

465 470 475 480

Lys Pro Lys Leu Lys Arg Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser

485 490 495

Ala Lys Arg Lys Lys Val Lys Lys

500

<210> 26

<211> 498

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 26

Met Ala Thr Trp Arg Pro Ser Glu Asn Lys Val Tyr Leu Pro Pro Thr

1 5 10 15

Pro Val Ser Lys Val Val Ala Thr Asp Ser Tyr Val Lys Arg Thr Ser

20 25 30

Ile Phe Tyr His Ala Gly Ser Ser Arg Leu Leu Ala Val Gly His Pro

35 40 45

Tyr Tyr Ser Val Thr Lys Asp Asn Thr Lys Thr Asn Ile Pro Lys Val

50 55 60

Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Arg Leu Pro Asp Pro Asn

65 70 75 80

Lys Phe Gly Leu Pro Asp Thr Asn Ile Tyr Asn Pro Asp Gln Glu Arg

85 90 95

Leu Val Trp Ala Cys Val Gly Leu Glu Val Gly Arg Gly Gln Pro Leu

100 105 110

Gly Ala Gly Leu Ser Gly His Pro Leu Phe Asn Arg Leu Asp Asp Thr

115 120 125

Glu Ser Ser Asn Leu Ala Asn Asn Asn Val Ile Glu Asp Ser Arg Asp

130 135 140

Asn Ile Ser Val Asp Gly Lys Gln Thr Gln Leu Cys Ile Val Gly Cys

145 150 155 160

Thr Pro Ala Met Gly Glu His Trp Thr Lys Gly Ala Val Cys Lys Ser

165 170 175

Thr Gln Val Thr Thr Gly Asp Cys Pro Pro Leu Ala Leu Ile Asn Thr

180 185 190

Pro Ile Glu Asp Gly Asp Met Ile Asp Thr Gly Phe Gly Ala Met Asp

195 200 205

Phe Lys Val Leu Gln Glu Ser Lys Ala Glu Val Pro Leu Asp Ile Val

210 215 220

Gln Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Lys Met Ser Ala Asp Ala

225 230 235 240

Tyr Gly Asp Ser Met Trp Phe Tyr Leu Arg Arg Glu Gln Leu Phe Ala

245 250 255

Arg His Tyr Phe Asn Arg Ala Gly Lys Val Gly Glu Thr Ile Pro Ala

260 265 270

Glu Leu Tyr Leu Lys Gly Ser Asn Gly Arg Glu Pro Pro Pro Ser Ser

275 280 285

Val Tyr Val Ala Thr Pro Ser Gly Ser Met Ile Thr Ser Glu Ala Gln

290 295 300

Leu Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn Asn

305 310 315 320

Gly Ile Cys Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp Thr Thr

325 330 335

Arg Ser Thr Asn Met Thr Ile Ser Thr Ala Thr Glu Gln Leu Ser Lys

340 345 350

Tyr Asp Ala Arg Lys Ile Asn Gln Tyr Leu Arg His Val Glu Glu Tyr

355 360 365

Glu Leu Gln Phe Val Phe Gln Leu Cys Lys Ile Thr Leu Ser Ala Glu

370 375 380

Val Met Ala Tyr Leu His Asn Met Asn Ala Asn Leu Leu Glu Asp Trp

385 390 395 400

Asn Ile Gly Leu Ser Pro Pro Val Ala Thr Ser Leu Glu Asp Lys Tyr

405 410 415

Arg Tyr Val Arg Ser Thr Ala Ile Thr Cys Gln Arg Glu Gln Pro Pro

420 425 430

Thr Glu Lys Gln Asp Pro Leu Ala Lys Tyr Lys Phe Trp Asp Val Asn

435 440 445

Leu Gln Asp Ser Phe Ser Thr Asp Leu Asp Gln Phe Pro Leu Gly Arg

450 455 460

Lys Phe Leu Leu Gln Ala Gly Leu Lys Ala Lys Pro Lys Leu Lys Arg

465 470 475 480

Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys Lys Val

485 490 495

Lys Lys

<210> 27

<211> 499

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 27

Met Ser Val Trp Arg Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Ser Arg Thr Ser

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Leu Ala Val Gly Asn Pro

35 40 45

Tyr Phe Ser Ile Lys Ser Pro Asn Asn Asn Lys Lys Val Leu Val Pro

50 55 60

Lys Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Val Arg Leu Pro Asp

65 70 75 80

Pro Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro Asp Thr

85 90 95

Gln Arg Leu Val Trp Ala Cys Val Gly Leu Glu Ile Gly Arg Gly Gln

100 105 110

Pro Leu Gly Val Gly Val Ser Gly His Pro Tyr Leu Asn Lys Phe Asp

115 120 125

Asp Thr Glu Thr Ser Asn Arg Tyr Pro Ala Gln Pro Gly Ser Asp Asn

130 135 140

Arg Glu Cys Leu Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Ile

145 150 155 160

Gly Cys Lys Pro Pro Thr Gly Glu His Trp Gly Lys Gly Val Ala Cys

165 170 175

Asn Asn Asn Ala Ala Ala Thr Asp Cys Pro Pro Leu Glu Leu Phe Asn

180 185 190

Ser Ile Ile Glu Asp Gly Asp Met Val Asp Thr Gly Phe Gly Cys Met

195 200 205

Asp Phe Gly Thr Leu Gln Ala Asn Lys Ser Asp Val Pro Ile Asp Ile

210 215 220

Cys Asn Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Lys Met Ala Ser Glu

225 230 235 240

Pro Tyr Gly Asp Ser Leu Phe Phe Phe Leu Arg Arg Glu Gln Met Phe

245 250 255

Val Arg His Phe Phe Asn Arg Ala Gly Lys Leu Gly Glu Ala Val Pro

260 265 270

Asp Asp Leu Tyr Ile Lys Gly Ser Gly Asn Thr Ala Val Ile Gln Ser

275 280 285

Ser Ala Phe Phe Pro Thr Pro Ser Gly Ser Ile Val Thr Ser Glu Ser

290 295 300

Gln Leu Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn

305 310 315 320

Asn Gly Ile Cys Trp Gly Asn Gln Leu Phe Val Thr Val Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Met Thr Leu Cys Thr Glu Val Thr Lys Glu Gly

340 345 350

Thr Tyr Lys Asn Asp Asn Phe Lys Glu Tyr Val Arg His Val Glu Glu

355 360 365

Tyr Asp Leu Gln Phe Val Phe Gln Leu Cys Lys Ile Thr Leu Thr Ala

370 375 380

Glu Ile Met Thr Tyr Ile His Thr Met Asp Ser Asn Ile Leu Glu Asp

385 390 395 400

Trp Gln Phe Gly Leu Thr Pro Pro Pro Ser Ala Ser Leu Gln Asp Thr

405 410 415

Tyr Arg Phe Val Thr Ser Gln Ala Ile Thr Cys Gln Lys Thr Ala Pro

420 425 430

Pro Lys Glu Lys Glu Asp Pro Leu Asn Lys Tyr Thr Phe Trp Glu Val

435 440 445

Asn Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro Leu Gly

450 455 460

Arg Lys Phe Leu Leu Gln Ser Gly Leu Lys Ala Lys Pro Lys Leu Lys

465 470 475 480

Arg Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys Lys

485 490 495

Val Lys Lys

<210> 28

<211> 499

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 28

Met Ser Val Trp Arg Pro Ser Glu Ala Thr Val Tyr Leu Pro Pro Val

1 5 10 15

Pro Val Ser Lys Val Val Ser Thr Asp Glu Tyr Val Ser Arg Thr Ser

20 25 30

Ile Tyr Tyr Tyr Ala Gly Ser Ser Arg Leu Leu Ala Val Gly His Pro

35 40 45

Tyr Phe Ser Ile Lys Asn Pro Thr Asn Ala Lys Lys Leu Leu Val Pro

50 55 60

Lys Val Ser Gly Leu Gln Tyr Arg Val Phe Arg Val Arg Leu Pro Asp

65 70 75 80

Pro Asn Lys Phe Gly Phe Pro Asp Thr Ser Phe Tyr Asn Pro Asp Thr

85 90 95

Gln Arg Leu Val Trp Ala Cys Val Gly Leu Glu Ile Gly Arg Gly Gln

100 105 110

Pro Leu Gly Val Gly Ile Ser Gly His Pro Leu Leu Asn Lys Phe Asp

115 120 125

Asp Thr Glu Thr Gly Asn Lys Tyr Pro Gly Gln Pro Gly Ala Asp Asn

130 135 140

Arg Glu Cys Leu Ser Met Asp Tyr Lys Gln Thr Gln Leu Cys Leu Leu

145 150 155 160

Gly Cys Lys Pro Pro Thr Gly Glu His Trp Gly Lys Gly Val Ala Cys

165 170 175

Thr Asn Ala Ala Pro Ala Asn Asp Cys Pro Pro Leu Glu Leu Ile Asn

180 185 190

Thr Ile Ile Glu Asp Gly Asp Met Val Asp Thr Gly Phe Gly Cys Met

195 200 205

Asp Phe Lys Thr Leu Gln Ala Asn Lys Ser Asp Val Pro Ile Asp Ile

210 215 220

Cys Gly Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Lys Met Thr Ser Glu

225 230 235 240

Pro Tyr Gly Asp Ser Leu Phe Phe Phe Leu Arg Arg Glu Gln Met Phe

245 250 255

Val Arg His Phe Phe Asn Arg Ala Gly Thr Leu Gly Glu Ala Val Pro

260 265 270

Asp Asp Leu Tyr Ile Lys Gly Ser Gly Thr Thr Ala Ser Ile Gln Ser

275 280 285

Ser Ala Phe Phe Pro Thr Pro Ser Gly Ser Met Val Thr Ser Glu Ser

290 295 300

Gln Leu Phe Asn Lys Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn

305 310 315 320

Asn Gly Ile Cys Trp Gly Asn Gln Val Phe Val Thr Val Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Met Thr Leu Cys Thr Gln Val Thr Ser Asp Ser

340 345 350

Thr Tyr Lys Asn Glu Asn Phe Lys Glu Tyr Ile Arg His Val Glu Glu

355 360 365

Tyr Asp Leu Gln Phe Val Phe Gln Leu Cys Lys Val Thr Leu Thr Ala

370 375 380

Glu Val Met Thr Tyr Ile His Ala Met Asn Pro Asp Ile Leu Glu Asp

385 390 395 400

Trp Gln Phe Gly Leu Thr Pro Pro Pro Ser Ala Ser Leu Gln Asp Thr

405 410 415

Tyr Arg Phe Val Thr Ser Gln Ala Ile Thr Cys Gln Lys Thr Val Pro

420 425 430

Pro Lys Glu Lys Glu Asp Pro Leu Gly Lys Tyr Thr Phe Trp Glu Val

435 440 445

Asp Leu Lys Glu Lys Phe Ser Ala Asp Leu Asp Gln Phe Pro Leu Gly

450 455 460

Arg Lys Phe Leu Leu Gln Ala Gly Leu Lys Ala Lys Pro Lys Leu Lys

465 470 475 480

Arg Ala Ala Pro Thr Ser Thr Arg Thr Ser Ser Ala Lys Arg Lys Lys

485 490 495

Val Lys Lys

<210> 29

<211> 508

<212> PRT

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 29

Met Ala Leu Trp Arg Ser Ser Asp Asn Lys Val Tyr Leu Pro Pro Pro

1 5 10 15

Ser Val Ala Lys Val Val Ser Thr Asp Glu Tyr Val Thr Arg Thr Ser

20 25 30

Ile Phe Tyr His Ala Gly Ser Ser Arg Leu Leu Thr Val Gly His Pro

35 40 45

Tyr Phe Lys Val Pro Lys Gly Gly Asn Gly Arg Gln Asp Val Pro Lys

50 55 60

Val Ser Ala Tyr Gln Tyr Arg Val Phe Arg Val Lys Leu Pro Asp Pro

65 70 75 80

Asn Lys Phe Gly Leu Pro Asp Asn Thr Val Tyr Asp Pro Asn Ser Gln

85 90 95

Arg Leu Val Trp Ala Cys Val Gly Val Glu Ile Gly Arg Gly Gln Pro

100 105 110

Leu Gly Val Gly Leu Ser Gly His Pro Leu Tyr Asn Lys Leu Asp Asp

115 120 125

Thr Glu Asn Ser His Val Ala Ser Ala Val Asp Thr Lys Asp Thr Arg

130 135 140

Asp Asn Val Ser Val Asp Tyr Lys Gln Thr Gln Leu Cys Ile Ile Gly

145 150 155 160

Cys Val Pro Ala Ile Gly Glu His Trp Thr Lys Gly Thr Ala Cys Lys

165 170 175

Pro Thr Thr Val Val Gln Gly Asp Cys Pro Pro Leu Glu Leu Ile Asn

180 185 190

Thr Pro Ile Glu Asp Gly Asp Met Val Asp Thr Gly Tyr Gly Ala Met

195 200 205

Asp Phe Lys Leu Leu Gln Asp Asn Lys Ser Glu Val Pro Leu Asp Ile

210 215 220

Cys Gln Ser Ile Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala Asp

225 230 235 240

Ala Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Arg Glu Gln Val Phe

245 250 255

Ala Arg His Phe Trp Asn Arg Ser Gly Thr Met Gly Asp Gln Leu Pro

260 265 270

Glu Ser Leu Tyr Ile Lys Gly Thr Asp Ile Arg Ala Asn Pro Gly Ser

275 280 285

Tyr Leu Tyr Ser Pro Ser Pro Ser Gly Ser Val Val Thr Ser Asp Ser

290 295 300

Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln Gly Leu Asn

305 310 315 320

Asn Gly Ile Cys Trp His Asn Gln Leu Phe Leu Thr Val Val Asp Thr

325 330 335

Thr Arg Ser Thr Asn Leu Ser Val Cys Ala Ser Thr Thr Ser Ser Ile

340 345 350

Pro Asn Val Tyr Thr Pro Thr Ser Phe Lys Glu Tyr Ala Arg His Val

355 360 365

Glu Glu Phe Asp Leu Gln Phe Ile Phe Gln Leu Cys Lys Ile Thr Leu

370 375 380

Thr Thr Glu Val Met Ser Tyr Ile His Asn Met Asn Thr Thr Ile Leu

385 390 395 400

Glu Asp Trp Asn Phe Gly Val Thr Pro Pro Pro Thr Ala Ser Leu Val

405 410 415

Asp Thr Tyr Arg Phe Val Gln Ser Ala Ala Val Thr Cys Gln Lys Asp

420 425 430

Thr Ala Pro Pro Val Lys Gln Asp Pro Tyr Asp Lys Leu Lys Phe Trp

435 440 445

Pro Val Asp Leu Lys Glu Arg Phe Ser Ala Asp Leu Asp Gln Phe Pro

450 455 460

Leu Gly Arg Lys Phe Leu Leu Gln Leu Gly Ala Arg Pro Lys Pro Thr

465 470 475 480

Ile Gly Pro Arg Lys Arg Ala Ala Pro Ala Pro Thr Ser Thr Pro Ser

485 490 495

Pro Lys Arg Val Lys Arg Arg Lys Ser Ser Arg Lys

500 505

<210> 30

<211> 1522

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 30

ctgggtacca tgtggagacc atctgacagc acagtctatg tgcctcctcc aaaccctgtg 60

agcaaggtgg tggctacaga tgcctatgtg accaggacca acatcttcta ccatgcctcc 120

tccagcagac tgctggctgt gggacaccca tacttcagca tcaagagggc taacaagaca 180

gtggtgccaa aggtgtctgg ctaccaatac agggtgttca aggtggtgct gcctgaccca 240

aacaagtttg ccctgcctga ctcctccctg tttgacccaa ccacccagag actggtgtgg 300

gcttgtactg gattggaggt gggcagggga caaccactgg gagtgggagt gtctggacac 360

ccattcctga acaaatatga tgatgtggag aactctggct ctggaggcaa ccctggacaa 420

gacaacaggg tgaatgtggg gatggactac aagcagaccc aactttgtat ggtgggctgt 480

gcccctccac tgggagaaca ctggggcaag ggcaagcagt gtaccaacac acctgtccag 540

gctggagact gtcctccatt ggaactgatt acctctgtga ttcaggatgg agatatggtg 600

gacacaggct ttggagctat gaactttgct gacctccaaa ccaacaagtc tgatgtgcca 660

attgacatct gtggcaccac ttgtaaatac cctgactacc tccaaatggc tgctgaccca 720

tatggagaca gactgttctt cttcctgagg aaggaacaga tgtttgccag acacttcttc 780

aacagggctg gagaggtggg agaacctgtg cctgacaccc tgattatcaa gggctctggc 840

aacaggacct ctgtgggctc cagcatctat gtgaacacac catctggctc cctggtgtcc 900

tctgaggctc aacttttcaa caagccatac tggctccaaa aggctcaagg acacaacaat 960

ggcatctgtt ggggcaacca actttttgtg acagtggtgg acaccaccag gagcaccaat 1020

atgaccctgt gtgcctctgt gaccacctcc agcacctaca ccaactctga ctacaaggaa 1080

tatatgaggc atgtggagga atatgacctc caattcatct tccaactttg tagcatcacc 1140

ctgtctgctg aggtgatggc ttacatccac acaatgaacc catctgtgtt ggaggactgg 1200

aactttggac tgagccctcc tccaaatggc accttggagg acacctacag atatgtccag 1260

agccaggcta tcacttgtca gaagccaaca cctgagaagg agaagcctga cccatacaag 1320

aacctgtcct tctgggaggt gaacctgaaa gagaagttct cctctgaact ggaccaatac 1380

ccactgggca ggaagttcct gctccaatct ggctacaggg gcaggtccag catcaggaca 1440

ggagtgaaga gacctgctgt gagcaaggca tctgctgccc caaagaggaa gagggctaag 1500

accaagaggt aaactcgagc tc 1522

<210> 31

<211> 1525

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 31

ctgggtacca tgtggagacc atctgacagc acagtctatg tgcctcctcc aaaccctgtg 60

agcaaggtgg tggctacaga tgcctatgtg aagaggacca acatcttcta ccatgcctcc 120

tccagcagac tgctggctgt gggacaccca tactacagca tcaagaaggt gaacaagaca 180

gtggtgccaa aggtgtctgg ctaccaatac agggtgttca aggtggtgct gcctgaccca 240

aacaagtttg ccctgcctga ctcctccctg tttgacccaa ccacccagag actggtgtgg 300

gcttgtactg gattggaggt gggcagggga caaccactgg gagtgggagt gtctggacac 360

ccactgctga acaaatatga tgatgtggag aactctggag gctatggagg caaccctgga 420

caagacaaca gggtgaatgt ggggatggac tacaagcaga cccaactttg tatggtgggc 480

tgtgcccctc cactgggaga acactggggc aagggcaccc agtgtagcaa cacctctgtc 540

cagaatggag actgtcctcc attggaactg attacctctg tgattcagga tggagatatg 600

gtggacacag gctttggagc tatgaacttt gctgacctcc aaaccaacaa gtctgatgtg 660

ccactggaca tctgtggcac agtgtgtaaa taccctgact acctccaaat ggctgctgac 720

ccatatggag acagactgtt cttctacctg aggaaggaac agatgtttgc cagacacttc 780

ttcaacaggg ctggcacagt gggagaacct gtgcctgatg acctgctggt gaagggaggc 840

aacaacaggt cctctgtggc atccagcatc tatgtgcata caccatctgg ctccctggtg 900

tcctctgagg ctcaactttt caacaagcca tactggctcc aaaaggctca aggacacaac 960

aatggcatct gttggggcaa ccacctgttt gtgacagtgg tggacaccac caggagcacc 1020

aatatgaccc tgtgtgcctc tgtgagcaag tctgccacct acaccaactc tgactacaag 1080

gaatatatga ggcatgtgga ggagtttgac ctccaattca tcttccaact ttgtagcatc 1140

accctgtctg ctgaggtgat ggcttacatc cacacaatga acccatctgt gttggaggac 1200

tggaactttg gactgagccc tcctccaaat ggcaccttgg aggacaccta cagatatgtc 1260

cagagccagg ctatcacttg tcagaagcca acacctgaga aggagaagca ggacccatac 1320

aaggatatga gtttctggga ggtgaacctg aaagagaagt tctcctctga actggaccag 1380

tttccactgg gcaggaagtt cctgctccaa tctggctaca ggggcaggac ctctgccagg 1440

acaggcatca agagacctgc tgtgagcaag ccaagcacag ccccaaagag gaagaggacc 1500

aagaccaaga agtaaactcg agctc 1525

<210> 32

<211> 1537

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 32

ctgggtacca tgagtctgtg gctgccatct gaggctacag tctacctgcc tcctgtgcct 60

gtgagcaagg tggtgagcac agatgaatat gtggcaagga ccaacatcta ctaccatgct 120

ggcaccagca gactgctggc tgtgggacac ccatactttc caatcaagaa gccaaacaac 180

aacaagattc tggtgccaaa ggtgtctgga ctccaataca gggtgttcag gattcacctg 240

cctgacccaa acaagtttgg ctttcctgac acctccttct acaaccctga cacccagaga 300

ctggtgtggg cttgtgtggg agtggaggtg ggcaggggac aaccactggg agtgggcatc 360

tctggacacc cactgctgaa caaactggat gacacagaga atgcctctgc ctatgctgcc 420

aatgctggag tggacaacag ggagtgtatc agtatggact acaagcagac ccaactttgt 480

ctgattggct gtaagcctcc aattggagaa cactggggca agggcagccc atgtaccaat 540

gtggctgtga accctggaga ctgtcctcca ttggaactga taaacacagt gattcaggat 600

ggagatatgg tggacacagg ctttggagct atggacttca ccaccctcca agccaacaag 660

tctgaggtgc cactggacat ctgtaccagc atctgtaaat accctgacta catcaagatg 720

gtgtctgaac catatggaga ctccctgttc ttctacctga ggagggaaca gatgtttgtg 780

agacacctgt tcaacagggc tggagcagtg ggagagaatg tgcctgatga cctctacatc 840

aagggctctg gcagcacagc caacctggca tccagcaact actttccaac accatctggc 900

agtatggtga cctctgatgc ccagattttc aacaagccat actggctcca aagggctcaa 960

ggacacaaca atggcatctg ttggggcaac caactttttg tgacagtggt ggacaccacc 1020

aggagcacca atatgagtct gtgtgctgcc atcagcacct ctgagaccac ctacaagaac 1080

accaacttca aggaatacct gagacatgga gaggaatatg acctccaatt catcttccaa 1140

ctttgtaaga ttaccctgac agcagatgtg atgacctaca tccacagtat gaacagcacc 1200

atcttggagg actggaactt tggactccaa cctcctcctg gaggcacctt ggaggacacc 1260

tacaggtttg tgaccagcca ggctattgcc tgtcagaaac acacacctcc tgccccaaag 1320

gaggacccac tgaaaaaata caccttctgg gaggtgaacc tgaaagagaa gttctctgct 1380

gacctggacc agtttccact gggcaggaag ttcctgctcc aagcaggact gaaagccaag 1440

ccaaagttca ccctgggcaa gaggaaggct acaccaacca cctccagcac cagcaccaca 1500

gccaagagga agaagaggaa actgtaaact cgagctc 1537

<210> 33

<211> 1543

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 33

ctgggtacca tggccctctg gagaccatcc gataacacag tgtacttgcc cccacccagc 60

gtcgcccggg tggtgaacac agacgactac gtcaccagaa cctcaatctt ctaccacgcc 120

gggtccagcc ggctgctgac cgtgggcaac ccctacttcc gcgtgcccgc cggcggcgga 180

aacaaacaag acatccccaa agtcagcgcc tatcagtacc gggtgttccg cgtccaactg 240

cccgatccca acaagttcgg cctgcccgac acctccatct acaaccccga gacccagagg 300

ctggtctggg cttgcgccgg cgtcgagatc gggaggggcc aacccctggg cgtggggttg 360

tccggccacc ccttctacaa caagctggac gataccgagt ccagccacgc agcaaccagc 420

aacgtctccg aagatgtgcg cgataacgtc agcgtggact acaaacaaac ccaactgtgc 480

atcctgggat gcgcacccgc catcggcgag cattgggcca aggggaccgc ctgcaagagc 540

aggcccctga gccaagggga ctgtccaccc ctggagttga agaataccgt gctcgaggac 600

ggcgacatgg tggacaccgg ctacggcgct atggatttct ccaccctcca ggacaccaag 660

tgcgaagtgc ccctcgacat ctgccaaagc atctgcaagt accccgacta cctccagatg 720

agcgccgacc cctacggcga cagcatgttc ttctgtctca gaagggaaca attgttcgcc 780

cgccacttct ggaaccgggc cggcacaatg ggagatacag tcccccagag cctgtacatc 840

aaggggaccg gaatgagggc cagccccggg tcctgcgtct acagcccaag cccctccggg 900

agcatcgtca caagcgatag ccaactcttc aacaagccct actggctcca caaagcccaa 960

ggccacaata acggggtgtg ttggcacaac cagctgttcg tgaccgtcgt ggacacaacc 1020

aggtccacaa acctgaccat ctgcgccagc acccaaagcc ccgtgcccgg ccagtacgac 1080

gccacaaagt tcaaacaata ctctcggcac gtggaagagt acgacctcca attcatcttc 1140

caactctgca ccatcaccct caccgccgac gtgatgagct acatccactc catgaactcc 1200

tccatcctgg aagactggaa tttcggcgtg ccaccacccc ctaccacctc cctcgtcgac 1260

acctacagat tcgtgcagag cgtggccatc acatgccaga aagacgccgc ccccgccgag 1320

aacaaagacc catacgacaa actgaaattc tggaacgtcg acctgaaaga gaaattcagc 1380

ctggatctgg accagtaccc attgggcagg aagttcctcg tgcaagccgg cctcaggaga 1440

aaaccaacaa tcgggcccag gaagaggagc gcccccagcg caaccaccag cagcaagccc 1500

gcaaaaaggg tcagagtgag ggcacgcaaa taaactcgag ctc 1543

<210> 34

<211> 1534

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 34

ctgggtacca tgagcctgtg gaggcccagc gaggccaccg tgtacctgcc ccccgtgccc 60

gtgagcaagg tggtgagcac cgacgagtac gtgaccagga ccaacatcta ctaccacgcc 120

ggcagcgcca ggctgctgac cgtgggccac cccactaca gcatccccaa gagcgacaac 180

cccaagaaga tcgtggtgcc caaggtgagc ggcctgcagt acagggtgtt cagggtgagg 240

ctgcccgacc ccaacaagtt cggcttcccc gacaccagct tctacaaccc cgagaacccag 300

aggctggtgt gggcctgcgt gggcctggag gtgggcaggg gccagcccct gggcgtgggc 360

atcagcggcc accccctgct gaacaagttc gacgacaccg agaacagcaa caggtacgcc 420

ggcggccccg gcaccgacaa cagggagtgc atcagcatgg actacaagca gacccagctg 480

tgcctgctgg gctgcaagcc ccccatcggc gagcactggg gcaagggcag cccctgcagc 540

aacaacgcca tcacccccgg cgactgcccc cccctggagc tgaagaacag cgtgatccag 600

gacggcgaca tggtggacac cggcttcggc gccatggact tcaccgccct gcaggacacc 660

aagagcaacg tgcccctgga catctgcaac agcatctgca agtaccccga ctacctgaag 720

atggtggccg agccctacgg cgacaccctg ttcttctacc tgaggaggga gcagatgttc 780

gtgaggcact tcttcaacag gagcggcacc gtgggcgaga gcgtgcccac cgacctgtac 840

atcaagggca gcggcagcac cgccaccctg gccaacagca cctacttccc cacccccagc 900

ggcagcatgg tgaccagcga cgcccagatc ttcaacaagc cctactggat gcagaggggcc 960

caggggccaca acaacggcat ctgctggggc aaccagctgt tcgtgaccgt ggtggacacc 1020

accaggagca ccaacatgag cgtgtgcgcc gccatcgcca acagcgacac caccttcaag 1080

agcagcaact tcaaggagta cctgaggcac ggcgaggagt tcgacctgca gttcatcttc 1140

cagctgtgca agatcaccct gagcgccgac atcatgacct acatccacag catgaacccc 1200

gccatcctgg aggactggaa cttcggcctg accacccccc ccagcggcag cctggaggac 1260

acctacaggt tcgtgaccag ccaggccatc acctgccaga agtccgcccc ccagaagccc 1320

aaggaggacc ccttcaagga ctacgtgttc tgggaggtga acctgaagga gaagttcagc 1380

gccgacctgg accagttccc cctgggcagg aagttcctgc tgcaggccgg ctacagggcc 1440

aggcccaagt tcaaggccgg caagaggagc gcccccagcg ccagcaccac cacccccgcc 1500

aagaggaaga agaccaagaa gtaaactcga gctc 1534

<210> 35

<211> 1528

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 35

ctgggtacca tgagtctgtg gaggagcaat gaggctacag tctacctgcc tcctgtgtct 60

gtgagcaagg tggtgagcac agatgaatat gtgaccagga ccaacatcta ctaccatgct 120

ggctccagca gactgctggc tgtgggacac ccatactatg ccatcaagaa gcaggacagc 180

aacaagattg ctgtgccaaa ggtgtctgga ctccaataca gggtgttcag ggtgaaactg 240

cctgacccaa acaagtttgg ctttcctgac acctccttct atgaccctgc cagccagaga 300

ctggtgtggg cttgtactgg agtggaggtg ggcaggggac aaccactggg agtgggcatc 360

tctggacacc cactgctgaa caaactggat gacacagaga acagcaacaa atatgtgggc 420

aactctggca cagacaacag ggagtgtatc agtatggact acaagcagac ccaactttgt 480

ctgattggct gtagacctcc aattggagaa cactggggca agggcacacc atgtaatgcc 540

aaccaggtga aggctggaga gtgtcctcca ttggaactgc tgaacacagt gctccaagat 600

ggagatatgg tggacacagg ctttggagct atggacttca ccaccctcca agccaacaag 660

tctgatgtgc cactggacat ctgttccagc atctgtaaat accctgacta cctgaaaatg 720

gtgtctgaac catatggaga tatgctgttc ttctacctga ggagggaaca gatgtttgtg 780

agacacctgt tcaacagggc tggcacagtg ggagagacag tgcctgctga cctctacatc 840

aagggcacca caggcaccct gccaagcacc tcctactttc caacaccatc tggcagtatg 900

gtgacctctg atgcccagat tttcaacaag ccatactggc tccaaagggc tcaaggacac 960

aacaatggca tctgttggag caaccaactt tttgtgacag tggtggacac caccaggagc 1020

accaatatga gtgtgtgttc tgctgtgtcc tcctctgaca gcacctacaa gaatgacaac 1080

ttcaaggaat acctgagaca tggagaggaa tatgacctcc aattcatctt ccaactttgt 1140

aagattaccc tgacagcaga tgtgatgacc tacatccaca gtatgaaccc aagcatcttg 1200

gaggactgga actttggact gacacctcct ccatctggca ccttggagga cacctacaga 1260

tatgtgacca gccaggctgt gacttgtcag aagccatctg ccccaaagcc aaaggatgac 1320

ccactgaaaa actacacctt ctgggaggtg gacctgaaag agaagttctc tgctgacctg 1380

gaccagtttc cactgggcag gaagttcctg ctccaagcag gactgaaagc cagaccaaac 1440

ttcagactgg gcaagagggc tgcccctgcc agcaccagca agaagtccag caccaagagg 1500

aggaaggtga agagctaaac tcgagctc 1528

<210> 36

<211> 1537

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 36

ctgggtacca tggctatgtg gaggtcctct gacagtatgg tctacctgcc tcctccatct 60

gtggctaagg tggtgaacac agatgactat gtgaccagga caggcatcta ctactatgct 120

ggctccagca gactgctgac agtgggacac ccatacttca aggtggggat gaatggaggc 180

aggaagcagg acatcccaaa ggtgtctgcc taccaataca gggtgttcag ggtgaccctg 240

cctgacccaa acaagttcag catccctgat gcctccctct acaaccctga gacccagaga 300

ctggtgtggg cttgtgtggg agtggaggtg ggcaggggac aaccactggg agtgggcatc 360

tctggacacc cactctacaa cagacaggat gacacagaga acagcccatt ctccagcacc 420

accaacaagg acagcaggga caatgtgtct gtggactaca agcagaccca actttgtatc 480

attggctgtg tgcctgccat tggagaacac tggggcaagg gcaaggcttg taagccaaac 540

aatgtgagca caggagactg tcctccatg gaactggtga acacaccaat tgaggatgga 600

gatatgattg acacaggcta tggagctatg gactttggag ccctccaaga gaccaagtct 660

gaggtgccac tggacatctg tcagagcatc tgtaaatacc ctgactacct ccaaatgagt 720

gctgatgtct atggagacag tatgttcttc tgtctgagga gggaacaact ttttgccaga 780

cacttctgga acaggggagg gatggtggga gatgccatcc ctgcccaact ctacatcaag 840

ggcacagaca tcagggctaa ccctggctcc tctgtctact gtccaagccc atctggcagt 900

atggtgacct ctgacagcca acttttcaac aagccatact ggctgcacaa ggctcaagga 960

cacaacaatg gcatctgttg gcacaaccaa cttttcctga cagtggtgga caccaccagg 1020

agcaccaact tcaccctgag caccagcatt gagtccagca tcccaagcac ctatgaccca 1080

agcaagttca aggaatacac caggcatgtg gaggaatatg acctccaatt catcttccaa 1140

ctttgtactg tgaccctgac cacagatgtg atgagttaca tccacacaat gaactccagc 1200

atcctggaca actggaactt tgctgtggct cctcctccat ctgcctccct ggtggacacc 1260

tacagatacc tccaatctgc tgccatcact tgtcagaagg atgcccctgc ccctgagaag 1320

aaggacccat atgatggact gaagttctgg aatgtggacc tgagggagaa gttctccttg 1380

gaactggacc agtttccact gggcaggaag ttcctgctcc aagccagggt gaggaggaga 1440

ccaaccattg gaccaaggaa gagacctgct gccagcacct cctcctcctc tgccaccaaa 1500

cacaagagga agaggtgag caagtaaact cgagctc 1537

<210> 37

<211> 1543

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 37

ctgggtacca tggctctgtg gagaccatct gacagcacag tctacctgcc tcctccatct 60

gtggcaaggg tggtgaacac agatgactat gtgagcagga ccagcatctt ctaccatgct 120

ggctccagca gactgctgac agtgggcaac ccatacttca gggtggtgcc aagtggagca 180

ggcaacaagc aggctgtgcc aaaggtgtct gcctaccaat acagggtgtt cagggtggct 240

ctgcctgacc caaacaagtt tggactgcct gacagcacca tctacaaccc tgagacccag 300

agactggtgt gggcttgtgt ggggatggag attggcaggg gacaaccact gggcattgga 360

ctgtctggac acccattcta caacaaactg gatgacacag agtctgccca tgctgccaca 420

gcagtgatta cccaggatgt gagggacaat gtgtctgtgg actacaagca gacccaactt 480

tgtatcctgg gctgtgtgcc tgccattgga gaacactggg ctaagggcac cctgtgtaag 540

cctgcccaac tccaacctgg agactgtcct ccattggaac tgaaaaacac catcattgag 600

gatggagata tggtggacac aggctatgga gctatggact tcagcaccct ccaagacacc 660

aagtgtgagg tgccactgga catctgtcag agcatctgta aataccctga ctacctccaa 720

atgagtgctg acccatatgg agacagtatg ttcttctgtc tgaggagga acaacttttt 780

gccagacact tctggaacag ggctggagtg atgggagaca cagtgccaac agacctctac 840

atcaagggca cctctgccaa tatgagggag acacctggct cctgtgtcta cagcccaagc 900

ccatctggca gcatcaccac ctctgacagc caacttttca acaagccata ctggctgcac 960

aaggctcaag gacacaacaa tggcatctgt tggcacaacc aactttttgt gacagtggtg 1020

gacaccacca ggagcaccaa cctgaccctg tgtgccagca cccagaaccc tgtgccaaac 1080

acctatgacc caaccaagtt caagcactac agcaggcatg tggaggaata tgacctccaa 1140

ttcatcttcc aactttgtac catcaccctg acagcagagg tgatgagtta catccacagt 1200

atgaactcca gcatcttgga gaactggaac tttggagtgc ctcctcctcc aaccacctcc 1260

ctggtggaca cctacaggtt tgtccagtct gtggctgtga cttgtcagaa ggacaccaca 1320

cctcctgaga agcaggaccc atatgacaaa ctgaagttct ggacagtgga cctgaaagag 1380

aagttctcct ctgacctgga ccaataccca ctgggcagga agttcctggt ccaggctgga 1440

ctgaggagga gaccaaccat tggaccaagg aagagacctg ctgccagcac cagcacagcc 1500

agcagacctg ccaagagggt gaggattagg agcaagaagt aaa 1543

<210> 38

<211> 1534

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 38

ctgggtacca tggctctgtg gaggaccaat gacagcaagg tctacctgcc tcctgcccct 60

gtgagcagga ttgtgaacac agaggaatac atcaccagga caggcatcta ctactatgct 120

ggctccagca gactgattac cctgggacac ccatactttc caatcccaaa gaccagcacc 180

agggctgcca tcccaaaggt gtctgccttc caatacaggg tgttcagggt ccaacttcct 240

gacccaaaca agtttggact gcctgaccca aacctctaca accctgacac agacagactg 300

gtgtggggct gtgtgggagt ggaggtgggc aggggacaac cactgggagt gggactgtct 360

ggacacccac tgttcaacaa atatgatgac acagagaaca gcaggattgc caatggcaat 420

gcccaacagg atgtgaggga caacacctct gtggacaaca agcagaccca actttgtatc 480

attggctgtg cccctccaat tggagaacac tggggcattg gcaccacttg taagaacaca 540

cctgtgcctc ctggagactg tcctccatg gaactggtgt cctctgtgat tcaggatgga 600

gatatgattg acacaggctt tggagctatg gactttgctg ccctccaagc caccaagtct 660

gatgtgccac tggacatcag ccagtctgtg tgtaaatacc ctgactacct gaaaatgagt 720

gctgacacct atggcaacag tatgttcttc cacctgagga gggaacagat ttttgccaga 780

cactactaca acaaactggt gggagtggga gaggacatcc caaatgacta ctacatcaag 840

ggctctggca atggcaggga cccaattgag tcctacatct actctgccac accatctggc 900

agtatgatta cctctgacag ccagattttc aacaagccat actggctgca cagggctcaa 960

ggacacaaca atggcatctg ttggaacaac caacttttca tcacttgtgt ggacaccacc 1020

aggagcacca acctgaccat cagcacagcc acagcagcag tgagcccaac cttcacacca 1080

agcaacttca agcaatacat cagacatgga gaggaatatg aactccaatt catcttccaa 1140

ctttgtaaga ttaccctgac cacagaggtg atggcttacc tgcacacaat ggacccaacc 1200

atcttggaac agtggaactt tggactgacc ctgcctccat ctgcctcctt ggagatgcc 1260

tacaggtttg tgaggaatgc tgccacctcc tgtcagaagg acacacctcc acaggctaag 1320

cctgacccac tggctaaata caagttctgg gatgtggacc tgaaagagag gttctccctg 1380

gacctggacc agtttgccct gggcaggaag ttcctgctcc aagtgggagt cgaggaag 1440

ccaagacctg gactgaaaag acctgcctcc tctgcctcct cctcctcctc ctcctctgcc 1500

aagaggaaga gggtgaagaa gtaaactcga gctc 1534

<210> 39

<211> 1531

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 39

ctgggtacca tgagcgtgtg gaggcccagc gaggccaccg tgtacctgcc ccccgtgccc 60

gtgagcaagg tggtgagcac cgacgagtac gtgagcagga ccagcatcta ctactacgcc 120

ggcagcagca ggctgctgac cgtgggccac ccctacttca gcatcaagaa caccagcagc 180

ggcaacggca agaaggtgct ggtgcccaag gtgagcggcc tgcagtacag ggtgttcagg 240

atcaagctgc ccgaccccaa caagttcggc ttccccgaca ccagcttcta caaccccgag 300

acccagaggc tggtgtgggc ctgcaccggc ctggagatcg gcaggggcca gcccctgggc 360

gtgggcatca gcggccaccc cctgctgaac aagttcgacg acaccgagac cagcaacaag 420

tacgccggca agcccggcat cgacaacagg gagtgcctga gcatggacta caagcagacc 480

cagctgtgca tcctgggctg caagcccccc atcggcgagc actggggcaa gggcaccccc 540

tgcaacaaca acagcggcaa ccccggcgac tgcccccccc tgcagctgat caacagcgtg 600

atccaggacg gcgacatggt ggacaccggc ttcggctgca tggacttcaa caccctgcag 660

gccagcaaga gcgacgtgcc catcgacatc tgcagcagcg tgtgcaagta ccccgactac 720

ctgcagatgg ccagcgagcc ctacggcgac agcctgttct tcttcctgag gagggagcag 780

atgttcgtga ggcacttctt caacagggcc ggcaccctgg gcgaccccgt gcccggcgac 840

ctgtacatcc agggcagcaa cagcggcaac accgccaccg tgcagagcag cgccttcttc 900

cccaccccca gcggcagcat ggtgaccagc gagagccagc tgttcaacaa gccctactgg 960

ctgcagaggg cccaggggcca caacaacggc atctgctggg gcaaccagct gttcgtgacc 1020

gtggtggaca ccaccaggag caccaacatg accctgtgcg ccgaggtgaa gaaggagagc 1080

acctacaaga acgagaactt caaggagtac ctgaggcacg gcgaggagtt cgacctgcag 1140

ttcatcttcc agctgtgcaa gatcaccctg accgccgacg tgatgaccta catccacaag 1200

atggacgcca ccatcctgga ggactggcag ttcggcctga cccccccccc cagcgccagc 1260

ctggaggaca cctacaggtt cgtgaccagc accgccatca cctgccagaa gaacaccccc 1320

cccaagggca aggaggaccc cctgaaggac tacatgttct gggaggtgga cctgaaggag 1380

aagttcagcg ccgacctgga ccagttcccc ctgggcagga agttcctgct gcaggccggc 1440

ctgcaggcca ggcccaagct gaagaggccc gccagcagcg cccccaggac cagcaccaag 1500

aagaagaagg tgaagaggta aactcgagct c 1531

<210> 40

<211> 1519

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 40

ctgggtacca tggctacctg gagaccatct gagaacaagg tctacctgcc tccaacacct 60

gtgagcaagg tggtggctac agactcctat gtgaagagga ccagcatctt ctaccatgct 120

ggctccagca gactgctggc tgtgggacac ccatactact ctgtgaccaa ggacaacacc 180

aagaccaaca tcccaaaggt gtctgcctac caatacaggg tgttcaggt gagactgcct 240

gacccaaaca agtttggact gcctgacacc aacatctaca accctgacca ggagagactg 300

gtgtgggctt gtgtgggatt ggaggtgggc aggggacaac cactgggagc aggactgtct 360

ggacacccac tgttcaacag actggatgac acagagtcca gcaacctggc taacaacaat 420

gtgattgagg acagcaggga caacatctct gtggatggca agcagaccca actttgtatt 480

gtgggctgta ctcctgctat gggagaacac tggaccaagg gagcagtgtg taagagcacc 540

caggtgacca caggagactg tcctccactg gctctgataa acacaccaat tgaggatgga 600

gatatgattg acacaggctt tggagctatg gacttcaagg tgctccaaga gagcaaggct 660

gaggtgccac tggacattgt ccagagcact tgtaaatacc ctgactacct gaaaatgagt 720

gctgatgcct atggagacag tatgtggttc tacctgagga gggaacaact ttttgccaga 780

cactacttca acagggctgg caaggtggga gagaccatcc ctgctgaact ctacctgaaa 840

ggcagcaatg gcagggaacc tcctccatcc tctgtctatg tggctacacc atctggcagt 900

atgattacct ctgaggctca acttttcaac aagccatact ggctccaaag ggctcaagga 960

cacaacaatg gcatctgttg gggcaaccaa ctttttgtga cagtggtgga caccaccagg 1020

agcaccaata tgaccatcag cacagccaca gaacaactta gcaaatatga tgccaggaag 1080

ataaaccaat acctgaggca tgtggaggaa tatgaactcc aatttgtgtt ccaactttgt 1140

aagattaccc tgtctgctga ggtgatggct tacctgcaca atatgaatgc caacctgttg 1200

gaggactgga acattggact gagccctcct gtggctacct ccttggagga caaatacaga 1260

tatgtgagga gcacagccat cacttgtcag agggaacaac ctccaacaga gaagcaggac 1320

ccactggcta aatacaagtt ctgggatgtg aacctccaag actccttcag cacagacctg 1380

gaccagtttc cactgggcag gaagttcctg atgcaacttg gcaccaggag caagcctgct 1440

gtggctacca gcaagaagag gtctgcccca accagcacca gcacacctgc caagaggaag 1500

aggaggtaaa ctcgagctc 1519

<210> 41

<211> 1507

<212> DNA

<213> Artificial sequence

<220>

<223> The sequence is artificially synthesized

<400> 41

ctgggtacca tgagcgtgtg gaggcccagc gaggccaccg tgtacctgcc ccccgtgccc 60

gtgagcaagg tggtgagcac cgacgagtac gtgagcagga ccagcatcta ctactacgcc 120

ggcagcagca ggctgctggc cgtgggcaac ccctacttca gcatcaagag ccccaacaac 180

aacaagaagg tgctggtgcc caaggtgagc ggcctgcagt acagggtgtt cagggtgagg 240

ctgcccgacc ccaacaagtt cggcttcccc gacaccagct tctacaaccc cgacaccag 300

aggctggtgt gggcctgcgt gggcctggag atcggcaggg gccagcccct gggcgtgggc 360

gtgagcggcc accctacct gaacaagttc gacgacaccg agaccagcaa caggtacccc 420

gcccagcccg gcagcgacaa cagggagtgc ctgagcatgg actacaagca gacccagctg 480

tgcctgatcg gctgcaagcc ccccaccggc gagcactggg gcaagggcgt ggcctgcaac 540

aacaacgccg ccgccaccga ctgccccccc ctggagctgt tcaacagcat catcgaggac 600

ggcgacatgg tggacaccgg cttcggctgc atggacttcg gcaccctgca ggccaacaag 660

agcgacgtgc ccatcgacat ctgcaacagc acctgcaagt accccgacta cctgaagatg 720

gccagcgagc cctacggcga cagcctgttc ttcttcctga ggagggagca gatgttcgtg 780

aggcacttct tcaacagggc cggcaagctg ggcgaggccg tgcccgacga cctgtacatc 840

aagggcagcg gcaacaccgc cgtgatccag agcagcgcct tcttccccac ccccagcggc 900

agcatcgtga ccagcgagag ccagctgttc aacaagccct actggctgca gagggcccag 960

ggccacaaca acggcatctg ctggggcaac cagctgttcg tgaccgtggt ggacaccacc 1020

aggagcacca acatgaccct gtgcaccgag gtgaccaagg agggcaccta caagaacgac 1080

aacttcaagg agtacgtgag gcacgtggag gagtacgacc tgcagttcgt gttccagctg 1140

tgcaagatca ccctgaccgc cgagatcatg acctacatcc acaccatgga cagcaacatc 1200

ctggaggact ggcagttcgg cctgaccccc ccccccagcg ccagcctgca ggacacctac 1260

aggttcgtga ccagccaggc catcacctgc cagaagaccg ccccccccaa ggagaaggag 1320

gaccccctga acaagtacac cttctgggag gtgaacctga aggagaagtt cagcgccgac 1380

ctggaccagt tccccctggg caggaagttc ctgctgcaga gcggcctgaa ggccaagccc 1440

aggctgaaga ggagcgcccc caccaccagg gcccccagca ccaagaggaa gaaggtgaag 1500

aagtaaa 1507

<---

Claims (57)

1. A stable preparation of a polyvalent vaccine from virus-like particles of human papillomavirus (HPV) for the prevention of diseases or infections associated with HPV, containing: (a) a plurality of human papillomavirus virus-like particles, wherein the concentration of any individual type of human papillomavirus virus-like particles included in the polyvalent human papillomavirus virus-like particles is from 40 to 120 μg/ml; (b) an adjuvant which is aluminum phosphate; (c) histidine buffer at a concentration of 10 to 26 mM; (d) an osmotic pressure regulator, which is sodium chloride at a concentration of 150 to 320 mM; and, optionally, (d) a surfactant, which is polysorbate 80 at a concentration of not more than 0.3 mg/ml, wherein said virus-like particles of human papillomavirus are selected from virus-like particles of HPV formed by L1 proteins of HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58; and one or more HPV virus-like particles formed by L1 proteins of other pathogenic HPV types selected from HPV types 35, 39, 51, 56 and 59, wherein the said virus-like particles of human papillomavirus are adsorbed on an adjuvant. 2. The preparation according to item 1, characterized in that The adjuvant, which is an aluminum phosphate, is aluminum hydroxyphosphate (AlPO ₄ ). 3. The drug according to paragraph 1 or 2, characterized in that: (a) the total concentration of virus-like particles of papillomaviruses of all types ranges from 80 to 740 μg/ml; (b) the buffer concentration is 10 mM, 18 mM or 26 mM; (c) the concentration of the osmotic pressure regulator is 150 mM or 320 mM; (d) the concentration of surfactant is from 0 to 0.02 wt.%; (d) the concentration of adjuvant is 1.0 mg/ml; (e) The pH of the preparation is in the range from 5.9 to 6.5, preferably 5.9, 6.2 or 6.5. 4. The preparation according to any one of claims 1-3, containing 0.74 mg/ml of all virus-like particles of papillomaviruses of all types, 1.0 mg/ml of aluminum phosphate adjuvant, 18 mM histidine buffer, 320 mM sodium chloride, pH 6.2; and, optionally, polysorbate 80 at a concentration of no more than 0.3 mg/ml. 5. The preparation according to claim 4, characterized in that at least one of the HPV virus-like particles is a chimeric HPV virus-like particle containing a chimeric HPV L1 protein; wherein said chimeric HPV L1 protein contains from its N-terminus to its C-terminus: a) an N-terminal fragment obtained from the L1 protein of the first papillomavirus, wherein said N-terminal fragment retains the immunogenicity of the L1 protein of the first papillomavirus and said L1 protein of the first papillomavirus is selected from HPV types 6, 11, 16, 18, 31, 35, 39, 45, 51, 52, 56, 58 and one or more other pathogenic types of HPV, wherein the L1 protein of the first papillomavirus type is selected from the L1 protein of HPV type 6, 11, 16, 18, 31, 35, 39, 45, 51, 52, 56 or 58; preferably, its natural sequence is an amino acid sequence encoded by the coding gene set forth in SEQ ID No: 30, SEQ ID No: 31, SEQ ID No: 32, SEQ ID No: 33, SEQ ID No: 34, SEQ ID No: 35, SEQ ID No: 36, SEQ ID No: 37, SEQ ID No: 38, SEQ ID No: 39, SEQ ID No: 40 or SEQ ID No: 41, respectively; and b) A C-terminal fragment obtained from the L1 protein of human papillomavirus type 2, wherein the L1 protein of human papillomavirus type 2 has a better level of expression and solubility compared to L1 proteins of other types, wherein the L1 protein of the second papillomavirus is selected from the L1 protein of HPV type 16, 28, 33, 59 or 68, preferably the L1 protein of the second papillomavirus is selected from the group consisting of the L1 proteins of HPV type 33 or 59; Moreover, the said chimeric protein has the immunogenicity of the L1 protein of the first type of papillomavirus. 6. The preparation according to item 5, characterized in that said N-terminal fragment is a fragment obtained by shortening the C-terminus of the natural sequence of said human papillomavirus type 1 L1 protein at any amino acid position within its α5 region, or a fragment having at least 98% identity thereto; and said C-terminal fragment is a fragment obtained by shortening the N-terminus of the natural sequence of said human papillomavirus type 2 L1 protein at any amino acid position within its α5 region, or a functional variant obtained as a result of additional mutations, deletions and/or additions to said fragment. 7. The preparation according to claim 6, characterized in that the said C-terminal fragment contains one or more nuclear localization sequences. 8. The preparation according to claim 5, characterized in that said C-terminal fragment is SEQ ID No: 1; or a fragment thereof having a length of m1 amino acids, preferably a fragment containing amino acids 1-m1 of SEQ ID No: 1, where m1 is an integer from 8 to 26; or this C-terminal fragment is SEQ ID No: 2, or fragments thereof having a length of m2 amino acids, preferably a fragment comprising amino acids 1-m2 of SEQ ID No: 2, where m2 is an integer from 13 to 31. 9. The preparation according to claim 5, characterized in that said C-terminal fragment is SEQ ID No: 3; or a fragment thereof having a length of n amino acids, preferably a fragment containing amino acids 1-n of SEQ ID No: 3; where n is an integer from 16 to 38. 10. The preparation according to item 5, characterized in that said N-terminal fragment of the HPV type 6 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 4 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 11 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 5 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 16 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 6 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 18 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 7 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 31 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 8 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 35 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 9 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 39 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 10 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 45 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 11 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 51 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 12 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 52 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to the fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 13 at any amino acid position within its α5 region; said N-terminal fragment of the HPV type 56 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to a fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 14 at any amino acid position within its α5 region; and said N-terminal fragment of the HPV type 58 L1 protein has 98%, 98.5%, 99%, 99.5%, 99% or 100% identity to a fragment obtained by shortening the C-terminus of the sequence presented in SEQ ID No: 15 at any amino acid position within its α5 region. 11. The preparation according to item 5, characterized in that the C-terminus of the N-terminal fragment is connected directly to the N-terminus of the C-terminal fragment or is connected to it via a linker. 12. The preparation according to claim 5, characterized in that when the C-terminus of said N-terminal fragment is connected to the N-terminus of said C-terminal fragment, the continuous amino acid sequence RKFL is present in the range of plus or minus 4 amino acid positions from the splicing site, preferably, the contiguous amino acid sequence LGRKFL is present within a range of plus or minus 6 amino acid positions from the splice site. 13. The preparation according to item 5, characterized in that chimeric HPV L1 proteins of types 6, 11, 16, 18, 31, 35, 39, 45, 51, 52, 56 and 58 have 98%, 98.5%, 99%, 99.5% or 100% identity to SEQ ID No: 16, SEQ ID No: 17, SEQ ID No: 18, SEQ ID No: 19, SEQ ID No: 20, SEQ ID No: 21, SEQ ID No: 22, SEQ ID No: 23, SEQ ID No: 24, SEQ ID No: 25, SEQ ID No: 26 and SEQ ID No: 27, respectively; and HPV type 33 L1 protein and HPV type 59 L1 protein have 98%, 98.5%, 99%, 99.5% or 100% identity to SEQ ID No: 28 and SEQ ID No: 29, respectively. 14. The preparation according to item 13, containing chimeric proteins of HPV L1 types 6, 11, 16, 18, 31, 35, 39, 45, 51, 52, 56 and 58 having the amino acid sequences shown in SEQ ID No: 16, SEQ ID No: 17, SEQ ID No: 18, SEQ ID No: 19, SEQ ID No: 20, SEQ ID No: 21, SEQ ID No: 22, SEQ ID No: 23, SEQ ID No: 24, SEQ ID No: 25, SEQ ID No: 26 and SEQ ID No: 27, respectively; and HPV type 33 L1 protein and HPV type 59 L1 protein having the amino acid sequences shown in SEQ ID No: 28 and SEQ ID No: 29, respectively. 15. A vaccine preparation against papillomavirus according to paragraphs 1-14, characterized in that it can be stably stored at a temperature of 2 to 8°C for at least 24 months and at 25°C for at least 16 weeks. 16. A method for preventing an HPV-associated disease or infection comprising administering to a subject a drug according to any one of claims 1-15. 17. Use of a preparation according to any of paragraphs 1-15 for obtaining a vaccine for the prevention of an HPV-associated disease or infection.